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Unn Kristin Hansen Haukvik

Professor II - Department of Adult Psychiatry

Email u.k.h.haukvik@medisin.uio.no

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Visiting address Administrasjonen sitter i bygg 20 3. etasje Gaustad sykehus 0372 Oslo

Postal address Postboks 1039 Blindern 0315 Oslo

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Research interests

Neuroimaging brain anatomy and function in psychotic disorders
The neurobiology, psychology, and social characteristics of violent and antisocial behaviour
Criminal responsibility, law and neuroscience.
Phenomenology and philosophy of psychosis

Teaching and institutional responsibilities

Head of the forensic psychiatry research group, Department of Mental Health and Addiction, Faculty of Medicine
Clinical psychiatry and forensic psychiatry for medical students
Member of the exam committee and subject committee MEDSEM 4500R
Supervision of Post Docs, PhD-candidates, and master students in psychiatry and cognitive neuroscience
Host of the podcast Psykopoden
Co-chair of the regional medical ethics committee REK Sørøst C

Academic background

Professor of psychiatry at the University of Oslo
Consultant psychiatrist at the Centre for forensic psychiatry research and education (SIFER), Oslo University Hospital
Post doctoral researcher in Neuroimaging and psychiatry at the University of Oslo and University of California San Diego
PhD at the University of Oslo in 2011
Medical Degree (MD), University of Oslo, 2004
Bachelor degree (Cand. mag.) in literature, social anthropology, and development studies in 2001

Heilskov, Søren Esben Rytter; Nordgaard, Julie; Haukvik, Unn Kristin Hansen & Friestad, Christine (2026). Making sense of “senseless actions” in relation to criminal insanity. Frontiers in Psychiatry. 17. doi: 10.3389/fpsyt.2026.1833835. Full text in Research Archive Show summary
In the assessment of criminal insanity, delusions play a particularly important role, because they express reality judgments, which, due to their verbalized form, serve well as “evidence” of psychosis. However, psychosis, understood as a fundamentally impaired sense of reality, can also involve disturbances that are neither verbalized nor inferential, but mainly enacted . In this paper, we revisit the psychopathological concept of “senseless actions”, employed by the German psychiatrist Klaus Conrad to describe the unintelligible actions observed in individuals in the early phase of schizophrenia. The forensic relevance of this concept is illustrated with a historical case study from the annals of Karl Wilmanns. We discuss how “senseless actions” express a global disturbance in the individual’s way of finding relevance, meaning, and constraint in the world, and argue that “senseless actions” may function as a behavioral indicator of the transition between a prodromal phase and manifest psychosis – pointing again to its forensic relevance. We stress the importance of considering contextual information and adopt a Gestalt view of how the actions inscribe themselves in the biography of the individual when determining whether “senseless actions” are indicative of psychosis. In conclusion, we suggest that the concept of “senseless action”, though imperfect and context sensitive, may offer a framework for identifying disturbances in reality understanding that risk being marginalized in contemporary approaches to criminal insanity.
Tesli, Natalia; Jaholkowski, Piotr Pawel; Rokicki, Jaroslav; Jangmo, Andreas; Ziaka, Laoura & Shadrin, Alexey [Show all 9 contributors for this article] (2026). Adolescents at the crossroads: genetic associations between psychotic symptoms and antisocial traits | European Child & Adolescent Psychiatry | Springer Nature Link. European Child and Adolescent Psychiatry. ISSN 1018-8827. doi: 10.1007/s00787-026-03153-w. Full text in Research Archive Show summary
Antisocial behaviour in youth has serious consequences at individual and societal level. Adolescence is also a critical period for the emergence of prodromal psychosis symptoms. Their co-occurrence may aggravate aggression and lead to severe adverse outcomes. Common genetic risk for psychosis, antisocial behaviour, and substance use has been suggested, but the putatively shared genetic architecture is unknown, and evidence in youth is limited. Here we examined whether common genetic liability indexed by polygenic risk scores (PRSs) relates to these complex traits in the Norwegian Mother, Father and Child Cohort Study (MoBa; n = 18960). Antisocial psychopathology was operationalised as three complementary dimensions: conduct-disorder (CD) traits, oppositional-defiant disorder (ODD) traits, and psychopathy traits. We first quantified phenotypic correlations between psychotic-like experiences (PLEs) and the antisocial dimensions. We then evaluated PRS-phenotype associations (single-PRS and joint multivariable models) using PRSs for antisocial behaviour (PRSASB) and schizophrenia (PRSSCZ), in addition to PRS for alcohol use disorder (PRSAUD). We found phenotypic correlations between antisocial traits and PLEs (rs=0.13–0.34, p < 0.0001). This overlap was reflected at the genetic level, as we found associations between PRSASB and PLEs (p = 0.0004). The associations between PRSSCZ and antisocial traits were present for CD (p = 0.005) and ODD (p = 0.003) traits. Both PLEs and antisocial traits were associated with PRSAUD. Patterns persisted in mutually adjusted models. These findings indicate cross-trait associations between polygenic liability for SCZ, ASB, AUD and adolescent PLEs and antisocial dimensions in the general youth population, consistent with partially shared common genetic influences. Future studies should further delineate underlying biological mechanisms.
Vaskinn, Anja; Haukvik, Unn Kristin Hansen & Friestad, Christine (2026). Autism Spectrum Disorders in Imprisoned Women: A Concise Systematic Review. Review Journal of Autism and Developmental Disorders. ISSN 2195-7177. doi: 10.1007/s40489-026-00572-y. Full text in Research Archive Show summary
Research suggests that autism rates may be higher in justice-involved populations than in the general population, but studies have focused on men. The aim of this concise systematic review was to report on the prevalence of autism spectrum disorder in women serving prison sentences, and to describe their biopsychosocial and criminal history characteristics. The systematic search yielded only two papers, from the same study. It reported prevalence rates among adolescents in secure care in England and Wales at a specific date in 2016. There were no young women with an autism spectrum condition in the youth justice system. Studies of imprisoned women with autism are scarce. There is a need for future studies of this important issue.
Rokicki, Jaroslav; Friestad, Christine; Haukvik, Unn Kristin Hansen; Bradshaw, Catherine P. & Ünlü, Ali (2026). Exploring mental health and violence narratives on X: insights from social media data. Critical Public Health. ISSN 0958-1596. 36(1). doi: 10.1080/09581596.2025.2612449. Full text in Research Archive
Walt, K. van der; Wootton, O.; Rokicki, Jaroslav; Vaskinn, Anja; Jonker, D. & Campbell, M. [Show all 11 contributors for this article] (2025). Exploring the relationships between Early Childhood Adversity, Social Cognition, and Aggression in a South African Study of People Living with Schizophrenia. Schizophrenia Research: Cognition. 42. doi: 10.1016/j.scog.2025.100382. Full text in Research Archive Show summary
People living with schizophrenia (PLS) are at increased risk of being both victims and perpetrators of violence. Recent research suggests that social cognitive impairments may contribute to heightened aggression in schizophrenia. Childhood trauma, a well-established risk factor for both schizophrenia and aggression, is also linked to more severe cognitive deficits in PLS. Few studies have explored the relationships between childhood trauma, social cognition, and aggression in large sample sizes, particularly in low- and middle-income settings, where varying socioeconomic factors and exposure to violence may influence these associations. In this study, a subsample of participants (PLS = 585; controls = 882) from the Genomics of Schizophrenia in the South African Xhosa People study completed The Childhood Trauma Questionnaire (CTQ), Penn Emotion Identification Test (ER), Life History of Aggression Questionnaire (LHA), and Structured Diagnostic Interview for DSM-IV Axis I Disorders. Group differences in CTQ, ER, LHA, and selected demographic and clinical factors were assessed using t-tests and chi-square tests. Multivariable linear regressions were employed to test for associations among CTQ, ER, and LHA. We found that PLS had significantly higher childhood trauma and lifetime aggression scores and poorer emotion recognition performance than controls. Higher childhood trauma was associated with higher lifetime aggression and worse emotion recognition performance. However, emotion recognition performance was not associated with lifetime aggression. In this setting, childhood trauma predicts lifetime aggression and poorer emotion recognition, but there is no evidence that emotion recognition ability is related to aggression.
Gröning, Anna Linda; Radovic, Susanna & Haukvik, Unn Kristin Hansen (2025). Reconsidering the Relationship Between Criminal Insanity and Delusions. The journal of the American Academy of Psychiatry and the Law. ISSN 1093-6793. 53(1), p. 35–44. doi: 10.29158/JAAPL.240085-24. Full text in Research Archive
Rokicki, Jaroslav; Campbell, Megan L.; Meer, Dennis van der; Sartorius, Alina Marie; Tesli, Natalia & Jaholkowski, Piotr Pawel [Show all 11 contributors for this article] (2025). Brain-based gene expression and corresponding behavioural relevance of risk genes for broad antisocial behaviour. NeuroImage. ISSN 1053-8119. 311. doi: 10.1016/j.neuroimage.2025.121198. Full text in Research Archive
Fischer-Vieler, Thomas; Rokicki, Jaroslav; Kim, Milin; Leonardsen, Esten Høyland; Wolfers, Thomas & Bell, Christina [Show all 14 contributors for this article] (2025). Mapping cerebellar subregional volumes and heterogeneity in schizophrenia spectrum disorders and violence. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. doi: 10.1007/s00406-025-02081-1. Full text in Research Archive Show summary
Cerebellar abnormalities have been linked to schizophrenia and aggressive behaviour. Subregional cerebellar morphology reflects structural organization and function and show great heterogeneity, which may be linked to shared or distinct underlying mechanisms of violence and psychosis but remain unexplored in these marginalized groups. Total and subregional cerebellar volumes were estimated from 3 T MRI scans from persons with schizophrenia spectrum disorders without (SSD-NV; n = 107) or with (SSD-V; n = 36) a history of severe violence, violent offenders without schizophrenia (NPV; n = 20), and 411 healthy controls. Group difference analyses by GLMs were complemented by novel heterogeneity analyses using pre-trained models and norm-charts of lifespan cerebellar volumes to assess individual deviation patterns. We found decreased grey matter volumes in the posterior cerebellar hemispheres and the vermal regions in both SSD-V and SSD-NV, but with a different subregional distribution. Specifically, SSD-V showed differences in the right Crus I (p = .045, Cohen’s d = .62) and Vermis IX (p < .001, Cohen’s d = .81) in the groupwise comparisons. In addition, individual-level extreme negative deviations were detected in the Vermis IX region in 11% of SSD-V and in some subregions of the posterior cerebellum and the vermis in > 10% of NPV. By applying novel analytical tools, we report different patterns of cerebellar subregion volume reductions associated with violence in individuals with or without schizophrenia spectrum disorders. The partly converging results from the group comparisons and the normative modelling analyses demonstrate the usefulness of complemental methodological approaches to disentangle the complex biological associations between violence and psychosis.
Bang, Nina; Nesset, Merete Berg; Rasmussen, Kirsten; Dahl, Hilde; Bell, Christina & Fischer-Vieler, Thomas [Show all 13 contributors for this article] (2025). Long-range temporal correlations in violence and psychosis: An EEG-based study. Journal of Psychiatric Research. ISSN 0022-3956. 193, p. 188–197. doi: 10.1016/j.jpsychires.2025.11.013. Full text in Research Archive Show summary
Background A subgroup of individuals with psychosis have increased violence risk. Long-range temporal correlations (LRTC) in electroencephalography (EEG) reflect neural dynamics, but their relevance to violence risk remains unclear. Methods Resting-state EEG was collected from four groups: healthy controls (HC, n = 134), individuals with psychosis and violence history (violent-PSY, n = 16), individuals with psychosis without such history (nonviolent-PSY, n = 38), and violent individuals without psychosis (violent non-PSY, n = 23). LRTC was quantified using detrended fluctuation analysis (DFA) of mean and peak amplitude dynamics in alpha and beta bands during eyes-closed (EC) and eyes-open (EO) conditions, yielding eight metrics: LRTC for mean and peak amplitudes of alphaEC, betaEC, alphaEO, and betaEO. Results No significant group differences in LRTC were observed in eyes-open conditions (all p > 0.05). In contrast, eyes-close conditions showed significantly reduced LRTC in the nonviolent-PSY group relative to controls for mean alphaEC, peak alphaEC, and mean betaEC (all p < 0.05; Cohen's d's = 0.49–0.59). No significant LRTC difference emerged between violent and nonviolent psychosis groups. Other group comparisons were non-significant. Lower alpha-band LRTC was associated with greater symptom severity, including higher total PANSS and depressive subscale scores (all p < 0.05; r's = −0.26 to −0.28). Conclusions LRTC was reduced in the nonviolent-PSY group compared to controls but not significantly altered in the violent-PSY group. Nor did it differentiate between psychosis with or without violence history. Although further studies are needed, these findings provide limited support for LRTC as a marker of violence propensity in psychosis.
Haukvik, Unn Kristin Hansen; Wolfers, Thomas; Tesli, Natalia; Bell, Christina; Hjell, Gabriela & Fischer-Vieler, Thomas [Show all 14 contributors for this article] (2025). Individual-level deviations from normative brain morphology in violence, psychosis, and psychopathy. Translational Psychiatry. 15(1), p. 1–8. doi: 10.1038/s41398-025-03343-1. Full text in Research Archive
Pentz, Atle Bråthen; Exposito, Veronica; Jole, Oda van; Nerland, Stener; Melle, Ingrid & Steen, Nils Eiel [Show all 13 contributors for this article] (2025). Auditory MMN is associated with the volume of thalamic higher order nuclei in individuals with psychotic disorders and healthy controls. Schizophrenia Research. ISSN 0920-9964. 276, p. 222–233. doi: 10.1016/j.schres.2025.01.031. Full text in Research Archive Show summary
Objective Predictive coding is a theoretical framework that integrates models of brain dysconnectivity and psychopathology in psychosis. Thalamocortical dysconnectivity as well as reduced thalamic volumes have been reported in psychotic disorders. However, the role of the thalamus in predictive coding is not clear. We examined the relationship between magnetic resonance imaging (MRI)- based thalamic nuclei volumes and mismatch negativity (MMN), a purported index of prediction error signaling known to be impaired in psychosis. Methods We obtained MRI and MMN using a roving paradigm from individuals with SCZ spectrum disorder (SSD, n = 60) or bipolar disorder (BD, n = 69) and HC (n = 252). We segmented volumes of 25 thalamic nuclei bilaterally and tested their associations with MMN amplitude using linear models while covarying for age, sex, diagnosis, and intracranial volumes (ICV). Results We did not find group differences in thalamic volumes that could account for differences in MMN, neither did we find significant volume × diagnosis interactions on MMN for any of the 25 nuclei examined. Across the whole sample, significant positive associations were found between MMN amplitude and the volumes of several higher-order thalamic nuclei, including the mediodorsal medial and lateral nuclei, anterior and medial pulvinar, nucleus reuniens, as well as the lateral geniculate nucleus. Conclusion The results demonstrate a positive association between MMN amplitude and volumes of thalamic association nuclei in patients with psychotic disorders and HC. These findings may suggest a modulatory role of the thalamus in prediction error signaling.
Pentz, Atle Bråthen; O'Connell, Kevin Sean; Jole, Oda van; Timpe, Clara Marie Fides; Slapø, Nora Berz & Melle, Ingrid [Show all 14 contributors for this article] (2024). Mismatch negativity and polygenic risk scores for schizophrenia and bipolar disorder. Schizophrenia Research. ISSN 0920-9964. 264, p. 314–326. doi: 10.1016/j.schres.2024.01.013. Full text in Research Archive Show summary
Objective: Auditory mismatch negativity (MMN) impairment is a candidate endophenotype in psychotic disorders, yet the genetic underpinnings remain to be clarified. Here, we examined the relationships between auditory MMN and polygenic risk scores (PRS) for individuals with psychotic disorders, including schizophrenia spectrum disorders (SSD) and bipolar disorder (BD) and in healthy controls (HC). Methods: Genotyped and clinically well-characterized individuals with psychotic disorders (n = 102), including SSD (n = 43) and BD (n = 59), and HC (n = 397) underwent a roving MMN paradigm. In addition MMN, we measured the memory traces of the repetition positivity (RP) and the deviant negativity (DN), which is believed to reflect prediction encoding and prediction error signals, respectively. SCZ and BD PRS were computed using summary statistics from the latest genome-wide association studies. The relationships between the MMN, RP, and DN and the PRSs were assessed with linear regressions. Results: We found no significant association between the SCZ or BD PRS and grand average MMN in the psychotic disorders group or in the HCs group (all p > 0.05). SCZ PRS and BD PRS were negatively associated with RP in the psychotic disorders group (β = 0.46, t = 2.86, p = 0.005 and β = 0.29, t = 0.21, p = 0.034, respectively). No significant associations were found between DN and PRS. Conclusion: These findings suggest that genetic variants associated with SCZ and BD may be associated with MMN subcomponents linked to predictive coding among patients with psychotic disorders. Larger studies are needed to confirm these findings and further elucidate the genetic underpinnings of MMN impairment in psychotic disorders.
Bell, Christina; Rokicki, Jaroslav; Tesli, Natalia; Gurholt, Tiril Pedersen; Hjell, Gabriela & Fischer-Vieler, Thomas [Show all 15 contributors for this article] (2024). Hypothalamic subunit volumes and relations to violence and psychopathy in male offenders with or without a psychotic disorder. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. doi: 10.1007/s00406-023-01725-4. Full text in Research Archive Show summary
Abstract The hypothalamus is key to body homeostasis, including regulating cortisol, testosterone, vasopressin, and oxytocin hormones, modulating aggressive behavior. Animal studies have linked the morphology and function of the hypothalamus to aggression and afliation, with a subregional pattern refecting the functional division between the hypothalamic nuclei. We explored the relationship between hypothalamic subunit volumes in violent ofenders with (PSY-V) and without (NPV) a psychotic disorder, and the association with psychopathy traits. 3T MRI scans (n=628, all male 18–70 years) were obtained from PSY-V, n=38, NPV, n=20, non-violent psychosis patients (PSY-NV), n=134, and healthy controls (HC), n=436. The total hypothalamus volume and its eleven nuclei were delineated into fve subunits using Freesurfer v7.3. Psychopathy traits were assessed with Psychopathy Checklist-revised (PCL-R). ANCOVAs and linear regressions were used to analyze associations with subunit volumes. Both groups with a history of violence exhibited smaller anterior–superior subunit volumes than HC (NPV Cohen’s d=0.56, p=0.01 and PSY-V d=0.38, p=0.01). There were no signifcant diferences between HC and PSY-NV. PCL-R scores were positively associated with the inferior tubular subunit on a trend level (uncorrected p=0.045, Cohen’s d=0.04). We found distinct hypothalamic subunit volume reductions in persons with a history of violence independent of concomitant psychotic disorder but not in persons with psychosis alone. The results provide further information about the involvement of the hypothalamus in aggression, which ultimately may lead to the development of targeted treatment for the clinical and societal challenge of aggression and violent behavior.
Fischer-Vieler, Thomas; Ringen, Petter Andreas; Kvig, Erling Inge; Bell, Christina; Hjell, Gabriela & Tesli, Natalia [Show all 14 contributors for this article] (2024). A phenomenological approach to violence in schizophrenia spectrum disorders: examination of anomalous self-experience. Journal of Forensic Psychiatry & Psychology. ISSN 1478-9949. doi: 10.1080/14789949.2024.2428167. Full text in Research Archive
Gröning, Linda & Haukvik, Unn Kristin Hansen (2024). Neuroscience. In Caeiro, Pedro; Gless, Sabine; Mitsilegas, Valsamis; Costa, Miguel João; Snaijer, Janneke De & Theodorakakou, Georgia (Ed.), Elgar Encyclopedia of Crime and Criminal Justice. Edward Elgar Publishing. ISSN 9781789902983. p. 747–758. doi: 10.4337/9781789902990.neuroscience. Full text in Research Archive
Andreou, Dimitrios; Steen, Nils Eiel; Mørch-Johnsen, Lynn Egeland; Jørgensen, Kjetil Nordbø; Wortinger, Laura Anne & Barth, Claudia [Show all 19 contributors for this article] (2024). Toxoplasma gondii infection associated with inflammasome activation and neuronal injury. Scientific Reports. 14(1). doi: 10.1038/s41598-024-55887-9. Full text in Research Archive Show summary
Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 735 patients with SMI (schizophrenia or bipolar spectrum) (mean age 32 years, 47% women), and 518 healthy controls (HC) (mean age 33 years, 43% women). TOXO IgG, expressed as seropositivity/seronegativity, NSE and IL-18 were measured with immunoassays. We searched for main and interaction effects of TOXO, patient/control status and sex on NSE and IL-18. In the whole sample as well as among patients and HC separately, IL-18 and NSE concentrations were positively correlated (p < 0.001). TOXO seropositive participants had significantly higher NSE (3713 vs. 2200 pg/ml, p < 0.001) and IL-18 levels (1068 vs. 674 pg/ml, p < 0.001) than seronegative participants, and evaluation within patients and HC separately showed similar results. Post-hoc analysis on cytomegalovirus and herpes simplex virus 1 IgG status showed no associations with NSE or IL-18 which may suggest TOXO specificity. These results may indicate ongoing inflammasome activation and neuronal injury in people with TOXO infections unrelated to diagnosis.
Bang, Nina; Pettersen, Johanne Hagen; Nesset, Merete Berg; Rasmussen, Kirsten; Dahl, Hilde & Tesli, Natalia [Show all 15 contributors for this article] (2024). The Startle Response and Prepulse Inhibition in Psychosis and Violence: A Combined Electromyography and Electroencephalography Study. Schizophrenia Bulletin Open. 6(1). doi: 10.1093/schizbullopen/sgae031. Full text in Research Archive Show summary
There is a pressing need for biomarkers of violent behavior risk in psychosis. Previous research indicates that electrophysiological measures of automatic defensive reactions may have potential. The purpose of this study was to investigate associations between violent behavior in individuals with and without psychosis and electromyography (EMG) and electroencephalography (EEG) responses to startling auditory stimuli. Electromyography and EEG were recorded during an auditory startle paradigm from healthy controls (HC, n = 211), individuals with psychosis and a history of violent behavior (violent-PSY, n = 18), individuals with psychosis without a history of violence (nonviolent-PSY, n = 32), and individuals with a history of violence without psychosis (violent non-PSY, n = 22). We estimated the auditory startle response (ASR) and prepulse inhibition (PPI) using EMG (ie, EMGASR and EMGPPI) and the auditory-evoked potential (ie, AEPASR and AEPPPI) of the EEG. There were no significant effects of group on the EMGASR (P = .10) or the 30-, 60-, and 120-ms prepulse + pulse EMGPPI amplitudes (P = .11, P = .19, and P = .50, respectively). The N1 amplitude of the AEPASR was reduced in the violent-PSY group (P < .001) and the nonviolent-PSY group (P = .015) compared with HC. The P2 amplitude of the AEPASR was reduced in violent-PSY relative to nonviolent-PSY (P = .003), violent non-PSY (P = .016), and HC (P < .001). Together, these results show that EEG-based neural responses to startling auditory stimuli are promising biomarkers of violence risk in psychosis.
García-Marín, Luis M.; Campos, Adrian I.; Diaz-Torres, Santiago; Rabinowitz, Jill A.; Ceja, Zuriel & Mitchell, Brittany L. [Show all 190 contributors for this article] (2024). Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries. Nature Genetics. ISSN 1061-4036. 56(11), p. 2333–2344. doi: 10.1038/s41588-024-01951-z. Full text in Research Archive
Vaskinn, Anja; Rokicki, Jaroslav; Bell, Christina; Tesli, Natalia; Bang, Nina & Hjell, Gabriela [Show all 9 contributors for this article] (2023). Violent Offending in Males With or Without Schizophrenia: A Role for Social Cognition? Schizophrenia Bulletin. ISSN 0586-7614. 50(3), p. 663–672. doi: 10.1093/schbul/sbad151. Full text in Research Archive Show summary
Abstract Background and Hypothesis Reduced social cognition has been reported in individuals who have committed interpersonal violence. It is unclear if individuals with schizophrenia and a history of violence have larger impairments than violent individuals without psychosis and non-violent individuals with schizophrenia. We examined social cognition in two groups with violent offenses, comparing their performance to non-violent individuals with schizophrenia and healthy controls. Study Design Two social cognitive domains were assessed in four groups: men with a schizophrenia spectrum disorder with (SSD-V, n = 27) or without (SSD-NV, n = 42) a history of violence, incarcerated men serving preventive detention sentences (V, n = 22), and healthy male controls (HC, n = 76). Theory of mind (ToM) was measured with the Movie for the Assessment of Social Cognition (MASC), body emotion perception with Emotion in Biological Motion (EmoBio) test. Study Results Kruskal–Wallis H-tests revealed overall group differences for social cognition. SSD-V had a global and clinically significant social cognitive impairment. V had a specific impairment, for ToM. Binary logistic regressions predicting violence category membership from social cognition and psychosis (SSD status) were conducted. The model with best fit, explaining 18%–25% of the variance, had ToM as the only predictor. Conclusions Social cognitive impairment was present in individuals with a history of violence, with larger and more widespread impairment seen in schizophrenia. ToM predicted violence category membership, psychosis did not. The results suggest a role for social cognition in understanding interpersonal violence.
Hjell, Gabriela; Rokicki, Jaroslav; Szabo, Attila; Holst, Rene; Tesli, Natalia & Bell, Christina [Show all 19 contributors for this article] (2023). Impulsivity across severe mental disorders: a cross-sectional study of immune markers and psychopharmacotherapy. BMC Psychiatry. 23(1). doi: 10.1186/s12888-023-05154-4. Full text in Research Archive Show summary
Background Impulsivity is a transdiagnostic feature linked to severe clinical expression and a potential target for psychopharmacological strategies. Biological underpinnings are largely unknown, but involvement of immune dysregulation has been indicated, and the effects of psychopharmacological agents vary. We investigated if impulsivity was associated with circulating immune marker levels and with a range of psychopharmacological treatment regimens in severe mental disorders. Methods Impulsivity was assessed in a sample (N = 657) of patients with schizophrenia or schizophreniform disorder (SCZ) (N = 116) or bipolar disorder (BD) (N = 159) and healthy participants (N = 382) using the Barratt Impulsiveness Scale (BIS-11) questionnaire. Plasma levels of systemic immune markers (RANTES, IL-1RA, IL-18, IL-18BP, sTNFR-1) were measured by enzyme immunoassays. Patients underwent thorough clinical assessment, including evaluation of psychotropic medication. Associations were assessed using linear regressions. Results Impulsivity was positively associated with SCZ (p < 0.001) and BD (p < 0.001) diagnosis and negatively associated with age (p < 0.05), but not significantly associated with any of the circulating immune markers independently of diagnostic status. Among patients, impulsivity was negatively associated with lithium treatment (p = 0.003) and positively associated with antidepressant treatment (p = 0.011) after controlling for diagnosis, psychotropic co-medications, manic symptoms, and depressive symptoms. Conclusions We report elevated impulsivity across SCZ and BD but no associations to systemic immune dysregulation based on the current immune marker selection. The present study reveals associations between impulsivity in severe mental disorders and treatment with lithium and antidepressants, with opposite directions. Future studies are warranted to determine the causal directionality of the observed associations with psychopharmacotherapy.
Friestad, Christine; Haukvik, Unn Kristin Hansen; Berit, Johnsen & Vatnar, Solveig Karin Bø (2023). Prevalence and characteristics of mental and physical disorders among female prisoners : a mixed-methods systematic review. International Journal of Prisoner Health. ISSN 1744-9200. 19(4), p. 599–627. doi: 10.1108/IJPH-12-2022-0080. Full text in Research Archive Show summary
Purpose: This study aims to provide an overview and quality appraisal of the current scientific evidence concerning the prevalence and characteristics of mental and physical disorders among sentenced female prisoners. Design/methodology/approach: A mixed-methods systematic literature review. Findings: A total of 4 reviews and 39 single studies met the inclusion criteria for the review. Mental disorders were the main area of investigation in the majority of single studies, with substance abuse, particularly drug abuse, as the most consistently gender biased disorder, with higher prevalence among women than men in prison. The review identified a lack of updated systematic evidence on the presence of multi-morbidity. Originality/value: This study provides an up-to-date overview and quality appraisal of the current scientific evidence concerning the prevalence and characteristics of mental and physical disorders among female prisoners. Keywords: childhood abuse, criminal justice system, forensic psychiatry, health in prison, offender health, prison psychiatry
Barth, Claudia; Nerland, Stener; Jørgensen, Kjetil Nordbø; Haatveit, Beathe; Bakke, Laura Anne Wortinger & Melle, Ingrid [Show all 10 contributors for this article] (2023). Altered Sex Differences in Hippocampal Subfield Volumes in Schizophrenia. Schizophrenia Bulletin. ISSN 0586-7614. 50(1), p. 107–119. doi: 10.1093/schbul/sbad091. Full text in Research Archive Show summary
Background and hypothesis: The hippocampus is a heterogenous brain structure that differs between the sexes and has been implicated in the pathophysiology of psychiatric illnesses. Here, we explored sex and diagnostic group differences in hippocampal subfield volumes, in individuals with schizophrenia spectrum disorder (SZ), bipolar disorders (BD), and healthy controls (CTL). Study design: One thousand and five hundred and twenty-one participants underwent T1-weighted magnetic resonance imaging (SZ, n = 452, mean age 30.7 ± 9.2 [SD] years, males 59.1%; BD, n = 316, 33.7 ± 11.4, 41.5%; CTL, n = 753, 34.1 ± 9.1, 55.6%). Total hippocampal, subfield, and intracranial volumes were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple regression models were fitted to examine sex-by-diagnostic (sub)group interactions in volume. In SZ and BD, separately, associations between volumes and clinical as well as cognitive measures were examined between the sexes using regression models. Study results: Significant sex-by-group interactions were found for the total hippocampus, dentate gyrus, molecular layer, presubiculum, fimbria, hippocampal-amygdaloid transition area, and CA4, indicating a larger volumetric deficit in male patients relative to female patients when compared with same-sex CTL. Subgroup analyses revealed that this interaction was driven by males with schizophrenia. Effect sizes were overall small (partial η < 0.02). We found no significant sex differences in the associations between hippocampal volumes and clinical or cognitive measures in SZ and BD. Conclusions: Using a well-powered sample, our findings indicate that the pattern of morphological sex differences in hippocampal subfields is altered in individuals with schizophrenia relative to CTL, due to higher volumetric deficits in males.
Pentz, Atle Bråthen; Timpe, Clara Marie Fides; Normann, Elizabeth Marie; Slapø, Nora Berz; Melle, Ingrid & Lagerberg, Trine Vik [Show all 13 contributors for this article] (2023). Mismatch negativity in schizophrenia spectrum and bipolar disorders: Group and sex differences and associations with symptom severity. Schizophrenia Research. ISSN 0920-9964. 261, p. 80–93. doi: 10.1016/j.schres.2023.09.012. Full text in Research Archive Show summary
Objective Research increasingly implicates glutamatergic dysfunction in the pathophysiologies of psychotic disorders. Auditory mismatch negativity (MMN) is an electroencephalography (EEG) waveform linked to glutamatergic neurotransmission and is consistently attenuated in schizophrenia (SCZ). MMN consists of two subcomponents, the repetition positivity (RP) and deviant negativity (DN) possibly reflecting different neural mechanisms. However, whether MMN reduction is present across different psychotic disorders, linked to distinct symptom clusters, or related to sex remain to be clarified. Methods Four hundred participants including healthy controls (HCs; n = 296) and individuals with SCZ (n = 39), bipolar disorder (BD) BD typeI (n = 35), or BD type II (n = 30) underwent a roving MMN paradigm and clinical evaluation. MMN, RP and DN as well their memory traces were recorded at the FCZ electrode. Analyses of variance and linear regression models were used both transdiagnostically and within clinical groups. Results MMN was reduced in SCZ compared to BD (p = 0.006, d = 0.55) and to HCs (p < 0.001, d = 0.63). There was a significant group × sex interaction (p < 0.003) and the MMN impairment was only detected in males with SCZ. MMN amplitude correlated positively with Positive and Negative Syndrome Scale total score and negatively with Global Assessment of Functioning Scale score. The deviant negativity was impaired in males with SCZ. No group differences in memory trace indices of the MMN, DN, or RP. Conclusion MMN was attenuated in SCZ and correlated with greater severity of psychotic symptoms and lower level of functioning. Our results may indicate sex-dependent differences of glutamatergic function in SCZ.
Tesli, Natalia; Jaholkowski, Piotr Pawel; Jaholkowski, Piotr Pawel; Haukvik, Unn Kristin Hansen; Jangmo, Andreas & Haram, Marit [Show all 16 contributors for this article] (2023). Conduct disorder - a comprehensive exploration of comorbidity patterns, genetic and environmental risk factors. Psychiatry Research. ISSN 0165-1781. 331, p. 1–10. doi: 10.1016/j.psychres.2023.115628. Full text in Research Archive
Fischer-Vieler, Thomas; Ringen, Petter Andreas; Kvig, Erling Inge; Bell, Christina; Hjell, Gabriela & Tesli, Natalia [Show all 11 contributors for this article] (2023). Associations Between Clinical Insight and History of Severe Violence in Patients With Psychosis. Schizophrenia Bulletin Open. 4(1). doi: 10.1093/schizbullopen/sgad011. Full text in Research Archive Show summary
Abstract Background and Hypothesis Violence is more prevalent in patients with psychotic disorders compared to the general population. Hence, adequate violence risk assessment is of high clinical importance. Impaired insight is suggested as a risk factor for violence in psychosis, but studies have yielded conflicting results. We hypothesized that impaired insight was associated with a history of severe violence in patients with psychotic disorders. Study Design Clinical insight was assessed both using the Birchwood Insight Scale (BIS) and the Positive and Negative Symptom Scale (PANSS) item G12 (lack of judgment and insight). The degree of impaired clinical insight was compared between psychosis patients with (N = 51) and without (N = 178) a history of severe violence. Multiple linear regression analyses were performed to investigate the effects of putative confounders. Study Results We found that a history of severe violence was significantly associated with lower insight in one of the three BIS components (the relabeling of symptoms) (P = .03, R2 = 0.02) and the PANSS item G12 (P = .03, R2 = 0.02) also after controlling for putative confounders. Conclusions The results suggest there is an association between impaired insight and severe violence in psychosis patients. We propose that examination of insight by validated instruments comprising different components may add useful information to clinical violence risk assessment in psychosis patients.
Tesli, Martin Steen; Nesvåg, Ragnar; Haukvik, Unn Kristin Hansen; Gustavson, Kristin; Tesli, Natalia & Friestad, Christine [Show all 12 contributors for this article] (2023). Common genetic and environmental risk for personality disorders and psychotic-like experiences in young adult twins. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 148(6), p. 561–569. doi: 10.1111/acps.13596. Full text in Research Archive Show summary
Abstract Introduction Psychotic‐like experiences (PLE) have been associated with the subsequent emergence of psychotic disorders as well as several other domains of psychopathology. In this twin study, we estimated the genetic and environmental correlations between PLE and 10 personality disorders (PD). Methods Diagnoses of 10 PDs according to the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) and PLE from the Composite International Diagnostic Interview (CIDI) were retrieved for 2793 young adult twins from the Norwegian Twin Registry. Risk for having a PD and PLEs was modeled using item response theory. Biometric twin models were fitted to estimate the genetic and environmental correlations between PDs and PLEs. Co‐twin control analysis was performed to estimate additional within‐family risk for PLEs when having a PD. Results Phenotypic overlap between PDs and PLEs ranged from 14% to 44% in males and from 11% to 39% in females, with the highest overlap for borderline PD in both sexes. In general, we found higher genetic correlations ( r = 0.14–0.72) than environmental correlations ( r = 0.06–0.28) between PDs and PLEs. The highest genetic correlations between PLE and PDs were found for borderline ( r = 0.72), paranoid ( r = 0.56), schizotypal ( r = 0.56) and antisocial PD (r = 0.49). Conclusion We found that the co‐occurrence between PDs and PLE is the best explained by shared genetic determinants, with minor contributions from environmental factors. Interestingly, borderline PD was highly genetically correlated with PLE, warranting molecular genetic studies of this association.
Tesli, Natalia; Bell, Christina; Hjell, Gabriela; Fischer-Vieler, Thomas; Maximov, Ivan & Richard, Geneviève [Show all 14 contributors for this article] (2022). The age of violence: Mapping brain age in psychosis and psychopathy. NeuroImage: Clinical. 36. doi: 10.1016/j.nicl.2022.103181. Full text in Research Archive Show summary
Young chronological age is one of the strongest predictors for antisocial behaviour in the general population and for violent offending in individuals with psychotic disorders. An individual's age can be predicted with high accuracy using neuroimaging and machine-learning. The deviation between predicted and chronological age, i.e., brain age gap (BAG) has been suggested to reflect brain health, likely relating partly to neurodevelopmental and aging-related processes and specific disease mechanisms. Higher BAG has been demonstrated in patients with psychotic disorders. However, little is known about the brain-age in violent offenders with psychosis and the possible associations with psychopathy traits. We estimated brain-age in 782 male individuals using T1-weighted MRI scans. Three machine learning models (random forest, extreme gradient boosting with and without hyper parameter tuning) were first trained and tested on healthy controls (HC, n = 586). The obtained BAGs were compared between HC and age matched violent offenders with psychosis (PSY-V, n = 38), violent offenders without psychosis (NPV, n = 20) and non-violent psychosis patients (PSY-NV, n = 138). We ran additional comparisons between BAG of PSY-V and PSY-NV and associations with Positive and Negative Syndrome Scale (PANSS) total score as a measure of psychosis symptoms. Psychopathy traits in the violence groups were assessed with Psychopathy Checklist-revised (PCL-R) and investigated for associations with BAG. We found significantly higher BAG in PSY-V compared with HC (4.9 years, Cohen's d = 0.87) and in PSY-NV compared with HC (2.7 years, d = 0.41). Total PCL-R scores were negatively associated with BAG in the violence groups (d = 1.17, p < 0.05). Additionally, there was a positive association between psychosis symptoms and BAG in the psychosis groups (d = 1.12, p < 0.05). While the significant BAG differences related to psychosis and not violence suggest larger BAG for psychosis, the negative associations between BAG and psychopathy suggest a complex interplay with psychopathy traits. This proof-of-concept application of brain age prediction in severe mental disorders with a history of violence and psychopathy traits should be tested and replicated in larger samples.
Andreou, Dimitrios; Jørgensen, Kjetil Nordbø; Nerland, Stener; Ueland, Torill; Vaskinn, Anja & Haukvik, Unn Kristin Hansen [Show all 9 contributors for this article] (2022). Herpes simplex virus 1 infection on grey matter and general intelligence in severe mental illness. Translational Psychiatry. 12(1). doi: 10.1038/s41398-022-02044-3. Full text in Research Archive Show summary
Abstract Schizophrenia and bipolar disorder are severe mental illnesses (SMI) linked to both genetic and environmental factors. Herpes simplex virus 1 (HSV1) is a common neurotropic pathogen which after the primary infection establishes latency with periodic reactivations. We hypothesized that the latent HSV1 infection is associated with brain structural abnormalities and cognitive impairment, especially in SMI. We included 420 adult patients with SMI (schizophrenia or bipolar spectrum) and 481 healthy controls. Circulating HSV1 immunoglobulin G concentrations were measured with immunoassays. We measured the total grey matter volume (TGMV), cortical, subcortical, cerebellar and regional cortical volumes based on T1-weighted MRI scans processed in FreeSurfer v6.0.0. Intelligence quotient (IQ) was assessed with the Wechsler Abbreviated Scale of Intelligence. Seropositive patients had significantly smaller TGMV than seronegative patients (642 cm 3 and 654 cm 3 , respectively; p = 0.019) and lower IQ (104 and 107, respectively; p = 0.018). No TGMV or IQ differences were found between seropositive and seronegative healthy controls. Post-hoc analysis showed that (a) in both schizophrenia and bipolar spectrum, seropositive patients had similarly smaller TGMV than seronegative patients, whereas the HSV1-IQ association was driven by the schizophrenia spectrum group, and (b) among all patients, seropositivity was associated with smaller total cortical ( p = 0.016), but not subcortical or cerebellar grey matter volumes, and with smaller left caudal middle frontal, precentral, lingual, middle temporal and banks of superior temporal sulcus regional cortical grey matter volumes. The results of this cross-sectional study indicate that HSV1 may be an environmental factor associated with brain structural abnormalities and cognitive impairment in SMI.
Rokicki, Jaroslav; Kaufmann, Tobias; Lange, Ann-Marie Glasø de; Meer, Dennis van der; Bahrami, Shahram & Sartorius, Alina [Show all 14 contributors for this article] (2022). Oxytocin receptor expression patterns in the human brain across development. Neuropsychopharmacology. ISSN 0893-133X. doi: 10.1038/s41386-022-01305-5. Full text in Research Archive
Gröning, Linda; Haukvik, Unn Kristin Hansen; Morse, Stephen & Radovic, Susanna (2022). Remodelling criminal insanity: Exploring philosophical, legal, and medical premises of the medical model used in Norwegian law. International Journal of Law and Psychiatry. ISSN 0160-2527. 81. doi: 10.1016/j.ijlp.2022.101776. Full text in Research Archive Show summary
This paper clarifies the conceptual space of discussion of legal insanity by considering the virtues of the ‘medical model’ model that has been used in Norway for almost a century. The medical model identifies insanity exclusively with mental disorder, and especially with psychosis, without any requirement that the disorder causally influenced the commission of the crime. We explore the medical model from a transdisciplinary perspective and show how it can be utilised to systematise and reconsider the central philosophical, legal and medical premises involved in the insanity debate. A key concern is how recent transdiagnostic and dimensional approaches to psychosis can illuminate the law's understanding of insanity and its relation to mental disorder. The authors eventually raise the question whether the medical model can be reconstructed into a unified insanity model that is valid across the related disciplinary perspectives, and that moves beyond current insanity models.
Bell, Christina; Tesli, Natalia; Gurholt, Tiril Pedersen; Rokicki, Jaroslav; Hjell, Gabriela & Fischer-Vieler, Thomas [Show all 14 contributors for this article] (2022). Psychopathy subdomains in violent offenders with and without a psychotic disorder. Nordic Journal of Psychiatry. ISSN 0803-9488. doi: 10.1080/08039488.2022.2128869. Full text in Research Archive Show summary
Background Violence in psychosis has been linked to antisocial behavior and psychopathy traits. Psychopathy comprises aspects of interpersonal, affective, lifestyle, and antisocial traits which may be differently involved in violent offending by persons with psychotic disorders. We explored psychopathy subdomains among violent offenders with and without a psychotic disorder. Methods 46 males, with a history of severe violence, with (n = 26; age 35.85 ± 10.34 years) or without (n = 20; age 39.10 ± 11.63 years) a diagnosis of a psychotic disorder, were assessed with the Psychopathy Checklist-Revised (PCL-R). PCL-R was split into subdomains following the four-facet model. Group differences in total and subdomain scores were analyzed with a general linear model with covariates. Results Total PCL-R scores did not differ between the groups (p = 0.61, Cohen’s d = 0.17). The violent offenders without psychotic disorders had higher facet 2 scores than the patient group with psychotic disorders (p = 0.029, Cohen’s d = 0.77). Facet 1, 3, or 4 scores did not differ between the groups. Controlling for age did not alter the results. Conclusion Patients with a psychotic disorder and a history of severe violence have lower affective psychopathy scores than violent offenders without psychotic disorders. This observation may point toward distinct underlying mechanisms for violence and may provide a target for focused treatment and prevention.
Hjell, Gabriela; Szabo, Attila; Mørch-Johnsen, Lynn Egeland; Holst, Rene; Tesli, Natalia & Bell, Christina [Show all 18 contributors for this article] (2022). Interleukin-18 signaling system links to agitation in severe mental disorders. Psychoneuroendocrinology. ISSN 0306-4530. 140:105721, p. 1–8. doi: 10.1016/j.psyneuen.2022.105721. Full text in Research Archive Show summary
Objective Agitation is a challenging clinical feature in severe mental disorders, but its biological correlates are largely unknown. Inflammasome-related abnormalities have been linked to severe mental disorders and implicated in animal models of agitation. We investigated if levels of circulating inflammasome-related immune markers were associated with agitation in severe mental disorders. Methods Individuals with a psychotic or affective disorder (N = 660) underwent blood sampling and clinical characterization. Plasma levels of interleukin (IL)‐18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), and IL-1 receptor antagonist (IL-1RA) were measured. Agitation levels were estimated with the Positive and Negative Syndrome Scale Excited Component. Multiple linear- and logistic regression were used to investigate the associations between agitation and the immune markers, while controlling for confounders. The influence of psychotic and affective symptoms was assessed in follow-up analyses. Results Agitation was positively associated with IL-18BP (β = 0.13, t = 3.41, p = 0.0007) after controlling for multiple confounders, including BMI, smoking, medication, and substance use. Adjustment for psychotic, manic, and depressive symptoms did not affect the results. There were no significant associations between agitation and the other investigated immune markers (IL-1RA (β = 0.06, t = 1.27, p = 0.20), IL-18 (β = 0.05, t = 1.25, p = 0.21), IL-18R1 (β = 0.04, t = 1.01, p = 0.31), IL-18RAP (odds ratio = 0.96, p = 0.30)). In a subsample (N = 463), we also adjusted for cortisol levels, which yielded unaltered results. Conclusion Our findings add to the accumulating evidence of immune system disturbances in severe mental disorders and suggest the IL-18 system as a part of the biological correlate of agitation independent of affective and psychotic symptoms.
Andreou, Dimitrios; Jørgensen, Kjetil Nordbø; Nerland, Stener; Yolken, Robert H.; Haukvik, Unn Kristin Hansen & Andreassen, Ole [Show all 7 contributors for this article] (2022). Cytomegalovirus Infection Associated with Smaller Total Cortical Surface Area in Schizophrenia Spectrum Disorders. Schizophrenia Bulletin. ISSN 0586-7614. 48(5), p. 1164–1173. doi: 10.1093/schbul/sbac036. Full text in Research Archive Show summary
Abstract Objectives Cytomegalovirus (CMV) congenital infection and in immunodeficiency can have deleterious effects on human cortex. In immunocompetent adults, the putative association between CMV infection and cortical measures has not been explored. We hypothesized that CMV exposure is associated with smaller cortical surface area or cortical thinning mainly in patients with schizophrenia spectrum disorders. Study Design We included 67 adult patients with schizophrenia spectrum disorders and 262 adult healthy controls. We measured circulating CMV IgG antibody concentrations with solid-phase immunoassay techniques. We measured the total cortical surface area, regional cortical surface areas and the overall mean cortical thickness based on T1-weighted MRI scans processed in FreeSurfer v6.0. Study Results In the whole sample analysis, we found a significant diagnostic group-by-CMV status interaction on the total surface area (P = .020). Among patients, CMV antibody positivity was significantly associated with smaller total surface area (P = .002, partial eta2 = 0.138) whereas no such association was found in healthy controls (P = .059). Post hoc analysis among patients showed that higher CMV antibody concentrations were also significantly associated with smaller total surface area (P = .038), and that CMV antibody positivity was significantly inversely associated with 14 left and 16 right regional surface areas mainly in the frontal and temporal lobes. CMV infection was not associated with the overall mean cortical thickness. Conclusions The results are indicative of a cortical surface area vulnerability to CMV infection in patients with schizophrenia spectrum disorders but not in healthy controls. CMV infection may contribute to the established cortical surface area aberrations in schizophrenia.
Tesli, Natalia; Rokicki, Jaroslav; Maximov, Ivan; Bell, Christina; Hjell, Gabriela & Gurholt, Tiril Pedersen [Show all 17 contributors for this article] (2021). White Matter Matters: Unraveling Violence in Psychosis and Psychopathy. Schizophrenia Bulletin Open. 2(1). doi: 10.1093/schizbullopen/sgab026. Full text in Research Archive Show summary
Individuals with psychotic disorders have an increased risk of committing acts of violence. Neurobiological support for the extent to which violence in psychosis is driven by psychotic symptoms and/or antisocial traits could have clinical and legal implications. Neuroimaging studies have reported white matter (WM) abnormalities in individuals with psychosis and in those with antisocial traits. However, it is unknown whether WM abnormalities in psychosis patients with a history of violence (violent-PSY) resemble those found in nonviolent psychosis patients (nonviolent PSY), violent nonpsychotic individuals (violent non-PSY), or both. Diffusion tensor imaging scans from 301 males including violent-PSY (n = 28), violent non-PSY (n = 20), nonviolent PSY (n = 58), and healthy controls (HC, n = 195) were analyzed with tract-based spatial statistics. Fractional anisotropy (FA), mean, axial and radial (RD) diffusivity were compared between groups. Psychopathic traits in the violent groups were measured with Psychopathy Checklist-revisited (PCL-R). Violent-PSY had globally lower FA and higher RD, compared with nonviolent PSY. Both psychosis groups and violent non-PSY group had widespread disruptions in WM compared with HC. There were no significant WM differences between violent-PSY and violent non-PSY. PCL-R scores did not differ between the violence groups and were associated with higher RD in corpus callosum. Here we demonstrate a widespread pattern of reduced WM integrity in violent-PSY compared with nonviolent PSY. The lack of significant WM and PCL-R differences between the violence groups, together with the positive association between PCL-R and WM deficits in violent-PSY and violent non-PSY may indicate shared neurobiological underpinnings of trait violence.
Gurholt, Tiril Pedersen; Kaufmann, Tobias; Frei, Oleksandr; Alnæs, Dag; Haukvik, Unn Kristin H. & Meer, Dennis van der [Show all 17 contributors for this article] (2021). Population-based body–brain mapping links brain morphology with anthropometrics and body composition. Translational Psychiatry. doi: 10.1038/s41398-021-01414-7. Full text in Research Archive Show summary
Abstract Understanding complex body–brain processes and the interplay between adipose tissue and brain health is important for understanding comorbidity between psychiatric and cardiometabolic disorders. We investigated associations between brain structure and anthropometric and body composition measures using brain magnetic resonance imaging (MRI; n = 24,728) and body MRI ( n = 4973) of generally healthy participants in the UK Biobank. We derived regional and global measures of brain morphometry using FreeSurfer and tested their association with (i) anthropometric measures, and (ii) adipose and muscle tissue measured from body MRI. We identified several significant associations with small effect sizes. Anthropometric measures showed negative, nonlinear, associations with cerebellar/cortical gray matter, and brain stem structures, and positive associations with ventricular volumes. Subcortical structures exhibited mixed effect directionality, with strongest positive association for accumbens. Adipose tissue measures, including liver fat and muscle fat infiltration, were negatively associated with cortical/cerebellum structures, while total thigh muscle volume was positively associated with brain stem and accumbens. Regional investigations of cortical area, thickness, and volume indicated widespread and largely negative associations with anthropometric and adipose tissue measures, with an opposite pattern for thigh muscle volume. Self-reported diabetes, hypertension, or hypercholesterolemia were associated with brain structure. The findings provide new insight into physiological body–brain associations suggestive of shared mechanisms between cardiometabolic risk factors and brain health. Whereas the causality needs to be determined, the observed patterns of body–brain relationships provide a foundation for understanding the underlying mechanisms linking psychiatric disorders with obesity and cardiovascular disease, with potential for the development of new prevention strategies.
Bell, Christina; Tesli, Natalia; Gurholt, Tiril Pedersen; Rokicki, Jaroslav; Hjell, Gabriela & Fischer-Vieler, Thomas [Show all 13 contributors for this article] (2021). Associations between amygdala nuclei volumes, psychosis, psychopathy, and violent offending. Psychiatry Research : Neuroimaging. ISSN 0925-4927. 319. doi: 10.1016/j.pscychresns.2021.111416. Full text in Research Archive Show summary
The amygdala is involved in fear perception and aggression regulation, and smaller volumes have been associated with psychotic and non-psychotic violence. We explored the relationship between amygdala nuclei volumes in violent offenders with and without psychosis, and the association to psychopathy traits. 3T MRI scans (n = 204, males, 18–66 years) were obtained from psychotic violent offenders (PSY-V, n = 29), non-psychotic violent offenders (NPV, n = 19), non-violent psychosis patients (PSY-NV, n = 67), and healthy controls (HC, n = 89). Total amygdala and 9 amygdala nuclei volumes were obtained with FreeSurfer. Psychopathy traits were measured with the Psychopathy Checklist-revised (PCL-R). Multivariate analyses explored diagnostic differences in amygdala nuclei volumes and associations to psychosis, violence, and psychopathy traits. PSY-V had a smaller basal nucleus, anterior amygdaloid area, and cortical amygdalar transition area (CATA), whereas PSY-NV had a smaller CATA than HC. Volumes in NPV did not differ from HC, and there were no associations between PCL-R total or factor scores and any of the nuclei or whole amygdala volumes. The lower volumes of amygdala nuclei involved in fear modulation, stress responses, and social interpretation may point towards some mechanisms of relevance to violence in psychosis, but the results warrant replication in larger subject samples.
Wortinger, Laura Anne; Barth, Claudia; Nerland, Stener; Jørgensen, Kjetil Nordbø; Shadrin, Alexey & Szabo, Attila [Show all 11 contributors for this article] (2021). Association of Birth Asphyxia With Regional White Matter Abnormalities Among Patients With Schizophrenia and Bipolar Disorders. JAMA Network Open. 4(12). doi: 10.1001/jamanetworkopen.2021.39759. Full text in Research Archive Show summary
Importance: White matter (WM) abnormalities are commonly reported in psychiatric disorders. Whether peripartum insufficiencies in brain oxygenation, known as birth asphyxia, are associated with WM of patients with severe mental disorders is unclear. Objective: To examine the association between birth asphyxia and WM in adult patients with schizophrenia and bipolar disorders (BDs) compared with healthy adults. Design, setting, and participants: In this case-control study, all individuals participating in the ongoing Thematically Organized Psychosis project were linked to the Medical Birth Registry of Norway (MBRN), where a subset of 271 patients (case group) and 529 healthy individuals (control group) had undergone diffusion-weighted imaging (DWI). Statistical analyses were performed from June 16, 2020, to March 9, 2021. Exposures: Birth asphyxia was defined based on measures from standardized reporting at birth in the MBRN. Main outcomes and measures: Associations between birth asphyxia and WM regions of interest diffusion metrics, ie, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), were compared between groups using analysis of covariance, adjusted for age, age squared, and sex. Results: Of the 850 adults included in the study, 271 were in the case group (140 [52%] female individuals; mean [SD] age, 28.64 [7.43] years) and 579 were in the control group (245 [42%] female individuals; mean [SD] age, 33.54 [8.31] years). Birth asphyxia measures were identified in 15% to 16% of participants, independent of group. The posterior limb of the internal capsule (PLIC) showed a significant diagnostic group × birth asphyxia interaction (F(1, 843) = 11.46; P = .001), reflecting a stronger association between birth asphyxia and FA in the case group than the control group. RD, but not AD, also displayed a significant diagnostic group × birth asphyxia interaction (F(1, 843) = 9.28; P = .002) in the PLIC, with higher values in patients with birth asphyxia and similar effect sizes as observed for FA. Conclusions and relevance: In this case-control study, abnormalities in the PLIC of adult patients with birth asphyxia may suggest a greater susceptibility to hypoxia in patients with severe mental illness, which could lead to myelin damage or impeded brain development. Echoing recent early-stage schizophrenia studies, abnormalities of the PLIC are relevant to psychiatric disorders, as the PLIC contains important WM brain pathways associated with language, cognitive function, and sensory function, which are impaired in schizophrenia and BDs.
Grøning, Linda; Haukvik, Unn Kristin H.; Meynen, Gerben & Radovic, Susanna (2020). Constructing criminal insanity: The roles of legislators, judges and experts in Norway, Sweden and the Netherlands. New Journal of European Criminal Law. ISSN 2032-2844. 11(3), p. 390–410. doi: 10.1177/2032284420950485. Full text in Research Archive Show summary
This article provides a discussion about criminal insanity regulation in Norway, Sweden and the Netherlands, with a focus on the roles of legislators, judges and experts in the concretisation of the legal meaning of criminal insanity. The authors recognise that these three countries reflect different ideal type rule constructions that are interesting to study comparatively. The article addresses the following overall questions: To what extent and in what way do the different rule constructions also involve different views on the roles of legislators, judges and experts? And in case of competing models, which is the better solution? To investigate and eventually answer these questions, the authors analyse the content and legislative considerations of the relevant rules, how these rules are applied and understood by judges and experts, and how different understandings of insanity, of legislators, judges and experts, depend on each other. The authors show how the different rule constructions represent different considerations on the adequate roles of the legislator, judges and experts. They argue that what is important is not what precise division of roles that is settled, but that this interplay functions to secure clear and robust rules, and that each of the three countries has room for improvement in this regard.
Storvestre, Guttorm Breivik; Jensen, Arvid; Bjerke, Espen; Tesli, Natalia; Røsæg, Cato & Friestad, Christine [Show all 9 contributors for this article] (2020). Childhood trauma in persons with schizophrenia and a history of interpersonal violence. Frontiers in Psychiatry. 11. doi: 10.3389/fpsyt.2020.00383. Full text in Research Archive Show summary
Background: Childhood trauma is a risk factor for psychosis as well for violent behavior and offending later in life. Childhood trauma comprises subdomains of abuse and neglect that may be differently related to later violence among patients with schizophrenia. The aim of this study was to map the subdomains of childhood trauma associated with violent offending in schizophrenia. Methods: Information on childhood trauma from predominantly male patients with a DSM-IV diagnosis of schizophrenia and a history of violent offending (interpersonal violence) (SCZ-V, n = 19), schizophrenia patients without a history of violence (SCZ-NV, n = 34), and healthy controls (HC, n = 66) was obtained with the Childhood Trauma Questionnaire (CTQ). Differences between groups in total maltreatment scores and the five subdomains including physical, emotional, and sexual abuse, as well as physical and emotional neglect were analyzed. Results: SCZ-V had the highest median CTQ scores for all sub-domains. SCZ-V reported significantly higher total CTQ scores than SCZ-NV and HC. SCZ-V had significantly higher scores than HC on all subdomains, and significantly higher than SCZ-NV on physical and emotional neglect. SCZ-NV had higher scores on all domains except sexual abuse compared to HC. Conclusion: SCZ-V patients had higher exposure to childhood trauma than SCZ-NV, and both schizophrenia groups had higher exposure than HC. The results suggest that childhood physical and emotional neglect may be of specific importance to later violence in schizophrenia.
Tønnesen, Siren; Kaufmann, Tobias; Lange, Ann-Marie Glasø de; Richard, Geneviève; Doan, Nhat Trung & Alnæs, Dag [Show all 33 contributors for this article] (2020). Brain age prediction reveals aberrant brain white matter in schizophrenia and bipolar disorder: A multisample diffusion tensor imaging study. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. ISSN 2451-9022. 5(12), p. 1095–1103. doi: 10.1016/j.bpsc.2020.06.014. Full text in Research Archive Show summary
Background Schizophrenia (SZ) and bipolar disorder (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, patients with BD, and healthy control (HC) subjects across 10 cohorts. Methods We trained 6 cross-validated models using different combinations of DTI data from 927 HC subjects (18–94 years of age) and applied the models to the test sets including 648 patients with SZ (18–66 years of age), 185 patients with BD (18–64 years of age), and 990 HC subjects (17–68 years of age), estimating the brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results. Results Tenfold cross-validation revealed high accuracy for all models. Compared with HC subjects, the model including all feature sets significantly overestimated the age of patients with SZ (Cohen’s d = −0.29) and patients with BD (Cohen’s d = 0.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy–based models showed larger group differences than the models based on other DTI-derived metrics. Conclusions Brain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.
Tesli, Natalia; Meer, Dennis van der; Rokicki, Jaroslav; Storvestre, Guttorm Breivik; Røsæg, Cato & Jensen, Arvid [Show all 14 contributors for this article] (2020). Hippocampal subfield and amygdala nuclei volumes in schizophrenia patients with a history of violence. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. doi: 10.1007/s00406-020-01098-y. Full text in Research Archive Show summary
Schizophrenia (SCZ) is associated with an increased risk of violence compared to the general population. Previous studies have indicated smaller hippocampal and amygdala volumes in violent than non-violent psychotic patients. However, little is known about volumetric differences at the subdivision level of these structures. In the present study, hippocampal subfields and amygdala nuclei volumes were estimated with FreeSurfer from 3 T MRI of SCZ patients with (SCZ-V, n = 24) and without (SCZ-NV, n = 51) a history of severe violence and 90 healthy controls (HC). Volumetric differences between groups were explored with a general linear model covarying for confounders, in addition to follow-up analyses in patient groups controlling for clinical characteristics such as antipsychotic medication, duration of illness and illicit substance use. SCZ-V had smaller total hippocampal volume and smaller CA1, HATA, fimbria, and molecular layer of DG volumes compared to HC. Total amygdala volume together with basal nucleus, accessory basal nucleus, CTA, and paralaminar nucleus volumes were smaller in SCZ-V compared to HC. In SCZ-NV, compared to HC, the observed smaller volumes were limited to basal and paralaminar nucleus. There were no significant differences in hippocampal subfield and amygdala nuclei volumes between SCZ-V and SCZ-NV. Follow-up analyses showed that the results in patient groups were not affected by clinical characteristics. The results suggest that smaller hippocampal subfield and amygdala nuclei volumes may be relevant to violence risk in SCZ. However, the neurobiological signature of violence in SCZ should be further investigated in larger cohorts.
Haukvik, Unn Kristin H.; Gurholt, Tiril Pedersen; Nerland, Stener; Elvsåshagen, Torbjørn; Akudjedu, Theophilus N. & Alda, Martin [Show all 97 contributors for this article] (2020). In vivo hippocampal subfield volumes in bipolar disorder—A mega‐analysis from The Enhancing Neuro Imaging Genetics through Meta‐Analysis Bipolar Disorder Working Group. Human Brain Mapping. ISSN 1065-9471. 43, p. 385–398. doi: 10.1002/hbm.25249. Full text in Research Archive Show summary
The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta‐Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1‐weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed‐effects models and mega‐analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = −0.20), cornu ammonis (CA)1 (d = −0.18), CA2/3 (d = −0.11), CA4 (d = −0.19), molecular layer (d = −0.21), granule cell layer of dentate gyrus (d = −0.21), hippocampal tail (d = −0.10), subiculum (d = −0.15), presubiculum (d = −0.18), and hippocampal amygdala transition area (d = −0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non‐users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.
Gurholt, Tiril Pedersen; Haukvik, Unn Kristin H.; Lonning, Vera; Jönsson, Erik Gunnar; Pasternak, Ofer & Agartz, Ingrid (2020). Microstructural white matter and links with subcortical structures in chronic schizophrenia: A free-water imaging approach. Frontiers in Psychiatry. 11. doi: 10.3389/fpsyt.2020.00056. Full text in Research Archive Show summary
Schizophrenia is a severe mental disorder with often a chronic course. Neuroimaging studies report brain abnormalities in both white and gray matter structures. However, the relationship between microstructural white matter differences and volumetric subcortical structures is not known. We investigated 30 long-term treated patients with schizophrenia and schizoaffective disorder (mean age 51.1 ± 7.9 years, mean illness duration 27.6 ± 8.0 years) and 42 healthy controls (mean age 54.1 ± 9.1 years) using 3 T diffusion and structural magnetic resonance imaging. The free-water imaging method was used to model the diffusion signal, and subcortical volumes were obtained from FreeSurfer. We applied multiple linear regression to investigate associations between (i) patient status and regional white matter microstructure, (ii) medication dose or clinical symptoms on white matter microstructure in patients, and (iii) for interactions between subcortical volumes and diagnosis on microstructural white matter regions showing significant patient-control differences. The patients had significantly decreased free-water corrected fractional anisotropy (FAt), explained by decreased axial diffusivity and increased radial diffusivity (RDt) bilaterally in the anterior corona radiata (ACR) and the left anterior limb of the internal capsule (ALIC) compared to controls. In the fornix, the patients had significantly increased RDt. In patients, positive symptoms were associated with localized increased free-water and negative symptoms with localized decreased FAt and increased RDt. There were significant interactions between patient status and several subcortical structures on white matter microstructure and the free-water compartment for left ACR and fornix, and limited to the free-water compartment for right ACR and left ALIC. The Cohen's d effect sizes were medium to large (0.61 to 1.20, absolute values). The results suggest a specific pattern of frontal white matter axonal degeneration and demyelination and fornix demyelination that is attenuated in the presence of larger structures of the limbic system in patients with chronic schizophrenia and schizoaffective disorder. Findings warrant replication in larger samples.
Ching, Christopher R. K.; Hibar, Derrek P.; Gurholt, Tiril Pedersen; Nunes, Abraham; Thomopoulos, Sophia I. & Abé, Chritsoph [Show all 51 contributors for this article] (2020). What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group. Human Brain Mapping. ISSN 1065-9471. 43, p. 56–82. doi: 10.1002/hbm.25098. Full text in Research Archive Show summary
MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness.
Hjell, Gabriela; Mørch-Johnsen, Lynn; Holst, René; Tesli, Natalia; Bell, Christina & Lunding, Synve Hoffart [Show all 13 contributors for this article] (2020). Disentangling the relationship between cholesterol, aggression, and impulsivity in severe mental disorders. Brain and Behavior. 10(9). doi: 10.1002/brb3.1751. Full text in Research Archive Show summary
Objective Low total cholesterol has been linked with adverse mental symptoms such as aggression and impulsivity in severe mental disorders (SMDs). This putative association may affect the clinician's decision making about cholesterol lowering in this patient group. Here, we investigated the associations between cholesterol levels, aggression, and impulsivity in a large representative sample of in‐ and outpatients with SMD. Methods Patients with schizophrenia‐ or bipolar spectrum disorders (N = 1 001) underwent thorough clinical characterization and blood sampling (total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol). Aggression was characterized by the Positive and Negative Syndrome Scale Excited Component. Impulsivity was measured with the Barratt Impulsiveness Scale in a subsample of patients (N = 288). We used a multinomial logistic regression model to analyze the association between cholesterol and aggression and a multiple linear regression model to analyze the association between cholesterol and impulsivity, while controlling for confounders. Results We found no significant associations between cholesterol levels and aggression or impulsivity. There were no significant interactions between cholesterol and diagnostic group or inpatient versus outpatient status. Controlling for medication use, body mass index, alcohol or illicit substance use did not affect the results. Conclusion In this large sample of patients with schizophrenia‐ and bipolar spectrum disorders, we found no associations between cholesterol levels and aggression or impulsivity. This has clinical implications as patients with SMD are at increased CVD risk and currently undertreated with statins.
Gurholt, Tiril Pedersen; Lonning, Vera Louise Hiorth; Nerland, Stener; Jørgensen, Kjetil Nordbø; Haukvik, Unn Kristin H. & Alloza, Clara [Show all 41 contributors for this article] (2020). Intracranial and subcortical volumes in adolescents with early‐onset psychosis: A multisite mega‐analysis from the ENIGMA consortium. Human Brain Mapping. ISSN 1065-9471. p. 373–384. doi: 10.1002/hbm.25212. Full text in Research Archive Show summary
Early‐onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early‐onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early‐onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early‐onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed‐effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early‐onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early‐onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early‐onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intrac
Tesli, Natalia; Westlye, Lars Tjelta; Storvestre, Guttorm Breivik; Gurholt, Tiril Pedersen; Agartz, Ingrid & Melle, Ingrid [Show all 8 contributors for this article] (2019). White matter microstructure in schizophrenia patients with a history of violence. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. doi: 10.1007/s00406-019-00988-0. Full text in Research Archive
Bakke, Laura A. Wortinger; Engen, Kristine; Barth, Claudia; Lonning, Vera Louise Hiorth; Jørgensen, Kjetil Nordbø & Andreassen, Ole Andreas [Show all 10 contributors for this article] (2019). Obstetric complications and intelligence in patients on the schizophrenia-bipolar spectrum and healthy participants. Psychological Medicine. ISSN 0033-2917. p. 1–9. doi: 10.1017/S0033291719002046. Full text in Research Archive
Favre, Pauline; Pauling, Melissa; Stout, Jacques; Hozer, Franz; Sarrazin, Samuel & Abé, Christoph [Show all 59 contributors for this article] (2019). Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals. Neuropsychopharmacology. ISSN 0893-133X. 44, p. 2285–2293. doi: 10.1038/s41386-019-0485-6. Full text in Research Archive
Satizabal, Claudia L.; Adams, Hieab H.H.; Hibar, Derrek; White, Charles C.; Knol, Maria J. & Stein, Jason L. [Show all 289 contributors for this article] (2019). Genetic architecture of subcortical brain structures in 38,851 individuals. Nature Genetics. ISSN 1061-4036. 51, p. 1624–1636. doi: 10.1038/s41588-019-0511-y. Full text in Research Archive Show summary
Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
Sørbye, Øystein; Dahl, Hanne-Sofie Johnsen; Eells, Tracy D.; Amlo, Svein; Hersoug, Anne Grete & Haukvik, Unn Kristin H. [Show all 9 contributors for this article] (2019). Psychodynamic case formulations without technical language: a reliability study. BMC Psychology. 7. doi: 10.1186/s40359-019-0337-5. Full text in Research Archive Show summary
Background To bridge the gap between symptoms and treatment, constructing case formulations is essential for clinicians. Limited scientific value has been attributed to case formulations because of problems with quality, reliability, and validity. For understanding, communication, and treatment planning beyond each specific clinician-patient dyad, a case formulation must convey valid information concerning the patient, as well as being a reliable source of information regardless of the clinician’s theoretical orientation. The first aim of the present study is to explore the completeness of unstructured psychodynamic formulations, according to four components outlined in the Case Formulation Content Coding Method (CFCCM). The second aim is to estimate the reliability of independent formulations and their components, using similarity ratings of matched versus mismatched cases. Methods This study explores psychodynamic case formulations as made by two or more experienced clinicians after listening to an evaluation interview. The clinicians structured the formulations freely, with the sole constraint that technical, theory-laden terminology should be avoided. The formulations were decomposed into components after all formulations had been written. Results The results indicated that most formulations were adequately comprehensive, and that overall reliability of the formulations was high (> 0.70) for both experienced and inexperienced clinician raters, although the lower bound reliability estimate of the formulation component deemed most difficult to rate - inferred mechanisms - was marginal, 0.61. Conclusions These results were achieved on case formulations made by experienced clinicians using simple experience-near language and minimizing technical concepts, which indicate a communicative quality in the formulations that make them clinically sound. Trial registration ClinicalTrials.gov Identifier: NCT00423462. https://doi.org/10.1007/s00432-018-2781-7 ., January 18, 2007.
Grøning, Linda; Haukvik, Unn Kristin H. & Melle, Karl Henrik (2019). Criminal Insanity, Psychosis and Impaired Reality Testing in Norwegian Law. Bergen Journal of Criminal Law & Criminal Justice (BJCLCJ). 7(1), p. 27–59. doi: 10.15845/bjclcj.v7i1.2879. Full text in Research Archive Show summary
How mental disorder relates to criminal insanity is a contested matter. Norway has a tradition of using a ‘medical model’ for the definition of criminal insanity that is unique in an international perspective. According to this model, insanity is determined only in relation to a medical criterion, so that all that is required is the presence of a qualifying mental disorder. Criminal insanity is, under the current rule, equated with psychosis, although this rule has recently been subject to a law reform. This article explains and discusses this medical model by gathering together legal, forensic, and clinical empirical perspectives on the legal meaning and relevance of psychosis. The article will provide an explanation of the background of the medical model in Norwegian law, and the justifications for tying criminal insanity to psychosis. It will also explain how criminal insanity is operationalised in forensic practice, and discuss the legal conceptualisation of psychosis from a medical perspective. A main conclusion is that the legal meaning of psychosis is unclear, and the authors describe several challenges in legal and forensic practice. The authors emphasise the need for further knowledge development in the intersection between law and medicine.
Storvestre, Guttorm Breivik; Valnes, Lars Magnus; Jensen, Arvid; Nerland, Stener; Tesli, Natalia & Hymer, Knut-Erik [Show all 14 contributors for this article] (2019). A preliminary study of cortical morphology in schizophrenia patients with a history of violence. Psychiatry Research : Neuroimaging. ISSN 0925-4927. 288, p. 29–36. doi: 10.1016/j.pscychresns.2019.04.013. Full text in Research Archive Show summary
Clinical studies of patients with schizophrenia and a history of violence are challenging both from an ethical and practical perspective, and the neurobiological underpinnings remain largely unknown. We here present a comprehensive account of the brain cortical characteristics associated with violence in schizophrenia. We obtained 3T MRI scans and thorough clinical characterization of schizophrenia patients with a history of violence (murder, attempted murder, criminal assault, SCZ-V, n=11), schizophrenia patients with no history of violence (SCZ-NV, n=17), and healthy controls (HC, n=19). Cortical thickness, area, and folding were analyzed vertexwise across the cortical mantle (FreeSurfer). SCZ-V had significantly increased cortical folding in the visual and orbitofrontal cortex, and reduced cortical thickness within the precentral-, parietal-, temporal-, and fusiform cortex compared to SCZ-NV, as well as widespread regional thinning and increased folding compared to HC. There were no group differences in cortical area. A major limitation is the small subject sample. If replicated, the results from this pilot study suggest cortical abnormalities in areas involved in sensory processing, emotion recognition, and reward to be of importance to the neurobiology of violence in schizophrenia.
Hibar, Derrek; Westlye, Lars Tjelta; Doan, Nhat Trung; Jahanshad, Neda; Cheung, J. W. & Ching, Christopher R K [Show all 123 contributors for this article] (2018). Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Molecular Psychiatry. ISSN 1359-4184. 23, p. 932–942. doi: 10.1038/mp.2017.73. Full text in Research Archive Show summary
Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen’s d=−0.293; P=1.71 × 10−21), left fusiform gyrus (d=−0.288; P=8.25 × 10−21) and left rostral middle frontal cortex (d=−0.276; P=2.99 × 10−19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
Erp, Theo G.M. Van; Walton, Esther; Hibar, Derrek; Schmaal, Lianne; Jiang, Wenhao & Glahn, David C. [Show all 151 contributors for this article] (2018). Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. Biological Psychiatry. ISSN 0006-3223. doi: 10.1016/j.biopsych.2018.04.023. Full text in Research Archive Show summary
Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11–78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10–87 years; 53% male) assessed with standardized methods at 39 centers worldwide. Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen’s d = −0.530/−0.516) and smaller surface area (left/right hemisphere: Cohen’s d = −0.251/−0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.
Haukvik, Unn Kristin H.; Tamnes, Christian Krog; Söderman, Erik & Agartz, Ingrid (2018). Neuroimaging hippocampal subfields in schizophrenia and bipolar disorder: A systematic review and meta-analysis. Journal of Psychiatric Research. ISSN 0022-3956. 104, p. 217–226. doi: 10.1016/j.jpsychires.2018.08.012. Full text in Research Archive Show summary
The hippocampus is a complex structure consisting of subregions with specialized cytoarchitecture and functions. Magnetic resonance imaging (MRI) studies in psychotic disorders show hippocampal subfield abnormalities, but affected regions differ between studies. We here present an overview of hippocampal anatomy and function relevant to psychosis, and the first systematic review and meta-analysis of MRI studies of hippocampal subfield morphology in schizophrenia and bipolar disorder. Twenty-one MRI studies assessing hippocampal subfield volumes or shape in schizophrenia or bipolar disorder were included (n 15–887 subjects). Nine volumetric group comparison studies (total n = 2593) were included in random effects meta-analyses of group differences. The review showed mixed results, with volume reductions reported in most subfields in schizophrenia and bipolar disorder. Volumetric studies using ex-vivo based image analysis templates corresponded best with the shape studies, with CA1 as the most affected region. The meta-analyses showed volume reductions in all subfields in schizophrenia and bipolar disorder compared to healthy controls (all p < .005; schizophrenia: d = 0.28-0.49, bipolar disorder: d = 0.20-0.35), and smaller left CA2/3 and right subiculum in schizophrenia than bipolar disorder. In conclusion, the hippocampal subfields appear to be differently affected in psychotic disorders. However, due to the lack of control for putative confounders such as medication, alcohol and illicit substance use, and illness stage, the results from the meta-analysis should be interpreted with caution. Methodological subfield segmentation weaknesses should be addressed in future studies.
Tønnesen, Siren; Kaufmann, Tobias; Doan, Nhat Trung; Alnæs, Dag; Palomera, Aldo Còrdova & Meer, Dennis van der [Show all 15 contributors for this article] (2018). White matter aberrations and age-related trajectories in patients with schizophrenia and bipolar disorder revealed by diffusion tensor imaging. Scientific Reports. 8. doi: 10.1038/s41598-018-32355-9. Full text in Research Archive Show summary
Supported by histological and genetic evidence implicating myelin, neuroinflammation and oligodendrocyte dysfunction in schizophrenia spectrum disorders (SZ), diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) abnormalities when compared to healthy controls (HC). The diagnostic specificity remains unclear, with bipolar disorders (BD) frequently conceptualized as a less severe clinical manifestation along a psychotic spectrum. Further, the age-related dynamics and possible sex differences of WM abnormalities in SZ and BD are currently understudied. Using tract-based spatial statistics (TBSS) we compared DTI-based microstructural indices between SZ (n = 128), BD (n = 61), and HC (n = 293). We tested for age-by-group and sex-by-group interactions, computed effect sizes within different age-bins and within genders. TBSS revealed global reductions in fractional anisotropy (FA) and increases in radial (RD) diffusivity in SZ compared to HC, with strongest effects in the body and splenium of the corpus callosum, and lower FA in SZ compared to BD in right inferior longitudinal fasciculus and right inferior fronto-occipital fasciculus, and no significant differences between BD and HC. The results were not strongly dependent on age or sex. Despite lack of significant group-by-age interactions, a sliding-window approach supported widespread WM involvement in SZ with most profound differences in FA from the late 20 s.
Hartberg, Cecilie Bhandari; Lange, Elisabeth Heffermehl; Lagerberg, Trine Vik; Haukvik, Unn Kristin H.; Andreassen, Ole Andreas & Melle, Ingrid [Show all 7 contributors for this article] (2018). Cortical thickness, cortical surface area and subcortical volumes in schizophrenia and bipolar disorder patients with cannabis use. European Neuropsychopharmacology. ISSN 0924-977X. 28(1), p. 37–47. doi: 10.1016/j.euroneuro.2017.11.019. Full text in Research Archive
Fjellvang, Maria; Grøning, Linda & Haukvik, Unn Kristin H. (2018). Imaging violence in schizophrenia: A systematic review and critical discussion of the MRI literature. Frontiers in Psychiatry. 9:333, p. 1–10. doi: 10.3389/fpsyt.2018.00333. Full text in Research Archive Show summary
Background: Persons with schizophrenia have a small but significant increase in risk of violence, which remains after controlling for known environmental risk factors. In vivo MRI-studies may point toward the biological underpinnings of psychotic violence, and neuroimaging has increasingly been used in forensic and legal settings despite unclear relevance. Objectives: (1) To present the first systematic review, following standardized guidelines, of MRI studies of violence with schizophrenia. (2) To critically discuss the promises and pitfalls of using this literature to understand violence in schizophrenia in clinical, forensic, and legal settings. Methods: Following the PRISMA guidelines and literature searches until January 2018, we found 21 original studies that fulfilled the inclusion criteria: (1) Studies of persons with schizophrenia, (2) a history of violence or aggressive behavior, (3) the use of one or more MRI-modalities (sMRI, DTI, fMRI). Results: The most consistent findings from the structural studies were reduced volumes of the hippocampus and the frontal lobe (in particular the orbitofrontal and anterior cingulate cortex) in schizophrenia patients with a history of violence or higher aggression scores. The functional studies mainly showed differences and aggression correlates in the frontal lobe and amygdala. However, the studies were methodologically heterogeneous, with four particular areas of concern: different definitions of violence, region of interest vs. whole-brain studies, small subject samples, and group comparisons in a heterogeneous diagnostic category (schizophrenia). Conclusion: The literature reports subtle, but inconsistent group level differences in brain structure and function associated with violence and aggression with schizophrenia, in particular in areas involved in the formation of psychosis symptoms and affective regulation. Due to methodological challenges the results should be interpreted with caution. In order to come closer to the neurobiological underpinnings of violence in schizophrenia future studies could: (1) address the neurobiological differences of premeditated and reactive violence, (2) use RDoC criteria, for example, or other symptom-based systems to categorize psychosis patients, (3) increase subject cohorts and apply new data driven methods. In this perspective, MRI-studies of violence in schizophrenia have the potential to inform clinical violence prediction and legal evaluations in the future
Jørgensen, Kjetil Nordbø; Nesvåg, Ragnar; Nerland, Stener; Mørch-Johnsen, Lynn; Westlye, Lars Tjelta & Lange, Elisabeth [Show all 11 contributors for this article] (2017). Brain volume change in first-episode psychosis: an effect of antipsychotic medication independent of BMI change. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 135(2), p. 117–126. doi: 10.1111/acps.12677. Full text in Research Archive
Hibar, Derrek; Adams, Hieab H.H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L. & Hofer, Edith [Show all 332 contributors for this article] (2017). Novel genetic loci associated with hippocampal volume. Nature Communications. 8:13624, p. 1–12. doi: 10.1038/ncomms13624. Full text in Research Archive Show summary
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Lange, Elisabeth; Nerland, Stener; Jørgensen, Kjetil Nordbø; Mørch-Johnsen, Lynn; Nesvåg, Ragnar & Hartberg, Cecilie Bhandari [Show all 11 contributors for this article] (2017). Alcohol use is associated with thinner cerebral cortex and larger ventricles in schizophrenia, bipolar disorder and healthy controls. Psychological Medicine. ISSN 0033-2917. 47(4), p. 655–668. doi: 10.1017/S0033291716002920. Full text in Research Archive
Dieset, Ingrid; Andreassen, Ole Andreas & Haukvik, Unn Kristin H. (2016). Somatic Comorbidity in Schizophrenia: Some Possible Biological Mechanisms Across the Life Span. Schizophrenia Bulletin. ISSN 0586-7614. 42(6), p. 1316–1319. doi: 10.1093/schbul/sbw028. Full text in Research Archive
Hibar, Derrek; Westlye, Lars Tjelta; Erp, TGM Van; Rasmussen, J; Leonardo, CD & Faskowitz, J [Show all 70 contributors for this article] (2016). Subcortical volumetric abnormalities in bipolar disorder. Molecular Psychiatry. ISSN 1359-4184. 21(12), p. 1710–1716. doi: 10.1038/mp.2015.227. Full text in Research Archive Show summary
Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case–control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen’s d=−0.232; P=3.50 × 10−7) and thalamus (d=−0.148; P=4.27 × 10−3) and enlarged lateral ventricles (d=−0.260; P=3.93 × 10−5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.
Haukvik, Unn Kristin H.; Hartberg, Cecilie Bhandari; Nerland, Stener; Jørgensen, Kjetil Nordbø; Lange, Elisabeth & Simonsen, Carmen Elisabeth [Show all 11 contributors for this article] (2016). No progressive brain changes during a 1-year follow-up of patients with first-episode psychosis. Psychological Medicine. ISSN 0033-2917. 46(3), p. 589–598. doi: 10.1017/S003329171500210X. Full text in Research Archive Show summary
Background. First-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a 1-year period compared with healthy controls, and if putative changes correlated with clinical characteristics and outcome. Method. MRIs of 79 FEP patients [SCID-I-verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (S.D. = 7.7) years, 66% male] and 82 healthy controls [age 29.3 (S.D. = 7.2) years, 66% male] were acquired from the same 1.5 T scanner at baseline and 1-year follow-up as part of the Thematically Organized Psychosis (TOP) study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer that creates an unbiased within-subject template image. General linear models were used to analyse longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations with clinical characteristics. Results. FEP patients and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use and remission at follow-up were not related to longitudinal brain change. Conclusions. We found no significant longitudinal brain changes over a 1-year period in FEP patients. Our results do not support early progressive brain changes in psychotic disorders.
Adams, Hieab H.H.; Hibar, Derrek; Chouraki, Vincent; Stein, Jason L.; Nyquist, Paul A. & Renteriá, Miguel E. [Show all 342 contributors for this article] (2016). Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature Neuroscience. ISSN 1097-6256. 19(12), p. 1569–1582. doi: 10.1038/nn.4398. Full text in Research Archive
Jørgensen, Kjetil Nordbø; Nerland, Stener; Norbom, Linn Christin Bonaventure; Doan, Nhat Trung; Nesvåg, Ragnar & Mørch-Johnsen, Lynn [Show all 11 contributors for this article] (2016). Increased MRI-based cortical grey/white-matter contrast in sensory and motor regions in schizophrenia and bipolar disorder. Psychological Medicine. ISSN 0033-2917. 46(9), p. 1971–1985. doi: 10.1017/S0033291716000593. Full text in Research Archive
Mørch-Johnsen, Lynn; Nesvåg, Ragnar; Jørgensen, Kjetil Nordbø; Lange, Elisabeth; Hartberg, Cecilie Bhandari & Haukvik, Unn Kristin H. [Show all 13 contributors for this article] (2016). Auditory cortex characteristics in schizophrenia: Associations with auditory hallucinations. Schizophrenia Bulletin. ISSN 0586-7614. 43(1), p. 75–83. doi: 10.1093/schbul/sbw130. Full text in Research Archive
Jørgensen, Kjetil Nordbø; Skjærvø, Ingeborg; Mørch-Johnsen, Lynn; Haukvik, Unn Kristin H.; Lange, Elisabeth & Melle, Ingrid [Show all 8 contributors for this article] (2015). Cigarette smoking is associated with thinner cingulate and insular cortices in patients with severe mental illness. Journal of Psychiatry & Neuroscience. ISSN 1180-4882. 40(4), p. 241–249. doi: 10.1503/jpn.140163. Full text in Research Archive
Hoseth, Eva Zsuzsanna; Westlye, Lars Tjelta; Hope, Sigrun; Dieset, Ingrid; Aukrust, Pål & Melle, Ingrid [Show all 11 contributors for this article] (2015). Association between cytokine levels, verbal memory and hippocampus volume in psychotic disorders and healthy controls. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 133(1), p. 53–62. doi: 10.1111/acps.12467. Full text in Research Archive Show summary
Objective: We investigated whether elevated plasma levels of immune markers were associated with verbal memory and hippocampal subfield volumes in patients with severe mental illnesses and in healthy controls. Method: 230 patients with a broad DSM-IV schizophrenia spectrum illness or bipolar disorder and 236 healthy controls were recruited. Memory was assessed using the Wechsler Memory ScaleThird Edition (WMS-III) Logical Memory immediate and delayed recall, and the California Verbal Learning Test summed recall over learning list (CVLT learning) and delayed free recall. We measured plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist, interleukin-6, von Willebrand factor, osteoprotegerin, high-sensitivity Creactive protein and sCD40 Ligand. Hippocampal subfield estimates were obtained using FreeSurfer. Results: We found a moderate negative association between sTNF-R1 and performance on verbal memory learning and recall tests as measured by the WMS-III Logical Memory after controlling for age, sex and diagnosis. We observed no interaction effect of diagnosis and sTNF-R1 on memory scores. We also found a nominally significant positive association between CVLT learning and hippocampal volumes. Conclusions: The findings suggest a role for immune involvement in memory independent of severe mental disorders, and may support the “bigger is better” hypothesis of hippocampal subfield volumes.
Mørch-Johnsen, Lynn; Nesvåg, Ragnar; Færden, Ann; Haukvik, Unn Kristin H.; Jørgensen, Kjetil Nordbø & Lange, Elisabeth [Show all 9 contributors for this article] (2015). Brain structure abnormalities in first-episode psychosis patients with persistent apathy. Schizophrenia Research. ISSN 0920-9964. 164(1-3), p. 59–64. doi: 10.1016/j.schres.2015.03.001. Full text in Research Archive Show summary
Background Apathy is an enduring and debilitating feature related to poor outcome in patients with first-episode psychosis (FEP). The biological underpinnings of apathy are unknown. We tested if FEP patients with persistent apathy (PA) differed from FEP patients without persistent apathy (NPA) in specific brain structure measures in the early phase of illness. Methods A total of 70 Norwegian FEP patients were recruited within 1 year of first adequate treatment. They were defined as having PA (N = 18) or NPA (N = 52) based on Apathy Evaluation Scale score at baseline and 1 year later. MRI measures of cortical thickness and subcortical structure volumes were compared between the PA and NPA groups. Results The PA group had significantly thinner left orbitofrontal cortex and left anterior cingulate cortex. The results remained significant after controlling for depressive symptoms and antipsychotic medication. Discussion FEP patients with persistent apathy in the early phase of their illness show brain structural changes compared to FEP patients without persistent apathy. The changes are confined to regions associated with motivation, occur early in the disease course and appear selectively in PA patients when both groups are compared to healthy controls.
Haukvik, Unn Kristin H.; Westlye, Lars Tjelta; Mørch-Johnsen, Lynn; Jørgensen, Kjetil Nordbø; Lange, Elisabeth & Dale, Anders M. [Show all 9 contributors for this article] (2015). In Vivo Hippocampal Subfield Volumes in Schizophrenia and Bipolar Disorder. Biological Psychiatry. ISSN 0006-3223. 77(6), p. 581–588. doi: 10.1016/j.biopsych.2014.06.020. Full text in Research Archive
Hartberg, Cecilie Bhandari; Jørgensen, Kjetil Nordbø; Haukvik, Unn Kristin H.; Westlye, Lars Tjelta; Melle, Ingrid & Andreassen, Ole Andreas [Show all 7 contributors for this article] (2015). Lithium treatment and hippocampal subfields and amygdala volumes in bipolar disorder. Bipolar Disorders. ISSN 1398-5647. 17(5), p. 496–506. doi: 10.1111/bdi.12295. Full text in Research Archive
Erp, Theo GM van; Hibar, Derrek; Rasmussen, JM; Glahn, David C; Pearlson, Godfrey D & Andreassen, Ole Andreas [Show all 58 contributors for this article] (2015). Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Molecular Psychiatry. ISSN 1359-4184. 21(4), p. 547–553. doi: 10.1038/mp.2015.63. Full text in Research Archive Show summary
The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen’s d = − 0.46), amygdala (d = − 0.31), thalamus (d = − 0.31), accumbens (d = − 0.25) and intracranial volumes (d = − 0.12), as well as larger pallidum (d = 0.21) and lateral ventricle volumes (d = 0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.
Dieset, Ingrid; Haukvik, Unn Kristin H.; Melle, Ingrid; Røssberg, Jan Ivar; Ueland, Thor & Hope, Sigrun [Show all 11 contributors for this article] (2015). Association between altered brain morphology and elevated peripheral endothelial markers — Implications for psychotic disorders. Schizophrenia Research. ISSN 0920-9964. 161(2-3), p. 222–228. doi: 10.1016/j.schres.2014.11.006. Full text in Research Archive
Hibar, Derrek; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivieres, Sylvane & Jahanshad, Neda [Show all 287 contributors for this article] (2015). Common genetic variants influence human subcortical brain structures. Nature. ISSN 0028-0836. 520(7546), p. 224–229. doi: 10.1038/nature14101. Full text in Research Archive
Lange, Elisabeth; Nesvåg, Ragnar; Ringen, Petter Andreas; Hartberg, Cecilie Bhandari; Haukvik, Unn Kristin H. & Andreassen, Ole Andreas [Show all 8 contributors for this article] (2014). One year follow-up of alcohol and illicit substance use in first-episode psychosis: Does gender matter? Comprehensive Psychiatry. ISSN 0010-440X. 55(2), p. 274–282. doi: 10.1016/j.comppsych.2013.08.018. Full text in Research Archive
Nesvåg, Ragnar; Schaer, M; Haukvik, Unn Kristin H.; Westlye, Lars Tjelta; Rimol, Lars Morten & Lange, Elisabeth [Show all 13 contributors for this article] (2014). Reduced brain cortical folding in schizophrenia revealed in two independent samples. Schizophrenia Research. ISSN 0920-9964. 152(2-3), p. 333–338. doi: 10.1016/j.schres.2013.11.032. Full text in Research Archive
Haukvik, Unn Kristin H.; McNeil, Thomas; Lange, Elisabeth; Melle, Ingrid; Dale, AM & Andreassen, Ole Andreas [Show all 7 contributors for this article] (2014). Pre- and perinatal hypoxia associated with hippocampus/amygdala volume in bipolar disorder. Psychological Medicine. ISSN 0033-2917. 44(5), p. 975–985. doi: 10.1017/S0033291713001529. Full text in Research Archive Show summary
Background Pre- and perinatal adversities may increase the risk for schizophrenia and bipolar disorder. Hypoxia-related obstetric complications (OCs) are associated with brain anatomical abnormalities in schizophrenia, but their association with brain anatomy variation in bipolar disorder is unknown. Method Magnetic resonance imaging brain scans, clinical examinations and data from the Medical Birth Registry of Norway were obtained for 219 adults, including 79 patients with a DSM-IV diagnosis of bipolar disorder (age 29.4 years, s.d. = 11.8 years, 39% male) and 140 healthy controls (age 30.8 years, s.d. = 12.0 years, 53% male). Severe hypoxia-related OCs throughout pregnancy/birth and perinatal asphyxia were each studied in relation to a priori selected brain volumes (hippocampus, lateral ventricles and amygdala, obtained with FreeSurfer), using linear regression models covarying for age, sex, medication use and intracranial volume. Multiple comparison adjustment was applied. Results Perinatal asphyxia was associated with smaller left amygdala volume (t = −2.59, p = 0.012) in bipolar disorder patients, but not in healthy controls. Patients with psychotic bipolar disorder showed distinct associations between perinatal asphyxia and smaller left amygdala volume (t = −2.69, p = 0.010), whereas patients with non-psychotic bipolar disorder showed smaller right hippocampal volumes related to both perinatal asphyxia (t = −2.60, p = 0.015) and severe OCs (t = −3.25, p = 0.003). No associations between asphyxia or severe OCs and the lateral ventricles were found. Conclusions Pre- and perinatal hypoxia-related OCs are related to brain morphometry in bipolar disorder in adulthood, with specific patterns in patients with psychotic versus non-psychotic illness.
Haukvik, Unn Kristin H.; Rimol, Lars Morten; Roddey, J Cooper; Hartberg, Cecilie Bhandari; Lange, Elisabeth & Vaskinn, Anja [Show all 10 contributors for this article] (2014). Normal Birth Weight Variation Is Related to Cortical Morphology Across the Psychosis Spectrum. Schizophrenia Bulletin. ISSN 0586-7614. 40(2), p. 410–419. doi: 10.1093/schbul/sbt005. Full text in Research Archive
Aas, Monica; Haukvik, Unn Kristin H.; Djurovic, Srdjan; Tesli, Martin Steen; Athanasiu, Lavinia & Bjella, Thomas [Show all 11 contributors for this article] (2014). Interplay between childhood trauma and BDNF val66met variants on blood BDNF mRNA levels and on hippocampus subfields volumes in schizophrenia spectrum and bipolar disorders. Journal of Psychiatric Research. ISSN 0022-3956. 59, p. 14–21. doi: 10.1016/j.jpsychires.2014.08.011. Full text in Research Archive
Thompson, Paul M; Stein, Jason L; Medland, Sarah E; Hibar, Derrek P; Vasquez, Alejandro Arias & Renteria, Miguel E [Show all 289 contributors for this article] (2014). The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging and Behavior. ISSN 1931-7557. 8(2), p. 153–182. doi: 10.1007/s11682-013-9269-5. Full text in Research Archive Show summary
The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA’s first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
Tesli, Martin Steen; Egeland, Randi; Sønderby, Ida Elken; Haukvik, Unn Kristin H.; Bettella, Franscesco & Hibar, Derrek [Show all 12 contributors for this article] (2013). No evidence for association between bipolar disorder risk gene variants and brain structural phenotypes. Journal of Affective Disorders. ISSN 0165-0327. 151(1), p. 291–297. doi: 10.1016/j.jad.2013.06.008. Full text in Research Archive
Bergmann, Ørjan; Haukvik, Unn Kristin H.; Brown, Andrew; Rimol, Lars Morten; Hartberg, Cecilie Bhandari & Athanasiu, Lavinia [Show all 11 contributors for this article] (2013). ZNF804A and cortical thickness in schizophrenia and bipolar disorder. Psychiatry Research : Neuroimaging. ISSN 0925-4927. 212(2), p. 154–157. doi: 10.1016/j.pscychresns.2013.01.007. Full text in Research Archive
Aas, Monica; Haukvik, Unn Kristin H.; Djurovic, Srdjan; Bergmann, Ørjan; Athanasiu, Lavinia & Tesli, Martin Steen [Show all 13 contributors for this article] (2013). BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses. Progress in Neuro-psychopharmacology and Biological Psychiatry. ISSN 0278-5846. 46, p. 181–188. doi: 10.1016/j.pnpbp.2013.07.008. Full text in Research Archive

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Friestad, Christine; Tesli, Martin Steen; Rokicki, Jaroslav; Ziaka, Laoura; Heilskov, Esben Rytter & Hartberg, Cecilie Bhandari [Show all 7 contributors for this article] (2024). UNDERSTANDING AND PREVENTING VIOLENCE IN HIGH RISK INDIVIDUALS – A MIXED-METHODS APPROACH (PreVio). Full text in Research Archive
Ziaka, Laoura; Tesli, Martin Steen; Haukvik, Unn Kristin Hansen; Rokicki, Jaroslav & Friestad, Christine (2024). Understanding and Preventing Violent Crime in Individuals with Severe Mental Disorders – a Mixed-Methods Approach (PreVio): A Study Protocol. Full text in Research Archive
Senneseth, Mette; Haukvik, Unn Kristin Hansen; Rosenvinge, Jan H; Søndenaa, Erik & Bjørkly, Stål Kapstø (2023). Forsknings- og utviklingsaktiviteter ved Nasjonalt Kompetansesenternettverk for sikkerhets-, fengsels- og rettspsykiatri (SIFER). LVSinfo. Full text in Research Archive
Holter, Katrine; Gröning, Linda & Haukvik, Unn Kristin Hansen (2022). Rett og Slett #29: Kongsberg-drapene og psykiske lidelser. [Radio]. Alle podkast-spillere. Full text in Research Archive Show summary
I fjor høst skjøt en antatt psykotisk mann tilfeldige ofre med pil og bue. Fem mennesker ble drept. Mannen er i ettertid utredet av sakkyndige som har konkludert med at han ikke har skyldevne på grunn av psykisk lidelse. I denne og i nok en episode gjør «Rett og Slett» et dypdykk i rettspsykiatrien. For hvorfor er det noen mennesker som mangler skyldevne? Når er noen så syke at de ikke kan straffes? I studio har jeg med journalist Torkjell Trædal som har dekket Kongsberg-saken tett for Aftenposten. Jeg har også fått med to forskere: Unn Haukvik er ekspert på psykoselidelser. Hun er ansatt som førsteamanuensis i psykiatri (UiO) og jobber også som overlege ved akuttpsykiatrisk avdeling. Linda Gröning er strafferettsprofessor (UiB) og leder av et større forskningsprosjekt om utilregnelighet. Podkasten er sponset av Karnov juridisk forlag.
Gröning, Linda; Radovic, Susanna & Haukvik, Unn Kristin H. (2021). Criminal Insanity - Medical. Philosophial and Legal Perspectives. Full text in Research Archive
Storvestre, Guttorm Breivik; Jensen, Arvid; Bjerke, Espen; Tesli, Natalia; Røsæg, Cato & Lagerberg, Trine Vik [Show all 10 contributors for this article] (2020). Is early debut of substance use Associated With violent offending in schizophrenia? Full text in Research Archive
Storvestre, Guttorm Breivik; Jensen, Arvid; Bjerke, Espen; Tesli, Natalia; Røsæg, Cato & Lagerberg, Trine Vik [Show all 10 contributors for this article] (2020). Is early debut of substance use Associated With violent offending in schizophrenia? Schizophrenia Bulletin. ISSN 0586-7614. 46, p. S24–S24. doi: 10.1093/schbul/sbaa028.055. Full text in Research Archive
Favre, Pauline; Pauling, Melissa; Stout, Jacques; Hozer, Franz; Sarrazin, Samuel & Abé, Christoph [Show all 59 contributors for this article] (2019). Correction: Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals (Neuropsychopharmacology, (2019), 44, 13, (2285-2293), 10.1038/s41386-019-0485-6). Neuropsychopharmacology. ISSN 0893-133X. 44(13), p. 2298–2298. doi: 10.1038/s41386-019-0521-6. Full text in Research Archive
Storvestre, Guttorm Breivik; Valnes, Lars Magnus; Jensen, Arvid; Agartz, Ingrid; Jacobsen, Morten & Andreassen, Ole [Show all 8 contributors for this article] (2017). Regional cortical folding and thickness differences between schizophrenia patients with and without a history of severe violence. Full text in Research Archive
Jørgensen, Kjetil Nordbø; Nerland, Stener; Norbom, Linn Christin Bonaventure; Doan, Nhat Trung; Nesvåg, Ragnar & Haukvik, Unn Kristin H. [Show all 10 contributors for this article] (2015). Increased cortical gray/white matter intensity contrast in schizophrenia and bipolar disorder compared to healthy controls. Full text in Research Archive
Mørch-Johnsen, Lynn; Nesvåg, Ragnar; Færden, Ann; Haukvik, Unn Kristin H.; Jørgensen, Kjetil Nordbø & Lange, Elisabeth [Show all 9 contributors for this article] (2014). Brain structure changes in first-episode psychosis patients with persistent apathy. Full text in Research Archive
Mørch-Johnsen, Lynn; Nesvåg, Ragnar; Færden, Ann; Haukvik, Unn Kristin H.; Jørgensen, Kjetil Nordbø & Lange, Elisabeth [Show all 9 contributors for this article] (2014). Brain structure changes in first-episode psychosis patients with persistent apathy. Schizophrenia Research. ISSN 0920-9964. 153, p. S210–S210. doi: 10.1016/S0920-9964(14)70608-5. Full text in Research Archive
Jørgensen, Kjetil Nordbø; Skjærvø, Ingeborg; Mørch-Johnsen, Lynn; Haukvik, Unn Kristin H.; Lange, Elisabeth & Melle, Ingrid [Show all 8 contributors for this article] (2014). Poster #T107 Cigarette smoking is associated with reduced cingulate and insular thickness among patients with psychosis and bipolar spectrum disorders. Schizophrenia Research. ISSN 0920-9964. 153(1), p. S327–S327. doi: 10.1016/S0920-9964(14)70924-7. Full text in Research Archive
Aas, Monica; Haukvik, Unn Kristin H.; Djurovic, Srdjan; Bergmann, Ørjan; Lorentzen, Steinar & Andreassen, Ole Andreas [Show all 8 contributors for this article] (2013). Is Met Variant of the BDNF VAL66MET-Combined with Childhood Trauma - A Risk Factor of Brain Abnormalities in Psychoses? Biological Psychiatry. ISSN 0006-3223. 73(9), p. 287S–287S. Full text in Research Archive
Erp, Theo G M van; Hibar, Derrek P; Rasmussen, Jerod; Andreassen, Ole Andreas; Haukvik, Unn Kristin H. & Agartz, Ingrid [Show all 18 contributors for this article] (2013). A Large-Scale Meta-Analysis of Subcortical Brain Volume Abnormalities in Schizophrenia via the Enigma Consortium. Biological Psychiatry. ISSN 0006-3223. 73(9), p. 299S–300S. Full text in Research Archive

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Published May 13, 2014 9:08 AM - Last modified Aug. 25, 2026 2:08 PM

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