PhD Candidate Carla P. D. Fernandes

Is there a genetic overlap between cognitive impairment and psychiatric disorders?

Carla P. D. Fernandes

Background for the PhD thesis

Schizophrenia and bipolar disorder are complex disorders most likely affected by the interaction of several genetic - and environmental - risk factors. Schizophrenia is a severe mental condition which comprises the so-called positive- and negative- symptoms.

Bipolar disorder is mostly characterized by swings in mood, ranging from manic to depressive episodes.

Furthermore, in both conditions patients often present great cognitive impairments, as well brain structure changes. Therefore cognitive traits and brain structure have been suggested as suitable endophenotypes for the study of these disorders.

Therefore, the main aims of my PhD were:

  • To select genes associated with cognitive abilities and test them for implication in schizophrenia and bipolar disorder
  • To replicate the genome wide association study’s (GWAS) results of several cognitive phenotypes in two independent healthy samples.
  • To test for association of a previously reported genetic variant implicated in psychiatric disorders, cognition and brain changes, with cognitive traits and diffusion tensor imaging indices of white matter microstructure

Main findings

Using Gene Set Enrichment Analysis (GSEA) software, genes involved in cognitive impairment were tested for association with bipolar disorder and schizophrenia. This study showed association for different cognitive abilities in both disorders.

A genome wide study was performed in a sample of healthy individuals, previously tested for cognitive abilities relevant for psychiatric conditions, followed by replication in an independent and comparable sample. In this study no genome wide significance was found for any of the common variants tested.

The rs1344706 SNP within the ZNF804A gene, known to be associated with bipolar disorder and schizophrenia as well as with some cognitive phenotypes and white matter microstructural properties, was tested in two healthy samples. In this study no significant association was found between the variant and the cognitive domains tested or the white matter microstructure.


Endophenotypes approaches are valuable tools to consider in the investigation of psychiatric disorders, namely cognitive impairments. Additionally, combining polygenic models with endophenotypes approaches may aid on the investigation of psychiatric conditions.

Further replication of the results, including bigger and different samples as well as a bigger amount and more controlled cognitive assessments is an urge. This will hopefully increase and improve the knowledge on psychiatric disorders and lead to a better prediction and prevention of such conditions.

Title of the thesis and papers

“A genetic study of schizophrenia and bipolar disorder: a cognitive endophenotype approach”

Publisert 31. okt. 2014 10:47 - Sist endret 9. apr. 2015 13:15