Related Experiment Video
Updated: Oct 27, 2025
Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia
Published on: December 2, 2015
Genetic risk for bipolar disorder and schizophrenia predicts structure and function of the ventromedial prefrontal
Christoph Abé1, Predrag Petrovic1, William Ossler1
1From the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Abé, Petrovic, Ossler, Thompson, Liberg, Fransson, Ingvar, Landén); the Department of Psychology, Stanford University, Stanford, California, USA (Thompson); the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Song, Bergen); the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (Sellgren); Karolinska University Hospital, Department of Neuroradiology, Stockholm, Sweden (Ingvar); and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Sweden (Landén).
Background:
Bipolar disorder is highly heritable and polygenic. The polygenic risk for bipolar disorder overlaps with that of schizophrenia, and polygenic scores are normally distributed in the population. Bipolar disorder has been associated with structural brain abnormalities, but it is unknown how these are linked to genetic risk factors for psychotic disorders.
Methods:
We tested whether polygenic risk scores for bipolar disorder and schizophrenia predict structural brain alterations in 98 patients with bipolar disorder and 81 healthy controls. We derived brain cortical thickness, surface area and volume from structural MRI scans. In post-hoc analyses, we correlated polygenic risk with functional hub strength, derived from resting-state functional MRI and brain connectomics.
Results:
Higher polygenic risk scores for both bipolar disorder and schizophrenia were associated with a thinner ventromedial prefrontal cortex (vmPFC). We found these associations in the combined group, and separately in patients and drug-naive controls. Polygenic risk for bipolar disorder was correlated with the functional hub strength of the vmPFC within the default mode network.
Limitations:
Polygenic risk is a cumulative measure of genomic burden. Detailed genetic mechanisms underlying brain alterations and their cognitive consequences still need to be determined.
Conclusion:
Our multimodal neuroimaging study linked genomic burden and brain endophenotype by demonstrating an association between polygenic risk scores for bipolar disorder and schizophrenia and the structure and function of the vmPFC. Our findings suggest that genetic factors might confer risk for psychotic disorders by influencing the integrity of the vmPFC, a brain region involved in self-referential processes and emotional regulation. Our study may also provide an imaging-genetics vulnerability marker that can be used to help identify individuals at risk for developing bipolar disorder.
Related Concept Videos
01:29Biological Causes of Schizophrenia
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
01:30Bipolar Disorder
01:29Psychological and Sociocultural Causes of Schizophrenia
01:27Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...
01:28Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
01:30Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....