Increased inferior frontal activation during word generation: A marker of genetic risk for schizophrenia but not bipolar disorder?

Abstract

During verbal-fluency tasks, impairments in performance and functional abnormalities in the inferior frontal cortex have been observed in both schizophrenia patients and their unaffected relatives. We sought to examine whether such functional abnormalities are a specific marker of genetic vulnerability to schizophrenia. We studied a sample of 132 subjects, comprising 39 patients with schizophrenia, 10 unaffected monozygotic (MZ) cotwins of schizophrenia probands, 28 patients with bipolar disorder, 7 unaffected MZ cotwins of bipolar disorder probands and 48 healthy controls. Blood oxygen level-dependent response was measured using functional magnetic resonance imaging during the performance of an overt verbal-fluency task with two levels of task difficulty, in a cytoarchitectonic region of interest encompassing Brodmann areas 44 and 45 bilaterally. Patients with schizophrenia and the unaffected MZ cotwins of schizophrenia probands showed increased activation in the inferior frontal cortex relative to healthy controls and bipolar patients. Increased engagement of the inferior frontal cortex during verbal-fluency may thus be a marker of genetic vulnerability to schizophrenia.

Neuroimaging-Based Biomarkers in Psychiatry: Clinical Opportunities of a Paradigm Shift

“…Distinguishing people with schizophrenia from those with BD and healthy control subjects has been achieved with a sensitivity and specificity of over 90% based on functional abnormalities in prefrontal and temporal cortices and within default neural networks. [49][50][51] Neuroimaging-based prediction has also shown promising results in classifying subjects with obsessive-compulsive disorder, 52 autism spectrum disorders, 53 BD, 46,54 and substance abuse. 55 Most of these studies have found abnormalities that were regionally distributed but of relatively small magnitudes, and therefore with much overlap between patients and control subjects for any given region, which machine learning approaches were able to integrate leading to accurate classification.…”

Mapping vulnerability to bipolar disorder: a systematic review and meta-analysis of neuroimaging studies

“…However, another verbal fluency study reported there were no significant differences between the HR and control groups, suggesting that hyperactivity during cognitive functioning is not a marker of genetic risk for bipolar disorder. 57 …”

“…Our findings can be interpreted in a similar fashion. 57 Abnormalities in prefrontal regions can be associated with suppression of task-induced negative emotion, leading to abnormal activation in regions associated with emotional arousal (e.g., insula), and further interfere with cognition in the HR group. 58 However, the neurochemical basis of the functional abnormalities in HR individuals is unclear.…”

Sexual Dimorphism in Monoamine Metabolism in BrdU-Treated Rats Showing Behavioral Dopamine Hypersensitivity: An Animal Model of Schizophrenia

“…This study also shows that striatal subdivision is negatively related to verbal fluency performance, but this is not the case for the limbic subdivision. Verbal fluency depends on prefrontal function [48]. The associative striatum regulates information flow to and from the prefrontal cortex [49,50].…”