ABSTRACT
BACKGROUND: Bipolar disorder and schizophrenia have both been associated with deficits in extra-dimensional set shifting (EDS). Deficits in reversal learning (RL) have also been shown in schizophrenia but not in bipolar disorder. This study sought to assess the specificity of these findings in a direct comparison of clinically stable patients with each disorder. METHOD: The intra-dimensional/extra-dimensional (IDED) set-shifting task, part of the Cambridge Neuropsychological Test Automated Battery (CANTAB), was administered to 30 patients with schizophrenia, 47 with bipolar disorder and a group of 44 unaffected controls. EDS and RL errors were compared between the groups and related to measures of current and past psychiatric symptoms and medication. RESULTS: Both groups of patients with schizophrenia or bipolar disorder made more EDS and RL errors than controls. Neither measure separated the two disorders, even when the analysis was restricted to euthymic patients. No relationship was found with prescribed medication. CONCLUSIONS: Patients with bipolar disorder or schizophrenia show common deficits in EDS and RL. These deficits do not seem to be attributable to current symptoms and are consistent with disrupted networks involving the ventral prefrontal cortex.
Subject(s)
Attention , Bipolar Disorder/diagnosis , Bipolar Disorder/psychology , Reversal Learning , Schizophrenia/diagnosis , Schizophrenic Psychology , Set, Psychology , Adult , Cohort Studies , Female , Humans , Intelligence , Male , Middle Aged , Neuropsychological Tests/statistics & numerical data , Psychiatric Status Rating Scales , PsychometricsABSTRACT
OBJECTIVE: We sought to address whether dorsal or ventral prefrontal gyrification is abnormal in bipolar disorder and to determine its diagnostic specificity and cognitive associations. METHOD: Forty-two out-patients with bipolar disorder, 28 with schizophrenia and 37 controls underwent magnetic resonance imaging. All subjects also underwent IQ and executive assessments using tasks whose performance has been localized to the ventral or dorsal prefrontal cortex. Cortical folding was quantified using the gyrification index (GI) and related to the cognitive measures. RESULTS: Patients with bipolar disorder showed reduced prefrontal gyrification compared with controls but did not differ from patients with schizophrenia. Neither ventral nor dorsal GI was preferentially affected in either disorder. Current IQ was positively and significantly correlated with GI. CONCLUSION: Patients with bipolar disorder and patients with schizophrenia have reduced prefrontal gyrification affecting both ventral and dorsal subregions. These reductions were significantly associated with cognitive impairments occurring in both disorders.
Subject(s)
Bipolar Disorder/physiopathology , Cognition Disorders/physiopathology , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Prefrontal Cortex/abnormalities , Schizophrenia/physiopathology , Adult , Bipolar Disorder/diagnosis , Cognition Disorders/diagnosis , Dominance, Cerebral/physiology , Female , Humans , Intelligence/physiology , Male , Middle Aged , Neuropsychological Tests/statistics & numerical data , Prefrontal Cortex/pathology , Prefrontal Cortex/physiopathology , Psychiatric Status Rating Scales/statistics & numerical data , Psychometrics , Reference Values , Schizophrenia/diagnosis , SoftwareABSTRACT
Theories of abnormal anatomical and functional connectivity in schizophrenia and bipolar disorder are supported by evidence from functional magnetic resonance imaging (MRI), structural MRI and diffusion tensor imaging (DTI). The presence of similar abnormalities in unaffected relatives suggests such disconnectivity is genetically mediated, albeit through unspecified loci. Neuregulin 1 (NRG1) is a psychosis susceptibility gene with effects on neuronal migration, axon guidance and myelination that could potentially explain these findings. In the current study, unaffected subjects were genotyped at the NRG1 single nucleotide polymorphism (SNP) rs6994992 (SNP8NRG243177) locus, previously associated with increased risk for psychosis, and the effect of genetic variation at this locus on white matter density (T(1)-weighted MRI) and integrity (DTI) was ascertained. Subjects with the risk-associated TT genotype had reduced white matter density in the anterior limb of the internal capsule and evidence of reduced structural connectivity in the same region using DTI. We therefore provide the first imaging evidence that genetic variation in NRG1 is associated with reduced white matter density and integrity in human subjects. This finding is discussed in the context of NRG1 effects on neuronal migration, axon guidance and myelination.
