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Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.
Methods.
Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.
Results.
Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.
Conclusion.
These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.
This chapter talks about a 45-year-old right-handed woman who was admitted to a Neurology clinic with several years of cognitive difficulty. She has a long-standing history of depression, which has been fairly well-controlled on sertraline 100mg daily. There are no other chronic medical problems or regular medications. CT of the head demonstrated very mild generalized atrophy with more pronounced atrophy of the head of the caudate nucleus. The initial diagnostic impression was Huntington disease, despite the lack of a clear family history. Genetic testing was performed, which demonstrated an expansion of the CAG repeat region in the huntingtin gene on chromosome 4. Additionally, a more thorough family history revealed that her father and several of his relatives had involuntary movements. Huntington disease (HD) is a neurodegenerative disease characterized clinically by the triad of a movement disorder, dementia, and behavioral disturbances.