Visual cortex neuroanatomical abnormalities in psychosis: neurodevelopmental, neurodegenerative, or both?
Adhan, Iniya Kumar
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BACKGROUND: Idiopathic psychotic disorders, which include schizophrenia, schizoaffective and bipolar disorder with psychosis, are debilitating disorders affecting about 3% of the world’s population. Neurodevelopmental and neurodegenerative hypotheses have been proposed in psychosis, but the literature is mixed in regards to whether psychosis pathogenesis involves one or both of these processes. Since the visual system matures early in development, studying visual pathway abnormalities stratified by disease onset may further inform our understanding of psychosis pathogenesis. OBJECTIVE: The objective of this thesis is to determine whether disease onset, independent of illness duration, has a differential effect on visual cortical abnormalities in psychosis. We examined visual cortical measures for thickness, surface area, and volume using a pseudo-longitudinal study design of first episode psychosis-schizophrenia (FEP-SZ), FEP-non-schizophrenia (FEP-NSZ), early onset psychosis (EOP, <15 years of age), adult onset psychosis (OP, >15 and <30 years of age), and late onset psychosis (LOP, >30 years of age) groups. Relationships between visual cortical metrics and clinical or functional outcomes were performed. METHODS: The FEP sample (n= 102) included healthy controls (n= 44), FEP-SZ (n= 36), and FEP-NSZ (n= 22). The chronic psychosis data included healthy controls (n= 311) and psychosis probands (n=510). Psychosis probands was stratified by disease onset: EOP (n=213), OP (n=257), and LOP (n=40). Propensity matching was performed to match healthy controls (HC) according to age, sex and race. Linear regression models were performed comparing the means of visual cortical measures between groups. Partial Spearman correlations controlling for confounding factors were performed between visual cortical regions and clinical data. For FEP, clinical outcomes were assessed using Clinical Global Impression scale (CGI), Scale of Positive Symptoms (SAPS), and Scale of Negative Symptoms (SANS). For onset groups, clinical and functional outcomes were assessed using Positive and Negative Syndrome Scale (PANSS), Montgomery–Åsberg Depression Rating Scale (MADRS), Brief Assessment of Cognition (BACS), Wecshler Memory Scale (WMS) spatial span, anti-saccade error rates, dot expectancy pattern test, emotion recognition test, and Birchwood Social Functioning Scale (SFS). Multiple comparisons were performed using the Benjamini-Hochberg procedure. RESULTS: FEP-SZ was associated with smaller V1 and V2 areas, higher MT area and lower MT thickness compared to HCs. Lower MT thickness was associated with worse negative symptoms. Compared to HC, patients with chronic psychosis had lower V1, V2, and MT areas, as well as smaller MT thickness. V1 and V2 area and MT thickness were lower in the EOP group in comparison to matched HC. OP and LOP had a thinner MT region compared to matched HC. Of particular note, it was observed that EOP had greater area differences as compared to thickness reductions in the LOP group. Increased hallucinations and delusions were associated with a thinner MT region in the EOP group. CONCLUSION: When stratified by disease onset, FEP, EOP, OP, and LOP appear to have different pathogenic mechanisms and the severity of visual cortex neuroanatomical abnormalities are dependent on when the disease onset occurs. EOP occurs earlier in neurodevelopment resulting in greater severity in symptom and visual cortical measures as compared to OP. On the contrary, LOP appears to have a neurodegenerative mechanism which is evidenced by accelerated visual cortical thinning.
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