Distinguishing patterns of impairment on inhibitory control and general cognitive ability among bipolar with and without psychosis, schizophrenia, and schizoaffective disorder.

BACKGROUND: Deficits in inhibitory control on a Stop Signal Task (SST) were previously observed to be of similar magnitude across schizophrenia, schizoaffective, and bipolar disorder with psychosis, despite variation in general cognitive ability. Understanding different patterns of performance on the SST may elucidate different pathways to the impaired inhibitory control each group displayed. Comparing nonpsychotic bipolar disorder to the psychosis groups on SST may also expand our understanding of the shared neurobiology of this illness spectrum. METHODS: We tested schizophrenia (n = 220), schizoaffective (n = 216), bipolar disorder with (n = 192) and without psychosis (n = 67), and 280 healthy comparison participants with a SST and the Brief Assessment of Cognition in Schizophrenia (BACS), a measure of general cognitive ability. RESULTS: All patient groups had a similar degree of impaired inhibitory control over prepotent responses. However, bipolar groups differed from schizophrenia and schizoaffective groups in showing speeded responses and inhibition errors that were not accounted for by general cognitive ability. Schizophrenia and schizoaffective groups had a broader set of deficits on inhibition and greater general cognitive deficit, which fully accounted for the inhibition deficits. No differences were found between the clinically well-matched bipolar with and without psychosis groups, including for inhibitory control or general cognitive ability. CONCLUSIONS: We conclude that 1) while impaired inhibitory control on a SST is of similar magnitude across the schizo-bipolar spectrum, including nonpsychotic bipolar, different mechanisms may underlie the impairments, and 2) history of psychosis in bipolar disorder does not differentially impact inhibitory behavioral control or general cognitive abilities.

Peripheral oxytocin and vasopressin modulates regional brain activity differently in men and women with schizophrenia.

BACKGROUND: Oxytocin (OT) and arginine vasopressin (AVP) exert sexually dimorphic effects on cognition and emotion processing. Abnormalities in these hormones are observed in schizophrenia and may contribute to multiple established sex differences associated with the disorder. Here we examined sex-dependent hormone associations with resting brain activity and their clinical associations in schizophrenia patients. METHODS: OT and AVP serum concentrations were assayed in 35 individuals with schizophrenia (23 men) and 60 controls (24 men) from the Chicago BSNIP study site. Regional cerebral function was assessed with resting state fMRI by measuring the amplitude of low-frequency fluctuations (ALFF) which are believed to reflect intrinsic spontaneous neuronal activity. RESULTS: In female patients, lower OT levels were associated with lower ALFF in frontal and cerebellar cortices (p's < 0.05) and in female controls AVP levels were inversely associated with ALFF in the frontal cortex (p = 0.01). In male patients, lower OT levels were associated with lower ALFF in the posterior cingulate and lower AVP levels were associated with lower ALFF in frontal cortex (p's < 0.05). In male controls, lower OT levels were associated with lower ALFF in frontal cortex and higher ALFF in the thalamus (p's < 0.05). There were some inverse ALFF-behavior associations in patients. CONCLUSIONS: Alterations in peripheral hormone levels are associated with resting brain physiology in a sex-dependent manner in schizophrenia. These effects may contribute to sex differences in psychiatric symptom severity and course of illness in schizophrenia.

Polygenic risk for schizophrenia and measured domains of cognition in individuals with psychosis and controls.

Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of polygenetic risk for schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychotic disorder patients, a measure of premorbid intelligence that is minimally affected by psychosis onset (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS and WRAT. Using genome-wide single nucleotide polymorphism (SNP) data from 314 psychotic and 423 healthy research participants in the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Consortium, we investigated the association of PRSSCZ with BACS, WRAT, and EY. Among apparently healthy individuals, greater genetic risk for schizophrenia (PRSSCZ) was significantly associated with lower BACS scores (r = -0.17, p = 6.6 × 10-4 at PT = 1 × 10-4), but not with WRAT or EY. Among individuals with psychosis, PRSSCZ did not associate with variations in any of these three phenotypes. We further investigated the association between PRSSCZ and WRAT in more than 4500 healthy subjects from the Philadelphia Neurodevelopmental Cohort. The association was again null (p > 0.3, N = 4511), suggesting that different cognitive phenotypes vary in their etiologic relationship with schizophrenia.

Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity.

Oxytocin (OT) and arginine vasopressin (AVP) exert robust and sexually dimorphic influences on cognition and emotion. How these hormones regulate relevant functional brain systems is not well understood. OT and AVP serum concentrations were assayed in 60 healthy individuals (36 women). Brain functional networks assessed with resting-state functional magnetic resonance imaging (rs-fMRI) were constructed with graph theory-based approaches that characterize brain networks as connected nodes. Sex differences were demonstrated in rs-fMRI. Men showed higher nodal degree (connectedness) and efficiency (information propagation capacity) in left inferior frontal gyrus (IFG) and bilateral superior temporal gyrus (STG) and higher nodal degree in left rolandic operculum. Women showed higher nodal betweenness (being part of paths between nodes) in right putamen and left inferior parietal gyrus (IPG). Higher hormone levels were associated with less intrinsic connectivity. In men, higher AVP was associated with lower nodal degree and efficiency in left IFG (pars orbitalis) and left STG and less efficiency in left IFG (pars triangularis). In women, higher AVP was associated with lower betweenness in left IPG, and higher OT was associated with lower nodal degree in left IFG (pars orbitalis). Hormones differentially correlate with brain networks that are important for emotion processing and cognition in men and women. AVP in men and OT in women may regulate orbital frontal cortex connectivity, which is important in emotion processing. Hormone associations with STG and pars triangularis in men and parietal cortex in women may account for well-established sex differences in verbal and visuospatial abilities, respectively. © 2016 Wiley Periodicals, Inc.

Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis.

BACKGROUND: In women with chronic schizophrenia, higher levels of peripheral oxytocin have been associated with lower levels of positive but not negative symptoms. Sex-specific associations between endogenous levels of oxytocin (OT) and arginine vasopressin (AVP) with clinical symptoms and cognition in untreated early course patients have not been examined. METHOD: Clinical ratings and neuropsychological testing were performed in thirty-eight acutely ill, unmedicated first-episode schizophrenia patients (14 women, 24 men). Serum hormone assays were obtained in patients and thirty-eight demographically similar healthy controls. RESULTS: Patients demonstrated increased AVP levels compared to controls (p = 0.01). Higher AVP levels were associated with greater positive symptoms (r = 0.58, p = 0.03) and worse verbal learning (r = -0.63, p = 0.02) in female, but not male, patients. OT levels did not statistically differ between patients and controls, and were unrelated to clinical symptoms or cognition in patients. CONCLUSION: Results suggest an association of endogenous AVP with increased positive symptom severity and worse cognition in untreated female, but not male, schizophrenia patients. Findings support the role of neuroendocrine alterations in acute psychosis and the importance of examining sex-specific neuroendocrine alterations early in the course of schizophrenia.