Antipsychotic medications: linking receptor antagonism to neuropsychological functioning in first episode psychosis.

Antipsychotic medications can contribute to neurocognitive and motor impairments, but specific links to individualized pharmacological treatment regimens are unclear. In 68 participants with stabilized first-episode psychosis (FEP), we investigated the links between neuropsychological functions and an established anticholinergic potency index and a new D(2) antagonist potency index developed in our lab. Each participant's psychiatric medication regimen was converted into estimated receptor antagonist loads based upon specific medication dosage(s) and reported in vitro brain muscarinic cholinergic and D(2) receptor antagonism. In addition to the global neuropsychological impairments of FEP participants, the findings supported the hypothesized links between receptor antagonist loads and specific deficits. Higher anticholinergic load was associated with poorer delayed verbal memory but was not related to motor functioning. In contrast, higher D(2) load was associated with poorer motor functioning but not verbal memory. These selective antagonist load associations explained 19% of the variance in motor functioning and 17% of the variance in delayed verbal memory. Evidently, some of the neuropsychological impairments found in persons with FEP are selectively related to the specific pharmacodynamics and the dosing of their medication regimens. Moreover, these effects can be readily estimated from practical and inexpensive indices.

Component Processes of Decision Making in a Community Sample of Precariously Housed Persons: Associations With Learning and Memory, and Health-Risk Behaviors.

The Iowa Gambling Task (IGT) is a widely used measure of decision making, but its value in signifying behaviors associated with adverse, "real-world" consequences has not been consistently demonstrated in persons who are precariously housed or homeless. Studies evaluating the ecological validity of the IGT have primarily relied on traditional IGT scores. However, computational modeling derives underlying component processes of the IGT, which capture specific facets of decision making that may be more closely related to engagement in behaviors associated with negative consequences. This study employed the Prospect Valence Learning (PVL) model to decompose IGT performance into component processes in 294 precariously housed community residents with substance use disorders. Results revealed a predominant focus on gains and a lack of sensitivity to losses in these vulnerable community residents. Hypothesized associations were not detected between component processes and self-reported health-risk behaviors. These findings provide insight into the processes underlying decision making in a vulnerable substance-using population and highlight the challenge of linking specific decision making processes to "real-world" behaviors.

Sex differences in cognitive functioning in patients with bipolar disorder who recently recovered from a first episode of mania: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

BACKGROUND: Studies investigating bipolar disorder (BD) showed that healthy patterns of sex differences in cognitive functioning are altered within this population, but is it unknown whether these alterations are present in BD patients early in their course of illness. METHODS: Patients with bipolar I disorder (36 males, 38 female), who had recently experienced their first manic or mixed episode were tested along with healthy controls (39 males, 59 females) similar in age, sex and premorbid IQ. Cognitive function was assessed through a comprehensive neuropsychological test battery. RESULTS: Significant group effects were found in a majority of administered tests (p<0.05) with patients performing worse than healthy controls. Significant sex effects (p<0.05) were observed on tasks of spatial working memory and sustained attention, with males performing better than females. No significant group by sex interaction was found in any of the tasks administered. LIMITATIONS: The cognitive battery employed in this study may not have been optimally sensitive in detecting sex differences. CONCLUSIONS: The results suggest that unlike patients with long standing multi-episode BD or schizophrenia, healthy cognitive sex differences are maintained in patients with early BD, following recovery from a first-episode of mania. These findings highlight the progressive nature of the illness and provide justification for an early intervention.

Neurocognitive profiles of marginally housed persons with comorbid substance dependence, viral infection, and psychiatric illness.

INTRODUCTION: Individuals living in single-room occupancy (SRO) hotels constitute a socially marginalized group with exposure to multiple factors with adverse effects on neurocognition, including substance use, viral infection, psychiatric illness, and brain injury. Consequently, marked heterogeneity in neurocognitive functioning is observed. This study aimed to identify and describe distinct neurocognitive profiles within a marginally housed sample. METHOD: Two hundred and forty-nine (N = 249) SRO hotel residents (mean age = 43.5 years) were recruited. A battery of tests assessed neurocognition across six domains: premorbid IQ, verbal memory, attention, inhibition, mental flexibility, and decision making. Clinical examinations collected information pertaining to substance use and psychiatric diagnoses, viral infection, psychiatric symptoms, risk behaviors, and everyday functioning. Cluster analysis was used to identify subgroups of individuals with similar neurocognitive profiles and was supplemented with a discriminant function analysis. Analyses of variance and chi-square tests were used to validate the derived clusters on key clinical and functional variables. RESULTS: A three-cluster solution was found to be optimal. Cluster 1 (n = 59) presented as overall higher functioning, whereas Cluster 3 (n = 87) exhibited overall lower functioning with a relative strength in decision-making skills. Cluster 2 (n = 103) was characterized by neurocognitive abilities that generally bisected the performance of the other groups, but with a relative weakness in decision-making skills. Discriminant function analysis indicated the six neurocognitive variables comprised two underlying dimensions that accounted for between-group variance. Clusters meaningfully differed on demographics, substance use, viral exposure, psychiatric symptoms, neurological soft signs, and risk behavior. CONCLUSION: Neurocognitive functioning provides the basis for identifying meaningful subgroups of marginally housed individuals, which can be reliably differentiated on key variables. This approach facilitates an understanding of the neurocognitive dysfunction and associated vulnerabilities of marginalized persons and ultimately may elucidate intervention targets.