Kristina Gicas

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.

Characterization of white matter integrity deficits in cocaine-dependent individuals with substance-induced psychosis compared with non-psychotic cocaine users

With sufficient drug exposure, some individuals develop transient psychotic symptoms referred to as ‘substance‐induced psychosis’ (SIP), which closely resemble the symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and the schizophrenias suggests that similar underlying neural deficits may contribute to the emergence of psychosis across these disorders. Only a small number of studies have investigated structural alterations in SIP, and all have been limited to volumetric imaging methods, with none controlling for the effects of chronic drug exposure. To investigate white matter abnormalities associated with SIP, diffusion tensor imaging was employed in a group of individuals with cocaine‐associated psychosis (CAP; n = 24) and a cocaine‐dependent non‐psychotic (CDN) group (n = 43). Tract‐based spatial statistics was used to investigate group differences in white matter diffusion parameters. The CAP group showed significantly lower fractional anisotropy values than the CDN group (p < 0.05) in voxels within white matter tracts of fronto‐temporal, fronto‐thalamic and interhemispheric pathways. The greatest differences in white matter integrity were present in the corpus callosum, corona radiata, bilateral superior longitudinal fasciculi and bilateral inferior longitudinal fasciculi. Additionally, the CAP group had voxels of significantly higher radial diffusivity in a subset of the previously mentioned pathways. These results are the first description of white matter integrity abnormalities in a SIP sample and indicate that differences in these pathways may be a shared factor in the expression of different forms of psychosis.

Factors affecting severity of positive and negative symptoms of psychosis in a polysubstance using population with psychostimulant dependence.

Approximately half of psychostimulant users experience psychotic symptoms, which include both positive and negative symptoms. Prior reports have exclusively used positive symptoms to characterize psychostimulant associated psychosis. Symptoms vary dramatically in severity, though most investigations categorize psychosis as a dichotomous occurrence. To explore the association between different substances of abuse and the severity of psychotic symptoms, we investigated 171 individuals meeting DSM-IV-TR criteria for psychostimulant (cocaine or methamphetamine) dependence in an observational cross-sectional study. Participants were predominantly male (72.5%), recruited from a socially disadvantaged neighborhood in Vancouver, Canada, with a mean age of 45.5(±8.8) years. Of the total sample, 85% were dependent on cocaine, and 28.1% were dependent on methamphetamine. Participants had a median total PANSS score of 63, ranging from 37 to 111. Demographic information, current substance use and early substance exposure were used to predict positive and negative psychotic symptom severity in linear regression models. Increased severity of positive psychotic symptoms was significantly related to greater methamphetamine and marijuana use in the past 28 days, and methadone-abstinence. Negative symptom severity was related to increased opioid use in the past 28 days. There was no overlap between predictors of positive and negative symptom severity.

The Hotel Study—Clinical and Health Service Effectiveness in a Cohort of Homeless or Marginally Housed Persons:

Objective: The Hotel Study was initiated in Vancouver’s Downtown East Side (DTES) neighborhood to investigate multimorbidity in homeless or marginally housed people. We evaluated the clinical effectiveness of existing, illness-specific treatment strategies and assessed the effectiveness of health care delivery for multimorbid illnesses. Method: For context, we mapped the housing locations of patients presenting for 552,062 visits to the catchment hospital emergency department (2005-2013). Aggregate data on 22,519 apprehensions of mentally ill people were provided by the Vancouver Police Department (2009-2015). The primary strategy was a longitudinal cohort study of 375 people living in the DTES (2008-2015). We analysed mortality and evaluated the clinical and health service delivery effectiveness for infection with human immunodeficiency virus or hepatitis C virus, opioid dependence, and psychosis. Results: Mapping confirmed the association between poverty and greater number of emergency visits related to substance use and mental illness. The annual change in police apprehensions did not differ between the DTES and other policing districts. During 1581 person-years of cohort observation, the standardized mortality ratio was 8.43 (95% confidence interval, 6.19 to 11.50). Physician visits were common (84.3% of participants over 6 months). Clinical treatment effectiveness was highest for HIV/AIDS, intermediate for opioid dependence, and lowest for psychosis. Health service delivery mechanisms provided examples of poor access, poor treatment adherence, and little effect on multimorbid illnesses. Conclusions: Clinical effectiveness was variable, and illness-specific service delivery appeared to have little effect on multimorbidity. New models of care may need to be implemented.

Structural brain markers are differentially associated with neurocognitive profiles in socially marginalized people with multimorbid illness

Objective: The authors examined associations between complementary fronto-temporal structural brain measures (gyrification, cortical thickness) and neurocognitive profiles in a multimorbid, socially marginalized sample. Method: Participants were recruited from single-room occupancy hotels and a downtown community courthouse (N = 299) and grouped on multiple neurocognitive domains using cluster analysis. Subsequently, the authors evaluated whether the fronto-temporal brain indices, and proxy measures of neurodevelopment and acquired brain insult/risk exposure differentiated members of the 3 distinct neurocognitive clusters. Results: Greater frontal and temporal gyrification and more proxies of aberrant neurodevelopment were associated with the lowest functioning neurocognitive cluster (Cluster 3). Further, for older participants (50+ years), increased cortical thickness in frontal regions was associated with the higher functioning neurocognitive cluster (Cluster 1). Finally, the greatest acquired brain insult/risk exposure was associated with the cluster characterized by selective decision-making impairment (Cluster 2). Conclusions: Fronto-temporal structural brain indices, and proxies of neurodevelopment and acquired brain insult/risk exposure were differentially associated with neurocognitive profiles in socially marginalized persons. These findings highlight the unique pathways to neurocognitive impairment in a heterogeneous population and help to clarify the vulnerabilities confronted by different subgroups.

Hippocampal volume and vasculature before and after exercise in treatment-resistant schizophrenia

BACKGROUND Schizophrenia is associated with poor cognitive function and elevated cardiometabolic disease risk. These health concerns may exacerbate neurocognitive dysfunction associated with hippocampal abnormalities, particularly hippocampal volume reductions. Regular exercise is thought to improve symptom severity, reduce depression, and improve cognition in schizophrenia, and may trigger exercise-mediated hippocampal growth. The potential for the benefits of exercise for treatment-resistant schizophrenia patients has not been clearly assessed. This study aims to assess the effect of exercise on hippocampal plasticity and clinical outcomes in chronic schizophrenia. METHODS Seventeen DSM-IV criteria schizophrenia or schizoaffective disorder patients completed a customized moderate intensity 12-week aerobic or weight-bearing exercise program. Adherence rates were 83% ± 9.4%) with 70% of participants completing the entire exercise program. Concomitant neuroimaging, clinical and cognitive assessments were obtained at baseline and 12-weeks. RESULTS At follow-up, symptom severity scores (t(16) = -16.8, p. ≤ 0.0001) and social functioning (t(16) = 4.4, p. = 0.0004) improved. A trend for improved depression scores (t(16) = -2.0, p. = 0.06) with no change in anxiety, or extrapyramidal symptoms were seen. Hippocampal volume increased (t(16) = -2.54, p. = 0.02), specifically in the left CA-1 field (F(16) = -2.33, p. = 0.03). Hippocampal vascular volume was unchanged. Change in hippocampal volume and vascular volume was not significantly correlated with change in symptom severity or affect scores. CONCLUSIONS Adjunct exercise may accelerate symptom improvement in treatment-resistant psychosis patients. While the underlying mechanism remains unclear, these results indicate that chronic schizophrenia patients experience hippocampal plasticity in response to exercise. STUDY REGISTRATION Clinical Trials.govNCT01392885.

Verbal memory improvement in first-episode psychosis APOE- ε4 carriers: a pleiotropic effect?

Background Verbal memory impairment is a core feature in schizophrenia even at early stages of the disease, but its etiopathogenesis is not fully understood. The APOE-ε4 is the main genetic risk factor for late-onset Alzheimer’s disease. Our primary goal was to ascertain whether APOE-ε4 status had a pleiotropic effect in early stages of the illness. Participants and methods A total of 86 first-episode psychosis (FEP) outpatients and 39 healthy volunteers were recruited. Demographic and clinical data, APOE genotyping, and a neuropsychological test battery including the California Verbal Learning Test – second edition (CVLT-II) were administered and assessed at study entry and at 1-year follow-up. Data were analyzed using mixed-model repeated measures, where the dependent variable was verbal memory indexed by California Verbal Learning Test (CVLT) Trials 1–5 total recall score. Results FEP-APOE-ε4 carriers and FEP-APOE-ε4 noncarriers had similar symptom severity, clinical outcomes, premorbid and current intelligence quotient, and exposure to antipsychotics. There was a main effect of group on CVLT 1–5 (FEP =43.30 vs control =58.25; F[1, 119.7]=42.97; P<0.001) as well as an APOE-ε4 by group by time (F[4, 116.2]=2.73, P=0.033) interaction with only FEP-APOE-ε4 carriers showing improved verbal memory at follow-up. Conclusion Our study is the first to report improvement in verbal memory in persons afflicted by FEP who are APOE-ε4 carriers and replicates the prominent verbal memory deficits present in FEP. Our work provides further evidence pointing to an antagonistic pleiotropic effect of APOE-ε4 in neuropsychiatric disorders. Our results merit further research into antagonistic pleiotropic effects in schizophrenia.