Diffusion tensor imaging of neurocognitive profiles in a community cohort living in marginal housing.

OBJECTIVE: We investigated white matter differences associated with distinct neurocognitive profiles derived from a large cohort of marginally housed persons with comorbid physical and mental illnesses. Our prior work identified three profile cluster groups: a high functioning group (Cluster 1), a low functioning group with relative strength in decision-making (Cluster 3), and an intermediary group with a relative decision-making weakness (Cluster 2). This study extends previous findings of cortical gray matter differences between these groups with evidence for putative neurodevelopmental abnormalities in the low cognitive functioning group (i.e., Cluster 3). We hypothesized that altered white matter diffusion would be associated with the lowest functioning neurocognitive profile and would be associated with previously observed gray matter differences. METHOD: Participants from a socially impoverished neighborhood in Vancouver, Canada underwent neurocognitive evaluation and neuroimaging. We performed Tract-Based Spatial Statistics using diffusion tensor imaging data from 184 participants to examine whole-brain differences in white matter microstructure between cluster analytically derived neurocognitive profiles, as well as unitary neurocognitive measures. Correlations between frontal gray and white matter were also examined. RESULTS: Cluster 3 showed increased diffusion in predominately bilateral frontal and interhemisphere tracts (vs. Clusters 1 and 2), with relatively greater diffusion in the left hemisphere (vs. Cluster 1). Differences in radial diffusivity were more prominent compared with axial diffusivity. A weak association between regional frontal fractional anisotropy and previously defined abnormalities in gyrification was observed. CONCLUSIONS: In a socially marginalized sample, we established several patterns in the covariation of white matter diffusion and neurocognitive functioning. These patterns elucidate the neurobiological substrates and vulnerabilities that are apt to underlie functional impairments inherent to this complex and heterogeneous population.

Volumes of the Hippocampal Formation Differentiate Component Processes of Memory in a Community Sample of Homeless and Marginally Housed Persons.

OBJECTIVE: Persons who are homeless or marginally housed exhibit significant cognitive dysfunction, with memory being the most impaired domain. Hippocampal subfield volumes have been found to differentially relate to component processes of memory. The neural correlates of memory have not been previously examined in marginalized persons who are understudied and underserved. We examined whether hippocampal subfields and entorhinal cortex volumes are uniquely related to indices of verbal episodic memory using the Hopkins Verbal Learning Test - Revised. METHOD: Data was used from a large sample of community dwelling homeless and marginally housed adults (N = 227). Regression analyses were conducted to examine hippocampal subfield volumes (CA1, CA3, CA4, dentate gyrus, subiculum) and entorhinal cortex, and their associations with measures of verbal immediate recall, learning slope, and verbal delayed recall. RESULTS: Greater CA3 subfield volume was associated with better performance on an index of encoding (immediate recall), but only in older individuals. Greater CA1 and subiculum volumes were associated with better performance on immediate and delayed recall (measures that tap into retrieval processes), but not with learning slope (a more pure index of encoding). Entorhinal cortex volume was related to all components of memory beyond total hippocampal volume. CONCLUSIONS: Our results suggest common neuroanatomical correlates of memory dysfunction in large sample of marginalized persons, and these are uniquely related to different components of memory. These findings have clinical relevance for marginalized populations and theoretical relevance to the growing literature on functional specialization of the hippocampal subfields.

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.

A comparison of psychotic symptoms in subjects with methamphetamine versus cocaine dependence.

RATIONALE: The psychostimulant drugs cocaine and methamphetamine are potent indirect dopamine receptor agonists which act through similar but not identical mechanisms. Studies in humans have observed that a large proportion of those who chronically use these drugs experience psychotic symptoms. However, direct comparisons of psychotic symptom severity between cocaine and methamphetamine users are lacking. OBJECTIVES: The goal of the present study was to directly compare severity of psychotic symptoms between cocaine- and methamphetamine-dependent individuals. Additionally, we sought to determine how concurrent cocaine + methamphetamine dependence would influence psychotic symptoms. METHODS: We recruited 153 polysubstance-using subjects meeting DSM-IV-TR criteria for cocaine dependence, 38 with methamphetamine dependence, and 32 with cocaine + methamphetamine dependence. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) and analyzed using a five-factor model. All participants were also assessed for physical and mental illnesses as well as recent substance use. Most subjects completed a comprehensive neurocognitive battery. RESULTS: While all three groups exhibited high total PANSS scores, the positive symptom subscale was significantly higher in the methamphetamine-dependent (17.03 ± 6.3) than the cocaine-dependent group (13.51 ± 4.12) and non-significantly higher (p = 0.08) than the cocaine + methamphetamine group (14.44 ± 5.50). Groups also differed on demographic variables, viral infection, and other indices of substance use, which were unlikely to account for the difference in positive symptoms. There were only modest differences between groups in neurocognitive function. CONCLUSIONS: Methamphetamine dependence was associated with more severe positive symptoms of psychosis than cocaine dependence. Concurrent cocaine + methamphetamine dependence did not increase psychosis severity.

Subcortical grey matter alterations in cocaine dependent individuals with substance-induced psychosis compared to non-psychotic cocaine users.

After prolonged psychostimulant abuse, transient psychotic symptoms referred to as "substance-induced psychosis" (SIP) can develop - closely resembling symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and schizophrenias suggests that similar underlying neural deficits may contribute to the expression of psychosis across these disorders. To date, neuroanatomical characterization of grey matter structural alterations in SIP has been limited to methamphetamine associated psychosis, with no studies controlling for potential neurotoxic effects of the psychostimulant that precipitates psychosis. To investigate grey matter subcortical alterations in SIP, a voxel-based analysis of magnetic resonance images (MRI) was performed between a group of 74 cocaine dependent nonpsychotic individuals and a group of 29 individuals with cocaine-associated psychosis. The cocaine-associated psychosis group had significantly smaller volumes of the thalamus and left hippocampus, controlling for age, total brain volume, current methamphetamine dependence, and current marijuana dependence. No differences were present in bilateral caudate structures. The findings of reduced thalamic and hippocampal volumes agree with previous reports in the schizophrenia literature, suggesting alterations of these structures are not specific to schizophrenia, but may be common to multiple forms of psychosis.

Treatment delay and pathways to care in early psychosis.

OBJECTIVE: To examine the treatment delay associated with community and inpatient pathways into care for persons experiencing a first episode of psychosis. METHODS: A total of 104 clients entering a specialized early psychosis intervention (EPI) program and their family members were assessed for help-seeking behaviours, psychiatric symptoms, level of functioning and duration of untreated psychosis (DUP). RESULTS: DUP (median = 30.5 weeks) was associated with younger age of onset, poorer engagement with the EPI program and more severe symptoms. Almost one-third of clients had four or more contacts before receiving antipsychotic medication or entering the EPI program and one in five received interventions not specifically indicated for psychosis. Referrals directly involving family members accounted for about 81% of hospital-initiated treatment (39% of all referrals) and 46% of community-initiated treatment (61% of all referrals). Community entry was associated with longer DUP, more time-seeking treatment, younger age of onset, younger age at referral, greater likelihood of receiving other medication or counselling before receiving antipsychotic medication, schizophrenia, less severe symptoms and less substance use in the previous year. Those with schizophrenia showed no differences across pathway type for time-seeking treatment, being provided interventions not specifically indicated for psychosis after onset or rates of substance use. CONCLUSIONS: Treatment delay and the provision of interventions not specifically indicated for psychosis may be increased in first-episode populations who are younger and have less severe symptoms. Improving literacy about early psychosis in both professionals and families merits greater attention.