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.

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.

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.

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. (PsycINFO Database Record

The Positive and Negative Syndrome Scale (PANSS): A Three-Factor Model of Psychopathology in Marginally Housed Persons with Substance Dependence and Psychiatric Illness.

Rates of psychopathology are elevated in marginalized and unstably housed persons, underscoring the need for applicable clinical measures for these populations. The Positive and Negative Syndrome Scale (PANSS) is a clinical instrument principally developed for use in schizophrenia to identify the presence and severity of psychopathology symptoms. The current study investigates whether a reliable and valid PANSS factor structure emerges in a marginally housed, heterogeneous sample recruited from the Downtown Eastside of Vancouver where substance use disorders and psychiatric illness are pervasive. Participants (n = 270) underwent structured clinical assessments including the PANSS and then were randomly assigned to either exploratory (EFA) or confirmatory factor analytic (CFA) subsamples. EFA pointed to a novel three factor PANSS. This solution was supported by CFA. All retained items (28 out of 30) load significantly upon hypothesized factors and model goodness of fit analyses are in the acceptable to good range. Each of the three first-order factor constructs, labeled Psychosis/Disorganized, Negative Symptoms/Hostility, and Insight/Awareness, contributed significantly to measurement of a higher-order psychopathology construct. Further, the latent structure of this 3-factor solution appears temporally consistent over one-year. This PANSS factor structure appears valid and reliable for use in persons with multimorbidity, including substance use disorders. The structure is somewhat distinct from existing solutions likely due to the unique characteristics of this marginally housed sample.

White matter deficits assessed by diffusion tensor imaging and cognitive dysfunction in psychostimulant users with comorbid human immunodeficiency virus infection.

BACKGROUND: Psychostimulant drug use is commonly associated with drug-related infection, including the human immunodeficiency virus (HIV). Both psychostimulant use and HIV infection are known to damage brain white matter and impair cognition. To date, no study has examined white matter integrity using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in chronic psychostimulant users with comorbid HIV infection, and determined the relationship of white matter integrity to cognitive function. METHODS: Twenty-one subjects (mean age 37.5 ± 9.0 years) with a history of heavy psychostimulant use and HIV infection (8.7 ± 4.3 years) and 22 matched controls were scanned on a 3T MRI. Fractional anisotropy (FA) values were calculated with DTI software. Four regions of interest were manually segmented, including the genu of the corpus callosum, left and right anterior limbs of the internal capsule, and the anterior commissure. Subjects also completed a neurocognitive battery and questionnaires about physical and mental health. RESULTS: The psychostimulant using, HIV positive group displayed decreased white matter integrity, with significantly lower FA values for all white matter tracts (p < 0.05). This group also exhibited decreased cognitive performance on tasks that assessed cognitive set-shifting, fine motor speed and verbal memory. FA values for the white matter tracts correlated with cognitive performance on many of the neurocognitive tests. CONCLUSIONS: White matter integrity was thus impaired in subjects with psychostimulant use and comorbid HIV infection, which predicted worsened cognitive performance on a range of tests. Further study on this medical comorbidity is required.

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.

Select neurocognitive impairment in HIV-infected women: associations with HIV viral load, hepatitis C virus, and depression, but not leukocyte telomere length.

BACKGROUND: Through implementation of combination antiretroviral therapy (cART) remarkable gains have been achieved in the management of HIV infection; nonetheless, the neurocognitive consequences of infection remain a pivotal concern in the cART era. Research has often employed norm-referenced neuropsychological scores, derived from healthy populations (excluding many seronegative individuals at high risk for HIV infection), to characterize impairments in predominately male HIV-infected populations. METHODS: Using matched-group methodology, we assessed 81 HIV-seropositive (HIV+) women with established neuropsychological measures validated for detection of HIV-related impairments, as well as additional detailed tests of executive function and decision-making from the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: On validated tests, the HIV+ women exhibited impairments that were limited to significantly slower information processing speed when compared with 45 HIV-seronegative (HIV-) women with very similar demographic backgrounds and illness comorbidities. Additionally, select executive impairments in shifting attention (i.e., reversal learning) and in decision-making quality were revealed in HIV+ participants. Modifiers of neurocognition in HIV-infected women included detectable HIV plasma viral load, active hepatitis C virus co-infection, and self-reported depression symptoms. In contrast, leukocyte telomere length (LTL), a marker of cellular aging, did not significantly differ between HIV+ and HIV- women, nor was LTL associated with overall neurocognition in the HIV+ group. CONCLUSIONS: The findings suggest that well-managed HIV infection may entail a more circumscribed neurocognitive deficit pattern than that reported in many norm-referenced studies, and that common comorbidities make a secondary contribution to HIV-related neurocognitive impairments.

Countervailing modulation of Ih by neuropeptide Y and corticotrophin-releasing factor in basolateral amygdala as a possible mechanism for their effects on stress-related behaviors.

Stress and anxiety-related behaviors controlled by the basolateral amygdala (BLA) are regulated in vivo by neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF): NPY produces anxiolytic effects, whereas CRF produces anxiogenic effects. These opposing actions are likely mediated via regulation of excitatory output from the BLA to afferent targets. In these studies, we examined mechanisms underlying the effects of NPY and CRF in the BLA using whole-cell patch-clamp electrophysiology in rat brain slices. NPY, even with tetrodotoxin present, caused a dose-dependent membrane hyperpolarization in BLA pyramidal neurons. The hyperpolarization resulted in the inhibition of pyramidal cells, despite arising from a reduction in a voltage-dependent membrane conductance. The Y(1) receptor agonist, F(7)P(34) NPY, produced a similar membrane hyperpolarization, whereas the Y(1) antagonist, BIBO3304 [(R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N(2)-(diphenylacetyl)-argininamide trifluoroacetate], blocked the effect of NPY. The NPY-inhibited current was identified as I(h), which is active at and hyperpolarized to rest. Responses to NPY were occluded by either Cs(+) or ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride), but unaffected by the G(IRK)-preferring blockers Ba(2+) and SCH23390 [(R)-(+)-7-chloro-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride]. Application of CRF, with or without TTX present, depolarized NPY-sensitive BLA pyramidal neurons, resulting from an increase in I(h). Electrophysiological and immunocytochemical data were consistent with a major role for the HCN1 subunit. Our results indicate that NPY, via Y(1) receptors, directly inhibits BLA pyramidal neurons by suppressing a postsynaptic I(h), whereas CRF enhances resting I(h), causing an increased excitability of BLA pyramidal neurons. The opposing actions of these two peptides on the excitability of BLA output cells are consistent with the observed behavioral actions of NPY and CRF in the BLA.