Associations of substance use, psychosis, and mortality among people living in precarious housing or homelessness: A longitudinal, community-based study in Vancouver, Canada.

BACKGROUND: The "trimorbidity" of substance use disorder and mental and physical illness is associated with living in precarious housing or homelessness. The extent to which substance use increases risk of psychosis and both contribute to mortality needs investigation in longitudinal studies. METHODS AND FINDINGS: A community-based sample of 437 adults (330 men, mean [SD] age 40.6 [11.2] years) living in Vancouver, Canada, completed baseline assessments between November 2008 and October 2015. Follow-up was monthly for a median 6.3 years (interquartile range 3.1-8.6). Use of tobacco, alcohol, cannabis, cocaine, methamphetamine, and opioids was assessed by interview and urine drug screen; severity of psychosis was also assessed. Mortality (up to November 15, 2018) was assessed from coroner's reports and hospital records. Using data from monthly visits (mean 9.8, SD 3.6) over the first year after study entry, mixed-effects logistic regression analysis examined relationships between risk factors and psychotic features. A past history of psychotic disorder was common (60.9%). Nonprescribed substance use included tobacco (89.0%), alcohol (77.5%), cocaine (73.2%), cannabis (72.8%), opioids (51.0%), and methamphetamine (46.5%). During the same year, 79.3% of participants reported psychotic features at least once. Greater risk was associated with number of days using methamphetamine (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.05-1.24, p = 0.001), alcohol (aOR 1.09, 95% CI 1.01-1.18, p = 0.04), and cannabis (aOR 1.08, 95% CI 1.02-1.14, p = 0.008), adjusted for demographic factors and history of past psychotic disorder. Greater exposure to concurrent month trauma was associated with increased odds of psychosis (adjusted model aOR 1.54, 95% CI 1.19-2.00, p = 0.001). There was no evidence for interactions or reverse associations between psychotic features and time-varying risk factors. During 2,481 total person years of observation, 79 participants died (18.1%). Causes of death were physical illness (40.5%), accidental overdose (35.4%), trauma (5.1%), suicide (1.3%), and unknown (17.7%). A multivariable Cox proportional hazard model indicated baseline alcohol dependence (adjusted hazard ratio [aHR] 1.83, 95% CI 1.09-3.07, p = 0.02), and evidence of hepatic fibrosis (aHR 1.81, 95% CI 1.08-3.03, p = 0.02) were risk factors for mortality. Among those under age 55 years, a history of a psychotic disorder was a risk factor for mortality (aHR 2.38, 95% CI 1.03-5.51, p = 0.04, adjusted for alcohol dependence at baseline, human immunodeficiency virus [HIV], and hepatic fibrosis). The primary study limitation concerns generalizability: conclusions from a community-based, diagnostically heterogeneous sample may not apply to specific diagnostic groups in a clinical setting. Because one-third of participants grew up in foster care or were adopted, useful family history information was not obtainable. CONCLUSIONS: In this study, we found methamphetamine, alcohol, and cannabis use were associated with higher risk for psychotic features, as were a past history of psychotic disorder, and experiencing traumatic events. We found that alcohol dependence, hepatic fibrosis, and, only among participants <55 years of age, history of a psychotic disorder were associated with greater risk for mortality. Modifiable risk factors in people living in precarious housing or homelessness can be a focus for interventions.

Cognitive Impairment in Marginally Housed Youth: Prevalence and Risk Factors.

Objective: Homeless and marginally housed youth are particularly vulnerable members of society, and are known to experience numerous health problems, including psychiatric illness, substance use, and viral infection. Despite the presence of these risk factors for cognitive compromise, there is limited research on the cognitive functioning of homeless and marginally housed youth. The present study examines the degree and pattern of cognitive impairment and associations with key risk factors in a sample of marginally housed young adults. Method: Participants (N = 101) aged 20-29 years old were recruited from single-room occupancy hotels, and underwent cognitive, psychiatric, neurological, and serological assessments. Results: Forty percent of participants were identified as mildly cognitively impaired across multiple domains, and 16% were moderately-severely impaired. Deficits in memory and attention were most prevalent, while impairments in inhibitory control/processing speed and cognitive flexibility were also present but tended to be less severe. Developmental and historical factors (premorbid intellectual functioning, neurological soft signs, earlier exposure to and longer duration of homelessness or marginal housing), as well as current health risks (stimulant dependence and hepatitis C exposure), were associated with cognitive impairment. Conclusions: The strikingly high rate of cognitive impairment in marginally housed young adults represents a major public health concern and is likely to pose a significant barrier to treatment and rehabilitation. These results suggest that the pathway to cognitive impairment involves both developmental vulnerability and modifiable risk factors. This study highlights the need for early interventions that address cognitive impairment and risk factors in marginalized young people.

Clinical and functional characteristics of young adults living in single room occupancy housing: preliminary findings from a 10-year longitudinal study.

OBJECTIVE: Young adults living in single room occupancy (SRO) hotels, a form of low-income housing, are known to have complex health and substance problems compared to their peers in the general population. The objective of this study is to comprehensively describe the mental, physical, and social health profile of young adults living in SROs. METHODS: This study reports baseline data from young adults aged 18-29 years, as part of a prospective cohort study of adults living in SROs in Vancouver, British Columbia, Canada. Baseline and follow-up data were collected from 101 young adults (median follow-up period 1.9 years [IQR 1.0-3.1]). The comprehensive assessment included laboratory tests, neuroimaging, and clinician- and patient-reported measures of mental, physical, and social health and functioning. RESULTS: Three youth died during the preliminary follow-up period, translating into a higher than average mortality rate (18.6, 95% CI 6.0, 57.2) compared to age- and sex-matched Canadians. High prevalence of interactions with the health, social, and justice systems was reported. Participants were living with median two co-occurring illnesses, including mental, neurological, and infectious diseases. Greater number of multimorbid illnesses was associated with poorer real-world functioning (ρ = - 0.373, p < 0.001). All participants reported lifetime alcohol and cannabis use, with pervasive use of stimulants and opioids. CONCLUSION: This study reports high mortality rates, multimorbid illnesses, poor functioning, poverty, and ongoing unmet mental health needs among young adults living in SROs. Frequent interactions with the health, social, and justice systems suggest important points of intervention to improve health and functional trajectories of this vulnerable population.

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. (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.

Mortality from treatable illnesses in marginally housed adults: a prospective cohort study.

OBJECTIVES: Socially disadvantaged people experience greater risk for illnesses that may contribute to premature death. This study aimed to evaluate the impact of treatable illnesses on mortality among adults living in precarious housing. DESIGN: A prospective cohort based in a community sample. SETTING: A socially disadvantaged neighbourhood in Vancouver, Canada. PARTICIPANTS: Adults (N=371) living in single room occupancy hotels or recruited from the Downtown Community Court and followed for median 3.8 years. MAIN OUTCOME MEASURES: Participants were assessed for physical and mental illnesses for which treatment is currently available. We compared cohort mortality rates with 2009 Canadian rates. Left-truncated Cox proportional hazards modelling with age as the time scale was used to assess risk factors for earlier mortality. RESULTS: During 1269 person-years of observation, 31/371 (8%) of participants died. Compared with age-matched and sex-matched Canadians, the standardised mortality ratio was 8.29 (95% CI 5.83 to 11.79). Compared with those that had cleared the virus, active hepatitis C infection was a significant predictor for hepatic fibrosis adjusting for alcohol dependence and age (OR=2.96, CI 1.37 to 7.08). Among participants <55 years of age, psychosis (HR=8.12, CI 1.55 to 42.47) and hepatic fibrosis (HR=13.01, CI 3.56 to 47.57) were associated with earlier mortality. Treatment rates for these illnesses were low (psychosis: 32%, hepatitis C virus: 0%) compared with other common disorders (HIV: 57%, opioid dependence: 61%) in this population. CONCLUSIONS: Hepatic fibrosis and psychosis are associated with increased mortality in people living in marginal conditions. Timely diagnosis and intervention could reduce the high mortality in marginalised inner city populations.

48 echo T2 myelin imaging of white matter in first-episode schizophrenia: evidence for aberrant myelination.

Myelin water imaging provides a novel strategy to assess myelin integrity and corresponding clinical relationships in psychosis, of particular relevance in frontal white matter regions. In the current study, T2 myelin water imaging was used to assess the myelin water fraction (MWF) signal from frontal areas in a sample of 58 individuals experiencing first-episode psychosis (FEP) and 44 healthy volunteers. No differences in frontal MWF were observed between FEP subjects and healthy volunteers; however, differences in normal patterns of associations between frontal MWF and age, education and IQ were seen. Significant positive relationships between frontal MWF and age, North American Adult Reading Test (NAART) IQ, and years of completed education were observed in healthy volunteers. In contrast, only the relationship between frontal MWF and NAART IQ was significant after Bonferroni correction in the FEP group. Additionally, significant positive relationships between age and MWF in the anterior and posterior internal capsules, the genu, and the splenium were observed in healthy volunteers. In FEP subjects, only the relationship between age and MWF in the splenium was statistically significant. Frontal MWF was not associated with local white matter volume. Altered patterns of association between age, years of education, and MWF in FEP suggest that subtle disturbances in myelination may be present early in the course of psychosis.

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.

Symptom changes in five dimensions of the Positive and Negative Syndrome Scale in refractory psychosis.

Refractory psychosis units currently have little information regarding which symptoms profiles should be expected to respond to treatment. In the current study, we provide this information using structural equation modeling of Positive and Negative Syndrome Scale (PANSS) ratings at admission and discharge on a sample of 610 patients admitted to a treatment refractory psychosis program at a Canadian tertiary care unit between 1990 and 2011. The hypothesized five-dimensional structure of the PANSS fit the data well at both admission and discharge, and the latent variable scores are reported as a function of symptom dimension and diagnostic category. The results suggest that, overall, positive symptoms (POS) responded to treatment better than all other symptoms dimensions, but for the schizoaffective and bipolar groups, greater response on POS was observed relative to the schizophrenia and major depression groups. The major depression group showed the most improvement on negative symptoms and emotional distress, and the bipolar group showed the most improvement on disorganization. Schizophrenia was distinct from schizoaffective disorder in showing reduced treatment response on all symptom dimensions. These results can assist refractory psychosis units by providing information on how PANSS symptom dimensions respond to treatment and how this depends on diagnostic category.

Personalized risk assessment of drug-related harm is associated with health outcomes.

BACKGROUND: The Independent Scientific Committee on Drugs (ISCD) assigned quantitative scores for harm to 20 drugs. We hypothesized that a personalized, ISCD-based Composite Harm Score (CHS) would be associated with poor health outcomes in polysubstance users. METHODS: A prospective community sample (n=293) of adults living in marginal housing was assessed for substance use. The CHS was calculated based on the ISCD index, and the personal substance use characteristics over four weeks. Regression models estimated the association between CHS and physical, psychological, and social health outcomes. RESULTS: Polysubstance use was pervasive (95.8%), as was multimorbid illness (median 3, possible range 0-12). The median CHS was 2845 (interquartile range 1865-3977). Adjusting for age and sex, every 1000-unit CHS increase was associated with greater mortality (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.07-2.01, p = 0.02), and persistent hepatitis C infection (OR 1.29, 95% CI 1.02-1.67, p = 0.04). The likelihood of substance-induced psychosis increased 1.39-fold (95% CI 1.13-1.67, p = 0.001). The amount spent on drugs increased 1.51-fold (1.40-1.62, p < 0.001) and the odds of having committed a crime increased 1.74-fold (1.46-2.10, p < 0.001). Multimorbid illness increased 1.43-fold (95% CI 1.26-1.63, p < 0.001). CONCLUSIONS: Greater CHS predicts poorer physical, psychological, and social health, and may be a useful quantitative, personalized measure of risk for drug-related harm.

The hotel study: multimorbidity in a community sample living in marginal housing.

OBJECTIVE: The health of people living in marginal housing is not well characterized, particularly from the perspective of multimorbid illness. The authors investigated this population in a community sample. METHOD: A prospective community sample (N=293) of adults living in single-room occupancy hotels was followed for a median of 23.7 months. Assessment included psychiatric and neurological evaluation, multimodal MRI, and viral testing. RESULTS: Previous homelessness was described in 66.6% of participants. Fifteen deaths occurred during 552 person-years of follow-up. The standardized mortality ratio was 4.83 (95% CI=2.91-8.01). Substance dependence was ubiquitous (95.2%), with 61.7% injection drug use. Psychosis was the most common mental illness (47.4%). A neurological disorder was present in 45.8% of participants, with definite MRI findings in 28.0%. HIV serology was positive in 18.4% of participants, and hepatitis C virus serology in 70.3%. The median number of multimorbid illnesses (from a list of 12) was three. Burden of multimorbidity was significantly correlated with lower role functioning score. Comorbid addiction or physical illness significantly decreased the likelihood of treatment for psychosis but not the likelihood of treatment for opioid dependence or HIV disease. Participants who died during follow-up appeared to have profiles of multimorbidity similar to those of the overall sample. CONCLUSIONS: This marginally housed cohort had greater than expected mortality and high levels of multimorbidity with adverse associations with role function and likelihood of treatment for psychosis. These findings may guide the development of effective health care delivery in the setting of marginal housing.

Effects of eight weeks of atypical antipsychotic treatment on middle frontal thickness in drug-naïve first-episode psychosis patients.

Atypical antipsychotic medications generally maintain or increase gray matter amount and functioning. First-episode psychosis patients have lower gray matter volume in the middle frontal gyrus, as well as worse performance on spatial working memory tasks compared to controls. This study investigated the effects of short-term four- and eight-week atypical treatment on middle frontal thickness and spatial working memory in first-episode psychosis patients. Nineteen drug-naïve first-episode psychosis patients treated with risperidone or quetiapine and 26 controls completed structural magnetic resonance imaging, a spatial working memory task, and clinical assessment at three intervals (baseline, four weeks, and eight weeks; all patients and 23 controls completed all three assessments). Caudal and rostral middle frontal thicknesses were measured using the automated program Freesurfer. Positive, negative, and general symptoms of the Positive and Negative Syndrome Scale (PANSS) decreased significantly in patients, with most of the change occurring in the first four weeks of treatment. Patients demonstrated an increase in rostral middle frontal thickness over eight weeks of treatment compared to controls. There was a medium effect size relationship between reduction in negative symptoms at four and eight weeks, and a change in rostral middle frontal thickness over eight weeks. No changes were found in spatial working memory ability. Short-term atypical treatment with risperidone or quetiapine can increase prefrontal cortical thickness in psychosis. These findings are notable given the role of the rostral middle frontal region in cognition and the relationship between better cognitive functioning and better functional outcome in psychosis.

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.

Hippocampal volume and the brain-derived neurotrophic factor Val66Met polymorphism in first episode psychosis.

INTRODUCTION: Small hippocampi and impaired memory are common in patients with psychosis and brain-derived neurotrophic factor (BDNF) plays a critical role in hippocampal neuroplasticity and memory. A common BDNF allele (Val66Met) has been the focus of numerous studies but results from the few BDNF-imaging studies are complex and contradictory. The objective of this study was to determine the association between Val66Met and hippocampal volume in patients with first episode psychosis. Secondary analyses explored age-related associations and the relationship between Val66Met and memory. METHOD: Hippocampal volume and BDNF genotyping were obtained for 58 patients with first-episode psychosis and 39 healthy volunteers. Patients were recruited from an early psychosis program serving a catchment-area population. RESULTS: Hippocampal volume was significantly smaller in patients than controls (F(1,92)=4.03, p<0.05) and there was a significant group-by-allele interaction (F(1,92)=3.99, p<0.05). Hippocampal volume was significantly smaller in patients than controls who were Val-homozygotes but no group differences were found for Met carriers. Findings were not affected by diagnosis, antipsychotic medication, or age, and there was no change in hippocampal volume during a one-year follow-up. Val-homozygous patients had worse immediate and delayed memory than their Met counterparts. CONCLUSIONS: Results suggest the effects of the BDNF Val66Met allele may be different in patients with psychosis than in healthy adults. Hippocampal volume in patient and control Met allele carriers was very similar suggesting that illness-related factors have minimal influence in this group. In contrast, Val homozygosity was related to smaller hippocampi and poorer memory functioning only in patients with psychosis.

Predictors of starting to smoke cigarettes in patients with first episode psychosis.

INTRODUCTION: Cigarette smoking is common in psychotic disorders and may be initiated in an attempt to control features of illness. However, genetic, obstetric and early life conditions are risks for starting to smoke in the general population but their role in psychotic patients is unclear. METHOD: Smoking history and the putative predictors of starting to smoke were assessed in a community-wide sample of 115 first episode psychosis patients. The proportion that initiated smoking was compared with that from population surveys and the impact of risk factors was assessed within the patient sample. RESULTS: Most patients began smoking before illness onset and the proportion who initiated smoking was significantly high by the onset of a functional decline. Gestational tobacco exposure was a risk for smoking and was also associated with low birthweight, poor academic achievement, and obesity. Low familial socioeconomic position but not familial psychiatric problems also predicted smoking initiation. DISCUSSION: In most cases, smoking preceded illness onset and was not a response to early features of illness. General population predictors of starting to smoke were also associated with smoking initiation in psychotic patients. Of these risks, exposure to tobacco during gestation is noteworthy in that it affects brain development and is associated with cognitive, behavioral, psychiatric and general health problems. In addition, nicotine interacts with other substances of abuse. The initiation of smoking before illness onset and the association with developmental problems raises the question of whether cigarette smoking influences some aspects of illness in patients with psychosis.

A longitudinal study on the effects of typical versus atypical antipsychotic drugs on hippocampal volume in schizophrenia.

BACKGROUND: Previous studies have reported that hippocampal volumes correlate with symptom severity in schizophrenia. This longitudinal study measured changes in symptoms and hippocampal volume in patients switched from typical antipsychotics to olanzapine. METHODS: MRI scans were acquired from patients with chronic schizophrenia (n=10) and healthy volunteers (n=20). At baseline, patients were treated with typical antipsychotics for at least one year, then switched to olanzapine, and rescanned approximately one year later. RESULTS: Olanzapine treatment resulted in no significant change in right or left hippocampal volume. Individual changes in right hippocampal volume correlated significantly with changes in symptoms. CONCLUSIONS: Hippocampal volume change may serve as a marker of symptom change in patients on olanzapine.

Reduced thalamic volume in patients with chronic schizophrenia after switching from typical antipsychotic medications to olanzapine.

OBJECTIVE: The authors performed a longitudinal study of the effects on thalamic volume of switching from typical to atypical antipsychotic medications. METHOD: Magnetic resonance imaging scans were acquired from 10 subjects with chronic schizophrenia taking typical antipsychotics and 20 healthy volunteers. Subjects with schizophrenia were switched to olanzapine; both groups were rescanned. RESULTS: At baseline, thalamic volumes in subjects with chronic schizophrenia were 5.8% greater than those of healthy volunteers. At follow-up, there was no significant difference between groups. Additional analysis revealed a significant positive correlation between baseline thalamic volume and dosage of typical antipsychotic medication. Higher dosages at baseline were correlated with larger reductions in volume after the switch to olanzapine. CONCLUSIONS: Antipsychotic medication effects may be a factor in the wide range of thalamic volume differences reported between subjects with schizophrenia and healthy volunteers.