Impact of patient-specific factors on clozapine metabolism in individuals with treatment-resistant schizophrenia or schizoaffective disorder.

BACKGROUND: There is high inter-individual variability in clozapine metabolism due to genetic and non-genetic differences. Patient-specific factors such as smoking, inflammation indicated by elevated C-reactive protein (CRP), and certain concurrent medications have a significant influence on clozapine metabolism. AIM: To assess which patient-specific factors best explain variability in clozapine metabolism estimated by clozapine concentration to dose (C/D) ratios. METHODS: A retrospective cohort analysis using electronic medical data was conducted on 172 inpatients at the BC Psychosis Program. Patients with normal renal and liver function were included if they were on clozapine and had at least one steady-state plasma concentration. The degree of influence of each factor on the variability of clozapine metabolism in the entire cohort and subgroups stratified by fluvoxamine use was evaluated using multiple linear regression analysis of C/D ratios. RESULTS: Model fit testing showed that the entire cohort model accounts for 52.7% of C/D ratio variability, while the no fluvoxamine and fluvoxamine models accounted for 40.8% and 43.8%. In the entire cohort (n = 172), fluvoxamine use explained the highest variance, and C/D ratios were higher by 30.6% on average. The second strongest predictor was elevated CRP > 10 mg/L, and C/D ratios were higher by 22.9% on average. Subsequently, obesity, nonsmoker status, and female sex explained a significant but modest proportion of variance. Among participants on fluvoxamine (n = 58), only fluvoxamine dose was associated with an increase, and for every 25 mg increase in dose, C/D ratios increased by 5% on average. CONCLUSION: In a clinical population, this study replicated the relationship between reduced rate of clozapine metabolism and the use of fluvoxamine, elevated CRP, obesity, nonsmoking status, and female sex; and the magnitude of the effects were large enough to be clinically relevant.

A systematic review and meta-analysis of synthetic cathinone use and psychosis.

RATIONALE: Synthetic cathinones (SC), commonly referred to as "bath salts", are stimulants resembling the natural alkaloid cathinone found in the khat plant. These substances have the potential to induce serious health risks such as hallucinations, delusions, paranoia and agitation which can lead to substance-induced psychotic disorders. Despite growing concerns, there is a limited understanding of the association between SC consumption and the devolvement of such psychopathologies. METHODS: We conducted a systematic review to investigate the frequency of substance-induced psychotic disorder (SIPD) and associated conditions in humans following synthetic cathinone consumption. We qualitatively and quantitatively analyzed SC exposure cases. RESULTS: A total of 32 studies were included, with a diverse range of demographics, synthetic cathinone types, and consumption patterns. The proportion of individuals developing psychotic symptoms was reported at 0.380 (Random-effects model, 95% CI 0.289 - 0.475). Additionally, the significant heterogeneity in diagnostic approaches limited our ability to provide a precise estimate of prevalence. CONCLUSIONS: Synthetic cathinone consumption is associated with the risk of developing psychotic symptoms as indicated by the prevalence of hallucinations and/or delusions. Due to the lack of information on classifying factors, particularly duration of symptoms, we are unable to conclude synthetic cathinone-induced psychosis. Further research is warranted to elucidate the underlying mechanism linking synthetic cathinone consumption and psychosis. This review underscores the urgency of addressing the growing health risks posed by synthetic cathinone use. Additionally, it highlights the necessity of proper quantification of psychotic symptoms through scales and reporting of classification criteria to accurately diagnose SIPD.

Differential sensitivity of intraindividual variability dispersion and global cognition in the prediction of functional outcomes and mortality in precariously housed and homeless adults.

OBJECTIVE: To examine cognitive intraindividual variability (IIV) dispersion as a predictor of everyday functioning and mortality in persons who are homeless or precariously housed. METHOD: Participants were 407 community-dwelling adults, followed for up to 13 years. Neurocognition was assessed at baseline and IIV dispersion was derived using a battery of standardized tests. Functional outcomes (social, physical) were obtained at baseline and last follow-up. Mortality was confirmed with Coroner's reports and hospital records (N = 103 deaths). Linear regressions were used to predict current social and physical functioning from IIV dispersion. Repeated measures Analysis of Covariance were used to predict long-term change in functioning. Cox regression models examined the relation between IIV dispersion and mortality. Covariates included global cognition (i.e. mean-level performance), age, education, and physical comorbidities. RESULTS: Higher IIV dispersion predicted poorer current physical functioning (B = -0.46 p = .010), while higher global cognition predicted better current (B = 0.21, p = .015) and change in social functioning over a period of up to 13 years (F = 4.23, p = .040). Global cognition, but not IIV dispersion, predicted mortality in individuals under 55 years old (HR = 0.50, p = .013). CONCLUSIONS: Our findings suggest that indices of neurocognitive functioning (i.e. IIV dispersion and global cognition) may be differentially related to discrete dimensions of functional outcomes in an at-risk population. IIV dispersion may be a complimentary marker of emergent physical health dysfunction in precariously housed adults and may be best used in conjunction with traditional neuropsychological indices.

A Novel Leu-Enkephalin Prodrug Produces Pain-Relieving and Antidepressant Effects.

Persistent pain is a significant healthcare problem with limited treatment options. The high incidence of comorbid chronic pain and depression significantly reduces life quality and complicates the treatment of both conditions. Antidepressants are less effective for pain and depression than for depression alone and they induce severe side effects. Opioids are highly efficacious analgesics, but rapid development of tolerance, dependence, and debilitating side effects limit their efficacy and safe use. Leucine-enkephalin (Leu-ENK), the endogenous delta opioid receptor agonist, controls pain and mood and produces potent analgesia with reduced adverse effects compared to conventional opioids. High proteolytic instability, however, makes Leu-ENK ineffective after systemic administration and limits its clinical usefulness. KK-103, a Leu-ENK prodrug, was developed to overcome these limitations of Leu-ENK via markedly increased plasma stability in mice. We showed rapid and substantially increased systemic adsorption and blood plasma exposure of KK-103 compared to Leu-ENK. We also observed brain uptake of radiolabeled KK-103 after systemic administration, indicating a central effect of KK-103. We then established KK-103's prolonged antinociceptive efficacy in the ramped hot plate and formalin test. In both models, KK-103 produced a comparable dose to the maximum antinociceptive-effect relationship. The pain-alleviating effect of KK-103 primarily resulted from activating the delta opioid receptor after the likely conversion of KK-103 to Leu-ENK in vivo. Finally, KK-103 produced an antidepressant-like activity comparable to the antidepressant desipramine, but with minimal gastrointestinal inhibition and no incidence of sedation.

Relationship between drug-induced movement disorders and psychosis in adults living in precarious housing or homelessness.

BACKGROUND: Studies have reported positive associations between drug-induced movement disorders (DIMDs) and symptoms of psychosis in patients with schizophrenia. However, it is not clear which subtypes of symptoms are related to each other, and whether one symptom precedes another. The current report assessed both concurrent and temporal associations between DIMDs and symptoms of psychosis in a community-based sample of homeless individuals. METHODS: Participants were recruited in Vancouver, Canada. Severity of DIMDs and psychosis was rated annually, allowing for the analysis of concurrent associations between DIMDs and Positive and Negative Syndrome Scale (PANSS) five factors. A brief version of the PANSS was rated monthly using five psychotic symptoms, allowing for the analysis of their temporal associations with DIMDs. Mixed-effects linear and logistic regression models were used to assess the associations. RESULTS: 401 participants were included, mean age of 40.7 years (SD = 11.2) and 77.4% male. DIMDs and symptoms of psychosis were differentially associated with each other, in which the presence of parkinsonism was associated with greater negative symptoms, dyskinesia with disorganized symptoms, and akathisia with excited symptoms. The presence of DIMDs of any type was not associated with depressive symptoms. Regarding temporal associations, preceding delusions and unusual thought content were associated with parkinsonism, whereas dyskinesia was associated with subsequent conceptual disorganization. CONCLUSIONS: The current study found significant associations between DIMDs and symptoms of psychosis in individuals living in precarious housing or homelessness. Moreover, there were temporal associations between parkinsonism and psychotic symptoms (delusions or unusual thought content), and the presence of dyskinesia was temporally associated with higher odds of clinically relevant conceptual disorganization.

Multilayer depressive symptom networks in adults with bodily pain living in precarious housing or homelessness.

Housing insecurity is associated with co-occurring depression and pain interfering with daily activities. Network analysis of depressive symptoms along with associated risk or protective exposures may identify potential targets for intervention in patients with co-occurring bodily pain. In a community-based sample of adults (n = 408) living in precarious housing or homelessness in Vancouver, Canada, depressive symptoms were measured by the Beck Depression Inventory; bodily pain and impact were assessed with the 36-item Short Form Health Survey. Network and bootstrap permutation analyses were used to compare depressive symptoms endorsed by Low versus Moderate-to-Severe (Mod + Pain) groups. Multilayer networks estimated the effects of risk and protective factors. The overall sample was comprised of 78% men, mean age 40.7 years, with 53% opioid use disorder and 14% major depressive disorder. The Mod + Pain group was characterized by multiple types of pain, more persistent pain, more severe depressive symptoms and a higher rate of suicidal ideation. Global network connectivity did not differ between the two pain groups. Suicidal ideation was a network hub only in the Mod + Pain group, with high centrality and a direct association with exposure to lifetime trauma. Antidepressant medications had limited impact on suicidal ideation. Guilt and increased feelings of failure represented symptoms from two other communities of network nodes, and completed the shortest pathway from trauma exposure through suicidal ideation, to the non-prescribed opioid exposure node. Interventions targeting these risk factors and symptoms could affect the progression of depression among precariously housed patients.

Rasch analysis of the beck depression inventory in a homeless and precariously housed sample.

The approach to analysis of and interpretation of findings from the Beck Depression Inventory (BDI), a self-report questionnaire, depends on sample characteristics. To extend work using conventional BDI scoring, the BDI's suitability in assessing symptom severity in a homeless and precariously housed sample was examined using Rasch analysis. Participants (n=478) recruited from an impoverished neighbourhood in Vancouver, Canada, completed the BDI. Rasch analysis using the partial credit model was done, and the structural validity, unidimensionality, and reliability of the BDI were studied. A receiver operating characteristic curve determined a Rasch cut-off score consistent with clinical depression, and Rasch scores were correlated with raw scores. Good fit to the Rasch model was observed after rescoring all items and removing Item 19 (Weight Loss), and unidimensionality and reliability were satisfactory. Item 9 (Suicidal Wishes) represented the most severe symptom. Rasch-based scores detected clinical depression with moderate sensitivity and specificity, and were positively correlated with conventional scores. The BDI in a community-based sample of homeless and precariously housed adults satisfied Rasch model expectations in a 20-item format, and is suitable for assessing symptom severity. Future research on depression in similar samples may reveal more information on using specific symptoms to determine clinical significance.

Reduction in Substance-Related Composite Harm Scores Through Street Soccer.

Introduction Street soccer makes the sport accessible to people affected by homelessness or precarious housing. There is overwhelming evidence that exercise improves physical and mental health. In addition, sport facilitates positive peer pressure that leads to beneficial life changes. Method To examine participants' accounts of the effects of street soccer in a sample of socially disadvantaged players from Western Canada, we collected 73 cross-sectional self-reports of life changes via a questionnaire. The questionnaire included questions on social, mental, and physical health, including substance use. This allowed the calculation of a modified composite harm score. Results Participants reported improved physical (46% of participants) and mental (43% of participants) health, reduced cigarette (50% of smokers), alcohol (45% of users), cannabis (42% of users), and other non-prescribed drug use, increased number of friends (88% of participants), improved housing (60% of participants), increased income (19% of participants), increased community medical supports (40% of participants), and decreased conflicts with police (47% of those with prior recent conflict). Perceived reductions in substance use were supported by significant changes in composite harm score. Conclusion Street soccer appears to promote improved physical, mental, and social health among people affected by homelessness or precarious housing, with reduction in substance use likely to be a key factor. This work builds upon past qualitative research showing the benefits of street soccer and supports future research which may help elucidate the mechanisms by which street soccer has beneficial effects.

Developing prediction models for symptom severity around the time of discharge from a tertiary-care program for treatment-resistant psychosis.

Antipsychotics are the only therapeutic class indicated in the symptomatic management of psychotic disorders. However, individuals diagnosed with schizophrenia or schizoaffective disorder may not always benefit from these first-line agents. This refractoriness to conventional treatment can be difficult to address in most clinical settings. Therefore, a referral to a tertiary-care program that is better able to deliver specialized care in excess of the needs of most individuals may be necessary. The average outcome following a period of treatment at these programs tends to be one of improvement. Nonetheless, accurate prognostication of individual-level responses may be useful in identifying those who are unlikely to improve despite receiving specialized care. Thus, the main objective of this study was to predict symptom severity around the time of discharge from the Refractory Psychosis Program in British Columbia, Canada using only clinicodemographic information and prescription drug data available at the time of admission. To this end, a different boosted beta regression model was trained to predict the total score on each of the five factors of the Positive and Negative Syndrome Scale (PANSS) using a data set composed of 320 hospital admissions. Internal validation of these prediction models was then accomplished by nested cross-validation. Insofar as it is possible to make comparisons of model performance across different outcomes, the correlation between predictions and observations tended to be higher for the negative and disorganized factors than the positive, excited, and depressed factors on internal validation. Past scores had the greatest effect on the prediction of future scores across all 5 factors. The results of this study serve as a proof of concept for the prediction of symptom severity using this specific approach.

Movement disorders associated with substance use in adults living in precarious housing or homelessness.

OBJECTIVE: Many individuals living in precarious housing or homelessness have multimorbid illnesses, including substance use, psychiatric, and neurological disorders. Movement disorders (MDs) associated substance use are amongst the poorly studied subtopics of drug-induced MDs. The aim of the present study was, therefore, to determine the proportion affected and severity of different signs of MDs, as well as their associations with substance use in a community-based sample of precariously housed and homeless individuals. METHODS: Participants were recruited from an impoverished urban neighborhood and were assessed for substance dependence and self-reported substance use (alcohol, cannabis, cocaine, methamphetamine, nicotine, and opioids), as well as for the severity of signs of MDs (akathisia, dyskinesia, dystonia, and parkinsonism). Adjusted regression models were used to estimate the associations of the severity of signs with the frequency of substance use over the past 4 weeks and with the baseline diagnosis of substance dependence. RESULTS: The proportion of the sample with clinically relevant signs of MDs in any of the four categories was 18.6% (n = 401), and these participants demonstrated lower levels of functioning than those without signs. Of the different types of substance use, only methamphetamine (its frequency of use and dependence) was significantly associated with greater severity of overall signs of MDs. Frequency of methamphetamine use significantly interacted with age and sex, whereby older female participants exhibited the greatest overall severity with increased methamphetamine use. Of the different signs of MDs, methamphetamine use frequency was positively associated with the severity of trunk/limb dyskinesia and hypokinetic parkinsonism. Relative to no use, concurrent use of antipsychotics demonstrated lower severity of trunk/limb dyskinesia and greater severity of hypokinetic parkinsonism with methamphetamine use, and greater severity of dystonia with cocaine use. CONCLUSIONS: Our study found a high proportion of MDs in a relatively young sample, and their severity was consistently associated with methamphetamine use, moderated by participant demographics and antipsychotic use. These disabling sequelae represent an important and understudied neurological condition that may affect quality of life and will require further study.

A scoping review of psychiatric conditions associated with chronic pain in the homeless and marginally housed population.

The present review sought to examine and summarise the unique experience of concurrent pain and psychiatric conditions, that is often neglected, within the population of homeless individuals. Furthermore, the review examined factors that work to aggravate pain and those that have been shown to improve pain management. Electronic databases (MEDLINE, EMBASE, psycINFO, and Web of Science) and the grey literature (Google Scholar) were searched. Two reviewers independently screened and assessed all literature. The PHO MetaQAT was used to appraise quality of all studies included. Fifty-seven studies were included in this scoping review, with most of the research being based in the United States of America. Several interacting factors were found to exacerbate reported pain, as well as severely affect other crucial aspects of life that correlate directly with health, within the homeless population. Notable factors included drug use as a coping mechanism for pain, as well as opioid use preceding pain; financial issues; transportation problems; stigma; and various psychiatric disorders, such as post-traumatic stress disorder, depression, and anxiety. Important pain management strategies included cannabis use, Accelerated Resolution Therapy for treating trauma, and acupuncture. The homeless population experiences multiple barriers which work to further impact their experience with pain and psychiatric conditions. Psychiatric conditions impact pain experience and can work to intensify already adverse health circumstances of homeless individuals.

Cannabis use preferences in women with myofascial pelvic pain: A cross-sectional study.

Objective: Myofascial tenderness is present in most chronic pelvic pain conditions and causes significant distress to patients. Treatment is challenging and often not curative. Cannabis is often used for self-management of chronic pelvic pain. However, we do not know which concentrations and routes of administration are most acceptable to users. We aimed to investigate patterns and willingness of cannabis product use among both habitual users and non-users with myofascial pelvic pain (MPP), to inform therapeutic development. Study design: We conducted a cross-sectional study of questionnaire responses from female patients with MPP from two tertiary pelvic pain centers. We aimed for a convenience sample of 100 responses with representation from both centers. Inclusion criteria were age over 18 with pelvic floor muscle tenderness on standard gynecologic examination. We collected information on demographics, pelvic pain history, cannabis use status, cannabis use preferences, validated opioid misuse risk assessment, and interest in using gynecologic cannabis products and used descriptive analyses. Results: 77/135 (57 %) questionnaire respondents were cannabis users and 58 (43 %) were non-users. Most users consume cannabis daily, (48.1 %) orally (66.2 %) or by smoking (60.7 %), and rated cannabis as effective at relieving pelvic pain. 37/58 (63.8 %) non-cannabis users responded that they would be willing to use cannabis for pelvic pain. Lack of information and potential adverse effects were the most common reasons for unwillingness to use. Approximately 3 of 4 respondents were willing to try vaginal or vulvar application of cannabis products for pelvic pain. Conclusions: This cross-sectional study describes cannabis use patterns in MPP patients. Topical vulvar and vaginal cannabis products are of strong interest to both cannabis users and non-users and warrant further research.

Cannabidiol-associated hepatotoxicity: A systematic review and meta-analysis.

BACKGROUND: Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI). METHODS: In this systematic review and meta-analysis, a search of EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, and Web of Science of records up to February 2022 was conducted. Clinical trials initiating daily cannabidiol treatment with serial liver enzyme measures were included. The proportion of liver enzyme elevations and DILI were independently extracted from published reports. Pooled proportions and probability meta-analyses were conducted. RESULTS: Cannabidiol use was associated with an increased probability of liver enzyme elevation (N = 12 trials, n = 1229; OR = 5.85 95% CI = 3.84-8.92, p < 0.001) and DILI (N = 12 trials, n = 1229; OR = 4.82 95% CI = 2.46-9.45, p < 0.001) compared to placebo controls. In participants taking cannabidiol (N = 28 trials, n = 1533), the pooled proportion of liver enzyme elevations was 0.074 (95% CI 0.0448-0.1212), and DILI was 0.0296 (95% CI 0.0136-0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) and concomitant antiepileptic drug use were identified as risk factors. No cases were reported in adults using cannabidiol doses <300 mg/day. No cases of severe DILI were reported. CONCLUSIONS: Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.

Using serial position effects to investigate memory dysfunction in homeless and precariously housed persons.

Background: Homeless and precariously housed persons exhibit significant memory impairment, but the component processes underlying memory dysfunction have not been explored. We examined the serial position profile (i.e., primacy and recency effects) of verbal memory and its neuroanatomical correlates to identify the nature of memory difficulties in a large cohort of homeless and precariously housed adults. Method: The sample included 227 community-dwelling homeless and precariously housed adults. Serial position scores (primacy, middle, recency) were computed using the Hopkins Verbal Learning Test-Revised. Paired sample t-tests were used to compare percent recall from each word list region. Age-adjusted correlations assessed associations between serial position scores and other cognitive domains (attention, processing speed, executive functioning). Regression analyses were conducted to examine regional brain volumes of interest (hippocampus, entorhinal cortex, dorsolateral prefrontal cortex [DLPFC]) and their differential associations with serial position scores. Results: The serial position profile was characterized by a diminished recency effect in relation to the primacy effect. Serial position scores positively correlated with sustained attention and cognitive control. Larger hippocampal volume was associated with better primacy item recall. DLPFC volume was not associated with serial position recall after adjustment for false discovery rate. There were no associations between regional brain volumes and recency item recall. Conclusion: Our results suggest that commonly reported memory difficulties in homeless and precariously housed adults are likely secondary to a core deficit in executive control due to compromised frontal lobe functioning. These findings have implications for cognitive rehabilitation in this complex and vulnerable group.

Differential age-associated brain atrophy and white matter changes among homeless and precariously housed individuals compared with the general population.

Background: Homeless or precariously housed individuals live with poor health and experience premature mortality compared with the general population, yet little is known about age-related brain changes among these individuals. We evaluated whether MRI measures of brain structure are differentially associated with age and selected risk factors among individuals who are homeless or precariously housed compared with a general population sample. Methods: We compared T1-weighted and diffusion tensor imaging measures of brain macrostructure and white matter microstructure in a well-characterised sample of 312 precariously housed participants with a publicly available dataset of 382 participants recruited from the general population. We used piecewise and multiple linear regression to examine differential associations between MRI measures and between the samples, and to explore associations with risk factors in the precariously housed sample. Results: Compared with the general population sample, older age in the precariously housed sample was associated with more whole-brain atrophy (ß=-0.20, p=0.0029), lower whole-brain fractional anisotropy (ß=-0.32, p<0.0001) and higher whole-brain mean diffusivity (ß=0.69, p<0.0001). Several MRI measures had non-linear associations with age, with further adverse changes after age 35-40 in the precariously housed sample. History of traumatic brain injury, stimulant dependence and heroin dependence was associated with more atrophy or alterations in white matter diffusivity in the precariously housed sample. Conclusions: Older age is associated with adverse MRI measures of brain structure among homeless and precariously housed individuals compared with the general population. Education, improvements in care provision and policy may help to reduce the health disparities experienced by these individuals.

Differences in those who prefer smoking cannabis to other consumption forms for mental health: what can be learned to promote safer methods of consumption?

Smoking cannabis in medical users is associated with exposure to harmful toxins. It is important to characterize cannabis-use profiles and risk-factors for medical cannabis users who smoke cannabis. 100 members of a medical cannabis dispensary with mental health concerns were interviewed in detail about their cannabis use. Forty seven percent of participants preferred smoking only, 18% preferred vaporizing, 25% preferred both smoking and vaping, and 10% preferred oral ingestion methods. Smokers differed from other users in multiple ways, including a greater preference for THC-dominant chemovars, and more frequent and greater amount of cannabis consumption. Smoking was also associated with greater rates of alcohol use disorder. These results may inform harm-reduction approaches to decrease the number of individuals smoking cannabis and use less harmful methods of medical cannabis ingestion.

Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity.

Background: There are currently relatively few effective pharmacological treatments for obesity, and existing ones may be associated with limiting side-effects. In the search for novel anti-obesity agents, drugs that modify central serotonergic systems have historically proven to be effective in promoting weight loss. Psilocin, which is rapidly metabolized from psilocybin, is an agonist at multiple serotonin receptors. In the present study we assessed the effects of psilocybin and a positive control (metformin) on changes in body weight in a rat model of obesity. Methods: Five groups of adult male rats were pre-conditioned with a cafeteria diet until obese (>600 g) and then treated with either psilocybin (0.1, 1, or 5 mg/kg, i.p.), metformin (300 mg/kg, p.o.) or vehicle control. Treatments were for 27 consecutive weekdays, and body weights and high calorie food intake were recorded daily. Fasting glucose levels were recorded after 11 days of treatment. At the end of treatment rats completed a glucose tolerance test, and multiple fat pads were dissected out to assess adiposity. Results: The medium dose psilocybin group had to be terminated from the study prematurely. Both the low and high dose psilocybin groups caused a significant decrease in changes in body weight compared to controls. The metformin group produced a greater decrease in change in body weight than either psilocybin groups or controls. Both high dose psilocybin and metformin decreased consumption of the high calorie diet, and exhibited decreased central adiposity. Conclusion: Psilocybin demonstrated modest but significant effects on weight gain. Further study is recommended.

Risk factors for hippocampal cavities in a marginally housed population.

Cavities in the hippocampus are morphological variants of uncertain significance. Aberrant neurodevelopment along with vascular and inflammatory etiologies have been proposed. We sought to characterize these cavities and their potential risk factors in a marginally housed population, with high rates of viral infection, addiction, and mental illness. (1) The volume of hippocampal cavities (HCavs) is greater in this highly multimorbid population compared to the general population. (2) Conventional vascular risk factors such as greater age and systolic blood pressure are associated with higher HCav volume. (3) Nonprescribed substance-related risk factors such as stimulant use or dependence, and smoking are associated with increased HCav volume independent of vascular risk factors. This is a retrospective analysis of an ongoing prospective study. We analyzed baseline data, including medical history, physical exam, psychiatric diagnosis, and MRI from a total of 375 participants. Hippocampal cavities were defined as spaces isointense to CSF on T1 MRI sequences, bounded on all sides by hippocampal tissue, with a volume of at least 1 mm3 . Risk factors were evaluated using negative binomial multiple regression. Stimulant use was reported by 87.3% of participants, with stimulant dependence diagnosed in 83.3% of participants. Prevalence of cavities was 71.6%, with a mean total bilateral HCav volume of 13.89 mm3 . On average, a 1 mmHg greater systolic blood pressure was associated with a 2.17% greater total HCav volume (95% CI = [0.57%, 3.79%], p = .0076), while each cigarette smoked per day trended toward a 2.69% greater total HCav volume (95% CI = [-0.87%, 5.54%], p = .058). A diagnosis of stimulant dependence was associated with a 95.6% greater total HCav volume (95% CI = [5.39%, 263.19%], p = .0335). Hypertension and diagnosis of stimulant dependence were associated with a greater total volume of HCav.

Long-acting injectable antipsychotics for early psychosis: A comprehensive systematic review.

AIM: Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients. METHODS: MEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years. RESULTS: 33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations. CONCLUSIONS: While the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.

Pain, opioid use, depressive symptoms, and mortality in adults living in precarious housing or homelessness: a longitudinal prospective study.

ABSTRACT: Pain and related consequences could contribute to comorbid illness and premature mortality in homeless and precariously housed persons. We analyzed longitudinal data from an ongoing naturalistic prospective study of a community-based sample (n = 370) to characterize risk factors and consequences of bodily pain. The aims were to describe bodily pain and associations with symptoms and psychosocial function, investigate factors that may increase or ameliorate pain, and examine the consequences of pain for symptoms, functioning, and all-cause mortality. Bodily pain severity and impact were rated with the 36-item Short Form Health Survey Bodily Pain Scale monthly over 5 years. Mixed-effects linear regression models estimated the effects of time-invariant and time-varying risk factors for pain, verified by reverse causality and multiple imputation analysis. Regression models estimated the associations between overall person-mean pain severity and subsequent functioning and suicidal ideation, and Cox proportional hazard models assessed association with all-cause mortality. Bodily pain of at least moderate severity persisted (>3 months) in 64% of participants, exceeding rates expected in the general population. Greater pain severity was associated with depressive symptom severity and month-to-month opioid use, overlaid on enduring risk associated with age, arthritis, and posttraumatic stress disorder. The frequency of prescribed and nonprescribed opioid use had nonlinear relationships with pain: intermittent use was associated with severe pain, without reverse association or change with the overdose epidemic. Greater longitudinal mean pain severity was associated with premature mortality, poorer functioning, and suicidal ideation. Considering the relationships between pain, intermittent opioid use, and depressive symptoms could improve health care for precariously housed patients.