Change in Severity of Mental Disorder of Remand Prisoners: An Observational Group-Based Trajectory Study.

BACKGROUND: Mental disorder is common among prisoners; however, little is known about how illness severity changes during incarceration, and especially to what extent there are different trajectories of change. AIMS: Our aims were to investigate trajectories of illness severity among male and female inmates with serious mental disorders, and to investigate whether clinical or demographic variables are associated with different trajectories. METHODS: We carried out a retrospective cohort study of newly remanded inmates who had three or more serial measures of illness severity as measured by psychiatrists using the Clinical Global Impression-Corrections (CGI-C), and used group-based trajectory modelling to identify trajectories. We investigated whether clinical and demographic variables were associated with different groups. RESULTS: We found an overall reduction in the severity of illness (mean change in CGI-C score -0.74, SD 1.5), with women showing greater improvement than men. We identified three distinct trajectories among men and three among women, all showing improvement in illness severity. Approximately 15% of the entire cohort had full resolution of symptoms, whereas the remainder showed partial improvement. Women, younger inmates, and those with substance use disorders were more likely to have full resolution of symptoms. CONCLUSIONS: Although most prisoners showed improvement, and a small proportion had full resolution of symptoms, a significant number continued to have moderately severe symptoms. There is a need for comprehensive treatment within the detention centre, but also a need for transfer to hospital for those with severe symptoms as improvement within the correctional setting tends to be modest.

N400 event-related brain potential and functional outcome in persons at clinical high risk for psychosis: A longitudinal study.

BACKGROUND: The N400 event-related brain potential (ERP) semantic priming effect is thought to reflect activation by meaningful stimuli of related concepts in semantic memory and has been found to be deficient in schizophrenia. We tested the hypothesis that, among individuals at clinical high risk (CHR) for psychosis, N400 semantic priming deficits predict worse symptomatic and functional outcomes after one year. METHODS: We measured N400 semantic priming at baseline in CHR patients (n = 47) and healthy control participants (n = 25) who viewed prime words each followed by a related or unrelated target word, at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured patients' psychosis-like symptoms with the Scale of Prodromal Symptoms (SOPS) Positive subscale, and academic/occupational and social functioning with the Global Functioning (GF):Role and Social scales, respectively, at baseline and one-year follow-up (n = 29). RESULTS: CHR patients exhibited less N400 semantic priming than controls across SOAs; planned contrasts indicated this difference was significant at the 750-ms but not the 300-ms SOA. In patients, reduced N400 semantic priming at the 750-ms SOA was associated with lower GF:Social scores at follow-up, and greater GF:Social decrements from baseline to follow-up. Patients' N400 semantic priming was not associated with SOPS Positive or GF:Role scores at follow-up, or change in these from baseline to follow-up. CONCLUSIONS: In CHR patients, reduced N400 semantic priming at baseline predicted worse social functioning after one year, and greater decline in social functioning over this period. Thus, the N400 may be a useful prognostic biomarker of real-world functional outcome in CHR patients.

Management of COVID-19 Response in a Secure Forensic Mental Health Setting: Réponse à la gestion de la COVID-19 dans un établissement sécurisé de santé mentale et de psychiatrie légale.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic presents major challenges to places of detention, including secure forensic hospitals. International guidance presents a range of approaches to assist in decreasing the risk of COVID-19 outbreaks as well as responses to manage outbreaks of infection should they occur. METHODS: We conducted a literature search on pandemic or outbreak management in forensic mental health settings, including gray literature sources, from 2000 to April 2020. We describe the evolution of a COVID-19 outbreak in our own facility, and the design, and staffing of a forensic isolation unit. RESULTS: We found a range of useful guidance but no published experience of implementing these approaches. We experienced outbreaks of COVID-19 on two secure forensic units with 13 patients and 10 staff becoming positive. One patient died. The outbreaks lasted for 41 days on each unit from declaration to resolution. We describe the approaches taken to reduction of infection risk, social distancing and changes to the care delivery model. CONCLUSIONS: Forensic secure settings present major challenges as some proposals for pandemic management such as decarceration or early release are not possible, and facilities may present challenges to achieve sustained social distancing. Assertive testing, cohorting, and isolation units are appropriate responses to these challenges.

An Examination of Predictive Validity and Change in Risk Factors for Stalking over Time.

This study investigates the predictive validity of two risk instruments for stalking, the Guidelines for Stalking Assessment and Management (SAM) and the Stalking Risk Profile (SRP), in a sample of 86 forensic psychiatric patients. We compare these tools against a well-validated violence risk assessment measure (Historical, Clinical, Risk Management-20, Version 3 (HCR-20V3)) for violent and stalking-related outcomes. Dynamic (mutable) components of each tool were rated at three annual intervals and revealed significant change across time. The HCR-20V3, SAM, and SRP measures showed comparable ability to classify those who recidivated with further stalking from those who did not (area under the curves = .72-.73, P < 001). Time-varying scores from the dynamic subscales of the HCR-20V3 and SAM contributed significantly to the prediction of stalking, whereas nonstalking violence was primarily forecast by the static (Historical) scale of the HCR-20V3. This suggests comparable validity of general violence and stalking risk tools for assessing the risk of stalking in forensic patients. Stalking-specific risk factors on the SAM and SRP will likely be of added clinical value in terms of tailoring risk management and treatment plans. Findings also emphasize the importance of attending to changes in risk status over time and incorporating time-sensitive methodologies into predictive models.

Evaluation of Hepatitis C Screening and Treatment Among Psychiatry Inpatients.

Objective: To evaluate uptake of hepatitis C virus (HCV) testing and treatment among psychiatry inpatients at Canada's largest mental health institution, the Centre for Addiction and Mental Health (CAMH).Methods: We reviewed medical records for all forensic and long-stay mental health patients from January 2017 to May 2021 to examine rates of HCV testing (antibody and RNA), treatment, and follow-up and completed a logistical regression to identify predictors associated with HCV antibody (Ab) screening among inpatients.Results: Of 1,031 patients, 73% (n = 753) were male, mean age was 44 years (range: 20-92), and mean length of stay was 7.1 months (range: 0 days-24 years). Most, 83% (n = 856), were diagnosed with schizophrenia spectrum disorders. In total, 652/1,031 (63%) of individuals in this cohort received HCV Ab screening. When broken down by admission rather than individual, 570/1,303 (44%) forensic admissions had an associated HCV Ab screening, and 318/1,450 (22%) non-forensic admissions had an associated HCV Ab screening. Individuals admitted to a forensic unit and those diagnosed with schizophrenia or substance use disorders were more likely to undergo HCV Ab screening, while individuals of Asian ethnicity were less likely (all P < .05). HCV Ab positivity was 4.9%, and most (84%, n = 27) HCV Ab-positive individuals had subsequent RNA testing, of whom 56% (n = 15) tested HCV RNA positive. Of 15 RNA-positive individuals, 10 initiated treatments, 7 on-site at CAMH and 3 at a local hepatology center. A total of 7 individuals (1 treated by specialists and 6 on-site) achieved sustained virological response or cure. The remaining 3 were lost to follow-up, 2 of whom were treated at the hepatology clinic.Conclusions: Based on the high prevalence of HCV, mental health inpatients should be included in groups for whom universal screening is recommended. Since on-site treatment was more successful than referral to external hepatology specialists, utilizing inpatient admission as an opportunity for HCV screening and treatment should receive more consideration.

N400 event-related brain potential as an index of real-world and neurocognitive function in patients at clinical high risk for schizophrenia.

AIM: The N400 event-related potential is a neurophysiological index of cognitive processing of real-world knowledge. In healthy populations, N400 amplitude is smaller in response to stimuli that are more related to preceding context. This 'N400 semantic priming effect' is thought to reflect activation of contextually related information in semantic memory (SM). N400 semantic priming deficits have been found in schizophrenia, and in patients at clinical high risk (CHR) for this disorder. Because this abnormality in processing relationships between meaningful stimuli could affect ability to navigate everyday situations, we hypothesized it would be associated with real-world functional impairment in CHR patients. Second, we hypothesized it would correlate with global neurocognitive impairment in this group. METHODS: We measured N400 semantic priming in 35 CHR patients who viewed prime words each followed by a related or unrelated target word, at stimulus-onset asynchrony (SOA) of 300 or 750 ms. We measured academic/occupational and social function with the global function (GF): Role and Social scales, and cognitive function with the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Decreased N400 semantic priming at the 300-ms SOA correlated with lower GF:Role scores. Decreased N400 semantic priming at the 750-ms SOA correlated with lower MCCB composite scores. CONCLUSIONS: Deficits in activating contextually related concepts in SM over short time intervals may contribute to functional impairment in CHR patients. Furthermore, N400 priming deficits over longer intervals may be a biomarker of global cognitive dysfunction in this population. Longitudinal studies are needed to determine whether these deficits are associated with schizophrenia risk within this population.

A Systematic Review of Reviews of Correctional Mental Health Services Using the STAIR Framework.

BACKGROUND: Rising demand for correctional mental health services (CMHS) in recent decades has been a global phenomenon. Despite increasing research, there are major gaps in understanding the best models for CMHS and how to measure their effectiveness, particularly studies that consider the overall care pathways and effectiveness of service responses. The STAIR (Screening, Triage, Assessment, Intervention, and Re-integration) model is an evidence-based framework that defines and measures CMHS as a clinical pathway with a series of measurable, and linked functions. METHOD: We conducted a systematic review of the reviews of CMHS elements employing PRISMA guidelines, organized according to STAIR pillars. We assessed the quality of included studies using the AMSTAR-2 criteria. Narrative reviews were read and results synthesized. RESULTS: We included 26 review articles of which 12 were systematic, metaanalyses, and 14 narrative reviews. Two systematic reviews and seven narrative reviews addressed screening and triage with strong evidence to support specific screening and triage systems. There was no evidence for standardised assessment approaches. Eight systematic reviews and seven narrative reviews addressed interventions providing some evidence to support specific psychosocial interventions. Three systematic reviews and six narrative reviews addressed reintegration themes finding relatively weak evidence to support reintegration methods, with interventions often being jurisdictionally specific and lacking generalizability. CONCLUSIONS: The STAIR framework is a useful way to organize the extant literature. More research is needed on interventions, assessment systems, care pathway evaluations, and reintegration models.

Validation of the Clinical Global Impression-Corrections Scale (CGI-C) by Equipercentile Linking to the BPRS-E.

Background: The Clinical Global Impression-Corrections (CGI-C) is an adaptation of the severity scale of the Clinical Global Impression for use in correctional facilities. Although it has been shown to have good inter-rater reliability, there have been no validation studies of this instrument. Method: We analyzed data from 726 initial assessments of persons detained in two correctional facilities and compared clinician's ratings for the CGI-C and modified Brief Psychiatric Rating Scale-Expanded (BPRS-E). We used equipercentile linkage and Spearman correlations to investigate concordance in the total sample, by diagnostic groups, and by gender. Results: We found that the CGI-C scores and BPRS-E scores among persons in remand settings were significantly correlated (ρ = 0.51, p < 0.001) and that correlations were the same for men and women. We found that points of equivalence can be reliably found between the two scales using equipercentile linkage, and that those with psychotic disorders had lower BPRS-E scores than those with mood/anxiety/situational stress for equivalent CGI-C scores. Conclusion: Overall, CGI-C ratings correspond well to BPRS-E ratings for both men and women remand prisoners across diagnoses, and the CGI-C appears to be a valid tool for the assessment of severity of symptoms in this setting.

Negative symptoms in the clinical high-risk state for psychosis: Connection with cognition and primacy in impacting functioning.

AIM: In the clinical high-risk (CHR) state for psychosis, both negative symptoms and lower cognitive function have been associated with poorer daily functioning. Recent evidence suggests that negative symptoms share overlapping variability with cognition and may partially mediate the relationship between cognition and functioning. However, the nature of this overlap is unknown, and the reverse mediation model remains untested leaving the precise nature of these associations unclear. METHODS: In order to clarify these relationships, a sample of community-dwelling youth meeting CHR criteria was collected from a specialty CHR clinic (n = 91, mean age = 21, 63% male). Bootstrapping methods were then applied in a mediation analysis to test both negative symptoms and cognition as independent variables and mediating variables predicting social and role functioning in CHR individuals. Canonical correlation analysis was used to characterize the overlapping variability between negative symptoms and cognition. RESULTS: Support for a primary role of negative symptoms in predicting functioning and cognition was observed. Canonical correlation revealed a single dimension of overlap between the two symptom types (r = .62), represented by a strong correlation between negative symptoms in general and tasks involving verbal working memory, vigilance and social cognition specifically. A single cognitive factor composed primarily of these tasks was found to predict role functioning (adjusted R 2 = .04). CONCLUSIONS: The results highlight the importance of considering specific cognitive mechanisms overlapping with negative symptoms in research and rehabilitative practice in CHR populations, as well as the primary importance of targeting negative symptoms.

Relationships between cognitive event-related brain potential measures in patients at clinical high risk for psychosis.

Neurophysiological measures of cognitive functioning that are abnormal in patients with schizophrenia are promising candidate biomarkers for predicting development of psychosis in individuals at clinical high risk (CHR). We examined the relationships among event-related brain potential (ERP) measures of early sensory, pre-attentional, and attention-dependent cognition, in antipsychotic-naïve help-seeking CHR patients (n = 36) and healthy control participants (n = 22). These measures included the gamma auditory steady-state response (ASSR; early sensory); mismatch negativity (MMN) and P3a (pre-attentional); and N400 semantic priming effects - a measure of using meaningful context to predict related items - over a shorter and a longer time interval (attention-dependent). Compared to controls, CHR patients had significantly smaller P3a amplitudes (d = 0.62, p = 0.03) and N400 priming effects over the long interval (d = 0.64, p = 0.02). In CHR patients, gamma ASSR evoked power and phase-locking factor were correlated (r = 0.41, p = 0.03). Reductions in mismatch negativity (MMN) and P3a amplitudes were also correlated (r = -0.36, p = 0.04). Moreover, lower gamma ASSR evoked power correlated with smaller MMN amplitudes (r = -0.45, p = 0.02). MMN amplitude reduction was also associated with reduced N400 semantic priming over the shorter but not the longer interval (r = 0.52, p < 0.002). This pattern of results suggests that, in a subset of CHR patients, impairment in pre-attentional measures of early information processing may contribute to deficits in attention-dependent cognition involving rapid, more automatic processing, but may be independent from pathological processes affecting more controlled or strategic processing. Thus, combining neurophysiological indices of cognitive deficits in different domains offers promise for improving their predictive power as prognostic biomarkers of clinical outcome.

Stress precedes negative symptom exacerbations in clinical high risk and early psychosis: A time-lagged experience sampling study.

The experience sampling method (ESM) has revealed associations between fluctuations in stress and positive symptoms in psychosis. It is unknown, however, how negative symptoms including anhedonia respond to stress. Stress is divided according to its source: event-related stress stemming from negative events, and activity-related stress stemming from engaging in tasks beyond one's skill or control. Anhedonia is divided into consummatory and anticipatory anhedonia, reflecting a lack of pleasure in current and expected activities. This study uses ESM to determine whether each form of anhedonia increases in response to stress. Antipsychotic-naïve individuals with first episode psychosis (n = 39), clinical high-risk states for psychosis (n = 44), and healthy controls (n = 34) responded to daily prompts on a palmtop computer for up to ten days by indicating levels of stress and anhedonia. Time-lagged multilevel modelling was employed to explore increases in anhedonia following increases in stress while controlling for prior levels of anhedonia. Mean levels of anhedonia were also compared across groups. Only activity-related stress produced increases in anhedonia. This effect did not vary between groups. Clinical groups showed greater overall levels of anhedonia than healthy controls, but did not differ from each other. Anhedonia responds only to activity-related stressors, suggesting that this form of stress has a specific causal role in anhedonia. The results also provide further evidence for global increases in anhedonia in antipsychotic-naïve psychosis spectrum individuals.

Mitochondrial function in individuals at clinical high risk for psychosis.

Alterations in mitochondrial function have been implicated in the etiology of schizophrenia. Most studies have investigated alterations in mitochondrial function in patients in which the disorder is already established; however, whether mitochondrial dysfunction predates the onset of psychosis remains unknown. We measured peripheral mitochondrial complex (I-V) function and lactate/pyruvate levels in 27 antipsychotic-naïve individuals at clinical high risk for psychosis (CHR) and 16 healthy controls. We also explored the association between mitochondrial function and brain microglial activation and glutathione levels using a translocator protein 18 kDa [18F]FEPPA PET scan and 1H-MRS scan, respectively. There were no significant differences in mitochondrial complex function and lactate/pyruvate levels between CHR and healthy controls. In the CHR group, mitochondrial complex III function (r = -0.51, p = 0.008) and lactate levels (r = 0.61, p = 0.004) were associated with prodromal negative symptoms. As previously reported, there were no significant differences in microglial activation and glutathione levels between groups, however, mitochondrial complex IV function was inversely related to microglial activation in the hippocampus in CHR (r = -0.42, p = 0.04), but not in healthy controls. In conclusion, alterations in mitochondrial function are not yet evident in CHR, but may relate to the severity of prodromal symptoms, particularly negative symptoms.

Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.

It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ) administered intraperitoneally (IP). Insulin IP (15 U/kg), in rats fasted (14-16 hours), induced hypoglycemia, defined as <3.5 mM blood glucose (BG), in 68% of diabetic (STZ) and 86% of control rats (CON). Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4 ± 1.3 mM) than in CON rodents (6.3 ± 0.3 mM), resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8 ± 0.2 mM) and CON animals (1.6 ± 0.1 mM) as well as between those that survived (S+S) and those that died (S+M) post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs) were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of underlying mechanisms. Our data demonstrate that severe hypoglycemia (<2.0 mM) is a necessary precondition for seizures, and the increased frequency of these seizures is associated with mortality.