Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome.

Multiscale neuroscience conceptualizes mental illness as arising from aberrant interactions across and within multiple biopsychosocial scales. We leverage this framework to propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impairments in episodic memory and social cognition, which lead to more severe negative symptoms and lower functional outcome. As psychosis represents a heterogeneous collection of biological and behavioral alterations that evolve over time, we further predict this disease progression for a subtype of the patient sample, with other patients showing normal-range performance on all variables. We sampled data from two cross-sectional datasets of first- and multi-episode psychosis, resulting in a sample of 163 patients and 119 non-clinical controls. To address our proposed disease progression model and evaluate potential heterogeneity, we applied a machine-learning algorithm, SuStaIn, to the patient data. SuStaIn uniquely integrates clustering and disease progression modeling and identified three patient subtypes. Subtype 0 showed normal-range performance on all variables. In comparison, Subtype 1 showed lower episodic memory, social cognition, functional outcome, and higher negative symptoms, while Subtype 2 showed lower hippocampal-cortical connectivity and episodic memory. Subtype 1 deteriorated from episodic memory to social cognition, negative symptoms, functional outcome to bilateral hippocampal-cortical dysconnectivity, while Subtype 2 deteriorated from bilateral hippocampal-cortical dysconnectivity to episodic memory and social cognition, functional outcome to negative symptoms. This first application of SuStaIn in a multiscale psychiatric model provides distinct disease trajectories of hippocampal-cortical connectivity, which might underlie the heterogeneous behavioral manifestations of psychosis.

Dynamic association of the first identifiable symptom with rapidity of progression to first-episode psychosis.

BACKGROUND: Rapid progression from the first identifiable symptom to the onset of first-episode psychosis (FEP) allows less time for early intervention. The aim of this study was to examine the association between the first identifiable symptom and the subsequent speed of illness progression. METHODS: Data were available for 390 patients attending a catchment-based early intervention service for FEP. Exposure to non-psychotic and subthreshold psychotic symptoms was retrospectively recorded using semi-structured interviews. Outcomes following the onset of the first identifiable symptom were (1) time to onset of FEP and (2) symptom incidence rate (i.e. number of symptoms emerging per person-year until FEP onset). These outcomes were respectively analyzed with Cox proportional hazards and negative binomial regressions. RESULTS: After Bonferroni correction, having a subthreshold psychotic (v. non-psychotic) symptom as the first symptom was not associated with time to FEP onset [hazard ratio (HR) = 1.39; 95% CI 0.94-2.04] but was associated with higher symptom incidence [incidence rate ratio (IRR) = 1.92; 95% CI 1.10-3.48]. A first symptom of suspiciousness was associated with shorter time to FEP onset (HR = 2.37; 95% CI 1.38-4.08) and higher symptom incidence rate (IRR = 3.20; 95% CI 1.55-7.28) compared to other first symptoms. In contrast, a first symptom of self-harm was associated with lower symptom incidence rate (IRR = 0.06; 95% CI 0.01-0.73) compared to other first symptoms. Several associations between symptoms and illness progression were moderated by the age at symptom onset. CONCLUSIONS: Appreciating the content and timing of early symptoms can identify windows and treatment targets for early interventions in psychosis.

Manualized group cognitive behavioral therapy for social anxiety in first-episode psychosis: a randomized controlled trial.

BACKGROUND: Social anxiety (SA), a prevalent comorbid condition in psychotic disorders with a negative impact on functioning, requires adequate intervention relatively early. Using a randomized controlled trial, we tested the efficacy of a group cognitive-behavioral therapy intervention for SA (CBT-SA) that we developed for youth who experienced the first episode of psychosis (FEP). For our primary outcome, we hypothesized that compared to the active control of group cognitive remediation (CR), the CBT-SA group would show a reduction in SA that would be maintained at 3- and 6-month follow-ups. For secondary outcomes, it was hypothesized that the CBT-SA group would show a reduction of positive and negative symptoms and improvements in recovery and functioning. METHOD: Ninety-six patients with an FEP and SA, recruited from five different FEP programs in the Montreal area, were randomized to 13 weekly group sessions of either CBT-SA or CR intervention. RESULTS: Linear mixed models revealed that multiple measures of SA significantly reduced over time, but with no significant group differences. Positive and negative symptoms, as well as functioning improved over time, with negative symptoms and functioning exhibiting a greater reduction in the CBT-SA group. CONCLUSIONS: While SA decreased over time with both interventions, a positive effect of the CBT-SA intervention on measures of negative symptoms, functioning, and self-reported recovery at follow-up suggests that our intervention had a positive effect that extended beyond symptoms specific to SA.ClinicalTrials.gov identifier: NCT02294409.

Examining the psychobiological response to acute social stress across clinical stages and symptom trajectories in the early psychosis continuum.

The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls (n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis - and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness.

A Descriptive Overview of Mental Health Services Offered in Post-Secondary Educational Institutions Across Canada.

OBJECTIVE: Access to adequate mental health (MH) services is necessary for nearly half of Canadian youth (18-24 years) who enroll in post-secondary education given the relatively high risk of MH problems. Our objectives were to determine the status of MH services available to students in post-secondary institutions in Canada and to determine the extent to which these services are based on the principles of a high-quality youth MH (YMH) service. METHOD: Information on MH services was collected from websites of a representative sample (N = 67) of post-secondary institutions across all provinces. Data were analysed descriptively according to four categories (universities with a Faculty of Medicine (FoM) n = 18, other large universities n = 15, small universities n = 16, and colleges n = 18). RESULTS: Most institutions provided 24-h crisis line support (84%) and indicated the availability of free counselling or psychotherapy (n = 62 of 67, 92.5%), while only a minority indicated provision of an initial clinical assessment (25%) and provision of multiple sessions of therapy (37%). Wait time for first contact was impressively low (<72 h) in the minority of institutions (40%) which provided this information. Access to either a prescribing physician or psychiatrist was infrequent, though several mentioned an unexplained model of "stepped care" and outside referrals. While relevant information was not uniformly easy to access, larger institutions both with and without a FoM appear to be better poised to provide MH services. None of the institutions appeared to follow all the principles of service delivery recommended for a high-quality YMH, with only two showing early identification activities. CONCLUSIONS: MH services in post-secondary institutions may need a transformation similar to YMH services, including a clear pathway to care, an initial clinical assessment, early identification of MHA disorders, and better utilization of institutional resources through greater collaboration and matching of timely interventions to the presenting problems.

Effects of Anticholinergic Burden on Verbal Memory Performance in First-Episode Psychosis.

OBJECTIVES: Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, that is, a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory, are a core feature of the disease. The present study sought to replicate this in a large cohort of well-characterized first-episode psychosis patients. We expected that patients in the highest anticholinergic burden group would exhibit the poorest verbal memory compared to those with low anticholinergic burden and healthy controls at baseline (3 months following admission). We further hypothesized that over time, at month 12, patients' verbal memory performance would improve but would remain inferior to controls. METHODS: Patients (n = 311; low anticholinergic burden [n = 241] and high anticholinergic burden [n = 70], defined by a Drug Burden Index cut-off of 1) and healthy controls (n = 128) completed a clinical and neurocognitive battery including parts of the Wechsler Memory Scale at months 3 and 12. RESULTS: Cross-sectionally, using an analysis of variance, patients in the highest anticholinergic burden group had the poorest performance in verbal memory when compared to the other groups at month 3, F(2,430) = 52.33, P < 0.001. Longitudinally, using a Generalized Estimating Equation model, the verbal memory performance of all groups improved over time. However, patients' performance overall remained poorer than the controls. CONCLUSION: These findings highlight the importance of considering the anticholinergic burden when prescribing medications in the early stages of the disease.

Context and Expectations Matter: Social, Recreational, and Independent Functioning among Youth with Psychosis in Chennai, India and Montreal, Canada.

OBJECTIVES: Most cross-cultural psychosis research has focused on a limited number of outcomes (generally symptom-related) and perspectives (often clinician-/observer-rated). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to patient-reported measures of social, recreational, and independent functioning. Addressing this gap, this study aimed to compare these outcomes in first-episode psychosis at a high-income site and a lower middle-income site. METHODS: Patients receiving similarly designed early intervention for psychosis in Chennai, India (N = 164) and Montreal, Canada (N = 140) completed the self-reported Social Functioning Scale-Early Intervention, which measures prosocial, recreation, and independence-performance functioning. Their case managers rated expected independence-performance functioning. Both sets of assessments were done at entry and Months 6, 18, and 24. Linear mixed model analyses of differences between sites and over time were conducted, accounting for other pertinent variables, especially negative symptoms. RESULTS: Linear mixed models showed that prosocial, recreation, and independence-performance functioning scores were significantly higher in Montreal than Chennai and did not change over time. Expected independence-performance was also higher in Montreal and increased over time. Negative symptoms and education independently predicted prosocial, recreation, and expected independence-performance functioning. When added to the model, expected independence-performance predicted actual independence-performance and site was no longer significant. At both sites, prosocial and recreation scores were consistently lower (<40%) than independence-performance (40-65%). CONCLUSION: This is the first cross-cultural investigation of prosocial, recreation, and independent functioning in early psychosis. It demonstrates that these outcomes differ by socio-cultural context. Differing levels of expectations about patients, themselves shaped by cultural, illness, and social determinants, may contribute to cross-cultural variations in functional outcomes. At both sites, social, recreational, and independent functioning were in the low-to-moderate range and there was no improvement over time, underscoring the need for effective interventions specifically designed to impact these outcomes.

Comparing treatment delays and pathways to early intervention services for psychosis in urban settings in India and Canada.

INTRODUCTION: Although extensively studied in high-income countries (HICs) and less so in low- and middle-income countries (LMICs), pathways to care and treatment delays in early psychosis have not been compared across contexts. We compared pathways to early intervention for psychosis in an HIC (Montreal, Canada) and an LMIC (Chennai, India). We hypothesised that the duration of untreated psychosis (DUP) would be longer in Chennai. METHODS: The number of contacts preceding early intervention, referral sources, first contacts, and DUP and its referral and help-seeking components of first-episode psychosis patients at both sites were similarly measured and compared using chi-square analyses and t tests/one-way ANOVAs. RESULTS: Overall and help-seeking DUPs of Chennai (N = 168) and Montreal (N = 165) participants were not significantly different. However, Chennai patients had shorter referral DUPs [mean = 12.0 ± 34.1 weeks vs. Montreal mean = 13.2 ± 28.7 weeks; t(302.57) = 4.40; p < 0.001] as the early intervention service was the first contact for 44% of them (vs. 5% in Montreal). Faith healers comprised 25% of first contacts in Chennai. Those seeing faith healers had significantly shorter help-seeking but longer referral DUPs. As predicted, most (93%) Montreal referrals came from medical sources. Those seeing psychologists/counsellors/social workers as their first contact had longer DUPs. CONCLUSION: Differences in cultural views about mental illnesses and organizational structures shape pathways to care and their associations with treatment delays across contexts. Both formal and informal sources need to be targeted to reduce delays. Early intervention services being the first portal where help is sought can reduce DUP especially if accessed early on in the illness course.

"The more things change "? Stability of delusional themes across 12 years of presentations to an early intervention service for psychosis.

PURPOSE: While the prevalence of delusional themes appears to be consistent across geographic contexts, little is known about the relative prevalence of such themes within a given setting over periods of time. We therefore investigated delusional themes across 12 years of presentation to a catchment-based early intervention service for first episode psychosis (FEP). METHODS: Systematically collected data from 500 patients at an early intervention service for FEP were analyzed. Four cohorts of 3 years each, from 2006 to 2017, were used to compare the frequency of delusion themes across cohorts. We also integrated into the analysis baseline sociodemographic factors such as gender, age, and highest level of education and clinical factors such as anxiety, depression, suicidality, hallucinations, and primary diagnosis (affective or non-affective psychosis). RESULTS: Sex and education level were stable across cohorts, while patient age varied (p = 0.047). Clinical anxiety, depression, and suicidality at entry were also stable. Across cohorts, the proportion of patients with affective versus non-affective diagnosis differed (p = 0.050), with no differences in global rating of delusion severity or theme prevalence except for delusions of guilt or sin (p = 0.001). This single theme difference was not correlated with age or diagnosis. CONCLUSION: Our study suggests relatively stable prevalence of delusion themes across cohorts of individuals experiencing FEP. This demonstrates the potential utility of studying thematic content both for understanding delusions in clinical populations and in research. Future explorations of the relationships between delusion themes and across individual patient episodes should be conducted.

Trust of patients and families in mental healthcare providers and institutions: a cross-cultural study in Chennai, India, and Montreal, Canada.

PURPOSE: Cross-cultural psychosis research has typically focused on a limited number of outcomes (generally symptom-related). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to fundamental treatment processes like trust. Addressing this gap, we studied two similar first-episode psychosis programs in Montreal, Canada, and Chennai, India. We hypothesized higher trust in healthcare institutions and providers among patients and families in Chennai at baseline and over follow-up. METHODS: Upon treatment entry and at months 3, 12 and 24, trust in healthcare providers was measured using the Wake Forest Trust scale and trust in the healthcare and mental healthcare systems using two single items. Nonparametric tests were performed to compare trust levels across sites and mixed-effects linear regression models to investigate predictors of trust in healthcare providers. RESULTS: The study included 333 patients (Montreal = 165, Chennai = 168) and 324 family members (Montreal = 128, Chennai = 168). Across all timepoints, Chennai patients and families had higher trust in healthcare providers and the healthcare and mental healthcare systems. The effect of site on trust in healthcare providers was significant after controlling for sociodemographic characteristics known to impact trust. Patients' trust in doctors increased over follow-up. CONCLUSION: This study uniquely focuses on trust as an outcome in psychosis, via a comparative longitudinal analysis of different trust dimensions and predictors, across two geographical settings. The consistent differences in trust levels between sites may be attributable to local cultural values and institutional structures and processes and underpin cross-cultural variations in treatment engagement and outcomes.

Context and contact: a comparison of patient and family engagement with early intervention services for psychosis in India and Canada.

BACKGROUND: It is unknown whether patient disengagement from early intervention services for psychosis is as prevalent in low- and middle-income countries (LMICs) like India, as it is in high-income countries (HICs). Addressing this gap, we studied two first-episode psychosis programs in Montreal, Canada and Chennai, India. We hypothesized lower service disengagement among patients and higher engagement among families in Chennai, and that family engagement would mediate cross-site differences in patient disengagement. METHODS: Sites were compared on their 2-year patient disengagement and family engagement rates conducting time-to-event analyses and independent samples t tests on monthly contact data. Along with site and family involvement, Cox proportional hazards regression included known predictors of patient disengagement (e.g. gender). RESULTS: The study included data about 333 patients (165 in Montreal, 168 in Chennai) and their family members (156 in Montreal, 168 in Chennai). More Montreal patients (19%) disengaged before 24 months than Chennai patients (1%), χ2(1, N = 333) = 28.87, p < 0.001. Chennai families had more contact with clinicians throughout treatment (Cohen's d = -1.28). Family contact significantly predicted patient disengagement in Montreal (HR = 0.87, 95% CI 0.81-0.93). Unlike in Chennai, family contact declined over time in Montreal, with clinicians perceiving such contact as not necessary (Cohen's d = 1.73). CONCLUSIONS: This is the first investigation of early psychosis service engagement across a HIC and an LMIC. Patient and family engagement was strikingly higher in Chennai. Maintaining family contact may benefit patient engagement, irrespective of context. Findings also suggest that differential service utilization may underpin cross-cultural variations in psychosis outcomes.

Unfinished business: Functional outcomes in a randomized controlled trial of a three-year extension of early intervention versus regular care following two years of early intervention for psychosis.

OBJECTIVE: To investigate whether first-episode psychosis patients receiving extended early intervention had better functional outcomes than those in regular care and to examine the predictors of functional outcomes. METHODS: This is a randomized controlled single-blind trial of 220 patients randomized after 2 years of early intervention to receive early intervention or regular care for the subsequent 3 years. Outcomes included cumulative time in functional recovery during the 3-year trial assessed using the Social and Occupational Functioning Assessment Scale (SOFAS); and employment/education at last assessment which were, respectively, analyzed using multiple linear regression and logistic regression, accounting for well-known predictors. Linear mixed and generalized linear models were also used to examine the course of SOFAS and employment/education over the 3-year period. RESULTS: The extended early intervention and regular care groups did not differ on time in functional recovery (mean = 50.17 weeks, SD = 46.62 vs. mean = 46.18 weeks, SD = 51.54); percent employed/in school (60.4% vs. 68.8%) or change in SOFAS or employment/education status over time. SOFAS scores were stable between years 2 and 5. Individuals with longer periods of total symptom remission experienced significantly longer periods of functional recovery and were likelier to be employed/in school. Those who had completed high school were nine times likelier to be employed/studying. CONCLUSION: Most individuals maintained functional gains accrued from 2 years of early intervention with no further improvement whether in extended early intervention or regular care. There was a gap between symptomatic and functional recovery, and one-third were unemployed/not in school at year 5. The lack of additional progress even in extended early intervention suggests that specific interventions addressing functional roles need to be provided beyond the first 2 years of early intervention. Sustaining symptom remission and high-school completion may be additional avenues for targeting functional recovery.

Demographic and Clinical Presentations of Youth using Enhanced Mental Health Services in Six Indigenous Communities from the ACCESS Open Minds Network.

OBJECTIVE: In many Indigenous communities, youth mental health services are inadequate. Six Indigenous communities participating in the ACCESS Open Minds (AOM) network implemented strategies to transform their youth mental health services. This report documents the demographic and clinical presentations of youth accessing AOM services at these Indigenous sites. METHODS: Four First Nations and two Inuit communities contributed to this study. Youth presenting for mental health services responded to a customized sociodemographic questionnaire and presenting concerns checklist, and scales assessing distress, self-rated health and mental health, and suicidal thoughts and behaviors. RESULTS: Combined data from the First Nations sites indicated that youth across the range of 11-29 years accessed services. More girls/women than boys/men accessed services; 17% identified as LBGTQ+. Most (83%) youth indicated having access to at least one reliable adult and getting along well with the people living with them. Twenty-five percent of youth reported difficulty meeting basic expenses. Kessler (K10) distress scores indicated that half likely had a moderate mental health problem and a fourth had severe problems. Fifty-five percent of youth rated their mental health as fair or poor, while 50% reported suicidal thoughts in the last month. Anxiety, stress, depression and sleep issues were the most common presenting problems. Fifty-one percent of youth either accessed services themselves or were referred by family members. AOM was the first mental health service accessed that year for 68% of youth. CONCLUSIONS: This report is the first to present a demographic and clinical portrait of youth presenting at mental health services in multiple Indigenous settings in Canada. It illustrates the acceptability and feasibility of transforming youth mental health services using core principles tailored to meet communities' unique needs, resources, and cultures, and evaluating these using a common protocol. Data obtained can be valuable in evaluating services and guiding future service design. Trial registration name and number at Clinicaltrials.gov: ACCESS Open Minds/ACCESS Esprits ouverts, ISRCTN23349893.

An observational study of antipsychotic medication discontinuation in first-episode psychosis: clinical and functional outcomes.

PURPOSE: To study the impact of supervised antipsychotic medication discontinuation on clinical and functional outcomes in first-episode psychosis (FEP) in two different cultural environments. METHOD: FEP patients(N = 253), treated in two early intervention services (Montreal, Canada and Chennai, India) for 2 years, were assessed for medication use, positive and negative symptom remission and social-occupational functioning at regular intervals. RESULTS: Between months 4 and 24 of treatment, 107 patients discontinued medication ('Off'group) as compared to 146 who stayed on medication ('On'group). Medication discontinuation was higher in Chennai as compared to Montreal (n = 80, 49.07% vs n = 27, 16.87%; χ2 37.80, p < 0.001), with no difference in time to discontinuation [Means(SDs) = 10.64(6.82) and 10.04(5.43), respectively, p = 0.71). At month 24 (N = 235), there were no differences in the rate of positive symptom remission between the on and Off groups (81.5 vs 88.0%, respectively) at both sites. The rate of negative symptom remission was lower among patients in the On compared to the Off group (63.2 vs 87.9%, respectively, χ2 = 17.91, p < 0.001), but only in Montreal (55.4% vs 80.0%, respectively, χ2 = 4.12, p < 0.05). Social and Occupational Functioning Assessment Scale scores were equally high in both Off and On medication groups in Chennai [Means (SDs) = 79.43(12.95) and 73.59(17.63), respectively] but higher in the Off compared to the On group in Montreal Means (SDs) = 77.47(14.97) and 64.94(19.02), respectively; Time × site interaction F = 3.96(1,217), p < 0.05]. Medication status (On-Off) had no impact on the outcomes, independent of other variables known to influence outcomes. CONCLUSION: Certain cultural environments and patient characteristics may facilitate supervised discontinuation of antipsychotic medication following treatment of an FEP without negative consequences.

Delusional content at initial presentation to a catchment-based early intervention service for psychosis.

BACKGROUND: During a psychotic episode, patients frequently suffer from severe maladaptive beliefs known as delusions. Despite the abundant literature investigating the simple presence or absence of these beliefs, there exists little detailed knowledge regarding their actual content and severity at the onset of illness. AIMS: This study reports on delusions during the initiation of indicated treatment for first-episode psychosis (FEP). METHOD: Data were systematically collected from a sample of 636 patients entering a catchment-based early intervention service for FEP. The average severity and frequency of each delusional theme at baseline was reported with the Scale for the Assessment of Positive Symptoms. Delusional severity (globally and per theme) was examined across a number of sociodemographic and clinical variables. RESULTS: Delusions were present in the vast majority of individuals experiencing onset of FEP (94%), with persecutory (77.7%) being the most common theme. Persecutory delusions remained consistent in severity across diagnoses, but were more severe with older age at onset of FEP. No meaningful differences in delusional severity were observed across gender, affective versus non-affective psychosis, or presence/absence of substance use disorder. Globally, delusion severity was associated with anxiety, but not depression. Delusions commonly referred to as passivity experiences were related to hallucinatory experiences. CONCLUSIONS: This community sample offers a rare clinical lens into the severity and content of delusions in FEP. Although delusional severity was consistent across certain sociodemographic and clinical variables, this was not always the case. Future research should now consider the course of delusion themes over time.

The reality of at risk mental state services: a response to recent criticisms.

BACKGROUND: In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. Recently Psychological Medicine published two articles that criticise these services and suggest that they should be dismantled or restructured. One paper also provides recommendations on how ARMS services should be operate. METHODS: In this paper we draw on the existing literature in the field and present the perspective of some ARMS clinicians and researchers. RESULTS: Many of the critics' arguments are refuted. Most of the recommendations included in the Moritz et al. paper are already occurring. CONCLUSIONS: ARMS services provide management of current problems, treatment to reduce risk of onset of psychotic disorder and monitoring of mental state, including attenuated psychotic symptoms. These symptoms are associated with a range of poor outcomes. It is important to assess them and track their trajectory over time. A new approach to detection of ARMS individuals can be considered that harnesses broad youth mental health services, such as headspace in Australia, Jigsaw in Ireland and ACCESS Open Minds in Canada. Attention should also be paid to the physical health of ARMS individuals. Far from needing to be dismantled we feel that the ARMS approach has much to offer to improve the health of young people.

Understanding Components of Duration of Untreated Psychosis and Relevance for Early Intervention Services in the Canadian Context: Comprendre les Composantes de la Durée de la Psychose Non Traitée et la Pertinence de Services D'intervention Précoce Dans le Contexte Canadien.

BACKGROUND: Clinical, functional, and cost-effectiveness outcomes from early intervention services (EIS) for psychosis are significantly associated with the duration of untreated psychosis (DUP) for the patients they serve. However, most EIS patients continue to report long DUP, while a reduction of DUP may improve outcomes. An understanding of different components of DUP and the factors associated with them may assist in targeting interventions toward specific sources of DUP. OBJECTIVES: To examine the components of DUP and their respective determinants in order to inform strategies for reducing delay in treatment in the context of an EIS. METHODS: Help-seeking (DUP-H), Referral (DUP-R), and Administrative (DUP-A) components of DUP, pathways to care, and patient characteristics were assessed in first episode psychosis (N = 532) patients entering an EIS that focuses on systemic interventions to promote rapid access. Determinants of each component were identified in the present sample using multivariate analyses. RESULTS: DUP-H (mean 25.64 ± 59.00) was longer than DUP-R (mean = 14.95 ± 45.67) and DUP-A (mean 1.48 ± 2.55). Multivariate analyses showed that DUP-H is modestly influenced by patient characteristics (diagnosis and premorbid adjustment; R2 = 0.12) and DUP-R by a combination of personal characteristics (age of onset and education) and systemic factors (first health services contact and final source of referral; R2 = 0.21). Comorbid substance abuse and referral from hospital emergency services have a modest influence on DUP-A (R2 = 0.08). Patients with health care contact prior to onset of psychosis had a shorter DUP-H and DUP-R than those whose first contact was after psychosis onset (F(1, 498) = 4.85, P < 0.03 and F(1, 492) = 3.34, P < 0.07). CONCLUSIONS: Although much of the variance in DUP is unexplained, especially for help-seeking component, the systemic portion of DUP may be partially determined by relatively malleable factors. Interventions directed at altering pathways to care and promote rapid access may be important targets for reducing DUP. Simplifying administrative procedures may further assist in reducing DUP.

Suicidality Over the First 5 Years of Psychosis: Does Extending Early Intervention Have Benefits?

OBJECTIVE: We aimed to investigate whether individuals with first-episode psychosis (FEP) receiving extended early intervention (EI) were less likely to experience suicidal ideation and behaviors than those transferred to regular care after 2 years of EI. Another objective was to examine the 5-year course of suicidality in FEP. METHODS: We conducted a secondary analysis of a randomized controlled trial where 220 patients were randomized after 2 years of EI to receive extended EI or regular care for the subsequent 3 years. Suicidality was rated using the Brief Psychiatric Rating Scale. Linear mixed model analysis was used to study time and group effects on suicidality. RESULTS: Extended EI and regular care groups did not differ on suicidality. There was a small decrease in suicidality over time, F(7, 1038) = 1.84, P = 0.077, with an immediate sharp decline within a month of treatment, followed by stability over the remaining 5 years. Patients who endorsed suicidality at entry (46.6%) had higher baseline positive, negative, and depressive symptoms. The 5-year course fell in 3 groups: never endorsed suicidality (33.9%), endorsed suicidality at low-risk levels (43.1%), and endorsed high-risk levels (23.0%). The high-risk group had a higher proportion of affective versus nonaffective psychosis diagnosis; higher baseline positive and depressive symptoms; higher 5-year mean depression scores, and fewer weeks of positive symptom remission over the 5-year course. CONCLUSIONS: The first month of treatment is a critical period for suicide risk in FEP. Although early reductions in suicidality are often maintained, our findings make the case for sustained monitoring for suicide risk management.

Altered hippocampal centrality and dynamic anatomical covariance of intracortical microstructure in first episode psychosis.

Hippocampal circuitry has been posited to be fundamental to positive symptoms in psychosis, but its contributions to other factors important for outcome remains unclear. We hypothesized that longitudinal changes in the hippocampal circuit and concomitant changes of intracortical microstructure are altered in first episode psychosis (FEP) patients and that such changes are associated with negative symptoms and verbal memory. Longitudinal brain scans (2-4 visits over 3-15 months) were acquired for 27 FEP and 29 age- and sex-matched healthy controls. Quantitative T1 maps, sensitive to myelin content, were used to sample the microstructure of the hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies), and intracortical regions. Dynamic anatomical covariance in pair-wise regional trajectories were assessed for each subject, and graph theory was used to calculate a participation coefficient metric that quantifies the similarity/divergence between hippocampal and intracortical microstructure. The mean participation coefficient of the hippocampus was significantly reduced in FEP patients compared with controls, reflecting differences in output hippocampal regions. Importantly, lower participation coefficient of the hippocampal circuit was associated with worse negative symptoms, a relationship that was mediated by changes in verbal memory. This study provides evidence for reduced hippocampal centrality in FEP and concomitant changes in intracortical anatomy. Myelin-rich output regions of the hippocampus may be an important biological trigger in early psychosis, with cascading effects on broader cortical networks and resultant clinical profiles.

Comparison of clinical outcomes following 2 years of treatment of first-episode psychosis in urban early intervention services in Canada and India.

BACKGROUND: Purported superior outcomes for treatment of psychosis in low- and middle-income (LMICs) compared with high-income (HICs) countries have not been examined in the context of early intervention services (EIS). AIMS: To compare 2-year clinical outcomes in first-episode psychosis (FEP) treated in EIS in Chennai (LMIC) and Montreal (HIC) using a similar EIS treatment protocol and to identify factors associated with any outcome differences. METHOD: Patients with FEP treated in EIS in Chennai (n = 168) and Montreal (n = 165) were compared on change in level of symptoms and rate and duration of positive and negative symptom remission over a 2-year period. Repeated-measures analysis of variance, and logistic and linear regression analyses were conducted. RESULTS: Four patients died in Chennai compared with none in Montreal. Family support was higher for Chennai patients (F = 14.05, d.f. = 1, P < 0.001, ƞp2 = 0.061) and increased over time at both sites (F = 7.0, d.f. = 1.915, P < 0.001, ƞp2 = 0.03). Negative symptom outcomes were significantly better in Chennai for level of symptoms (time × site interaction F = 7.36, d.f. = 1.49, P = 0.002, ƞp2 = 0.03), duration of remission (mean 16.1 v. 9.78 months, t = -7.35, d.f. = 331, P < 0.001, Cohen's d = 0.80) and the proportion of patients in remission (81.5% v. 60.3%, χ2 = 16.12, d.f. = 1, P < 0.001). The site differences in outcome remained robust after adjusting for inter-site differences in other characteristics. Early remission and family support facilitated better outcome on negative symptoms. No significant differences were observed in positive symptom outcomes. CONCLUSIONS: Patients with FEP treated in EIS in LMIC contexts are likely to show better outcome on negative symptoms compared with those in HIC contexts. Early remission and family support may benefit patients across both contexts.