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.

Intersection of verbal memory and expressivity on cortical contrast and thickness in first episode psychosis.

BACKGROUND: Longitudinal studies of first episode of psychosis (FEP) patients are critical to understanding the dynamic clinical factors influencing functional outcomes; negative symptoms and verbal memory (VM) deficits are two such factors that remain a therapeutic challenge. This study uses white-gray matter contrast at the inner edge of the cortex, in addition to cortical thickness, to probe changes in microstructure and their relation with negative symptoms and possible intersections with verbal memory. METHODS: T1-weighted images and clinical data were collected longitudinally for patients (N = 88) over a two-year period. Cognitive data were also collected at baseline. Relationships between baseline VM (immediate/delayed recall) and rate of change in two negative symptom dimensions, amotivation and expressivity, were assessed at the behavioral level, as well as at the level of brain structure. RESULTS: VM, particularly immediate recall, was significantly and positively associated with a steeper rate of expressivity symptom decline (r = 0.32, q = 0.012). Significant interaction effects between baseline delayed recall and change in expressivity were uncovered in somatomotor regions bilaterally for both white-gray matter contrast and cortical thickness. Furthermore, interaction effects between immediate recall and change in expressivity on cortical thickness rates were uncovered across higher-order regions of the language processing network. CONCLUSIONS: This study shows common neural correlates of language-related brain areas underlying expressivity and VM in FEP, suggesting deficits in these domains may be more linked to speech production rather than general cognitive capacity. Together, white-gray matter contrast and cortical thickness may optimally inform clinical investigations aiming to capture peri-cortical microstructural changes.

Structural Associations of Cortical Contrast and Thickness in First Episode Psychosis.

There is growing evidence that psychosis is characterized by brain network abnormalities. Analyzing morphological abnormalities with T1-weighted structural MRI may be limited in discovering the extent of deviations in cortical associations. We assess whether structural associations of either cortical white-gray contrast (WGC) or cortical thickness (CT) allow for a better understanding of brain structural relationships in first episode of psychosis (FEP) patients. Principal component and structural covariance analyses were applied to WGC and CT derived from T1-weighted MRI for 116 patients and 88 controls, to explore sets of brain regions that showed group differences, and associations with symptom severity and cognitive ability in patients. We focused on 2 principal components: one encompassed primary somatomotor regions, which showed trend-like group differences in WGC, and the second included heteromodal cortices. Patients' component scores were related to general psychopathology for WGC, but not CT. Structural covariance analyses with WGC revealed group differences in pairwise correlations across widespread brain regions, mirroring areas derived from PCA. More group differences were uncovered with WGC compared with CT. WGC holds potential as a proxy measure of myelin from commonly acquired T1-weighted MRI and may be sensitive in detecting systems-level aberrations in early psychosis, and relationships with clinical/cognitive profiles.

A minimum evaluation protocol and stepped-wedge cluster randomized trial of ACCESS Open Minds, a large Canadian youth mental health services transformation project.

BACKGROUND: Many Canadian adolescents and young adults with mental health problems face delayed detection, long waiting lists, poorly accessible services, care of inconsistent quality and abrupt or absent inter-service transitions. To address these issues, ACCESS Open Minds, a multi-stakeholder network, is implementing and systematically evaluating a transformation of mental health services for youth aged 11 to 25 at 14 sites across Canada. The transformation plan has five key foci: early identification, rapid access, appropriate care, the elimination of age-based transitions between services, and the engagement of youth and families. METHODS: The ACCESS Open Minds Research Protocol has multiple components including a minimum evaluation protocol and a stepped-wedge cluster randomized trial, that are detailed in this paper. Additional components include qualitative methods and cost-effectiveness analyses. The services transformation is being evaluated at all sites via a minimum evaluation protocol. Six sites are participating in the stepped-wedge trial whereby the intervention (a service transformation along the key foci) was rolled out in three waves, each commencing six months apart. Two sites, one high-population and one low-population, were randomly assigned to each of the three waves, i.e., randomization was stratified by population size. Our primary hypotheses pertain to increased referral numbers, and reduced wait times to initial assessment and to the commencement of appropriate care. Secondary hypotheses pertain to simplified pathways to care; improved clinical, functional and subjective outcomes; and increased satisfaction among youth and families. Quantitative measures addressing these hypotheses are being used to determine the effectiveness of the intervention. DISCUSSION: Data from our overall research strategy will help test the effectiveness of the ACCESS Open Minds transformation, refine it further, and inform its scale-up. The process by which our research strategy was developed has implications for the practice of research itself in that it highlights the need to actively engage all stakeholder groups and address unique considerations in designing evaluations of complex healthcare interventions in multiple, diverse contexts. Our approach will generate both concrete evidence and nuanced insights, including about the challenges of conducting research in real-world settings. More such innovative approaches are needed to advance youth mental health services research. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, ISRCTN23349893 (Retrospectively registered: 16/02/2017).

"Everyone Has a Role": Perspectives of Service Users With First-Episode Psychosis, Family Caregivers, Treatment Providers, and Policymakers on Responsibility for Supporting Individuals With Mental Health Problems.

Varying perceptions of who should be responsible for supporting individuals with mental health problems may contribute to their needs remaining unmet. A qualitative descriptive design was used to explore these perceptions among key stakeholders. Focus groups were conducted with 13 service users, 12 family members, and 18 treatment providers from an early psychosis intervention program in Montreal, Canada. Individual interviews were conducted with six mental health policy-/decision-makers. Participants across stakeholder groups assigned a range of responsibilities to individuals with mental health problems, stakeholders in these individuals' immediate and extended social networks (e.g., families), macro-level stakeholders with influence (e.g., government), and society as a whole. Perceived failings of the health care system and the need for greater sharing of roles and responsibilities also emerged as important themes. Our findings suggest that different stakeholders should collectively assume certain responsibilities and that systems-level failings may contribute to unmet needs for mental health support.

Evaluating accuracy of striatal, pallidal, and thalamic segmentation methods: Comparing automated approaches to manual delineation.

Accurate automated quantification of subcortical structures is a greatly pursued endeavour in neuroimaging. In an effort to establish the validity and reliability of these methods in defining the striatum, globus pallidus, and thalamus, we investigated differences in volumetry between manual delineation and automated segmentations derived by widely used FreeSurfer and FSL packages, and a more recent segmentation method, the MAGeT-Brain algorithm. In a first set of experiments, the basal ganglia and thalamus of thirty subjects (15 first episode psychosis [FEP], 15 controls) were manually defined and compared to the labels generated by the three automated methods. Our results suggest that all methods overestimate volumes compared to the manually derived "gold standard", with the least pronounced differences produced using MAGeT. The least between-method variability was noted for the striatum, whereas marked differences between manual segmentation and MAGeT compared to FreeSurfer and FSL emerged for the globus pallidus and thalamus. Correlations between manual segmentation and automated methods were strongest for MAGeT (range: 0.51 to 0.92; p<0.01, corrected), whereas FreeSurfer and FSL showed moderate to strong Pearson correlations (range 0.44-0.86; p<0.05, corrected), with the exception of FreeSurfer pallidal (r=0.31, p=0.10) and FSL thalamic segmentations (r=0.37, p=0.051). Bland-Altman plots highlighted a tendency for greater volumetric differences between manual labels and automated methods at the lower end of the distribution (i.e. smaller structures), which was most prominent for bilateral thalamus across automated pipelines, and left globus pallidus for FSL. We then went on to examine volume and shape of the basal ganglia structures using automated techniques in 135 FEP patients and 88 controls. The striatum and globus pallidus were significantly larger in FEP patients compared to controls bilaterally, irrespective of the method used. MAGeT-Brain was more sensitive to shape-based group differences, and uncovered widespread surface expansions in the striatum and globus pallidus bilaterally in FEP patients compared to controls, and surface contractions in bilateral thalamus (FDR-corrected). By contrast, after using a recommended cluster-wise thresholding method, FSL only detected differences in the right ventral striatum (FEP>Control) and one cluster of the left thalamus (Control>FEP). These results suggest that different automated pipelines segment subcortical structures with varying degrees of variability compared to manual methods, with particularly pronounced differences found with FreeSurfer and FSL for the globus pallidus and thalamus.

[Early intervention in psychosis: concepts, current knowledge and future directions]. / Intervention précoce pour la psychose : concepts, connaissances actuelles et orientations futures.

OBJECTIVES: This paper seeks to provide an overview of the motives, rationale, theoretical underpinnings and foundational literature of the early intervention movement for psychoses. It also seeks to review the current status of the field, highlight its significant developments and identify its emergent trends. METHODS: This paper begins by contextualizing the burden of psychosis. It then traces the origins of the early intervention movement and surveys the seminal literature that established and shapes the field. It describes the movement's characteristic elements, types, approaches, strengths, criticisms and trajectories in select Western nations. It closes with a presentation of how the early intervention movement is informing broader endeavours to transform youth mental health. RESULTS: We find that the early intervention movement is predicated on the critical period hypothesis that emphasizes the significance of the early stages of the illness; and on findings that the duration of untreated psychosis influences prognoses. Early intervention redresses this situation by facilitating access to specialized, phase-specific treatment. Access is enhanced through open referral, fast response times, and public and practitioner education. Ideally, the intervention, provided for the first two years after detection, features intensive case management; low-dose antipsychotic medication; an emphasis on social functioning; family intervention; early attention to comorbid concerns; and due regard for the needs and priorities of youth and their families. Evidence suggests that specialized early intervention yields better outcomes than routine care. The cost-effectiveness of such services has not yet been definitely investigated. Criticisms of early intervention pertain to the quality of evidence for, the manner of implementation of, the allocation of resources to early intervention and its utility for persons at high risk for developing psychosis. We also identify advocacy within the field for extending early intervention to the first five years of the course of psychosis. CONCLUSION: We conclude that the status of the early intervention movement (in terms of availability and policy) in Western public healthcare systems can be resolved into a spectrum. The United Kingdom is shown to be the leader while Canada appears at the middle of the spectrum (with the United States bringing up the rear). In the Quebec context, the picture is found to be mixed and recommendations for further research and investment are made. Finally, an examination is undertaken of how the early intervention for psychosis movement has provided the impetus for and dovetails into the larger effort to transform youth mental healthcare in general, a development that is in its nascent stages in Canada.

Determinants of negative pathways to care and their impact on service disengagement in first-episode psychosis.

PURPOSE: Although there have been numerous studies on pathways to care in first-episode psychosis (FEP), few have examined the determinants of the pathway to care and its impact on subsequent engagement with mental health services. METHODS: Using a sample of 324 FEP patients from a catchment area-based early intervention (EI) program in Montréal, we estimated the association of several socio-demographic, clinical, and service-level factors with negative pathways to care and treatment delay. We also assessed the impact of the pathway to care on time to disengagement from EI services. RESULTS: Few socio-demographic or clinical factors were predictive of negative pathways to care. Rather, service-level factors, such as contact with primary care providers, have a stronger impact on patterns of health service use across multiple indicators. Patients who were in contact with primary care had a reduced likelihood of negative pathways to care, but also had longer referral delays to EI services. Socio-demographic and clinical factors were more relevant for predicting subsequent engagement with EI services, and indicators of negative pathways to care were not associated with service disengagement. CONCLUSIONS: Primary care providers may be an efficacious target for interventions aimed at reducing overall treatment delay. Increasing the uptake of primary care services may also reduce the likelihood of negative pathways to care. Our findings draw attention to the need for further investigations of the role that the primary care system plays in early intervention for FEP, and strategies for supporting service providers in this role.

"There are too many steps before you get to where you need to be": help-seeking by patients with first-episode psychosis.

BACKGROUND: There has been substantial research on pathways to care in first-episode psychosis (FEP); however, few studies have used a qualitative research paradigm or have been done from the perspective of the person experiencing the psychotic episode. OBJECTIVE: We sought to describe the experiences of patients with FEP on their pathway to care and to identify factors that help or hinder help-seeking efforts. METHODS: Using a qualitative descriptive approach, we conducted semi-structured interviews with 16 patients recruited from an early intervention program. Data were analyzed using content analysis to organize the findings into themes. FINDINGS: Self-stigma and a pervasive lack of knowledge regarding the symptoms of psychosis and availability of services were barriers to help-seeking. Participants highlighted the crucial role of significant others in initiating the help-seeking process. Participants typically described a complex series of contacts along the pathway to care which resulted in feelings of being misunderstood and losing control, but many individuals identified unexpected benefits of their experience. CONCLUSIONS: Our findings suggest a shift in the philosophy and orientation of service delivery towards the creation of services that address these concerns and are relevant to the young people who utilize them.

Severe childhood trauma and emotion recognition in males and females with first-episode psychosis.

AIM: Childhood trauma increases social functioning deficits in first-episode psychosis (FEP) and is negatively associated with higher-order social cognitive processes such as emotion recognition (ER). We investigated the relationship between childhood trauma severity and ER capacity, and explored sex as a potential factor given sex differences in childhood trauma exposure. METHODS: Eighty-three FEP participants (52 males, 31 females) and 69 nonclinical controls (49 males, 20 females) completed the CogState Research Battery. FEP participants completed the Childhood Trauma Questionnaire. A sex × group (FEP, controls) ANOVA examined ER differences and was followed by two-way ANCOVAs investigating sex and childhood trauma severity (none, low, moderate, and severe) on ER and global cognition in FEP. RESULTS: FEP participants had significantly lower ER scores than controls (p = .035). No significant sex × group interaction emerged for ER F(3, 147) = .496, p = .438 [95% CI = -1.20-0.57], partial η2  = .003. When controlling for age at psychosis onset, a significant interaction emerged in FEP between sex and childhood trauma severity F(3, 71) = 3.173, p = .029, partial η2  = .118. Males (n = 9) with severe trauma showed ER deficits compared to females (n = 8) (p = .011 [95% CI = -2.90 to -0.39]). No significant interaction was observed for global cognition F(3, 69) = 2.410, p = .074, partial η2  = .095. CONCLUSIONS: These preliminary findings provide support for longitudinal investigations examining whether trauma severity differentially impacts ER in males and females with FEP.

Transsyndromic trajectories from pre-onset self-harm and subthreshold psychosis to the first episode of psychosis: A longitudinal study.

Across subthreshold psychotic and nonpsychotic syndromes, symptoms experienced before the onset of a first episode of psychosis (FEP) may index distinct illness trajectories. We aimed to examine the associations between three types of pre-onset symptoms (self-harm, suicide attempts, and subthreshold psychotic) and outcome trajectories during FEP. Participants with FEP were recruited from PEPP-Montreal, a catchment-based early intervention service. Pre-onset symptoms were systematically assessed through interviews with participants (and their relatives) and reviews of health and social records. Over 2 years of follow-up at PEPP-Montreal, 3-8 repeated measures were collected for positive, negative, depressive, and anxiety symptoms, as well as functioning. We applied linear mixed models to examine associations between pre-onset symptoms and outcome trajectories. We found that on average over follow-up, participants with pre-onset self-harm had more severe positive, depressive, and anxiety symptoms compared with other participants (standardized mean differences: 0.32-0.76), while differences in negative symptoms and functioning were not significant. Associations did not differ by gender and remained similar after adjusting for the duration of untreated psychosis, substance use disorder, or baseline diagnosis of affective psychosis. Over time, depressive and anxiety symptoms improved among individuals with pre-onset self-harm, such that they converged with other individuals by the end of the follow-up. Similarly, pre-onset suicide attempts were associated with elevated depressive symptoms that improved over time. Pre-onset subthreshold psychotic symptoms were not associated with outcomes, except for a slightly different trajectory of functioning. Individuals with pre-onset self-harm or suicide attempts may benefit from early interventions that target their transsyndromic trajectories. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Combinations and Temporal Associations Among Precursor Symptoms Before a First Episode of Psychosis.

BACKGROUND AND HYPOTHESIS: Symptoms that precede a first episode of psychosis (FEP) can ideally be targeted by early intervention services with the aim of preventing or delaying psychosis onset. However, these precursor symptoms emerge in combinations and sequences that do not rest fully within traditional diagnostic categories. To advance our understanding of illness trajectories preceding FEP, we aimed to investigate combinations and temporal associations among precursor symptoms. STUDY DESIGN: Participants were from PEPP-Montréal, a catchment-based early intervention program for FEP. Through semistructured interviews, collateral from relatives, and a review of health and social records, we retrospectively measured the presence or absence of 29 precursor symptoms, including 9 subthreshold psychotic and 20 nonpsychotic symptoms. Sequences of symptoms were derived from the timing of the first precursor symptom relative to the onset of FEP. STUDY RESULTS: The sample included 390 participants (68% men; age range: 14-35 years). Combinations of precursor symptoms most frequently featured depression, anxiety, and substance use. Of 256 possible pairs of initial and subsequent precursor symptoms, many had asymmetrical associations: eg, when the first symptom was suspiciousness, the incidence rate ratio (IRR) of subsequent anxiety was 3.40 (95% confidence interval [CI]: 1.79, 6.46), but when the first symptom was anxiety, the IRR of subsequent suspiciousness was 1.15 (95% CI: 0.77, 1.73). CONCLUSIONS: A detailed examination of precursor symptoms reveals diverse clinical profiles that cut across diagnostic categories and evolve longitudinally prior to FEP. Their identification may contribute to risk assessments and provide insights into the mechanisms of illness progression.

Predictors of treatment attrition of cognitive health interventions in first episode psychosis.

AIM: Dropping out of psychological interventions is estimated to occur in up to a third of individuals with psychosis. Given the high degree of attrition in this population, identifying predictors of attrition is important to develop strategies to retain individuals in treatment. We observed a particularly high degree of attrition (48%) in a recent randomized controlled study assessing cognitive health interventions for first-episode psychosis participants with comorbid social anxiety. Due to the importance of developing interventions for social anxiety in first episode psychosis, the aim of the present study was to identify putative predictors of attrition through a secondary analysis of data. METHODS: Participants (n = 96) with first episode psychosis and comorbid social anxiety were randomized to receive cognitive behavioural therapy for social anxiety or cognitive remediation. Differences between completers and non-completers (<50% intervention completed) were compared using t-tests or chi-square analyses; statistically significant variables were entered into a multivariate logistic regression model. RESULTS: Non-completers tended to be younger, had fewer years of education and had lower levels of social anxiety compared to completers. Lower baseline social anxiety and younger age were statistically significant predictors of non-completion in the logistic regression model. CONCLUSIONS: Age and social anxiety were predictors of attrition in cognitive health interventions in first episode psychosis populations with comorbid social anxiety. In the ongoing development of social anxiety interventions for this population, future studies should investigate specific engagement strategies, intervention formats and outcome monitoring to improve participant retention in treatment.

Return on investment from service transformation for young people experiencing mental health problems: Approach to economic evaluations in ACCESS Open Minds (Esprits ouverts), a multi-site pan-Canadian youth mental health project.

Introduction: Mental health problems are common globally, and typically have their onset in adolescence and early adulthood-making youth (aged 11-25) an optimal target for prevention and early intervention efforts. While increasing numbers of youth mental health (YMH) initiatives are now underway, thus far few have been subject to economic evaluations. Here we describe an approach to determining the return on investment of YMH service transformation via the pan-Canadian ACCESS Open Minds (AOM) project, for which a key focus is on improving access to mental health care and reducing unmet need in community settings. Approach: As a complex intervention package, it is hoped that the AOM transformation will: (i) enable early intervention through accessible, community-based services; (ii) shift care away toward these primary/community settings and away from acute hospital and emergency services; and (iii) offset at least some of the increased costs of primary care/community-based mental health services with reductions in the volume of more resource-intensive acute, emergency, hospital or specialist services utilized. Co-designed with three diverse sites that represent different Canadian contexts, a return on investment analysis will (separately at each site) compare the costs generated by the intervention, including volumes and expenditures associated with the AOM service transformation and any contemporaneous changes in acute, emergency, hospital or service utilization (vs. historical or parallel comparators). Available data from health system partners are being mobilized to assess these hypotheses. Anticipated results: Across urban, semi-urban and Indigenous sites, the additional costs of the AOM transformation and its implementation in community settings are expected to be at least partially offset by a reduction in the need for acute, emergency, hospital or specialist care. Discussion: Complex interventions such as AOM aim to shift care "upstream": away from acute, emergency, hospital and specialist services and toward community-based programming which is more easily accessible, often more appropriate for early-stage presentations, and more resource-efficient. Carrying out economic evaluations of such interventions is challenging given the constraints of available data and health system organization. Nonetheless, such analyses can advance knowledge, strengthen stakeholder engagement, and further implementation of this public health priority.

Functional magnetic resonance imaging correlates of memory encoding in relation to achieving remission in first-episode schizophrenia.

BACKGROUND: Previous studies in schizophrenia have shown a strong relationship between memory deficits and a poor clinical outcome. However, no previous study has identified the functional neural correlates of memory encoding in relation to remission. AIMS: To determine whether functional magnetic resonance imaging (fMRI) activation patterns differed between individuals that later achieved remission v. those who did not. METHOD: Forty-two participants with first-episode schizophrenia were divided into two groups after 1 year of treatment as per the 2005 remission in schizophrenia consensus definition. We then examined fMRI activation using three contrasts (associative v. item-oriented strategy, semantically unrelated v. related image pairs, and successful v. unsuccessful memory encoding) among 15 participants who had achieved remission (remitted group), 27 who had not (non-remitted group) and 31 healthy controls (control group). RESULTS: Participants in the non-remitted group displayed a positive activation in the posterior cingulate compared with those in the remitted group when encoding related images; no significant differences between the two groups were identified for the other contrasts. From the behavioural data, compared with the remitted and control groups, the non-remitted group demonstrated an inability to encode related images and displayed worse recognition memory overall. CONCLUSIONS: This is the first study to identify differential neural activation between individuals with first-episode schizophrenia that later achieved remission v. those who did not. The behavioural and functional results together add to the growing evidence relating a poor clinical outcome in schizophrenia to memory-related deficits.

Case manager- and patient-rated alliance as a predictor of medication adherence in first-episode psychosis.

OBJECTIVE: The objective of this study was to evaluate the association between adherence to antipsychotic medication and working alliance (WA) ratings as reported separately by case manager (CM) and patient in first-episode psychosis (FEP) and to identify whether other factors previously related to adherence influence this relationship. METHODS: Adherence was evaluated every month in 81 participants who met criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, psychotic disorder (affective or nonaffective) and were treated in a specialized early intervention program. Adherence was measured, taking into account information from patient and clinician reports and pill counting. The WA, as assessed by both CM and patient, was assessed using the Working Alliance Inventory. RESULTS: The WA was stable during the course of the study as rated by both patient and CM. The "task" domain of WA was the subdomain most significantly correlated to adherence in cross-sectional analysis. The WA as measured by CM at study baseline was a significant predictor of the number of subsequent months with "good" adherence independently of other variables, including adherence at treatment onset (ß = 0.011; P = 0.020; 95% confidence interval, 0.002-0.020). However, the WA as measured by patients was not similarly predictive of subsequent adherence (ß = 0.003; P = 0.31; 95% confidence interval, -0.003 to 0.010). CONCLUSIONS: The CM-rated WA is a significant predictor of future medication adherence in FEP, suggesting that good alliance can improve adherence in this population.

Neural markers of early remission in first-episode schizophrenia: a volumetric neuroimaging study of the parahippocampus.

Using voxel-based morphometry (VBM), our laboratory recently identified significantly lower grey matter concentration in the parahippocampal gyrus bilaterally in non-remitted patients with a first episode of psychosis (FEP) compared with remitted FEP patients. These results identified a localized difference but did not reveal which cortex (entorhinal, perirhinal, or parahippocampal), if any, was predominantly affected. So, the parahippocampal gyrus was manually segmented and grey matter volumes from the three cortices were compared between 42 non-remitted and 17 remitted patients with a first episode of schizophrenia (FES). Remission was defined as mild or less on eight key symptoms and maintained for 6 consecutive months following the 2005 consensus definition. The non-remitted patients displayed smaller volumes in the parahippocampal cortex - trend-level difference on the left [mm(3), mean (S.D.): non-remitted=2486 (413); remitted=2775 (593)] and significant difference on the right [mm(3), mean (S.D.): non-remitted=2546 (463); remitted=2926 (525)]. No notable differences were found in the entorhinal or perirhinal cortices. This result supported our VBM finding of reduced parahippocampal grey matter bilaterally in non-remitted patients and further suggested differences may be selectively limited to the parahippocampal cortex. A smaller parahippocampal cortex may represent a neural marker in FES patients who do not achieve remission after 1 year of treatment.

Identifying persistent negative symptoms in first episode psychosis.

BACKGROUND: Although persistent negative symptoms (PNS) are known to contribute significantly to poor functional outcome, they remain poorly understood. We examined the heuristic value of various PNS definitions and their respective prevalence in patients with first episode psychosis (FEP). We also contrasted those definitions to the Proxy for the Deficit Syndrome (PDS) to identify deficit syndrome (DS) in the same FEP cohort. METHODS: One hundred and fifty-eight FEP patients were separated into PNS and non-PNS groups based on ratings from the Scale for Assessment of Negative Symptoms (SANS). PNS was defined in the following ways: 1) having a score of 3 or greater on at least 1 global subscale of the SANS (PNS_1); 2) having a score of 3 or more on at least 2 global subscales of the SANS (PNS_2); and 3) having a score of 3 or more on a combination of specific SANS subscales and items (PNS_H). For all three definitions, symptoms had to be present for a minimum of six consecutive months. Negative symptoms were measured upon entry to the program and subsequently at 1,2,3,6,9 and 12 months. Functional outcome was quantified at first assessment and month 12. RESULTS: PNS prevalence: PNS_1 (27%); PNS_2 (13.2%); PNS_H (13.2%). The prevalence of DS was found to be 3% when applying the PDS. Regardless of the definition being applied, when compared to non-PNS, patients in the PNS group were shown to have significantly worse functioning at month 12. All three PNS definitions showed similar associations with functional outcome at month 12. CONCLUSION: Persistent negative symptoms are present in about 27% of FEP patients with both affective and non-affective psychosis. Although there has previously been doubt as to whether PNS represents a separate subdomain of negative symptoms, the current study suggests that PNS may be more applicable to FEP when compared to DS. Although all three PNS definitions were comparable in predicting functional outcome, we suggest that the PNS definition employed is dependent on the clinical or research objective at hand.