Search

Objectives: This study had two aims: to measure the prevalence of long-term prescribing of high doses of antipsychotics and antipsychotic polypharmacy in a large Canadian province and to estimate the relative contributions of patient-, physician-, and hospital-level factors., Methods: Government hospital discharge, physician, and pharmaceutical claims data were linked to identify individuals with schizophrenia who in 2004 had antipsychotics available to them for at least 11 months. Individuals on a high dose throughout that period, as well as individuals on multiple concurrent antipsychotics (polypharmacy), were identified. Logistic and generalized linear mixed models using patient-, physician-, and hospital-level predictors were estimated., Results: Among the 12,150 individuals identified, 11.9% were on a high dose and 10.4% on antipsychotic polypharmacy continually, with 3.7% in both groups. After adjustment for potential confounders, analyses showed that systematic propensity for physicians to prescribe high doses accounted for 10.9% of the remaining unexplained variance, and physicians as a group who prescribed high doses across a hospital or psychiatry department accounted for 3.0%. For antipsychotic polypharmacy the corresponding percentages were 9.7% and 6.2%. Even after adjustment, the variation in high-dose prescribing and antipsychotic polypharmacy remained substantial., Conclusions: Long-term high-dose and antipsychotic polypharmacy prescribing appeared partly driven by some physicians' and some hospitals' propensities to prescribe in this way independently of patient characteristics. Given the weight of the evidence against high-dose prescribing and antipsychotic polypharmacy, measures addressed to physicians and hospitals most likely to prescribe high doses, antipsychotic polypharmacy, or both should be considered.

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.

Background: Negative symptoms represent an unmet therapeutic need in many patients with schizophrenia. In an extension to our previous voxel-based morphometry findings, we employed a more specific, vertex-based approach to explore cortical thinning in relation to persistent negative symptoms (PNS) in non-affective first-episode of psychosis (FEP) patients to advance our understanding of the pathophysiology of primary negative symptoms., Methods: This study included 62 non-affective FEP patients and 60 non-clinical controls; 16 patients were identified with PNS (i.e., at least 1 primary negative symptom at moderate or greater severity sustained for at least 6 consecutive months). Using cortical thickness analyses, we explored for differences between PNS and non-PNS patients as well as between each patient group and healthy controls; cut-off threshold was set at p<0.01, corrected for multiple comparisons., Results: A thinner cortex prominently in the right superior temporal gyrus extending into the temporo-parietal junction (TPJ), right parahippocampal gyrus, and left orbital frontal gyrus was identified in PNS patients vs. non-PNS patients. Compared with healthy controls, PNS patients showed a thinner cortex prominently in the right superior temporal gyrus, right parahippocampal gyrus, and right cingulate; non-PNS patients showed a thinner cortex prominently in the parahippocampal gyrus bi-laterally., Conclusion: Cortical thinning in the early stages of non-affective psychosis is present in the frontal and temporo-parietal regions in patients with PNS. With these brain regions strongly related to social cognitive functioning, our finding suggests a potential link between primary negative symptoms and social cognitive deficits through common brain etiologies.

With the introduction of a clear definition of symptomatic remission from the Remission in Schizophrenia Working Group (RSWG), studies have sought to characterize cognitive functioning in remitted and non-remitted schizophrenia patients. However, most investigations of cognition and remission are cross-sectional or have studied samples of chronically ill patients. Therefore, the aim of this study was to compare cognitive performance between remitted and non-remitted first-episode psychosis (FEP) patients longitudinally. Seventy patients were categorized as remitted (n=17) or non-remitted (n=53) using the full RSWG criteria after being treated for approximately 15months, during which cognition was evaluated twice. Since our previous investigations in FEP have isolated verbal memory as a potential cognitive marker of symptomatic remission, analyses were limited to verbal, visual and working memory. We have found that non-remitted patients had a significantly worse verbal memory performance than remitted patients after 3months (F(1,68)=6.47, p=0.006) and 15months of treatment (F(1,68)=19.49, p<0.001). Visual memory was also significantly lower in non-remitted patients compared to those in remission but only at initial assessment (F(1,68)=8.21, p=0.003) while working memory performance was similar at both time points. Our findings suggest that verbal memory may be a specific and stable marker of clinical remission in FEP patients. This cognitive domain can easily be evaluated at treatment intake in the hope of identifying early on patients who are less likely to remit., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Increasing evidence supports the role of childhood trauma in the etiology of psychosis but underlying mechanisms are poorly understood. Early maltreatment has been linked to dissociative symptoms in psychosis patients. We explored associations between childhood trauma (Childhood Trauma Questionnaire) and dissociation (Dissociative Experiences Scale) in first-episode psychotic patients (n=62), chronic psychotic patients (n=43), and non-psychotic community controls (n=66). Multivariate analyses of covariance were used to test associations between childhood trauma and dissociation by group while controlling for sex. Chronic patients reported the highest level of dissociation. More severe childhood trauma was associated with greater dissociative symptoms in all groups although most strongly in chronic patients. Emotional abuse showed the strongest associations with dissociation, with these being strongest for chronic patients, followed by first-episode patients--and least for controls. Men showed a stronger association between physical neglect and dissociation than women, irrespective of group. There were no significant group by sex interactions. Our findings replicate the strong association between childhood trauma and dissociative symptoms in chronic and first-episode psychotic patients relative to non-psychotic control subjects. We also demonstrate the salience of emotional abuse in explaining variance in dissociation, especially in chronic patients., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Diagnostic stability is an important indicator of the reliability and validity of psychiatric diagnoses and has implications in clinical practice and research. While several studies have investigated the diagnostic stability of first-episode psychosis (FEP) disorders, less is known about psychiatric comorbidity in FEP and the persistence of such comorbid conditions over time. Our study aimed to confirm the diagnostic stability of FEP disorders and determine the variation in persistence of comorbid substance use disorders (SUDs), mood disorders, and anxiety disorders over 1 year., Method: The Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Patient Edition was conducted at first presentation and repeated after 1 year (or reconstructed) for 214 FEP patients at the Prevention and Early Intervention Program for Psychoses-Montreal., Results: Psychotic disorder diagnoses were retained by 76.2% of patients at 1 year, schizophrenia being the most stable diagnosis (92.1%). Most diagnostic shifts were to schizophrenia and schizophrenia spectrum disorders. Comorbid SUDs, anxiety disorders, and mood disorders persisted for 50.7%, 64.0%, and 16.7% of patients, respectively. Many new cases of each of these disorders also emerged at 1-year follow-up., Conclusions: These findings demonstrate the stability of primary psychotic disorder diagnoses and greater fluidity of comorbid psychiatric diagnoses, with anxiety disorders persisting as comorbid conditions more than mood disorders and SUDs. These results highlight the importance of repeating a structured diagnostic assessment longitudinally, especially for consideration of comorbid conditions.

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.

Negative symptoms are present early on during the first episode of psychosis (FEP). The severity of these symptoms has been linked to cognitive deficits, including memory; however, its relationship with persistent negative symptoms (PNS) remains unclear. Thus, the goals of the current paper were to explore memory profiles in FEP patients identified as having PNS and to delineate this relationship in PNS over a 1-year period. Patients diagnosed as having a first episode of psychosis were segregated into groups of patients who met the criteria for PNS (N = 39) and patients who did not, or non-PNS (N = 97). At an initial assessment, all subjects were administered neurocognitive tests for three memory domains including verbal, visual and working memory. In addition, in FEP patients, clinical symptoms including negative, positive and depressive symptoms were also measured at the initial assessment as well as months 1, 2, 3, 6, 9, and 12. A significant interaction of memory × group was observed (F = 4.997, d.f. = 1,181, P = 0.002), with post hoc comparisons indicating that the PNS group performed more poorly than non-PNS only in the verbal memory domain. All three-memory domains remained stable over time. Hence, in comparison to non-PNS patients, FEP patients with PNS appear to have greater (selective) verbal memory impairments throughout the first year of treatment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We recently reported that individuals at ultra-high risk for the development of psychosis (UHR) have elevated levels of chronic stress and deficits in the putative protective factors self-esteem, social support and coping skills. The aim of the present study was to assess endocrine and autonomic responses to acute psychosocial stress and their associations with self-ratings of stress and protective factors in individuals at UHR. Twenty-one patients diagnosed with an "at risk mental state" (12 male, 9 female; mean age 20.8 ± 3.27) and 21 healthy age and gender matched community controls were exposed to the Trier Social Stress Test (TSST). Saliva samples for cortisol assessment and measurements of heart rate and blood pressure were taken throughout the testing period. Levels of perceived chronic stress, protective factors and depression were assessed with reference to the preceding month and year (stress only). Compared to healthy controls, individuals at UHR reported significantly higher levels of depression, deficits in protective factors, and a trend for higher chronic stress levels. Cortisol levels and systolic blood pressure during the TSST were significantly lower in the UHR group, while heart rate changes were comparable to controls. Lower cortisol levels in the UHR group were associated with higher self-ratings of stress in the past year and a lower level of education. Attenuated cortisol responses to acute psychosocial stress in the presence of high chronic stress could indicate a desensitization of the HPA axis. Associated poor metabolic and psychological adjustment to stress might increase vulnerability for the development of psychosis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Early life adversity has been associated with an increased risk for the development of mental health problems, including psychotic disorders, perhaps mediated by a changed regulation of the Hypothalamic Pituitary Adrenal (HPA) axis. Aim of the present study was to confirm our previous finding of an attenuated cortisol awakening response (CAR) in men with first episode psychosis (FEP) and to explore a possible link between a blunted CAR and early adversity as indicated by perceived parental bonding. Fifty-eight patients (38 men, 20 women; mean age 23.25±3.86) with a FEP and 33 healthy community controls (16 men, 17 women; mean age 22.91±3.64) participated in the study. Saliva samples for assessment of the CAR were collected immediately, 30 and 60min after awakening. Complete cortisol samples were available in a reduced sample of 56 patients (37 men) and 30 controls (13 men). Parental bonding during the first 16 years of life was assessed retrospectively with the Parental Bonding Inventory. Results showed a significantly blunted CAR in male compared to female patients, confirming our previously reported findings. We also found a lower CAR in the total FEP group compared to controls, which failed to reach significance after controlling for time of awakening. A significantly lower percentage of patients than controls reported optimal maternal parenting. Within the patient group, significantly fewer male than female patients reported optimal maternal and paternal parenting. Only in patients, unfavorable paternal parenting was related to a blunted CAR. Dysregulation of the HPA axis in male patients might be a consequence of non-optimal parenting and contribute to the less favorable course of psychosis in men compared to women., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aim: In psychotic disorders, a limited number of studies have documented the presence of symptoms of anxiety, especially in first-episode psychosis (FEP). There is a growing interest in better understanding how these symptoms may affect the severity of psychotic symptoms and clinical outcome. This study examined the association between symptoms of anxiety, as measured by the Hamilton Anxiety Rating Scale (HARS) and the Positive and Negative Syndrome Scale (PANSS), and short-term clinical outcome. We first examined the potential association between anxiety symptom severity among FEP patients and remission. A secondary objective explored the relation between the PANSS single item subscale 'anxiety' item and the total score value of the HARS., Method: Data were collected on 201 FEP patients divided into remitted and unremitted groups based on clinical data at 6 months. Anxiety ratings were compared between 67 remitted and 99 unremitted patients with the HARS, and for 72 remitted and 103 unremitted patients with the (G2) PANSS., Results: A significant interaction Time × Group was observed on the HARS and on the PANSS G2 item. Looking at the two time points specifically, groups did not significantly differ at baseline on either the HARS or the PANSS. At 6 months, these two groups were significantly different on both anxiety rating scores - HARS [t(170) = 3.48, P = 0.001)] and PANSS G2 [t(173) = 2.51, P = 0.013)]., Conclusion: Anxiety severity is marked in FEP, and appears to be linked to poor short-term clinical outcome. The PANSS single item (G2) seems to represent a good indicator of anxiety as it significantly correlates with a more systematic measure of anxiety, namely the HARS score. Anxiety severity appears to vary across diagnosis type., (© 2013 Wiley Publishing Asia Pty Ltd.)

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.

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&#95;1); 2) having a score of 3 or more on at least 2 global subscales of the SANS (PNS&#95;2); and 3) having a score of 3 or more on a combination of specific SANS subscales and items (PNS&#95;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&#95;1 (27%); PNS&#95;2 (13.2%); PNS&#95;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.

Objective: There has been increasing interest in the psychiatric literature on research and service delivery focused on first-episode psychosis (FEP), and accurate information on the incidence of FEP is crucial for the development of services targeting patients in the early stages of illness. We sought to obtain a population-based estimate of the incidence of first-episode schizophrenia-spectrum psychosis (SSP) among adolescents and young adults in Montreal., Methods: Population-based administrative data from physician billings, hospitalizations, pharmacies, and public health clinics were used to estimate the incidence of first-episode SSP in Montreal. A 3-year period (2004-2006) was used to identify patients with SSP aged 14 to 25 years. We used a 4- to 6-year clearance period to remove patients with a history of any psychotic disorder or prescription for an antipsychotic., Results: We identified 456 patients with SSP, yielding a standardized annual incidence of 82.9 per 100 000 for males (95% CI 73.7 to 92.1), and 32.2 per 100 000 for females (95% CI 26.7 to 37.8). Using ecologic indicators of material and social deprivation, we found a higher-incidence proportion of SSP among people living in the most deprived areas, relative to people living in the least deprived areas., Conclusions: Clinical samples obtained from psychiatric services are unlikely to capture all treatment-seeking patients, and epidemiologic surveys have resource-intensive constraints, making this approach challenging for rare forms of psychopathology; therefore, population-based administrative data may be a useful tool for studying the frequency of psychotic disorders.

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 (β = 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 (β = 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.

Objective: There is little understanding of service users' conceptions of recovery in the early phase of psychotic disorders. An enhanced understanding of personal notions of recovery may help with the development and evaluation of interventions that address the concerns of service users. This study examined personal definitions of recovery among individuals recently treated in a specialized early-intervention service in Canada., Methods: Semistructured interviews were carried out with 30 individuals three to five years after initial treatment of a first episode of psychosis. Interpretative phenomenological analysis was used to examine participants' personal meanings of recovery. A typology of recovery definitions was constructed., Results: A majority of individuals considered themselves to be recovered. Responses indicated that recovery is a multidimensional experience and is often a personalized and achievable goal at this early stage in treatment. Individuals described recovery as improvement in one or more of three domains: illness recovery, psychological and personal recovery, and social and functional recovery. There was variation in the extent to which individuals perceived that recovery involved alleviation of symptoms and elimination of underlying vulnerability to illness., Conclusions: There were several components of the personal meanings of recovery from a first episode of psychosis and variations in the emphasis that individuals placed on each component. An overall positive outlook may be a function of younger age, shorter duration of illness, and receipt of client-centered comprehensive and phase-specific treatment. Improved understanding of personal notions of recovery can guide clinical practices to address service users' recovery goals.

Objectives: An important subset of patients with schizophrenia present clinically significant persistent negative symptoms (PNS). Identifying the neural substrates of PNS could help improve our understanding and treatment of these symptoms., Methods: This study included 64 non-affective first-episode of psychosis (FEP) patients and 60 healthy controls; 16 patients displayed PNS (i.e., at least one primary negative symptom at moderate or worse severity sustained for at least six consecutive months). Using voxel-based morphometry (VBM), we explored for gray matter differences between PNS and non-PNS patients; patient groups were also compared to controls. All comparisons were performed at p < 0.05, corrected for multiple comparisons., Results: PNS patients had smaller gray matter in the right frontal medial-orbital gyrus (extending into the inferior frontal gyrus) and right parahippocampal gyrus (extending into the fusiform gyrus) compared to non-PNS patients. Compared to controls, PNS patients had smaller gray matter in the right parahippocampal gyrus (extending into the fusiform gyrus and superior temporal gyrus); non-PNS patients showed no significant differences to controls., Conclusion: Neural substrates of PNS are evident in FEP patients. A better understanding of the neural etiology of PNS may encourage the search for new medications and/or alternative treatments to better help those affected.

Objective: To explore differences in severity and nature of symptoms of first-episode psychosis (FEP) according to ethnic group and migrant status., Method: We administered rating scales to assess positive and negative symptoms, as well as general psychopathology, to 301 consecutive patients presenting with an FEP within a defined catchment area in Montreal, Quebec, classified according to ethnicity and migrant status. Symptom scores of Euro-Canadian patients without a recent history of migration, that is, the reference group (n = 145), were compared with those of African and Afro-Caribbean (n = 39), Asian (n = 27), Central and South American (n = 15), Middle Eastern and North African (n = 24), and European and North American (n = 39) patients., Results: Except for referral source, there were no significant differences between ethnic groups on any demographic variables. The African and Afro-Caribbean group had a higher level of negative symptoms (especially alogia) and general psychopathology scores on the Positive and Negative Syndrome Scale (especially, uncooperativeness, preoccupation, and poor attention), compared with the reference group. Ethnic groups did not differ on the Scale for the Assessment of Positive Symptoms scores., Conclusions: A comparison of FEP patients from different ethnic groups and native-born Euro-Canadians revealed no significant differences in the nature of positive symptoms at first presentation or in age at onset, suggesting that there was no evidence for the hypothesis that ethnic minorities are misdiagnosed as psychotic. Increased severity of negative symptoms and general psychopathology, specifically among the black ethnic minority group, may have implications for the role of ethnicity for the treatment and outcome of the initial episode of psychotic disorders.

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.

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., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aim: Our objective was to describe the goals identified by patients upon entering a specialized programme for treatment of first-episode psychosis (FEP) in Chennai, India., Methods: 68 patients with FEP completed the Goal Attainment section of the Wisconsin Quality of Life-Client Questionnaire upon entry into treatment. Patients were asked to identify a maximum of three treatment goals and rate each identified goal on its importance and the extent of its achievement., Results: In the order of frequency of endorsement, the primary goals identified pertained to work, family/interpersonal relationships, education, symptom relief and psychological recovery, living condition, religion, finances, and household responsibilities. All patients identified at least one goal, 41 patients identified two goals, and 11 patients identified three goals., Conclusion: Individuals with FEP in India present with a range of realistic and reasonable goals. Findings have implications for improving early intervention services in India by targeting patient-identified goals., (© 2011 Blackwell Publishing Asia Pty Ltd.)

Stress-vulnerability models of schizophrenia regard psychosocial stress as an important factor in the onset and aggravation of psychotic symptoms, but such research in the early phases of psychosis is limited. Protective factors against the effects of stress might be the key to understanding some inconclusive findings and to the development of optimal psychosocial interventions. The present study compared self-reported levels of stress, self-esteem, social support and active coping in 32 patients with a first episode of psychosis (FEP), 30 individuals at ultra-high risk for psychosis (UHR) and 30 healthy controls. Associations with symptoms of psychosis were assessed in both patient groups. Individuals at UHR reported significantly higher stress levels compared to FEP patients. Both patient groups showed lower self-esteem compared to controls, and the UHR group reported lower social support and active coping than controls. These group differences could not be explained by age and dose of antipsychotic medication in the FEP group. In the UHR group, higher stress levels and lower self-esteem were associated with more severe positive and depressive symptoms on the Brief Psychiatric Rating Scale. Multiple regression analyses revealed that stress was the only significant predictor for both symptom measures and that the relationship was not moderated by self-esteem. Our findings show that individuals at UHR for psychosis experience high levels of psychosocial stress and marked deficits in protective factors. The results suggest that psychosocial interventions targeted at reducing stress levels and improving resilience in this population may be beneficial in improving outcomes., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Aim: Our aim was to examine the concerns reported by family members and other caregivers of individuals with first-episode psychosis (FEP)., Methods: Family members who attended group psychoeducation selected their top two concerns from a list of nine concerns: stigma, medication, substance abuse, social behaviour, stressful situations, self-esteem and identity, sexuality and intimacy, early warning signs, and resources and support., Results: Parents, particularly mothers, were a significant majority of those who attended psychoeducation sessions. In order of frequency of endorsement, the concerns endorsed were self-esteem and identity, social behaviour, substance abuse, medications, stressful situations, early warning signs, resources and support, stigma, and sexuality and intimacy., Conclusion: Families were most concerned about the self-esteem and identity of their young relatives with FEP. Our findings suggest that early intervention programmes should specifically address issues of self-esteem and identity. Further research on the concerns shared by families of individuals with FEP is needed., (© 2011 Blackwell Publishing Asia Pty Ltd.)

Introduction: Outcome from psychotic disorders is heterogeneous with poor long-term clinical outcome associated with such markers as decreased internal capsule volume and increased ventricular volumes. No previous study has examined neuroimaging markers in relation to early remission., Methods: This neuroimaging study included 68 previously untreated first episode of psychosis (FEP) patients, of whom 28 achieved remission and 40 did not after six months of treatment, and 42 healthy controls. Using voxel-based morphometry (VBM), we set out to determine if specific neural correlates could be identified in FEP patients not achieving remission in a specialized early-intervention service., Results: Nonremitted patients had significant lower grey matter concentration (GMC) in the parahippocampal gyrus bilaterally compared to remitted patients. A classification model utilizing parahippocampal GMC correctly classified remission status 79% of the time and accounted for 56% of the variance. Moreover, GMC on the left (r=-0.35, p=0.004) and right (r=-0.47, p<0.0001) side correlated with social withdrawal while only the left side correlated with verbal memory (r=0.21, p=0.03)., Conclusions: Neural markers of early remission are present in first-episode patients. A better understanding of the neural etiology of psychosis and its relationship to outcome may encourage the search for new medications to help improve outcome in relation to the identified brain regions like the parahippocampal gyrus.

Background: Although there is agreement on the association between delay in treatment of psychosis and outcome, less is known regarding the pathways to care of patients suffering from a first psychotic episode. Pathways are complex, involve a diverse range of contacts, and are likely to influence delay in treatment. We conducted a systematic review on the nature and determinants of the pathway to care of patients experiencing a first psychotic episode.MethodWe searched four databases (Medline, HealthStar, EMBASE, PsycINFO) to identify articles published between 1985 and 2009. We manually searched reference lists and relevant journals and used forward citation searching to identify additional articles. Studies were included if they used an observational design to assess the pathways to care of patients with first-episode psychosis (FEP)., Results: Included studies (n=30) explored the first contact in the pathway and/or the referral source that led to treatment. In 13 of 21 studies, the first contact for the largest proportion of patients was a physician. However, in nine of 22 studies, the referral source for the greatest proportion of patients was emergency services. We did not find consistent results across the studies that explored the sex, socio-economic, and/or ethnic determinants of the pathway, or the impact of the pathway to care on treatment delay., Conclusions: Additional research is needed to understand the help-seeking behavior of patients experiencing a first-episode of psychosis, service response to such contacts, and the determinants of the pathways to mental health care, to inform the provision of mental health services.

Objective: The temporolimbic region has been implicated in the pathophysiology in schizophrenia. More specifically, significantly smaller hippocampal volumes but not amygdala volumes have been identified at onset in first-episode schizophrenia (FES) patients. However, volumetric differences (namely, in the hippocampus) exhibit an ambiguous relationship with long-term outcome. So, we examined the relationship between hippocampus and amygdala volumes and early remission status., Methods: We compared hippocampus and amygdala volumes between 40 non-remitted and 17 remitted FES patients and 57 healthy controls. Amygdala and hippocampus were manually traced with the hippocampus additionally segmented into three parts: body, head, and tail. Remission was defined as mild or less on both positive and negative symptoms over a period of 6 consecutive months as per the 2005 Remission in Schizophrenia Working Group criteria., Results: A significant [group x structure x side] interaction revealed outcome groups differed in hippocampus tail volumes; significantly on the left (non-remitted=694+/-175 mm(3); remitted=855+/-133 mm(3); p=0.001) with a trend difference on the right (non-remitted=723+/-162 mm(3); remitted=833+/-126 mm(3); p=0.023). Groups did not differ in body, head, or amygdala volumes bi-laterally., Conclusions: A smaller hippocampal tail volume may represent a neural marker in FES patients who do not achieve early remission after the first 6 months of treatment. The early identification of patients with poor outcome with respect to the hippocampus tail may encourage the search for new, more target-specific, medications in hope of improving outcome and moving us towards a better understanding of the pathophysiology of schizophrenia., ((c) 2010 Elsevier B.V. All rights reserved.)

Background: This article reports preliminary findings from a multi-year investigation of onset and course of previously untreated first-episode psychosis in two similarly structured treatment programs in Canada and India. Specifically, the aim of this study was to examine whether one year clinical and functional outcomes of first-episode psychosis varied between these two programs., Method: Patients with first-episode non-affective psychosis receiving similar treatment in Chennai, India (N=61) and in Montreal, Canada (N=88) were evaluated for demographic variables, duration of untreated psychosis, and baseline diagnosis, and for positive, negative, and general psychopathology symptoms and overall functioning at baseline and one year., Results: At both sites, there was a significant improvement in symptoms and functioning over the one year course of treatment. There was also a significant time-by-site interaction on negative symptoms and functioning, after controlling for age, sex, and marital status. On these domains, patients in India showed greater improvement over time than their Canadian counterparts. The time-by-site interactions were not significant for positive symptoms and general psychopathology., Conclusion: First-episode patients in the Indian program demonstrated higher rates of improvement at one year in negative symptoms and functioning than patients receiving similar treatment in Canada. There was no difference in improvement between the sites on positive symptoms and general psychopathology. These results suggest that the sociocultural context of treatment can influence outcomes early in the course of psychotic disorders. Further, outcomes are not uniformly better or worse in one sociocultural context compared to another, but seem to vary from one outcome domain to another., (Copyright 2010 Elsevier B.V. All rights reserved.)

Objective: In psychotic disorders, impairments in cognition have been associated with both clinical and functional outcome, while deficits in social cognition have been associated with functional outcome. As an extension to a recent report on neurocognition and short-term clinical outcome in first-episode psychosis (FEP), the current study explored whether social cognitive deficits could also identify poor short-term clinical outcome among FEP patients., Methods: We defined the social-cognition domain based on the scores from the Hinting Task and the Four Factor Tests of Social Intelligence. Data were collected in 45 FEP patients and 26 healthy controls. The patients were divided into good- and poor-outcome groups based on clinical data at six months following initiation of treatment. Social cognition was compared among 27 poor-outcome, 18 good-outcome, and 26 healthy-control participants., Results: Outcome groups significantly differed in the social cognition domain (z-scores: poor outcome=-2.0 [SD=1.4]; good outcome=-1.0 [SD=1.0]; p=0.005), with both groups scoring significantly lower than the control group (p<0.003). Moreover, outcome groups differed significantly only on the Cartoon Predictions subtest (z-scores: poor outcome=-2.7 [SD=2.7]; good outcome=-0.7 [SD=1.8]; p=0.001) among the five subtests used., Conclusions: Overall, social cognition appears to be compromised in all FEP patients compared to healthy controls. More interestingly, significant differences in social cognitive impairments exist between good and poor short-term clinical outcome groups, with the largest effect found in the Cartoon Predictions subtest.

Alterations of the fornix in chronic patients with psychosis are well established, but its integrity in the early stage of schizophrenia remains unknown. Thirty-two patients experiencing first-episode schizophrenia (FES) and 25 matched controls completed a DTI scan. DTI-tractography was used to estimate fractional anisotropy (FA) in bilateral fornices. The analysis showed significant overall FA reductions in the fornix in FES patients relative to controls. No significant correlations were found between FA values and clinical and sociodemographic data in FES patients. These findings revealed slight alterations along the fornix in early stage of schizophrenia., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Background: Family members of individuals with schizophrenia suffer from elevated rates of schizophrenia-spectrum disorders (SSD) and other forms of psychopathology. However, few studies have examined familial psychopathology in probands with a first episode of psychosis (FEP). We systematically evaluated family history in patients experiencing an affective or non-affective FEP., Methods: The Family Interview for Genetic Studies was used to obtain diagnostic information on all first- and second-degree relatives of probands admitted to a specialized FEP program. Probands were 94 previously untreated patients suffering from a first-episode of affective or schizophrenia spectrum psychosis, aged 14 to 30. The interview ascertained diagnoses of psychotic disorders, affective disorders, substance-use disorders (SUD), and schizophrenia-related personality disorders., Results: One in five probands (19.1%) had a history of psychosis among their first-degree relatives, while 34.0% had any relative with psychosis. Fewer probands had a family history of SSD (7.4% with a first-degree history and 18.1% with a history among any relatives). Over half (53.2%) of probands had a first-degree relative with Major Depressive Disorder, and 38.3% had a first-degree relative with a SUD. Overall, 69.9% of probands had a first-degree relative with a mental disorder. The proportion of probands with a family history of any of these diagnoses did not vary by proband diagnosis (affective or SS Psychosis), though probands with co-morbid SUD were more likely to have a family history of substance abuse., Conclusions: Diverse psychopathology is commonly present in families of FEP patients and may imply a generalized vulnerability to psychiatric disorders to be greater in such families compared to specific vulnerability to SS or affective psychosis. These findings may also have implications for provision of care for the probands.

A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a factor in the etiology and exacerbation of psychosis, but has not been reported consistently. Sex differences are apparent in many aspects of psychotic disorders and may explain some of the equivocation associated with the regulation of the HPA axis in the illness. The present study compared the cortisol response to awakening (CRA) in 27 patients (16 men and 11 women) with recent onset of psychosis (within the past 2 years) and 40 age and gender matched controls. Within the patient group, we also assessed the relationship between the CRA and positive and negative symptoms of psychosis, anxiety and depression. The CRA in patients was not significantly different from controls. However, within the patient group, we observed a significant sex difference, with a blunted cortisol response to awakening in men but not in women (F=7.26; p<0.002). This difference could not be explained by differences between male and female patients in awakening time, medication, or diagnosis of schizophrenia vs. affective psychosis. Cortisol levels were not related to symptom measures. Our findings demonstrate a dysregulation of the HPA axis in male patients with recent onset of psychosis. This sex specificity might be related to and explain in part the unfavorable course of the illness observed in men.

Several studies have demonstrated that patients with schizophrenia show impairments in social cognition and current evidence indicate that this deficit is associated with abnormal activity in specific brain regions. In addition to functional imaging studies, we believe that the identification of structural correlates of social cognitive processes may help to better understand the neural underpinnings of these specific skills. The main objective of this study was to investigate the relationship between gray matter density and social cognitive deficits in first episode of schizophrenia spectrum psychosis, using a comprehensive assessment that we previously demonstrated to be a highly sensitive measure of social cognitive deficits in this population. Thirty-eight patients with a first episode of psychosis participated in this study, and the Four Factor Test of Social Intelligence was used as a measure of social cognition. Social cognitive impairments in first episode psychosis were significantly correlated with reduced gray-matter density in the left middle frontal gyrus other regions within the mirror neuron system network (MSN), namely the right supplementary motor cortex, the left superior temporal gyrus and the left inferior parietal lobule. We concluded that structural abnormalities within the MSN may account for the social cognitive deficits present in some psychiatric disorders, such as schizophrenia.

Background: Progressive volumetric changes in the brains of people with schizophrenia have been attributed to a number of factors., Aims: To determine whether glutamatergic changes in patients with schizophrenia correlated with grey-matter losses during the first years of illness., Method: Left anterior cingulate and thalamic glutamatergic metabolite levels and grey-matter volumes were examined in 16 patients with first-episode schizophrenia before and after 10 months and 30 months of antipsychotic treatment and in 16 healthy participants on two occasions 30 months apart., Results: Higher than normal glutamine levels were found in the anterior cingulate and thalamus of never-treated patients. Thalamic levels of glutamine were significantly reduced after 30 months. Limited grey-matter reductions were seen in patients at 10 months followed by widespread grey-matter loss at 30 months. Parietal and temporal lobe grey-matter loss was correlated with thalamic glutamine loss., Conclusions: Elevated glutamine levels in never-treated patients followed by decreased thalamic glutamine and grey-matter loss in connected regions could indicate either neurodegeneration or a plastic response to reduced subcortical activity.

Context: Memory is one of the cognitive functions most affected in schizophrenia, with deficits observed from the first episode of psychosis (FEP). Previous studies have indicated that some memory processes may be more affected than others., Objective: To examine the neural correlates of 3 specific memory processes in FEP by means of functional magnetic resonance imaging (fMRI)., Design: Case-control study., Setting: Prevention and Early Intervention Program for Psychoses of the Douglas Hospital and Montreal Neurological Institute, McGill University. Subjects Twenty-six patients with FEP and 20 healthy controls., Main Outcome Measures: Behavioral performance and regional brain activity measured during memory encoding by fMRI. Our fMRI design included 3 within-subject contrasts (associative vs item-oriented encoding, encoding of arbitrary vs semantically related image pairs, and successful vs unsuccessful memory encoding) that were then used for group conjunctions and between-group analyses., Results: Patients with FEP showed normal activation of several brain regions, including the prefrontal cortex, hippocampus, and parahippocampal cortex, during successful memory encoding and associative encoding. In contrast, the hippocampus and surrounding medial temporal areas showed reduced activity during the encoding of arbitrary pairs. This selective dysfunction reflected by abnormal brain activation during encoding was accompanied by a greater deficit for subsequent recognition of arbitrary pairs relative to the semantically related pairs., Conclusions: This study demonstrated that, in the same group of patients with FEP, the hippocampus could show either normal or abnormal modulation of activation depending on the specific cognitive process that was examined. The normal modulation of hippocampal activation observed during successful memory encoding in FEP argues against a general inability to recruit this region. Instead, the dysfunction was specifically linked to semantic relatedness. This selective deficit seems to affect memory performance in FEP and denotes an important representational problem that may confer greater vulnerability to psychotic disorders and would thus be interesting to examine in high-risk populations.

Objectives: Shorter duration of untreated psychosis (DUP) is often correlated with a poorer response to treatment. In this paper we test the hypothesis that the importance of DUP is moderated by early premorbid adjustment., Method: Three year prospective data were collected for 154 first episode patients. DUP, premorbid adjustment and symptoms were assessed at time of presentation for treatment and symptoms were reassessed after three years of treatment., Results: DUP was correlated with level of symptoms at three years only for patients with better premorbid adjustment in childhood and early adolescence., Conclusions: These results suggest that DUP may have more of an impact on treatment response for those with a less pernicious, more reversible form of illness.

Background: Social cognition is a complex phenomenon involving several distinct processes. Numerous studies have shown that individuals with schizophrenia are largely impaired on this domain of cognition. However, most have focused on a single aspect of social cognition, namely "theory of mind" and/or included patients with long standing illness., Objective: The main objective of the present study was to identify social cognition deficits in first episode of schizophrenia spectrum psychosis using a case control design and a comprehensive assessment that allowed the exploration of several dimensions of this phenomenon., Subjects: 36 patients with a first episode of psychosis and 25 healthy controls participated in this study., Material: Measures of social cognition included the Hinting Task and the Four Factor Test of Social Intelligence., Results: Significant group differences were found on both tasks, but the Four Factor Test of Social Intelligence revealed a stronger group effect and the effects observed remained significant once IQ was covaried. Social cognition did not show any correlations with level of symptoms., Conclusion: Social cognition deficits are present during the first episode of psychosis. These impairments do not seem to be a consequence of group differences in overall intellectual functioning and are likely to be state-independent.

Previous positron emission tomography (PET) studies have shown greater medial temporal lobe activation (MTL) for associative memory encoding relative to deep item-oriented encoding. Greater MTL activation has also been reported for associative novelty detection. Although it has been suggested that these patterns of MTL activation could reflect the creation of novel associations into memory, it is unclear whether associative encoding and associative novelty detection rely on the same MTL substructures. In this study, we used event-related functional magnetic resonance imaging (er-fMRI) to reproduce previous reports of greater hippocampal activation for associative encoding using both arbitrary and semantically related object pairs. This paradigm allowed us to assess whether the requirement for associative processing at encoding interacts with associative novelty. Contrasting the pattern of activation for associative versus item-oriented encoding revealed greater right hippocampal activation as well as parahippocampal activation bilaterally, reproducing the findings from previous PET experiments. The orthogonal contrast between arbitrary and related pairs revealed greater activation in the left parahippocampal region, but no significant interaction between the type of encoding (associative or item oriented) and the type of pairs (arbitrary or semantically related) was observed in the medial temporal lobe (MTL). These results suggest that both associative processing and associative novelty detection can activate the MTL. Most importantly, this study suggests that associative processing can activate the MTL regardless of the pre-existence of an association between the items of a pair.

Background: Recent evidence that treatment delay may compromise the potential for recovery from psychotic disorders has resulted in increased interest in factors that influence help seeking. In this paper, we test the hypotheses, derived from past research, that having a positive family history of a psychotic disorder in first or second degree relatives will be associated with a shorter duration of untreated psychosis (DUP), but a longer duration of untreated illness (DUI). Data were derived from 169 patients who presented for treatment to a first episode psychotic disorders program. Information was collected concerning family history, DUP, DUI and the timing of family recognition of the need for help., Results: The findings failed to confirm a positive family history being associated with shorter DUP, but did support the prediction of such a history being related to longer DUI. Paradoxically, given the latter findings, families with a history of psychotic illness were more likely to recognize the need for help for the ill person prior to the onset of psychotic symptoms. The difference in DUI appears to reflect the presence of a longer period of early signs prior to the emergence of psychosis in those cases with a positive family history., Conclusions: These findings suggest the importance of examining family history as a possible confound of any relationship between DUI and long-term course of illness.

Unlabelled: Objective. To conduct a naturalistic, longitudinal study of prescribing patterns of atypical neuroleptics in predominantly drug-naïve first episode non-affective psychosis patients. Methods. Patients with a first episode psychosis were prescribed an antipsychotic as part of a clinical protocol and followed-up for 2 years. Comparisons were made between risperidone and olanzapine, the two most commonly prescribed antipsychotics. Socio-demographic variables and clinical characteristics such as diagnosis, duration of untreated illness and psychosis and level of positive and negative symptoms were assessed using well-established methods. We examined the first antipsychotic given, starting dose, time taken to start and to reach the maximum dose, time on first medication, maximum dose, medication change and concomitant medication use. Results. One hundred and ninety-three consecutive patients consented to start on antipsychotic. The results are provided for risperidone (N = 133) and olanzapine (N=38). The time to initiate antipsychotic medications was significantly longer for outpatients than inpatients. There were no differences between the two groups for time taken to reach the maximum dose, drop out rates or concomitant medication use. The percentage of patients taking an antipsychotic agent at any given time was high (range 79-91%), but half of the patients had changed from their first antipsychotic by 6 months., Conclusions: The reality of clinical practice can be much different than rigid protocols or treatment algorithms of pre-marketing studies or clinical trials. In this sample of first episode psychosis patients, although the majority of patients remained on an antipsychotic, changes in medication over the first 2 years were common. Polypharmacy was not a common practice.

This paper presents the first published findings examining the relationship of social support to three-year symptom outcome and hospitalizations for a group of first episode patients with psychotic disorders. Social support was measured using items from the provider version of the Wisconsin Quality of Life Scale as assessed at the time of initiation of treatment for 113 patients. Outcome was assessed by level of positive and negative symptoms at three-year follow-up and number of psychiatric admissions during those three years. Higher levels of social support were found to correlate with lower levels of positive symptoms and few hospitalizations at follow-up. The relationship of social support to follow-up symptoms and hospitalization was independent of other potential predictors such as gender, age, premorbid adjustment and duration of untreated illness.

This study was carried out to identify characteristics of patients with schizophrenia spectrum disorder who continue to have persistent psychoses (15%) for 2 years after initiation of treatment by comparing them to those who maintained full recovery of positive symptoms (42%) up to 2 years. Compared to those in recovery, significantly more patients with persistent psychoses were single, male, had a higher prevalence of drug abuse and abnormal EEG findings at presentation for treatment. Duration of untreated psychoses or untreated illness did not discriminate between the groups.

Objective: There has been increased interest in the potential of early intervention to positively influence outcome in first-episode psychosis (FEP) and, consequently, to influence mental health policy and practice. This study's objective was to examine the concept of early intervention and the evidence that currently exists to support such a shift in the delivery of care., Method: We examined the evidence for phase-specific treatment of FEP, looking for interventions that attempt to arrest the transition from a putative prodromal state to full psychosis, as well as for interventions that attempt to reduce delay in treatment., Results: Some evidence supports specialized FEP interventions for short-term outcome in terms of symptom reduction, relapse rates, and greater adherence to and retention in treatment. As well, there is modest support for benefits to aspects of social and community functioning and satisfaction with life. Limited evidence supports a positive effect of community-wide case detection in terms of reduced delays in treatment and pharmacologic and psychological interventions in the prodromal phase., Conclusions: The field of early intervention in psychosis is young, with encouraging preliminary results, especially for improving outcome in established FEP. It requires further study, especially of longer-term outcome. Further studies need to examine the effects of a specialized approach on longer-term outcome and to explore cost-effective methods to reduce delays in treatment and provide interventions in the prodromal phase.

Objective: Recent evidence suggests that premorbid adjustment in schizophrenia and related disorders can be separated into social and academic domains. In this paper, we examine the correlates of and prognostic significance of social and academic premorbid adjustment in a sample of 113 patients., Method: Premorbid adjustment, symptoms and cognitive functioning were assessed at presentation for treatment and symptoms were re-assessed after a year of treatment., Results: Females and those with a diagnosis of schizoaffective disorder were found to have better premorbid adjustment in the academic domain, but not in the social domain. Neurocognitive functioning was more consistently related to academic than social adjustment. Better social and academic premorbid adjustment was correlated with lower negative symptoms after 1 year of treatment, but neither was a significant predictor of positive symptoms., Conclusion: Social and academic premorbid adjustments show different relations to gender, specific diagnosis and neurocognitive functioning in schizophrenia and related disorders., (Copyright Blackwell Munksgaard 2005.)

From the very inception of the modern diagnostic scheme for psychotic disorders, abnormalities in motor function have been observed in these conditions. Despite convergence from multiple areas of research supporting the notion that multiple frontal-subcortical circuits regulate motor and limbic behavior, the precise relationship between motor abnormalities and psychopathology has not been elucidated. The goals of this study were to examine the prevalence of extrapyramidal signs (EPS) in first-episode schizophrenia patients and their relationships to three psychopathological dimensions (positive psychosis syndrome, negative syndrome, and disorganization). We assessed EPS using traditional observer-based as well as quantitative instrumental measures in 39 neuroleptic-naive first-episode schizophrenia subjects. Subjects were followed for 6 months after initiating antipsychotic treatment to examine the stability of motor-limbic relationships. Four main findings emerged from this study. First, depending on the measure used the prevalence of dyskinesia prior to treatment ranged from 13% to 20%. The prevalence of parkinsonism ranged from 18% to 28%. Second, severity of dyskinesia was associated with the positive psychotic syndrome; whereas parkinsonism was associated with the positive psychosis, negative syndrome and disorganization. Third, psychopathology improved significantly across all symptom dimensions following antipsychotic treatment, while EPS remained stable. This suggests that some motor abnormalities in schizophrenia may reflect trait characteristics. Fourth, abnormalities on the pre-treatment instrumental measure of parkinsonism predicted greater improvement on positive psychosis symptoms following treatment (p=0.008). Our findings support the notion that neuromotor disturbances may be a core feature of schizophrenia in a substantial proportion of patients and implicate multiple fronto-striatal circuits regulating limbic and neuromotor behavior in schizophrenia.

The frequency of various early signs of illness was examined in 96 first-episode patients suffering from schizophrenia, schizoaffective, or schizophreniform disorder. A factor analysis of these early signs was performed, and each of the five dimensions identified was examined for its relation to symptoms of psychosis at presentation and after 1 year of treatment. The results suggested five primary dimensions of early signs: emotional dysphoria and odd perceptual and cognitive content, impaired functioning, changes related to psychobiological or vegetative functioning, suspiciousness accompanied by difficulties in concentration, and irritability/aggression. Impaired functioning in the prepsychosis period was associated with higher negative symptoms at presentation for treatment, and higher levels of psychobiological changes were associated with lower positive symptoms of psychosis after a year of treatment. The latter findings may indicate that patients with more profound indications of affective disturbance or stress have a better prognosis.

N-acetylaspartate (NAA) has been associated with neuronal integrity and function, and choline-containing compounds have been linked to neuronal membrane integrity. This study examined the influence of the duration of untreated psychosis, duration of prodromal symptoms and total length of untreated illness on these markers of neuronal loss or damage. In vivo 1H magnetic resonance spectroscopy data were acquired from 1.5-cc volumes in the left anterior cingulate and left thalamus of 19 never-treated first episode schizophrenic subjects using STEAM20 at 4.0 Tesla. Duration of untreated psychosis, prodrome and total length of untreated illness were correlated with levels of NAA and choline. No significant correlation was observed between NAA and duration of untreated psychosis and untreated illness in both regions examined. Thalamic NAA negatively correlated with duration of prodromal symptoms. A positive correlation between choline and duration of untreated psychosis was identified in both regions studied. Delays in treatment of psychotic symptoms of schizophrenia were not associated with a reduction in markers of neuronal integrity or function in contrast to longer prodromal periods, which were associated with lower NAA. Neuronal damage, potentially detectable via lower NAA, may be occurring before the onset of psychosis. Increased choline is associated with longer duration of untreated psychosis and could indicate that psychosis-related membrane alterations precede the appearance of NAA reductions observed by studies of chronic schizophrenia.

Patients with schizophrenia who show persistent negative symptoms are an important subgroup, but they are difficult to identify early in the course of illness. The objective of this study was to examine characteristics that discriminate between first-episode psychosis (FEP) patients in whom primary negative symptoms did or did not persist after 1 year of treatment. Patients with a DSM-IV diagnosis of FEP whose primary negative symptoms did (N = 36) or did not (N = 35) persist at 1 year were contrasted on their baseline and 1-year characteristics. Results showed that patients with persistent primary negative symptoms (N = 36) had a significantly longer duration of untreated psychosis (p < .005), worse premorbid adjustment during early (p < .001) and late adolescence (p < .01), and a higher level of affective flattening (p < .01) at initial presentation compared with patients with transitory primary negative symptoms. The former group also showed significantly lower remission rates at 1 year (p < .001). Multiple regression analysis confirmed the independent contribution of duration of untreated psychosis, premorbid adjustment, and affective flattening at baseline to the patients' likelihood of developing persistent negative symptoms. It may therefore be possible to distinguish a subgroup of FEP patients whose primary negative symptoms are likely to persist on the basis of characteristics shown at initial presentation for treatment.

Background: A lengthy delay often occurs between the onset of symptoms of psychotic disorders and initiation of adequate treatment. In this paper we examine the extent to which this represents a delay in individuals contacting health professionals or a delay in receiving treatment once such contact is made., Method: Pathways to care were examined in 110 patients of the Prevention and Early Intervention Program for Psychosis in London, Canada. Data were collected using structured interviews with patients, family members, consultation with clinicians and review of case records., Results: Family physicians and hospital emergency rooms were prominent components of pathways to care. Both delay to contact with a helping professional and delay from such contact to initiation of adequate treatment appear to be about equally important for the sample as a whole, but some individuals appear to be at risk for particularly lengthy delay in the second component. Individuals with younger age of onset, or who had initial contact with professional helpers before the onset of psychosis and were being seen on an ongoing basis at the time of onset of psychosis, had longer delays from first service contact after onset to initiation of adequate treatment. The greater delay to treatment for those being seen at the onset of psychosis does not appear to reflect differences in age, gender, symptoms, drug use or willingness to take medication., Conclusions: Interventions to reduce treatment delay should increase the public's awareness of the symptoms of psychotic illness and the need to seek treatment, but of equal importance is the education of service providers to recognize such illness and the potential benefits of earlier intervention.

Objective: To assess patient and/or illness characteristics associated with aspects of quality of life (QOL) in first-episode psychosis (FEP)., Method: Patient characteristics, symptom ratings and Wisconsin QOL scale (client version) were assessed. Data were analysed with correlation coefficients and a hierarchical regression analysis., Results: Patients presented with varying levels of QOL on different domains. The level of 'general satisfaction' was related to age of onset and social premorbid adjustment; 'weighted index of QOL' to social premorbid adjustment and inversely to educational premorbid adjustment; 'social relations' inversely to duration of untreated psychosis (DUP), length of prodrome and negative symptoms; 'psychological well-being' inversely to depression and educational premorbid adjustment; 'activities of daily living' to social premorbid adjustment and inversely to negative symptoms; and 'outlook on symptoms' to level of depression., Conclusion: Domains of self-rated QOL in FEP patients are differentially associated with malleable and non-malleable aspects of patient and illness characteristics.

Objective: To describe changes aimed at removing barriers to appropriate and timely assessment and treatment of first-episode psychosis (FEP) and to present descriptive data regarding the potential impact of such changes on treated incidence, referral patterns, and treatment delay., Method: We collected demographic and clinical information, including duration of untreated psychosis (DUP), on 196 persons referred for an initial assessment over a 3-year period., Results: The number of identified FEP cases increased and DUP decreased over the 3-year period. The data suggest a differentially greater reduction in DUP in cases referred from sources other than health care., Conclusion: These preliminary results suggest that, when setting up programs for FEP, relatively simple changes designed to improve access may improve treated incidence and reduce treatment delays.