Measurement Based Care in a first episode psychosis program: Development of an algorithm of care based on the Clinical Global Impressions Scale.

INTRODUCTION: Adherence to therapeutic guidelines in psychiatry is anchored and facilitated by rating scales. However, they are rarely used in routine care, particularly for psychotic disorders. Consequently, adherence to treatment guidelines are not ideal and patient outcomes are often sub-optimal. In this study, we used the clinician-rated Clinical Global Impressions Scale (CGI) to implement a measurement-based care (MBC) approach and derive indices of quality of care at a first episode psychosis (FEP) program. METHODS: At the individual level, an algorithm was created using CGI scores and their changes over time to define the concept of Patient Requiring Clinical Attention (PRCA) that encompasses several categories (e.g. episode of severity, treatment inertia, or treatment resistance). At the service level, CGI scores were used to derive several indices of quality of care: severity of illness and its change over time, conformity to the use of low doses of antipsychotic medications, and clozapine offer index. RESULTS: 135 Patients were included in this study of whom 19 patients were identified as PRCA. Of these, 12 (63%) received timely medication, and 7 (37%) were suspected cases of therapeutic inertia. Additionally, 15 patients met criteria for treatment resistance of whom 7 were offered clozapine (47%). At the service level, the average CGI improved by 2 points from baseline to month 1 and average doses of antipsychotic medications prescribed were in line with prescription guidelines for FEP patients. CONCLUSION: The proposed CGI-based treatment algorithm and service evaluation strategy can help to optimize quality care and services for patients.

Pragmatic implementation of the Clinical Global Impression Scale of Severity as a tool for measurement-based care in a first-episode psychosis program.

INTRODUCTION: Measurement-based care (MBC) is an evidence-based practice wherein clinical decisions are informed by patient data collected throughout treatment. MBC has yielded superior patient outcomes compared to standard care. However, the implementation of MBC in the day-to-day practice, particularly in psychotic disorders, poses several challenges. This study evaluates the clinician-rated Clinical Global Impressions Scale of Severity (CGI-S), for MBC implementation at a first-episode psychosis program. METHODS: The CGI-S was evaluated in the context of routine care on fidelity to practice, inter-rater reliability among psychiatrists and concurrent validity with scales measuring different domains of psychopathology (SAPS, SANS, GAF, BPRS, PANSS-6). RESULTS: A high fidelity to practice (67%) and inter-rater reliability was found (rwg = 0.92). CGI-S correlations were significant and strongest with BPRS (r = 0.55; p < 0.01), GAF (r = 0.53; p < 0.01), SAPS (r = 0.52, p < 0.01), and PANSS-6 (r = 0.41; p < 0.05) scores. However, correlations with SANS and PANSS-6 Negative sub-scale were weak. CONCLUSION: Findings suggest the CGI may be used to overcome important barriers towards MBC implementation within the context of first episode psychosis. However, as suggested by data, further improvements in capturing negative symptoms by rating clinicians are needed. TWITTER: A novel strategy for measurement-based care to optimize treatment for individuals with first episode psychosis and related psychotic disorders.

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

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

Impact of childhood trauma on positive and negative symptom remission in first episode psychosis.

OBJECTIVE: Early life adversity is suspected to play an important role for onset and course of psychosis, but its relationship with longer-term clinical outcome is not entirely clear. In this longitudinal study, we investigated the impact of childhood trauma (CT) on positive and negative symptom remission in first episode psychosis (FEP) patients over two years. METHODS: A total of 210 FEP patients were assessed with the Childhood Trauma Questionnaire. Patients reporting moderate to severe trauma (CT; N = 114; 54.3%) were compared to those without trauma (N-CT; N = 96; 45.7%). Positive (PSR) and negative symptom remission (NSR) were determined monthly over 24 months following established criteria using the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms. Global Functioning was evaluated at baseline and 24 months of follow-up. RESULTS: Compared to N-CT patients, CT patients had achieved significantly lower rates of PSR at 12 months and significantly lower rates of NSR at 24 months. A dose-response relationship was observed between the number of trauma categories fulfilled and the number of patients not achieving PSR and NSR at these time points. Higher trauma scores were significantly associated with poor functioning and higher positive and negative symptom severity at 24 months, but not at baseline and 12 months of follow-up. CONCLUSION: Differential effects of CT on clinical outcome may not be apparent at psychosis onset, but only become evident through poor symptomatic remission and general functioning over time. Targeted diagnostic and therapeutic efforts after illness onset might limit these detrimental consequences.

Patient satisfaction with random assignment to extended early intervention for psychosis vs regular care: Relationship with service engagement.

AIM: We investigated whether individuals varied in their satisfaction with being randomized to an extension of early intervention (EI) for psychosis or regular care after 2 years of EI, and whether satisfaction was associated with service engagement 3 years later. METHODS: Following randomization, patients (N = 220) indicated if they were happy with, unhappy or indifferent to their group assignment. Follow-up with service providers was recorded monthly. RESULTS: Patients randomized to extended EI were more likely to express satisfaction with their group assignment than those in the regular care group (88.2% vs 31.5%, χ2 = 49.96, P < .001). In the extended EI group, those happy with their assigned group were likelier to continue seeing their case manager for the entire five-year period than those who were unhappy/indifferent (χ2 = 5.61, P = .030). CONCLUSIONS: Perceptions about EI, indicated by satisfaction with being assigned to extended EI, may have lasting effects on service engagement.

Economic Evaluation of Extended Early Intervention Service vs Regular Care Following 2 Years of Early Intervention: Secondary Analysis of a Randomized Controlled Trial.

Cost-effectiveness studies of early intervention services (EIS) for psychosis have not included extension beyond the first 2 years. We sought to evaluate the cost-effectiveness of a 3-year extension of EIS compared to regular care (RC) from the public health care payer's perspective. Following 2 years of EIS in a university setting in Montreal, Canada, patients were randomized to a 3-year extension of EIS (n = 110) or RC (n = 110). Months of total symptom remission served as the main outcome measure. Resource use and cost data for publicly covered health care services were derived mostly from administrative systems. The incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve were produced. Relative cost-effectiveness was estimated for those with duration of untreated psychosis (DUP) of 12 weeks or less vs longer. Extended early intervention had higher costs for psychiatrist and nonphysician interventions, but total costs were not significantly different. The ICER was $1627 per month in total remission. For the intervention to have an 80% chance of being cost-effective, the decision-maker needs to be willing to pay $5942 per month of total symptom remission. DUP ≤ 12 weeks was associated with a reduction in costs of $12 276 even if no value is placed on additional months in total remission. Extending EIS for psychosis for people, such as those included in this study, may be cost-effective if the decision-maker is willing to pay a high price for additional months of total symptom remission, though one commensurate with currently funded interventions. Cost-effectiveness was much greater for people with DUP ≤12 weeks.

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

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

The Trier Social Stress Test in first episode psychosis patients: Impact of perceived stress, protective factors and childhood trauma.

Psychosis has been associated with abnormalities in hypothalamic-pituitary-adrenal axis functioning, which may emerge through heightened stress sensitivity following early life adversity - ultimately resulting in illness onset and progression. The present study assessed cortisol levels during an established psychosocial stress task and their association with current stress perception, putative protective factors and adverse childhood experiences in patients with a first episode of psychosis (FEP). A total of 100 volunteers participated in the study, 57 of whom were patients with a FEP (mean age 23.9 ± 3.8) and 43 healthy community controls (mean age 23.2 ± 3.9). Salivary cortisol, heart rate and blood pressure were measured at eight time points before and after the Trier Social Stress Test. Subjective stress and protective factors were assessed with the Perceived Stress Scale, the Self-Esteem Rating Scale and the Brief COPE. Early life adversity was assessed with the Childhood Trauma Questionnaire. Patients compared to controls showed significantly lower cortisol levels (F = 7.38; p = .008) throughout the afternoon testing period, but no difference in the cortisol response to the TSST. Heart rate was elevated and protective factors were lower in patients compared to controls. Attenuated cortisol levels were associated with higher levels of perceived stress, poor protective factors and more physical neglect during childhood. Our results suggest that attenuated baseline cortisol levels and not a blunted response during an acute stress task might be an indicator of heightened stress vulnerability and poor resilience in psychosis. The possible influence of childhood adversity and antipsychotic medication is discussed.

Progress of negative symptoms over the initial 5 years of a first episode of psychosis.

BACKGROUND: Specialized early intervention (EI) following a first episode of psychosis (FEP) are effective at reducing negative symptoms, although its trajectory warrants systematic assessment. However, findings are equivocal as to whether extended gains are made post 2 years of EI and whether there is additional benefit of extending EI for an additional 3 years. METHODS: Data on 178 FEP patients, from a randomized controlled trial of a 3-year extension of EI service v. transfer to regular care following 2 years of EI service, were used for this report. Repeated measures analysis of variance were conducted separately for the initial 2 years of treatment in an EI service, and for the 3-year post-randomization to examine trajectories of negative symptoms over the two periods in the two arms of the study. RESULTS: There were significant improvements in total negative symptoms over the first 2 years of EI F(4.612, 797.905) = 25.263, p < 0.001 and in domains of 'expressivity' and 'motivation'. In the following 3 years, there were further significant improvements in negative symptoms F(4.318, 759.908) = 4.182, p = 0.002 with no difference between groups F(4.318, 759.908) = 1.073, p = 0.371. Changes in negative symptoms over the extension period were driven by expressivity F(4.01, 674.73) = 7.19, p < 0.01, but not motivation F(6.58, 1112.18) = 0.95, p = 0.46. CONCLUSION: Negative symptoms improve significantly over the first 2 years of EI. Subsequent amelioration was largely the result of expressivity. Motivation deficits remained stable. Extended EI offered no advantage over regular care post-randomization.

Gender differences in childhood trauma in first episode psychosis: Association with symptom severity over two years.

Early life adversity is associated with increased risk for psychosis onset and poor clinical outcome. Male compared to female patients often show a more severe course of psychotic illness. The aim of the present study was to investigate gender differences in childhood trauma (CT) and their impact on symptomatic and functional outcome following psychosis onset. The study included 210 patients (144 men, 66 women) diagnosed with a first-episode of psychosis (FEP). Early adversity was assessed with the Childhood Trauma Questionnaire. Psychotic symptoms and general functioning were rated with the Brief Psychiatric Rating Scale and Global Assessment of Functioning scale at baseline, 12 and 24 months of follow-up in an established early intervention service. Male patients reported higher rates of physical or emotional neglect, whereas female patients indicated significantly higher rates of emotional abuse. More severe CT was related to higher levels of depression in women and to negative symptoms in men. Distinct CT effects were observed on positive and negative symptom severity and global functioning in male patients at 24 months. Emotional abuse was the strongest predictor of depression in both genders. In male patients only, emotional abuse predicted positive symptom severity and impaired global functioning, whereas emotional neglect predicted more severe negative symptoms. Our results suggest differences in CT experiences in male and female FEP patients, with a more pronounced impact on longer-term outcome in male patients. The findings support the notion that sex differences in stress vulnerability account for the relatively poor illness course in male psychosis patients.

Description, evaluation and scale-up potential of a model for rapid access to early intervention for psychosis.

AIM: This paper aims to describe the entry protocol of the Prevention and Early Intervention for Psychosis Program (PEPP)-Montreal, an early intervention program for psychosis. The protocol is designed to fulfil a key objective of the early intervention movement-reducing delays to accessing high-quality care. The paper also aims to describe how this rapid entry protocol can be deployed in other services interested in reducing delays in initiating treatment. METHODS: PEPP provides rapid, easy access to quality care by placing a single, well-trained professional, the intake clinician, at the point of entry. Anyone can refer a youth directly and without formalities to the intake clinician who responds promptly and sensitively to all help-seeking, whether by a youth, a family member, a school counsellor or anyone acting on behalf of a youth in need. To promote accessibility, PEPP guarantees an initial assessment within 72 hours; maintains relationships with referral sources; and conducts awareness-enhancing outreach activities. RESULTS: Since 2003, PEPP has received 1750 referrals, which have all been responded to within 72 hours. Families have been involved in the intake process in 60% of the cases and hospitalization may have been averted in over half of the referrals originating from emergency-room services. Another indicator of success is the very low turnover in the intake clinician's position. Overall, the PEPP model has succeeded in providing rapid, engaging, easy and youth-friendly access to high-quality care. CONCLUSION: The success of this protocol at PEPP has inspired the entry protocols at other first-episode psychosis services. Its ability to provide rapid, engaging access to high-quality services may allow this protocol to become a model for other early intervention services for psychosis and other mental illnesses.

Comparing three-year extension of early intervention service to regular care following two years of early intervention service in first-episode psychosis: a randomized single blind clinical trial.

This study aimed to determine if, following two years of early intervention service for first-episode psychosis, three-year extension of that service was superior to three years of regular care. We conducted a randomized single blind clinical trial using an urn randomization balanced for gender and substance abuse. Participants were recruited from early intervention service clinics in Montreal. Patients (N=220), 18-35 years old, were randomized to an extension of early intervention service (EEIS; N=110) or to regular care (N=110). EEIS included case management, family intervention, cognitive behaviour therapy and crisis intervention, while regular care involved transfer to primary (community health and social services and family physicians) or secondary care (psychiatric outpatient clinics). Cumulative length of positive and negative symptom remission was the primary outcome measure. EEIS patients had a significantly longer mean length of remission of positive symptoms (92.5 vs. 63.6 weeks, t=4.47, p<0.001), negative symptoms (73.4 vs. 59.6 weeks, t=2.84, p=0.005) and both positive and negative symptoms (66.5 vs. 56.7 weeks, t=2.25, p=0.03) compared to regular care patients. EEIS patients stayed in treatment longer than regular care patients (mean 131.7 vs. 105.3 weeks, t=3.98, p<0.001 through contact with physicians; 134.8 ± 37.7 vs. 89.8 ± 55.2, t=6.45, p<0.0001 through contact with other health care providers) and received more units of treatment (mean 74.9 vs. 39.9, t=4.21, p<0.001 from physicians, and 57.3 vs. 28.2, t=4.08, p<0.001 from other health care professionals). Length of treatment had an independent effect on the length of remission of positive symptoms (t=2.62, p=0.009), while number of units of treatment by any health care provider had an effect on length of remission of negative symptoms (t=-2.70, p=0.008) as well as total symptoms (t=-2.40, p=0.02). Post-hoc analysis showed that patients randomized to primary care, based on their better clinical profile at randomization, maintained their better outcome, especially as to remission of negative symptoms, at the end of the study. These data suggest that extending early intervention service for three additional years has a positive impact on length of remission of positive and negative symptoms compared to regular care. This may have policy implications for extending early intervention services beyond the current two years.

The Clinic for Assessment of Youth at Risk (CAYR): 10 years of service delivery and research targeting the prevention of psychosis in Montreal, Canada.

AIM: In the context of an increasing focus on indicated prevention of psychotic disorders, we describe the operation of the Clinic for Assessment of Youth at Risk (CAYR) over 10 years, a specialized service for identification, monitoring and treatment of young individuals who meet ultra-high risk (UHR) criteria for psychosis, and its integration within the Prevention and Early Intervention Program for Psychosis (PEPP) in Montreal, Canada. METHODS: We outline rationale, development, inclusion and exclusion criteria, assessment, services offered, community outreach and liaison with potential referral sites, and our research focus on risk and protective factors related to the neural diathesis-stress model of psychosis. RESULTS: Between January 2005 and December 2014, CAYR has received 370 referrals and accepted 177 patients who met UHR criteria based on the Comprehensive Assessment for At Risk Mental States. Conversion rates to a first episode of psychosis were 11%. Our research findings point to high subjective stress levels, poor self-esteem, social support and coping skills, and a dysregulation of the hypothalamus-pituitary-adrenal axis during the high-risk phase. CONCLUSIONS: Our efforts at community outreach have resulted in increasing numbers of referrals and patients accepted to CAYR, highlighting the relevance of and need for a high-risk programme in the Montreal area. Patients with psychotic symptoms can be immediately assigned to the first-episode psychosis clinic within PEPP, which has likely contributed to the low conversion rates observed in the UHR group. Our research findings on stress and protective factors emphasize the importance of psychosocial interventions for high-risk patients.

Therapeutic effectiveness and tolerability of aripiprazole as initial choice of treatment in first episode psychosis in an early intervention service: A one-year outcome study.

INTRODUCTION: Aripiprazole has been associated with a low prevalence of metabolic side effects as compared to other second generation antipsychotic (SGA) medications mostly in patients with long standing illness. The purpose of the present study was to assess specifically the effectiveness and safety of aripiprazole as a first choice for antipsychotic therapy for young patients presenting with a previously untreated first episode of a psychotic disorder (FEP). METHODS: Seventy-three patients presenting with a FEP and with minimal prior exposure to antipsychotic medications were recruited to be part of an open label naturalistic outcome study using aripiprazole as the first choice of antipsychotic medication. Data on positive, negative and total symptom severity including general psychopathological symptoms, level of functioning and metabolic indices were collected prospectively over a one-year period. RESULTS: As compared to baseline, patients treated with aripiprazole (mean dose 9.6mg) improved significantly on measures of positive (p<0.001), negative (p<0.001) and total severity-general psychopathology symptoms (p<0.001) and level of functioning (p<0.001). Seventy two percent of the participants achieved positive symptom remission and 50% achieved total remission (positive and negative) at one year of follow up. Unlike reports on patients with longer standing illness, significant weight gain (p<0.001) was observed, with 44% of participants experiencing >7% increase in body weight. CONCLUSION: FEP patients starting treatment with aripiprazole improved on symptoms and social and occupational functioning. Aripiprazole was well tolerated except for a significant weight gain.

A five-year randomized parallel and blinded clinical trial of an extended specialized early intervention vs. regular care in the early phase of psychotic disorders: study protocol.

BACKGROUND: Specialized Early Intervention services (SEI) for first episode psychosis are shown to be effective for the treatment of positive and negative symptoms, medication adherence, rates of relapse, substance abuse disorders, functional outcome and quality of life at two-year treatment follow up. However, it is also reported that these benefits are not maintained when SEI is not sustained. The objective of this trial is to test the efficacy of a 3-year extension of a SEI service (following 2 years of SEI prior to randomization) for the maintenance and consolidation of therapeutic gains as compared to regular care in the community. METHODS: Following an initial 2 years of SEI, patients are randomized to receive either 3-years of continued SEI or regular care. SEI provided at three sites within the McGill network of SEI services, using a model of treatment comprised of: modified assertive case management; psycho education for families; multiple family intervention; cognitive behavioural therapy; and substance abuse treatment and monitoring. Blinded research assistants conduct ongoing evaluation of the outcome variables every three months. The primary outcome measure is remission status measured both as the proportion of patients in complete remission and the mean length of remission achieved following randomization during the additional three years of follow up. Based on preliminary data, it is determined that a total of 212 patients are needed to achieve adequate statistical power. Intent to treat with the last observation carried forward will be the primary method of statistical analysis. DISCUSSION: The "critical period" hypothesis posits that there is a five year window during which the effects of the nascent psychotic illness can be countered and the impact of the disorder on symptomatic and functional outcomes can be offset through active and sustained treatment. Providing SEI throughout this critical period may solidify the benefits of treatment such that gains may be more sustainable over time as compared to intervention delivered for a shorter period. Findings from this study will have implications for service provision in first episode psychosis. TRIAL REGISTRATION: ISRCTN11889976.

Medication-adherent first-episode psychosis patients also relapse: why?

OBJECTIVE: Poor adherence to medication is a major determinant of relapse following treatment of first-episode psychosis (FEP). However, medication-adherent patients also relapse. We examined what factors influence the risk of relapse after controlling for adherence. METHOD: We selected a sample of fully adherent patients (n = 65) who had achieved remission at one point. We then compared patients who relapsed, using 2 different definitions of relapse, to those who did not relapse by 12 months on age, sex, premorbid adjustment, duration of untreated psychosis, length of prodrome, and substance abuse. RESULTS: Among the 65 medication-adherent patients in remission, 9 (14%) relapsed according to criteria for relapse requiring a change in medication. These patients differed from those who remained in remission only in the pattern of premorbid adjustment (greater proportion with deteriorating pattern), although this was not independent of other variables. No differences were found on any other variable. Using a more commonly used metric for relapse, based on symptom ratings alone, an additional 14 (21.5%) patients relapsed. Substance abuse significantly predicted relapse, with substance abusers having more than 25 times the odds of relapsing by 12 months (OR 25.6; 95% CI 2.4 to 278.1, P = 0.008). CONCLUSION: Using a more conservative definition of relapse in this adherent-to-medication population, we find a very low rate of relapse associated, at least partially, with poor premorbid adjustment. As substance abuse was a significant predictor of symptomatic relapse, this would suggest that there should be a greater emphasis on interventions focused on reducing substance abuse in FEP.

Sex differences in the cortisol response to awakening in recent onset psychosis.

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.