Hypothalamic subunit volumes and relations to violence and psychopathy in male offenders with or without a psychotic disorder.

The hypothalamus is key to body homeostasis, including regulating cortisol, testosterone, vasopressin, and oxytocin hormones, modulating aggressive behavior. Animal studies have linked the morphology and function of the hypothalamus to aggression and affiliation, with a subregional pattern reflecting the functional division between the hypothalamic nuclei. We explored the relationship between hypothalamic subunit volumes in violent offenders with (PSY-V) and without (NPV) a psychotic disorder, and the association with psychopathy traits. 3T MRI scans (n = 628, all male 18-70 years) were obtained from PSY-V, n = 38, NPV, n = 20, non-violent psychosis patients (PSY-NV), n = 134, and healthy controls (HC), n = 436. The total hypothalamus volume and its eleven nuclei were delineated into five subunits using Freesurfer v7.3. Psychopathy traits were assessed with Psychopathy Checklist-revised (PCL-R). ANCOVAs and linear regressions were used to analyze associations with subunit volumes. Both groups with a history of violence exhibited smaller anterior-superior subunit volumes than HC (NPV Cohen's d = 0.56, p = 0.01 and PSY-V d = 0.38, p = 0.01). There were no significant differences between HC and PSY-NV. PCL-R scores were positively associated with the inferior tubular subunit on a trend level (uncorrected p = 0.045, Cohen's d = 0.04). We found distinct hypothalamic subunit volume reductions in persons with a history of violence independent of concomitant psychotic disorder but not in persons with psychosis alone. The results provide further information about the involvement of the hypothalamus in aggression, which ultimately may lead to the development of targeted treatment for the clinical and societal challenge of aggression and violent behavior.

Mental health disorders, functioning and health-related quality of life among extensively hospitalized patients due to severe self-harm - results from the Extreme Challenges project.

Background: Severe self-harm leading to extensive hospitalization generates extreme challenges for patients, families, and health services. Controversies regarding diagnoses and health care often follow. Most evidence-based treatments targeting self-harm are designed for borderline personality disorder (BPD). However, current knowledge about mental health status among individuals with severe self-harm is limited. Objectives: To investigate psychopathology among patients extensively hospitalized due to severe or frequent self-harming behaviors. Method: A cross sectional study (period 2019-2021) targeting psychiatric inpatients (>18 years) with frequent (>5) or long (>4 weeks) admissions last year due to self-harm. The target sample (N = 42, from 12 hospitals across all Norwegian health regions) was compared to individuals admitted to outpatient personality disorder (PD) treatment within specialist mental health services in the same period (N = 389). Clinicians performed interviews on self-harm and psychopathology, supplemented by self-report. Results: The target sample were young adults, mainly female, with considerable hospitalization and self-harming behaviors, both significantly more extensive than the comparison group. The majority in both groups reported self-harm onset <18 years. The target sample reported increasing severity of self-harm acts and suicidal intention over time. Both samples had high levels of childhood trauma, impaired personality functioning, and a majority fulfilled criteria for PD. In the target sample, comorbid depression, PTSD, anxiety disorders, and substance use occurred more frequently and in 50%, psychosis/dissociative disorder/autism spectrum disorder/ADHD was reported (outpatient comparison sample: 9%). 35% in the target sample screened over cut-off for possible intellectual disability. The target sample reported poor psychosocial functioning and health-related quality of life - greater impairment than the outpatient comparison sample. Conclusion: The study reveals that severe self-harm inpatients have complex psychopathology and highlights the importance of individualized and thorough assessment among patients with severe and/or repetitive self-harm.

Tobacco smoking related to childhood trauma mediated by cognitive control and impulsiveness in severe mental disorders.

BACKGROUND: People with severe mental disorders (SMDs) show an increased prevalence of tobacco smoking compared to the general population. Tobacco smoking and other adult adverse health behaviors have been associated with traumatic experiences in childhood. In the present study we investigated the relationship between childhood trauma and tobacco smoking in people with SMDs, including the possible mediating role of cognitive- and personality characteristics, i.e. cognitive control, impulsiveness, affective lability and self-esteem. METHODS: Enrolled in the study were 871 participants with schizophrenia (SCZ, N = 484) and bipolar (BD, N = 387) spectrum disorders. We assessed tobacco smoking behavior (yes/no and amount), and history of childhood trauma with the Childhood Trauma Questionnaire. Data on cognitive control, impulsiveness, affective lability, and self-esteem were available in subsamples. We performed linear and logistic regressions, and conducted mediation analyses in PROCESS. All analyses were as standard adjusted for age, sex, and diagnostic group. RESULTS: Experience of one or more subtypes of childhood trauma was significantly associated with smoking tobacco in SMDs (p = 0.002). There were no significant associations between childhood trauma and amount of tobacco smoking. Cognitive control and impulsiveness were significant mediators between childhood trauma and tobacco smoking. CONCLUSIONS: These findings indicate the experience of childhood trauma as a predisposing factor for tobacco smoking in SMDs. Cognitive control and impulsiveness were suggested as mediating mechanisms, indicating the importance of considering inhibition related self-regulatory aspects in efforts to improve health behavior in individuals with SMDs and childhood trauma.

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. Funding: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

Vocational rehabilitation augmented with cognitive behavioral therapy or cognitive remediation for individuals with schizophrenia: a 5-year follow-up study.

INTRODUCTION: Although employment is an important part of recovery for individuals with schizophrenia spectrum disorders, the employment rate for this group remains low. Increasing evidence supports the use of augmented vocational rehabilitation (VR) programs to improve occupational outcome. The aim of this study is to explore 5-year follow-up registry data from the JUMP study, a VR program for individuals with schizophrenia spectrum disorders, specifically with regard to competitive employment outcome and predictors of competitive employment. The VR was augmented with either cognitive remediation (CR) or elements from cognitive behavior therapy (CBT). METHODS: One hundred and forty eight participants with schizophrenia spectrum disorders from six Norwegian counties received 10 months VR augmented with either CR (n = 64) or CBT (n = 84). Both competitive and sheltered workplaces were used. Assessments were conducted at baseline, at post intervention and at 2-year follow-up. Data on employment status at 5-year follow-up was obtained by registry. RESULTS: At 5-year follow-up 55.4% were engaged in working activity, of which 22.3% had obtained competitive employment. A further 18.2% had work placements in competitive workplaces. Number of received intervention hours and competitive employment at 2-year follow-up emerged as significant predictors of competitive employment. IQ and intervention type in marginal favor of CBT were predictors on trend level. CONCLUSION: To the best of our knowledge, this is the first study investigating competitive employment at 5-year follow-up for individuals with schizophrenia spectrum disorders. The results add to existing evidence that competitive employment is attainable for this group.

Psychopathy subdomains in violent offenders with and without a psychotic disorder.

BACKGROUND: Violence in psychosis has been linked to antisocial behavior and psychopathy traits. Psychopathy comprises aspects of interpersonal, affective, lifestyle, and antisocial traits which may be differently involved in violent offending by persons with psychotic disorders. We explored psychopathy subdomains among violent offenders with and without a psychotic disorder. METHODS: 46 males, with a history of severe violence, with (n = 26; age 35.85 ± 10.34 years) or without (n = 20; age 39.10 ± 11.63 years) a diagnosis of a psychotic disorder, were assessed with the Psychopathy Checklist-Revised (PCL-R). PCL-R was split into subdomains following the four-facet model. Group differences in total and subdomain scores were analyzed with a general linear model with covariates. RESULTS: Total PCL-R scores did not differ between the groups (p = 0.61, Cohen's d = 0.17). The violent offenders without psychotic disorders had higher facet 2 scores than the patient group with psychotic disorders (p = 0.029, Cohen's d = 0.77). Facet 1, 3, or 4 scores did not differ between the groups. Controlling for age did not alter the results. CONCLUSION: Patients with a psychotic disorder and a history of severe violence have lower affective psychopathy scores than violent offenders without psychotic disorders. This observation may point toward distinct underlying mechanisms for violence and may provide a target for focused treatment and prevention.

Severe Mental Illness and Cardiovascular Disease: JACC State-of-the-Art Review.

People with severe mental illness, consisting of schizophrenia, bipolar disorder, and major depression, have a high burden of modifiable cardiovascular risk behaviors and conditions and have a cardiovascular mortality rate twice that of the general population. People with acute and chronic cardiovascular disease are at a higher risk of developing mental health symptoms and disease. There is emerging evidence for shared etiological factors between severe mental illness and cardiovascular disease that includes biological, genetic, and behavioral mechanisms. This state-of-the art review will describe the relationship between severe mental illness and cardiovascular disease, explore the factors that lead to poor cardiovascular outcomes in people with severe mental illness, propose strategies to improve the cardiovascular health of people with severe mental illness, and present areas for future research focus.

Coping, Social Support and Loneliness during the COVID-19 Pandemic and Their Effect on Depression and Anxiety: Patients' Experiences in Community Mental Health Centers in Norway.

Background: Little is known about psychiatric patients' experiences during the COVID-19 pandemic. The purpose of this study was to investigate associations of coping strategies, social support and loneliness with mental health symptoms among these patients. Methods: We recruited 164 patients from Community Mental Health Centers in June-July 2020. Participants responded to an online questionnaire on corona-related questions, Brief Coping Orientation to Problems Experience, Crisis Support Scale, a 3-item Loneliness Scale, and Hopkins Symptom Checklist-25. We used linear regression models to investigate associations between these and symptoms of depression and anxiety. Results: Almost 51% were aged 31-50 years and 77% were females. Forty-six (28%) participants reported worsened overall mental health due to the pandemic. The reported rates of clinical depression and anxiety were 84% and 76%, respectively. Maladaptive coping was independently associated with both depression and anxiety symptoms. Loneliness was independently associated with depression symptoms. Conclusions: Patients in Community Mental Health Centers in Norway reported high rates of depression and anxiety symptoms. Many of them reported worsening of their mental health due to the pandemic, even at a time when COVID-19 infections and restrictive measures were relatively low. Maladaptive coping strategies and loneliness may be possible explanations for more distress.

Childhood trauma and cardiometabolic risk in severe mental disorders: The mediating role of cognitive control.

BACKGROUND: Cardiometabolic risk is increased in severe mental disorders (SMDs), and there appears to be a relationship between childhood trauma and cardiometabolic risk, possibly related to adverse health behavior. The current study examined the association between childhood trauma and serum lipids and adiposity in SMDs and the potential mediating role of cognitive and personality characteristics. METHODS: Participants with schizophrenia and bipolar spectrum disorders (N = 819) were included, cardiometabolic risk factors (serum lipids, body mass index, and waist circumference) were measured, and history of childhood trauma was assessed by the Childhood Trauma Questionnaire. Cognitive and personality characteristics were available in subsamples, with assessments of cognitive control, impulsiveness, self-esteem, and affective lability. Linear regressions and mediation analyses with Hayes' PROCESS were performed, adjusting for age, sex, antipsychotic agent propensity of metabolic side-effect, and diagnostic group. RESULTS: Experience of three or more subtypes of childhood trauma was positively associated with waist circumference in patients with SMDs (p = 0.014). There were no other significant associations between trauma variables and lipid or adiposity measures in the total sample. Cognitive control was a significant mediator between experience of one or two subtypes of childhood trauma and waist circumference. CONCLUSIONS: The results indicate childhood trauma as a predisposing factor for increased waist circumference in individuals with SMDs. Poorer cognitive control, suggestive of adverse health behavior, might be a mediating factor of the association, and the findings indicate the potential importance of increased focus on these factors in prevention and treatment regimens targeting cardiometabolic health.

Improving quality of antipsychotic polypharmacy: a pilot study.

Background: Concurrent prescription of more than one type of antipsychotic for the same patient - antipsychotic polypharmacy (APP) - is associated with increased incidence of side effects, uncertain therapeutic benefit and general guidelines advise against it. Nevertheless, APP is common and there is little evidence about possible interventions to improve practice.Aims: To investigate the prevalence and documentation quality of APP in specialized psychiatric care and assess the feasibility and effect of a simple intervention to improve clinical practice.Methods: We examined the prevalence and the quality of documentation of APP in medical records from a large inpatient treatment department before and 6 months after an intervention, which consisted of giving feedback to doctors on their prescription practices as well as teaching about current guidelines. Prescription and documentation before and after intervention were compared between intervention and control wards.Results: One hundred and twenty-one medical records were examined at baseline. 43% of these had APP, of these 27% was satisfactory documented. After the intervention, the proportion with APP was reduced from 42% to 29% in the intervention group. There was a statistically significant interaction effect of the intervention group and the after-intervention condition on this reduction. The percentage with satisfactory documentation of APP was increased after the intervention in both groups, but we found no corresponding interaction effect.Conclusion: APP is prevalent in inpatient treatment of patients with mainly psychotic disorders but documentation of this is insufficient. Simple education and feedback on prescription and records documentation practices may increase adherence to guidelines.

Predictors for Antipsychotic Dosage Change in the First Year of Treatment in Schizophrenia Spectrum and Bipolar Disorders.

Background: Use of antipsychotic medication is central in the treatment of psychotic disorders. However, there is limited knowledge about prescription practice of antipsychotics in the critical early phase of these disorders. Clinical guidelines recommend low dosages, but no discontinuation of antipsychotic medication during the first year of treatment in first episode patients. The main aim of this study was to identify clinical predictors for dosage change or discontinuation of antipsychotics during this period. Methods: A total of 426 antipsychotic-using patients with schizophrenia spectrum or bipolar disorder, including both a first treatment sample and a sample of patients with previous treated episodes ("multi-episode" sample) from the same diagnostic groups, underwent thorough clinical and sociodemographic assessment at study baseline and after 1 year. Prescribed dosage levels at baseline and follow-up and change in dosage or discontinuation of antipsychotics from baseline to follow-up were compared between groups, controlling for possible confounders. Results: We found reduced dosages over the first year in both first treatment groups across diagnoses, but not in multi-episode groups. Weight increase predicted dosage reduction in the schizophrenia group, while the level of psychotic symptoms at baseline predicted dosage reduction in the bipolar group. We found higher baseline levels of antipsychotic use in the schizophrenia group than in the bipolar group. Conclusion: We found indications of a trans-diagnostic reduction of prescribed dosages of antipsychotics over the first year in treatment, but with different predictors for this reduction in the two diagnostic groups. The findings increase the understanding of drivers of early medication change in psychotic disorder.

A preliminary study of cortical morphology in schizophrenia patients with a history of violence.

Clinical studies of patients with schizophrenia and a history of violence are challenging both from an ethical and practical perspective, and the neurobiological underpinnings remain largely unknown. We here present a comprehensive account of the brain cortical characteristics associated with violence in schizophrenia. We obtained 3T MRI scans and thorough clinical characterization of schizophrenia patients with a history of violence (murder, attempted murder, criminal assault, SCZ-V, n = 11), schizophrenia patients with no history of violence (SCZ-NV, n = 17), and healthy controls (HC, n = 19). Cortical thickness, area, and folding were analyzed vertex-wise across the cortical mantle (FreeSurfer). SCZ-V had significantly increased cortical folding in the visual and orbitofrontal cortex, and reduced cortical thickness within the precentral-, parietal-, temporal-, and fusiform cortex compared to SCZ-NV, as well as widespread regional thinning and increased folding compared to HC. There were no group differences in cortical area. A major limitation is the small subject sample. If replicated, the results from this pilot study suggest cortical abnormalities in areas involved in sensory processing, emotion recognition, and reward to be of importance to the neurobiology of violence in schizophrenia.

Extreme challenges: psychiatric inpatients with severe self-harming behavior in Norway: a national screening investigation.

BACKGROUND: Extreme self-harming behavior is a major challenge for patients and health services. Nevertheless, this patient population is poorly described in research literature. AIMS: The aim of this study was to assess the volume of patients with extensive psychiatric hospitalization due to extreme self-harming behaviors, the extent of severe medical sequelae, and collaboration problems within health services. METHODS: In a national screening investigation, department managers in 83 adult psychiatric inpatient institutions across all health regions in Norway were invited to participate in a brief, prepared, telephone interview. RESULTS: Sixty-one interviews were completed. Extensive hospitalization (prolonged or multiple) due to extreme self-harm was reported for the last year in all health regions and in 427 individual cases. Mean number of cases did not differ by region. Psychiatric hospitalizations were more frequent in hospital units than mental health centers. In 109 of the cases, self-harming behavior had severe medical consequences, including five deaths. In 122 of the cases, substantial collaboration problems within the health services were reported (disagreements on diagnosis, treatment needs and resources). Extensive (long-term) hospitalization was particularly associated with the combination of severe medical sequelae and collaboration problems. CONCLUSION: This investigation confirms a noteworthy, nationwide, population of severely self-harming inpatients with extensive health service use, prevalent severe medical complications, and unsatisfactory collaboration within health services. These preliminary results are alarming, and indicate a need for more profound understanding of highly complex and severe cases.

Using motivational techniques to reduce cardiometabolic risk factors in long term psychiatric inpatients: a naturalistic interventional study.

BACKGROUND: People with severe mental illness have markedly reduced life expectancy; cardiometabolic disease is a major cause. Psychiatric hospital inpatients have elevated levels of cardiometabolic risk factors and are to a high degree dependent of the routines and facilities of the institutions. Studies of lifestyle interventions to reduce cardiometabolic risk in psychiatric inpatients are few. The current study aimed at assessing the feasibility and effects of a lifestyle intervention including Motivational Interviewing (MI) on physical activity levels, cardiometabolic risk status and mental health status in psychotic disorder inpatients. METHODS: Prospective naturalistic intervention study of 83 patients at long term inpatient psychosis treatment wards in South-Eastern Norway. Patients were assessed 3-6 months prior to, at start and 6 months after a life-style intervention program including training of staff in MI, simple changes in routines and improvements of facilities for physical exercise. Assessments were done by clinical staff and included level of physical activity, motivation, life satisfaction, symptom levels (MADRS, AES-C, PANSS, and GAF) as well as anthropometric and biochemical markers of cardiometabolic risk. A mixed model was applied to analyze change over time. RESULTS: A total of 88% of patients received MI interventions, with a mean of 2.5 MI interventions per week per patient. The physical activity level was not increased, but activity level was positively associated with motivation and negatively associated with positive symptoms. Triglyceride levels and number of smokers were significantly reduced and a significant decrease in symptom levels was observed. CONCLUSIONS: The current results suggest that a simple, low cost life-style intervention program focusing on motivational change is feasible and may reduce symptoms and improve lifestyle habits in psychosis patients in long term treatment facilities. Similar programs may easily be implemented in other psychiatric hospitals. TRIAL REGISTRATION: ClinicalTrials.gov . NCT03528278 , date of registration: 05/16/2018 (retrospectively registered).

Reliability and validity of the self-report version of the apathy evaluation scale in first-episode Psychosis: Concordance with the clinical version at baseline and 12 months follow-up.

Negative symptoms have traditionally been assessed based on clinicians' observations. The subjective experience of negative symptoms in people with psychosis may bring new insight. The Apathy Evaluation Scale (AES) is commonly used to study apathy in psychosis and has corresponding self-rated (AES-S) and clinician-rated (AES-C) versions. The aim of the present study was to determine the validity and reliability of the AES-S by investigating its concordance with the AES-C. Eighty-four first-episode (FEP) patients completed the shortened 12-item AES-S and AES-C at baseline (T1) and 12 months (T2). Concordance was studied by degree of correlation, comparison of mean scores, and change and difference between diagnostic groups. The Positive and Negative Symptom Scale (PANSS) was used to study convergent and discriminative properties. High concordance was found between AES-S and AES-C at both T1 and T2 regarding mean values, change from T1 to T2, and the proportion with high levels of apathy. Both versions indicated high levels of apathy in FEP, while associations with PANSS negative symptoms were weaker for AES-S than AES-C. Controlling for depression did not significantly alter results. We concluded that self-rated apathy in FEP patients is in concordance with clinician ratings, but in need of further study.

Cardiometabolic risk factors, physical activity and psychiatric status in patients in long-term psychiatric inpatient departments.

PURPOSE: Cardiovascular diseases are a major cause for the markedly reduced life expectancy in people with severe mental illness (SMI). Hospital departments should provide adequate prevention of cardiometabolic risk by optimizing prevention and treatment. Characteristics of cardiometabolic risk factors in inpatients are still not well known. We aimed to describe the status of cardiometabolic risk factors in inpatients with SMI and identify associations with psychiatric status and treatment. METHODS: A cross sectional descriptive study of inpatients with SMI from long term psychosis treatment wards in South Eastern Norway was performed. Comprehensive assessments of cardiometabolic risk factors, physical activity, lifestyle habits, symptoms, life satisfaction and treatment were made. Associations and potential prognostic factors were analyzed using linear and logistic regressions. RESULTS: A total of 83 patients were included in the study, but many individual datasets were incomplete. Over half of the subjects had unhealthy eating habits. Obesity (class 1-3) was found in 44%, 23% had elevated fasting triglycerides, 26% had elevated blood pressure and 78% smoked daily. Low levels of physical activity were significantly associated with higher levels of depression (p = .007). A nominal increase in cardiometabolic risk factors was found for olanzapine and clozapine users. CONCLUSION: Inpatients in long term psychosis treatment wards have alarmingly high cardiometabolic risk. Level of physical activity was associated with both psychiatric and somatic health. Focus on lifestyle and somatic health should be an integral part of the treatment for hospitalized SMI patients.

Duration of untreated illness in first-treatment bipolar I disorder in relation to clinical outcome and cannabis use.

There is little knowledge about the role of the duration of untreated bipolar (DUB) illness in first-treatment bipolar disorder I (BD I), its association with symptoms at start of first treatment, and development over the first year, and limited knowledge about factors that influence the length of DUB. Substance use has shown to delay identification of primary psychiatric disorders, and while cannabis use is common in BD the role of cannabis in relationship to DUB is unclear. The aim of the present study is to examine the associations between DUB and key clinical outcomes at baseline in BD I, and at one year follow-up, and to evaluate the influence of cannabis use. Patients with first-treatment BD I (N=62) completed comprehensive clinical evaluations, which included both DUB and the number of previous episodes. There were no significant associations between DUB and key clinical outcomes. Longer duration from first manic episode to treatment was associated with risk of starting excessive cannabis use after onset of the bipolar disorder. The main finding is the lack of significant associations between features of previous illness episodes and clinical outcomes. Long duration of untreated mania seems to increase the risk for later cannabis use.

Cannabis use is associated with 3years earlier onset of schizophrenia spectrum disorder in a naturalistic, multi-site sample (N=1119).

BACKGROUND: Patients with schizophrenia spectrum disorders and substance use may have an earlier onset of illness compared to those without substance use. Most previous studies have, however, too small samples to control for confounding variables and the effect of specific types of substances. The present study aimed to examine the relationship between substance use and age at onset, in addition to the influence of possible confounders and specific substances, in a large and heterogeneous multisite sample of patients with schizophrenia spectrum disorders. METHODS: The patients (N=1119) were recruited from catchment areas in Oslo, Stavanger and Bergen, Norway, diagnosed according to DSM-IV and screened for substance use history. Linear regression analysis was used to examine the relationship between substance use and age at onset of illness. RESULTS: Patients with substance use (n=627) had about 3years earlier age at onset (23.0years; SD 7.1) than the abstinent group (n=492; 25.9years; SD 9.7). Only cannabis use was statistically significantly related to earlier age at onset. Gender or family history of psychosis did not influence the results. CONCLUSION: Cannabis use is associated with 3years earlier onset of psychosis.