Age at initiation of amphetamine use and age at onset of psychosis: The Australian Survey of High Impact Psychosis

Individuals with a psychotic disorder who had a premorbid history of amphetamine use (n = 382) were analyzed in groups according to age of initiation to amphetamine (AIA) and mean number of years of duration of premorbid exposure to amphetamine (DPEA) was calculated. Univariate General Linear Models were used to test for group differences in age at onset of psychotic illness (AOI) and DPEA. Although a temporal direct relationship between AIA and AOI was detected (mean duration 5.3 years), our findings suggested this association was spurious and better explained by a later initiation to amphetamine than to cannabis (by 2–3 years).     

The effect of cannabis use and cognitive reserve on age at onset and psychosis outcomes in first-episode schizophrenia

Objective: Cannabis use is associated with a younger age at onset of psychosis, an indicator of poor prognosis, but better cognitive function, a positive prognostic indicator. We aimed to clarify the role of age at onset and cognition on outcomes in cannabis users with first-episode schizophrenia as well as the effect of cannabis dose and cessation of use.Methods: Ninety-nine patients without alcohol or substance abuse other than cannabis were divided into lifetime users and never-users of cannabis and compared on measures of premorbid function, cognition, and clinical outcome.Results: Cannabis users demonstrated better cognition at psychosis onset, which was explained by higher premorbid IQ. They also showed better social function and neither measure changed over the subsequent 15 months. Cannabis users had an earlier age at onset of psychosis, and there was a strong linear relationship between age at first cannabis use and age at onset of both prodromal and psychotic symptoms. Cannabis use spontaneously declined over time with 3-quarters of users giving up altogether. Later age at first cannabis use predicted earlier cessation of use and this in turn was linked to fewer positive psychotic symptoms and days in hospital during the first 2 years.Conclusions: Cannabis use brings forward the onset of psychosis in people who otherwise have good prognostic features indicating that an early age at onset can be due to a toxic action of cannabis rather than an intrinsically more severe illness. Many patients abstain over time, but in those who persist, psychosis is more difficult to treat.     

Indications of a dose–response relationship between cannabis use and age at onset in bipolar disorder

Cannabis use seems to play a causal role in the development of psychotic disorders. Recent evidence suggests that it may also precipitate onset in bipolar disorder. We here investigate if there is a dose–response relationship between cannabis use and age at onset in bipolar disorder, and whether there are interactions between cannabis use and illness characteristics (presenting polarity and presence of psychosis). Consecutively recruited patients with a DSM-IV, SCID verified diagnosis of bipolar I, II or NOS disorder (n=324) participated. Two-way ANCOVAS were used to investigate the effect of levels of cannabis use (<10 times during one month lifetime, >10 times during one month lifetime or a cannabis use disorder) on age at onset, including interaction effects with illness characteristics, while controlling for possible confounders. There was a significant association indicating a dose–response relationship between cannabis use and age at onset, which remained statistically significant after controlling for possible confounders (gender, bipolar subtype, family history of severe mental illness and alcohol or other substance use disorders). There were no interaction effects between cannabis use and presenting polarity or presence of psychosis. Doses of cannabis used may affect the age at onset of bipolar disorder.     

Clinical characteristics influencing age at onset in psychotic disorders

Background

Age at onset of psychosis may carry clinical significance across psychotic disorders and appears to be associated with specific genetic abnormalities.

Methods

We used the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) to examine clinical characteristics contributing to age at onset variability in patients with schizophrenia (n = 80), schizoaffective disorder (n = 61), and bipolar disorder with psychotic features (n = 92).

Results

Age at onset did not differ across DSM-IV diagnostic groups. Multiple regression analyses revealed that comorbid lifetime cannabis, but not alcohol, abuse/dependence was associated with a statistically significant 3 years earlier age at onset of psychosis. Patients developed cannabis abuse/dependence an additional 3 years before psychosis. Patients with comorbid lifetime panic disorder also had a 4-year earlier age at onset of psychosis. The effects of panic disorder and cannabis abuse/dependence were independent of one another.

Conclusions

Early onset of psychosis, regardless of the specific DSM-IV diagnosis, is characterized by differential clinical features, notably a history of lifetime cannabis abuse/dependence. Panic disorder comorbidity is also associated with earlier age at onset of psychosis. Our findings indicate that examination of clinical and biological characteristics of patients with psychosis regardless of DSM-IV diagnosis can uncover relevant information.     

Psychosis risk as a function of age at onset

BACKGROUND: Little is known about late-onset psychosis (onset after the age 45 years) and how it relates to early-onset psychosis (before age 45 years). The aims of this study were to calculate the incidence of non-affective, non-organic psychotic symptoms across the life span and to explore the contribution of different sets of risk factors in relation to age at onset. METHODS: Data were obtained from the three measurements of the Netherlands Mental Health Survey and Incidence Study. Symptoms of psychosis were assessed in individuals aged 18-64 years using the Composite International Diagnostic Interview. All individuals reporting first-onset of psychotic symptoms within a three-year interval were included. The degree to which sets of risk factors affected the psychosis outcome similarly across age groups was assessed. RESULTS: The number of subjects displaying incident psychotic symptoms was similar across age groups. Cumulative incidence rates ranged from 0.3% to 0.4%. Age differences were found for life-time depressive symptoms (risk difference = 5%, 95% CI = 1%, 9%) and baseline neuroticism (risk difference = 3%, 95% CI = 0%, 6%), indicating that late-onset psychosis was less often preceded by these. In contrast, no effect modification by age was observed for female sex, hearing impairment, being single, or life-time cannabis use. CONCLUSIONS: Onset of psychotic symptoms in late life is no rare event. Compared to early onset psychosis, the late-onset counterpart less often arises in a context of emotional dysfunction and negative affectivity, suggesting qualitative differences in aetiology and more effective premorbid coping styles.     

Early exposure to cannabis and risk for psychosis in young adolescents in Trinidad

Objective: Cannabis use increases the risk for psychosis, but psychotogenic effects of cannabis may be restricted to exposure during early adolescence. Method: Four hundred and seventy‐two participants (aged 12–23 years), randomly selected from the general population in Trinidad, completed questionnaires on past and current cannabis use and psychotic symptoms (using the Community Assessment of Psychic Experiences). Results: Cannabis use increased the risk of experiencing psychotic symptoms and this effect was conditional on early exposure, defined around the mean age of onset of cannabis use. Thus, exposure before but not after the age of 14 years predicted psychotic symptoms (respectively β: 0.71, 95% CI 0.22; 1.19, P = 0.004 and β: ?0.11, 95% CI ?0.57; 0.36, P = 0.66). The developmental effect of cannabis use was independent of use of other drugs or current use of cannabis. Conclusion: Early adolescence may be a critical period with regard to the psychotogenic effect of cannabis across geographical settings and ethnic groups.     

Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism

Estrada G, Fatjó‐Vilas M, Muñoz MJ, Pulido G, Miñano MJ, Toledo E, Illa JM, Martín M, Miralles ML, Miret S, Campanera S, Bernabeu C, Navarro ME, Fañanás L. Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Objective: To examine, in a sample of young psychiatric patients, (n = 157, mean age 17.01 years (SD = 3.6)) whether i) age at first cannabis use and age at emergence of psychiatric disorders are related and ii) such a relationship is modulated by the Val158Met polymorphism in the COMT gene. Method: Cannabis use profiles and COMT Val158Met genotypes were obtained from 80 inpatients with schizophrenia‐spectrum disorders and 77 inpatients with other non‐psychotic disorders. Results: First, age at first cannabis use correlates with age at onset in both schizophrenia‐spectrum and other psychiatric disorder groups: those who started using cannabis earlier had an earlier age at onset of psychiatric disorders. Second, the distribution of the Val158Met genotypes was not different either between diagnosis groups or between cannabis users and non‐users. Third, an interaction between Val158Met genotypes and cannabis use was observed specifically on age at emergence of psychotic disorders, with Val/Val genotype carriers showing an earlier age at onset than Met carriers. Conclusion: Our results suggest the importance of brain maturation timing in which exposure to cannabis occurs. The COMT Val158Met genotype seems to modulate the association between cannabis and age at onset of psychotic disorders. These results are consistent with previous studies.     

Cannabis use and outcome of recent onset psychosis.

PURPOSE: To test the hypothesis that recent onset psychotic patients who use cannabis will have psychotic symptoms that are more severe and more persistent than those who do not use cannabis. SUBJECTS AND METHODS: We carried out a 4-year follow-up study of a cohort of 119 patients with recent onset of psychosis. The patients were divided into four groups according to duration of cannabis use, taking index admission and follow-up as reference points. RESULTS: Those subjects who persisted in the use of cannabis had more positive (but not negative) symptoms and a more continuous illness at follow-up. LIMITATIONS: The main limitations of the study were: the relatively small sample size, and that the excess of male subjects and the presence of cannabis induced psychosis could have a confusing impact on the interpretation of the results. CONCLUSION: It is possible that psychotic patients who use cannabis are at a greater risk of a more continuous illness with more positive symptoms than those who do not.     

The Impact of Cannabis Use on Clinical Outcomes in Recent Onset Psychosis

Background: There are inconsistencies in findings as to whether cannabis use has a negative impact on clinical outcomes for people with established psychosis. Effects may be more evident on patients with recent onset psychosis. Aim: To investigate the relationship between cannabis use and clinical outcome, including whether change in cannabis use affects psychotic symptoms, affective symptoms, functioning and psychotic relapse in a sample of people in early psychosis with comorbid cannabis abuse or dependence. Methods: One hundred and ten participants were examined prospectively with repeated measures of substance use antecedent to psychopathology at baseline, 4.5, 9, and 18 months. We used random intercept models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes. Results: There was no evidence of a specific association between cannabis use and positive symptoms, or negative symptoms, relapse or hospital admissions. However, a greater dose of cannabis was associated with subsequent higher depression and anxiety. Change in the amount of cannabis used was associated with statistically significant corresponding change in anxiety scores, but not depression. Additionally, reductions in cannabis exposure were related to improved patient functioning. Conclusions: Reducing cannabis may be directly associated with improvements in anxiety and functioning, but not other specific symptoms.Key words: psychosis, cannabis, substance use, dual diagnosis     

Impact of substance use on the onset and course of early psychosis

The strong comorbidity between psychosis and substance use is already identifiable in early psychosis, raising the question of the direction of the association between substance use and psychosis onset. It has long been considered that this association was explained by the self-medication hypothesis. This hypothesis has been recently challenged by several prospective studies carried out in population-based samples, showing a dose-response relationship between cannabis exposure and risk of psychosis. This association was independent from potential confounding factors such as exposure to other drugs and pre-existence of psychotic symptoms. As a large percentage of subjects from the general population is now exposed to this drug, even a small increase in the risk of adverse effects may have significant deleterious consequences for the health of the population. Hence, reducing exposure to cannabis may contribute to prevention of some incident cases of psychosis. Regarding prognosis, persistent substance misuse after the onset of psychosis has a deleterious impact on clinical outcome. Therapeutic programs for subjects with dual diagnosis should be implemented early in the course of psychosis to maximise their impact on the course of illness.     

Duration of psychosis and outcome in first-episode schizophrenia.

OBJECTIVE: This study was undertaken to assess the potential effect of duration of untreated illness on outcome in a group of first-episode schizophrenic patients. METHOD: Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission of acute psychotic symptoms as well as degree of symptom remission. RESULTS: The mean duration of psychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level of remission. The effect of duration of illness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration of illness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study. CONCLUSIONS: Duration of psychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed.     

Daily Use,Especially of High-Potency Cannabis,Drives the Earlier Onset of Psychosis in Cannabis Users

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16–1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11–1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06–1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.Key words: psychotic disorders, age of onset, gender, cannabis, survival plots, drug use, high-potency cannabis     

Gene-environment interplay between cannabis and psychosis

Cannabis use is considered a contributory cause of schizophrenia and psychotic illness. However, only a small proportion of cannabis users develop psychosis. This can partly be explained by the amount and duration of the consumption of cannabis and by its strength but also by the age at which individuals are first exposed to cannabis. Genetic factors, in particular, are likely to play a role in the short- and the long-term effects cannabis may have on psychosis outcome. This review will therefore consider the interplay between genes and exposure to cannabis in the development of psychotic symptoms and schizophrenia. Studies using genetic, epidemiological, experimental, and observational techniques will be discussed to investigate gene-environment correlation gene-environment interaction, and higher order interactions within the cannabis-psychosis association. Evidence suggests that mechanisms of gene-environment interaction are likely to underlie the association between cannabis and psychosis. In this respect, multiple variations within multiple genes--rather than single genetic polymorphisms--together with other environmental factors (eg, stress) may interact with cannabis to increase the risk of psychosis. Further research on these higher order interactions is needed to better understand the biological pathway by which cannabis use, in some individuals, may cause psychosis in the short- and long term.     

Cannabis use is not associated with the development of psychosis in an 'ultra' high-risk group

BACKGROUND: The association between cannabis use and the development of a first psychotic episode was studied in a group of 100 young people identified as being at very high risk for the onset of psychosis. METHOD: The 'ultra' high risk cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-two per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of cannabis use by participants in the year prior to enrollment in the study was assessed at intake. RESULTS: Cannabis use or dependence in the year prior to recruitment to this study was not associated with a heightened risk of developing psychosis over the following 12-month period and therefore did not appear to contribute to the onset of a psychotic disorder. CONCLUSION: The results of this study suggest that cannabis use may not play an integral role in the development of psychosis in a high-risk group. While this study does not support a role for cannabis in the development of first-episode psychosis, we cannot conclude that cannabis use should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study (the low level of cannabis use in the current sample, the lack of monitoring of cannabis use after intake) suggest that it may be premature to dismiss cannabis use as a risk factor for the development of psychosis and further research is urged in this area.     

Early course of schizophrenia in a representative Dutch incidence cohort

PURPOSE: To describe the early course of psychotic disorders in general and to examine whether certain variables can predict the early course of schizophrenic disorders (DSM-IV: schizophrenia, schizophreniform or schizoaffective disorder). SUBJECTS AND METHOD: Follow-up and re-diagnosis of a highly representative Dutch incidence cohort (N=181), thirty months after first contact with a physician for a psychotic disorder. Poor course was defined as a continuous psychotic illness or a score of less than 39 on the Global Assessment of Functioning scale. RESULTS: The follow-up rate was 92%. 125 Subjects were diagnosed with a schizophrenic disorder. Poor course was present in 70 of these subjects (56%). Univariable analysis showed that male sex, heavy cannabis use during the follow-up period (sometimes or often more than one joint a day) and long duration of dysfunctioning before psychosis onset (>1 month) were predictors of poor course, while age at onset, ethnicity, socioeconomic status and duration of untreated psychosis (trend, p=0.08) were not. The effect of cannabis was confounded by sex. Multivariable analysis showed that male sex was the sole significant and independent predictor of poor course and explained 13% of the variation. The odds ratio for males, adjusted for duration of pre-psychotic dysfunctioning and cannabis use during the follow-up period, was 3.0 (95% CI, 1.0-8.9). STRENGTHS AND LIMITATIONS: This is the first study to examine the influence of cannabis in an epidemiological, highly representative sample. A limitation was the sample size. CONCLUSION: Male sex is an independent risk factor for an unfavorable early course in schizophrenia.     

Temporal relationship of first-episode non-affective psychosis with cannabis use: A clinical verification of an epidemiological hypothesis

Background

We analyzed the association of age at onset of psychosis treatment (AOPT) with having a history of cannabis use in patients with a first episode of non-affective psychosis. We also investigated the impact on the AOPT of exposure to cannabis in adolescence, compared with young adulthood, and of the additional exposure to cocaine.

Method

We recruited 112 consecutive patients (66 men and 46 women; age range, 18-57 years) with a first psychotic episode. The composite international diagnostic interview (CIDI) was used to assess drug use and to define the age at onset of heaviest use (AOHU) of a drug, defined as the age when drug was used the most for each patient. The effect of cannabis and cocaine AOHU on AOPT was explored through Kruskal-Wallis and Mann-Whitney tests, and logistic regression. Sex-adjusted cumulative hazard curves and Cox regression models were used to compare the AOPT of patients with and without a history of cannabis use, or associated cocaine use.

Results

We found that the AOPT was significantly associated with the use of cannabis, independently of sex, use of cocaine, tobacco smoking or excessive alcohol consumption. There was a dose-response relationship between cannabis AOHU and AOPT: the earlier the AOHU the earlier the AOPT. Hazard curves showed that patients with a history of cannabis use had a higher hazard of having a first-episode psychosis than the rest of the patients (sex-adjusted log-rank χ² = 23.43, df = 1, p < 0.001). Their respective median AOPT (25th, 75th percentiles) were 23.5 (21, 28) and 33.5 years (27, 45) (for log-transformed AOPT, t = 5.6, df = 110, p < 0.001). The sex-adjusted hazard ratio of psychosis onset comparing both groups was 2.66 (95% CI, 1.74-4.05).

Conclusions

Our results are in favor of a catalytic role for cannabis use in the onset of psychosis.     

Is adolescent-onset first-episode psychosis different from adult onset?

OBJECTIVE: To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). METHOD: Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated psychosis, diagnosis, length of prodromal period, premorbid adjustment, level of psychotic, negative, depressive, anxiety, and extrapyramidal symptoms, and alcohol and drug use. RESULTS: Eighty-two patients (40.8%) had an onset of psychosis during adolescence (ages 15-18) and 119 (59.2%) during young adulthood (ages 19-30). The adolescent-onset group experienced longer delays in treatment of psychosis (duration of untreated psychosis) (p < .02), showed modestly worse premorbid functioning during late adolescence (p < .05), and were more likely to present with bizarre behavior (p < .01) and primary negative symptoms (p < .01). CONCLUSIONS: Patients with adolescent onset of psychosis are more likely to present with clinical characteristics that portend a poorer outcome and may require a different approach to early identification and treatment.     

Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis

Dragt S, Nieman DH, Schultze‐Lutter F, van der Meer F, Becker H, de Haan L, Dingemans PM, Birchwood M, Patterson P, Salokangas RKR, Heinimaa M, Heinz A, Juckel G, Graf von Reventlow H, French P, Stevens H, Ruhrmann S, Klosterkötter J, Linszen DH, on behalf of the EPOS group. Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis. Objective: Numerous studies have found a robust association between cannabis use and the onset of psychosis. Nevertheless, the relationship between cannabis use and the onset of early (or, in retrospect, prodromal) symptoms of psychosis remains unclear. The study focused on investigating the relationship between cannabis use and early and high‐risk symptoms in subjects at clinical high risk for psychosis. Method: Prospective multicenter, naturalistic field study with an 18‐month follow‐up period in 245 help‐seeking individuals clinically at high risk. The Composite International Diagnostic Interview was used to assess their cannabis use. Age at onset of high risk or certain early symptoms was assessed retrospectively with the Interview for the Retrospective Assessment of the Onset of Schizophrenia. Results: Younger age at onset of cannabis use or a cannabis use disorder was significantly related to younger age at onset of six symptoms (0.33 < r_s < 0.83, 0.004 < P < 0.001). Onset of cannabis use preceded symptoms in most participants. Conclusion: Our results provide support that cannabis use plays an important role in the development of psychosis in vulnerable individuals. Cannabis use in early adolescence should be discouraged.