Cannabis, vulnerability, and the onset of schizophrenia: an epidemiological perspective

OBJECTIVE: Second to alcohol, cannabis is the most frequently misused substance among patients with schizophrenia. The aim of this paper is to examine at early onset of psychosis whether the high comorbidity of schizophrenia and cannabis abuse is due to a causal relationship between the two disorders. Previous studies have mostly included chronic patients or samples with mixed stages of the psychotic illness. METHOD: In a German catchment area with a population of 1,500,000, a representative first-episode sample of 232 patients with schizophrenia was included in the Age, Beginning and Course of Schizophrenia Study. By means of a structured interview, the Retrospective Assessment of the Onset of Schizophrenia, the onset and course of schizophrenic symptoms and of substance abuse was systematically assessed retrospectively. Information given by relatives validated the patients' reports. RESULTS: Thirteen per cent of the sample had a history of cannabis abuse, which was twice the rate of matched normal controls. Male sex and early symptom onset were major risk factors. While cannabis abuse almost always preceded the first positive symptoms of schizophrenia, the comparison of the onset of cannabis abuse and of the first (prodromal) symptoms of schizophrenia differentiated three approximately equal groups of patients: group 1 had been abusing cannabis for several years before the first signs of schizophrenia emerged, group 2 experienced the onset of both disorders within the same month, and group 3 had started to abuse cannabis after the onset of symptoms of schizophrenia. CONCLUSIONS: The vulnerability-stress-coping model of schizophrenia suggests possible interpretations of these findings. Group 1 might suffer from the chronic deteriorating influence of cannabis reducing the vulnerability threshold and/or coping resources. Group 2 consists of individuals which are already vulnerable to schizophrenia. Cannabis misuse then is the (dopaminergic) stress factor precipitating the onset of psychosis. Group 3 uses cannabis for self-medication against (or for coping with) symptoms of schizophrenia, particularly negative and depressive symptoms. These patients probably learn to counterbalance a hypodopaminergic prefrontal state by the dopaminergic effects of cannabis. The implications of these very preliminary results include issues of treatment and prognosis, but replication studies are needed.     

Is there an association between duration of untreated psychosis and 24-month clinical outcome in a first-admission series?

OBJECTIVE: The authors examined the duration of untreated psychosis, defined as the interval from first psychotic symptom to first psychiatric hospitalization, in a county-wide sample of first-admission inpatients who had received no previous antipsychotic medication. Differences between diagnostic groups in 24-month illness course and clinical outcomes as well as relationships between outcomes and duration of untreated psychosis were evaluated. METHOD: The data were derived from subjects in the Suffolk County Psychosis Project who were diagnosed at 24-month follow-up according to DSM-IV as having schizophrenia or schizoaffective disorder (N=155), bipolar disorder with psychotic features (N=119), or major depressive disorder with psychotic features (N=75). Duration of untreated psychosis was derived from the Structured Clinical Interview for DSM-III-R, medical records, and information from significant others. Measures at 24-month follow-up included consensus ratings of illness course, Global Assessment of Functioning Scale scores for the worst week in the month before interview, and current affective and psychotic symptoms. RESULTS: The median duration of untreated psychosis was 98 days for schizophrenia, 9 days for psychotic bipolar disorder, and 22 days for psychotic depression. Duration of untreated psychosis was not significantly associated with 24-month illness course or clinical outcomes in any of the diagnostic subgroups. CONCLUSIONS: Although these findings require replication in other epidemiologically based first-admission samples, at face value they do not support the suggestion of a psychotoxic effect of prolonged exposure to untreated psychosis.     

Cannabis abuse and risk for psychosis in a prodromal sample

The goal of the present study was to examine the rate of cannabis use among participants in the Cognitive Assessment and Risk Evaluation (CARE) Program, a longitudinal program for individuals who are "at risk" for developing a psychotic disorder. Cannabis abuse was assessed in 48 individuals identified as at risk for psychosis based on subsyndromal psychotic symptoms and/or family history. At 1 year follow-up, 6 of the 48 (12.5%) at risk subjects had made the transition to psychosis. Of the 32 subjects who had no use or minimal cannabis use, one subject (3.1%) converted to psychosis. Of the 16 subjects who met criteria for cannabis abuse/dependence, five (31.3%) converted to psychosis. The results show a significant association between cannabis abuse and conversion to psychosis in this sample. Nicotine use was also found to be significantly associated with later conversion. The significant associations between cannabis and nicotine abuse and conversion to psychosis in individuals at risk for schizophrenia suggest that early identification and intervention programs should screen for and provide education about the deleterious effects of these substances.     

Cannabinoids and psychosis

Recent advances in knowledge about cannabinoid receptor function have renewed interest in the association between cannabis and psychosis. Case series, autobiographical accounts, and surveys of cannabis users in the general population suggest an association between cannabis and psychosis. Cross-sectional studies document an association between cannabis use and psychotic symptoms, and longitudinal studies suggest that early exposure to cannabis confers a close to two-fold increase in the risk of developing schizophrenia. Pharmacological studies show that cannabinoids can induce a full range of transient positive, negative, and cognitive symptoms in healthy individuals that are similar to those seen in schizophrenia. There is considerable evidence that in individuals with an established psychotic disorder such as schizophrenia, exposure to cannabis can exacerbate symptoms, trigger relapse, and worsen the course of the illness. Only a very small proportion of the general population exposed to cannabis develop a psychotic illness. It is likely that cannabis exposure is a ‘component cause’ that interacts with other factors to ‘cause’ schizophrenia or other psychotic disorder, but is neither necessary nor sufficient to do so alone. Further work is necessary to identify the factors that underlie individual vulnerability to cannabinoid-related psychosis and to elucidate the biological mechanisms underlying this risk.     

Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features

The identification of individuals at high risk of developing a psychotic disorder has long been a goal of clinicians because it is thought that early treatment of this group may prevent onset of the disorder. However, little is known of predictive factors of psychosis, even within a high-risk group. This study followed up 104 young people thought to be at 'ultra high risk' for schizophrenia and other psychotic disorders by virtue of having a family history of psychotic disorder combined with some functional decline or the presence of subthreshold or self-limiting psychotic symptoms. All subjects were therefore symptomatic, but not psychotic, at intake. Thirty-six subjects (34.6%) developed frank psychotic symptoms within 12 months. Measures of symptom duration, functioning, disability and psychopathology were made at intake, 6 and 12 months. Poor functioning, long duration of symptoms, high levels of depression and reduced attention were all predictors of psychosis. A combination of family history of psychosis, a recent significant decrease in functioning and recent experience of subthreshold psychotic symptoms was also predictive of psychosis. Combining highly predictive variables yielded a method of psychosis prediction at 12 months with good positive predictive value (80.8%), negative predictive value (81.8%) and specificity (92.6%) and moderate sensitivity (60.0%). Within our symptomatic high-risk group, therefore, it appears possible to identify those individuals who are at particularly high risk of developing a psychotic disorder such as schizophrenia. Given the very high PPV and low false positive rate with this two-step process, it may be justifiable to target these individuals for intensive monitoring of mental state and even low-dose neuroleptic medication or other biological and psychosocial treatments depending on clinical condition. This indicated prevention approach could be further developed and preventive strategies in the psychoses refined.     

Duration of untreated psychosis as a predictor of outcome in first-episode schizophrenia: a retrospective study.

The aim of this study was to investigate possible clinical predictors of the outcome of first-episode schizophrenia. The clinical charts of the first episode of psychosis and the follow-up period over at least 4 years for 67 DSM-III-R schizophrenic patients were reviewed. According to the number of psychotic relapses observed during the follow-up period, patients were sub-divided into two groups: mono- and multi-episode patients. The main demographic and clinical variables recorded at the first episode were compared between the two groups. A logistic regression analysis was performed to test a model for the possible predictors of the two different patterns of outcome.Multi-episode patients had an earlier onset of the illness and a longer "duration of untreated psychosis" (DUP), defined as the interval between the onset of the first psychotic symptoms and the first antipsychotic treatment. The Brief Psychiatric Rating Scale (BPRS) total scores were lower and the "avolition/apathy" scores of the scale for the assessment of negative symptoms (SANS) were higher in multi-episode patients. The logistic regression analysis results confirmed the DUP and the pre-treatment BPRS scores to be significant predictors of the outcome. These findings confirm that the timing in recognizing and treating the early symptoms of schizophrenia, even when subtle, is a core issue for the clinical management of the disorder.     

Age at Initiation of Cannabis Use Predicts Age at Onset of Psychosis: The 7- to 8-Year Trend

We investigated the existence of a temporal association between age at initiation of cannabis use and age at onset of psychotic illness in 997 participants from the 2010 Survey of High Impact Psychosis (SHIP) in Australia. We tested for group differences in age at onset of psychotic illness and in the duration of premorbid exposure to cannabis (DPEC). Analyses were repeated in subgroups of participants with a schizophrenia-spectrum disorder (SSD), a diagnosis of lifetime cannabis dependence (LCD), and a comorbid SSD/LCD diagnosis. The association between age at initiation of cannabis use and age at onset of psychotic illness was linear and significant, F(11, 984) = 13.77, P < .001, even after adjusting for confounders. The effect of age at initiation of cannabis use on DPEC was not significant (mean duration of 7.8 years), and this effect was similar in participants with a SSD, LCD, and comorbid SSD/ LCD diagnosis although a shift toward shorter premorbid exposure to cannabis was noted in the SSD/LCD subgroup (mean duration of 7.19 years for SSD/LCD). A temporal direct relationship between age at initiation of cannabis use and age at onset of psychotic illness was detected with a premorbid exposure to cannabis trend of 7–8 years, modifiable by higher severity of premorbid cannabis use and a diagnosis of SSD. Cannabis may exert a cumulative toxic effect on individuals on the pathway to developing psychosis, the manifestation of which is delayed for approximately 7–8 years, regardless of age at which cannabis use was initiated.Key words: cannabis, psychosis, schizophrenia, age at onset, causality, DIP, SHIP     

Cannabis and schizophrenia: a longitudinal study of cases treated in Stockholm County

By means of the Stockholm County inpatient care register we identified all cases treated with a diagnosis of cannabis dependence and psychosis, not necessarily at the same occasion, during 1971–1983. By scrutinizing medical records, we evaluated the diagnosis according to DSM-III-R and we assessed the history of substance abuse as well as the psychiatric history and clinical course. We identified 229 cases during the follow-up; 112 of these cases (49%) fulfilled the DSM-III-R criteria for schizophrenia. The majority of the schizophrenics had prominent positive symptoms and a sudden onset of disease, and 69% of the cases had a record of heavy cannabis abuse at least 1 year before onset of psychotic symptoms. The high number of verified DSM-III-R cases of schizophrenia in this cohort and the temporal relation between cannabis abuse and schizophrenia further support the hypothesis that cannabis abuse may be a risk factor for schizophrenia. We confirmed previous observations that cannabis-associated schizophrenia often has a sudden onset and prominent positive symptoms.     

Psychosis prediction: 12-month follow up of a high-risk ("prodromal") group

Intervention in the prodromal phase of schizophrenia and related psychoses may result in attenuation, delay or even prevention of the onset of psychosis in some individuals. However, a "prodrome" is difficult to recognise prospectively because of its nonspecific symptoms.This study set out to recruit and follow up subjects at high risk of transition to psychosis with the aim of examining the predictive power for psychosis onset of certain mental state and illness variables.Symptomatic individuals with either a family history of psychotic disorder, schizotypal personality disorder, subthreshold psychotic symptoms or brief transient psychotic symptoms were assessed and followed up monthly for 12 months or until psychosis onset.Twenty of 49 subjects (40.8%) developed a psychotic disorder within 12 months. Some highly significant predictors of psychosis were found: long duration of prodromal symptoms, poor functioning at intake, low-grade psychotic symptoms, depression and disorganization. Combining some predictive variables yielded a strategy for psychosis prediction with good sensitivity (86%), specificity (91%) positive predictive value (80%) and negative predictive value (94%) within 6 months.This study illustrates that it is possible to recruit and follow up individuals at ultra high risk of developing psychosis within a relatively brief follow-up period. Despite low numbers some highly significant predictors of psychosis were found. The findings support the development of more specific preventive strategies targeting the prodromal phase for some individuals at ultra high risk of schizophrenia.     

Diagnostic stability over 3 years in a total group of first-episode psychosis patients

First-episode psychosis (FEP) patients are often given diagnoses that later have to be changed. The aim of this study was to measure the diagnostic stability in a total group of FEP patients; 146 FEP patients were followed longitudinally and prospectively. Their revised baseline diagnoses were compared with their 3-year follow-up diagnoses. The schizophrenic spectrum disorders showed a high diagnostic stability as a group, but there was a great flow of patients between the different schizophrenic spectrum diagnoses. Also schizophrenia was a stable diagnosis. The affective psychosis group was homogenous without interaction of other psychosis groups. The other psychosis diagnoses, both regarded as a group and individually, turned out to be quite heterogeneous, with low stability values and a split course, often ending up in the schizophrenic spectrum. Fifty one per cent did not fulfil the criteria for DSM-IV axis 1 psychosis diagnosis at follow-up. In conclusion, our findings suggest that in the early phase of psychosis. Only three different diagnostic categories would be sufficient; "schizophrenic spectrum type", "affective psychosis," and for the rest "psychotic disorder NOS."     

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.     

Course of adolescent psychotic disorder with schizoaffective episodes

This study examines educational/occupational outcome and social functioning of adolescents treated for psychosis (mean onset age 16.1 yrs±1.3). In a sample of 157 subjects, 26 patients with schizoaffective episodes (defined as any episode meeting ICD-9 criteria for schizoaffective psychosis, occurring at any time during the course of illness) were compared to 101 patients with schizophrenia, and to 30 affective disordered patients, all without schizoaffective episodes. Follow-up information (mean interval 7.3 yrs ±4.3) was obtained on 130 subjects. The three groups did not differ concerning sex, duration of first inpatient treatment, symptoms and social competence at discharge, nor at follow-up. At the time of outcome subjects with schizoaffective episodes showed greater similarities to schizophrenic than to severe affective disorder. Educational and occupational impairment was found in 72% of the schizoaffective group (schizophrenic group 79%, affective group 40%), obvious or more severe social disability in 86% of the schizoaffective group (schizophrenic 79%, affective 40%). Disabilities regarding performance of specific social roles and specific downward educational and occupational drifts were found to be more marked in schizoaffective than in affective disorder. Implications for further research and clinical practice are discussed.     

A comparison of symptoms and family history in schizophrenia with and without prior cannabis use: implications for the concept of cannabis psychosis

BACKGROUND: There is considerable interest in cannabis use in psychosis. It has been suggested that the chronic psychosis associated with cannabis use, is symptomatically distinct from idiopathic schizophrenia. Several studies have reported differences in psychopathology and family history in people with schizophrenia according to whether or not they were cannabis users. We set out to test the hypotheses arising from these studies that cannabis use is associated with more bizarre behaviour, more thought disorder, fewer negative symptoms including blunted affect, more delusions of reference, more paranoid delusions and a stronger family history of schizophrenia. METHOD: We used a case register that contained 757 cases of first onset schizophrenia, 182 (24%) of whom had used cannabis in the year prior to first presentation, 552 (73%) had not and 3% had missing data. We completed the OPCRIT checklist on all patients and investigated differences in the proportion of people with distractibility, bizarre behaviour, positive formal thought disorder, delusions of reference, well organised delusions, any first rank symptom, persecutory delusions, abusive/accusatory hallucinations, blunted affect, negative thought disorder, any negative symptoms (catatonia, blunted affect, negative thought disorder, or deterioration), lack of insight, suicidal ideation and a positive family history of schizophrenia, using chi square tests. Logistic regression modelling was then used to determine whether prior cannabis use affected the presence of the characteristics after controlling for age, sex and ethnicity. RESULTS: There was no statistically significant effect of cannabis use on the presence of any of the above. There remained however a non-significant trend towards more insight (OR 0.65 p=0.055 for "loss of insight") and a finding of fewer abusive or accusatory hallucinations (OR 0.65 p=0.049) of borderline significance amongst the cannabis users. These were in the hypothesised direction. There was no evidence of fewer negative symptoms or greater family history amongst cannabis users. CONCLUSION: We found few appreciable differences in symptomatology between schizophrenic patients who were or were not cannabis users. There were no differences in the proportion of people with a positive family history of schizophrenia between cannabis users and non-users. This argues against a distinct schizophrenia-like psychosis caused by cannabis.     

Intellectual impairment in adolescent psychosis. A controlled psychometric study

The relationship of cognitive impairment to the course of schizophrenia remains uncertain. By studying psychotic adolescents, 90% of whom were hospitalized for the first time, we hoped to reduce the influence of such confounding variables as lengthy disease process, neuroleptic treatment, and institutionalization. 39 psychotic adolescent subjects who fulfilled DSM-III criteria for schizophrenia, schizophreniform psychosis, paranoid schizophrenia, or atypical psychosis were compared to 41 non-psychotic adolescent psychiatric controls. Subjects were administered the Wechsler Intelligence Scale for Children-Revised, Peabody Individual Achievement tests of reading, reading comprehension, and mathematics, Bender-Gestalt, and Purdue Pegboard test within 3 weeks of admission to a psychiatric hospital. Performance IQ was significantly lower in the psychotic group (72 versus 93, P = 0.03). Thus, the IQ pattern in adolescent psychotic patients at an early stage in their illness was similar to the pattern displayed by chronic adult schizophrenic patients. Results were not consistent with theories of left hemisphere involvement in schizophrenia. Academic achievement was similar in both groups despite marked differences in performance IQ. Psychotropic medication had no significant impact on the results. In summary, deficits in processing novel material seem at the very least to be present at the onset of the psychotic disorder, though they may be non-progressive thereafter.     

Contributions of genetic risk and fetal hypoxia to hippocampal volume in patients with schizophrenia or schizoaffective disorder,their unaffected siblings,and healthy unrelated volunteers

OBJECTIVE: The authors examined in an epidemiologic sample the contributions of genetic predisposition and history of fetal hypoxia to hippocampal volume in patients with psychosis. METHOD: High-resolution magnetic resonance imaging was used to measure hippocampal volumes in 72 psychotic probands (60 with schizophrenia and 12 with schizoaffective disorder, ascertained so as to be representative of all such probands in a Helsinki birth cohort), 58 nonpsychotic full siblings of the probands, and 53 demographically similar healthy comparison subjects with no family history of psychosis. RESULTS: Hippocampal volume differences occurred in a stepwise fashion with each increase in genetic load for schizophrenia. The probands had smaller hippocampal volumes than did their full siblings, who in turn had smaller hippocampal volumes than did the healthy comparison subjects. Among the probands, smaller hippocampal volumes were seen in those who experienced fetal hypoxia than in those who did not, a difference not noted within the other two groups. Finally, within the schizophrenic/schizoaffective disorder patients, smaller hippocampal volumes correlated positively with age at onset independent of duration of illness. CONCLUSIONS: These findings suggest that in patients with schizophrenia spectrum disorders, hippocampal volume is influenced in part by schizophrenia susceptibility genes and an interaction of these genes with fetal hypoxia. They further suggest that hippocampal volume in schizophrenia or schizoaffective disorder may be linked to time of disease onset.     

Characteristics of early psychosis

There is little research on characteristics related to course and prognosis of early-onset psychosis. The present article aims to advance our knowledge of this disorder for the purpose of proper diagnosis and treatment. It focuses on premorbid and prodromal characteristics, treatment history, symptoms and classifications, and differences between subgroups with affective and schizophrenic psychosis. A chart review was constructed to study a group of 129 subjects (12-18 years) with psychotic symptoms referred to the University Medical Center in Utrecht. The group was characterized by early-but nonspecific-treatment, developmental problems (mostly social), and clear prodromal symptoms. Drug abuse, depressive symptoms, and suicidal behavior were also frequent. Male sex, a relatively long prodromal phase, school problems, and drug abuse were more indicative of the schizophrenic subgroup. Introversion was characteristic for boys with schizophrenia. Classifications, however, were not stable. These findings suggest that early recognition of psychosis can be enhanced in health and youth care facilities. Careful examination of the prodromal phase seems helpful to differentiate between schizophrenic and affective psychosis.     

Obsessive-compulsive and panic symptoms in patients with first-admission psychosis

OBJECTIVE: The occurrence, persistence and specificity of the association between comorbid obsessive-compulsive and panic symptoms and three psychotic disorders--schizophrenia/schizoaffective disorder, bipolar disorder with psychosis, and major depression with psychosis--were examined in a first-admission, epidemiologically defined group of patients with psychotic symptoms. METHOD: The Structured Clinical Interview for DSM-III-R obsessive-compulsive and panic modules were administered at baseline and 24-month follow-up to patients with schizophrenia/schizoaffective disorder (N=225), bipolar disorder with psychosis (N=138), and major depression with psychosis (N=87) participating in the Suffolk County (N.Y.) Mental Health Project. The rates of subsyndromal symptoms and disorder criteria met were compared across the three psychosis groups. Recognition and treatment of anxiety symptoms at initial discharge and impact of the baseline presence of anxiety symptoms on 24-month clinical status were also examined. RESULTS: Obsessive-compulsive and panic symptoms were present at baseline in 10%-20% of all three groups. There was no specific association between obsessive-compulsive symptoms and any specific psychosis diagnosis; however, women with major depression with psychosis had a significantly higher rate of panic symptoms than the other two groups, and schizophrenia/schizoaffective disorder patients with baseline panic symptoms were significantly more likely to exhibit positive symptoms of psychosis after 24 months. CONCLUSIONS: The authors found no specific association between obsessive-compulsive symptoms and diagnosis early in the illness course, but the finding of an association between panic symptoms and psychotic depression among female patients and between baseline panic and positive psychotic symptoms in schizophrenia/schizoaffective disorder patients at 24 months suggests the need for further study.     

Untreated initial psychosis: its relation to quality of life and symptom remission in first-episode schizophrenia

OBJECTIVE: Previous studies have suggested that there may be an association between longer duration of untreated psychosis and poor outcome in schizophrenia. These studies have been interpreted as providing evidence that untreated psychosis may constitute an "active morbid process" that is "toxic" to the brain. If untreated psychosis is neurotoxic, this would form a strong basis for early intervention in schizophrenia. METHOD: Seventy-four neuroleptic-naive patients with DSM-IV schizophrenia were evaluated 6 months after their first inpatient hospitalization. The authors examined the relationship between untreated initial psychosis duration (measured from onset of first symptom as well as from onset of full positive syndrome) and quality of life, symptom severity, and time to remission of positive symptoms. RESULTS: Earlier age at illness onset was associated with longer duration of untreated prodromal psychotic symptoms. There were no significant gender differences in duration of untreated initial psychosis, nor were there any significant associations between untreated initial psychosis duration and premorbid functioning. After controlling for the effects of age at onset, the duration of untreated initial psychosis did not significantly impair subsequent quality of life, symptom severity, or remission of positive symptoms. CONCLUSIONS: Duration of untreated initial psychosis was not prognostic of poor outcome early in the course of schizophrenia. Biological measures of neurotoxicity are needed to examine the "toxic psychosis" hypothesis more directly.     

The role of cannabis use in psychosis

The link between cannabis use and psychosis has been studied intensively and debated hotly for decades. The authors review the research that has been done on the topic, including the studies which produced evidence of a relationship between the two phenomena, and give a detailed analysis of the hypotheses about the nature of the link (the direction of causality). According to the reviewed literature an increased prevalence of cannabis use can be found in the schizophrenic population. The use of the drug is associated with a worse prognosis and an earlier onset of schizophrenia. However, findings about the possible effect of cannabis use on the specific symptoms of schizophrenia have been contradictory. An association has also been observed between cannabis use and schizotypal personality traits, but evidence for a specific, cannabis induced functional psychosis is still lacking. Based on the data of longitudinal studies, cannabis use should be recognized as a risk factor for later psychosis. The abuse of the drug increases the likelihood of later psychotic symptoms especially among individuals with vulnerability or when the use starts in early adolescence. At the same time, the role of self-medication or a common genetic background cannot be excluded either, and a circular causality is very possible.     

Cannabis and schizophrenia: impact on onset,course, psychopathology and outcomes

Cannabis consuming schizophrenic patients are younger at onset, are likely to have started abuse before onset of schizophrenia and show more prominent positive symptoms than nonabusers. It has been suggested that cannabis is a risk-factor for schizophrenia. Our aim was to assess prevalence and pattern of cannabis use in 125 chronic male schizophrenic subjects and its impact on socioepidemiological and clinical variables as well as which disorder precedes the other in onset. Assessment of consumption was made with a semi-structured clinical interview. Clinical status was assessed by means of the SANS, SAPS, PANSS and BPRS scales. Cannabis consumption was found in 54 subjects (43%), 66.7% of whom started it at least three years before onset of schizophrenia. Consumers were younger and with lower negative symptoms, specially abusers and polysubstance abusers. Family history positive for psychosis was more frequent in consumers, especially when consumption started before onset of schizophrenia. Subjects whose onset of schizophrenia preceded the beginning of cannabis abuse had more positive symptoms than those who started abuse before the onset of schizophrenia. On these grounds, our sample could be subdivided into two main groups, one that uses substances to counter distressing symptoms of schizophrenia and another in which cannabis might be one of the factors predisposing to the disease; the former had less negative symptoms than nonabusers. Our data support both heterogeneity of schizophrenia and genetic susceptibility to environmental agents.