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.     

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.     

Schizophreniform disorder,delusional disorder and psychotic disorder not otherwise specified: clinical features,outcome and familial psychopathology

The relationship between DSM-III-R schizophreniform disorder, delusional disorder (DD) and psychotic disorder not otherwise specified (PD-NOS) and schizophrenia and affective illness (AI) remains uncertain. We explore this question in the Roscommon Family Study by examining symptoms, outcome and patterns of psychopathology in relatives. Probands were selected from a population-based case registry in the west of Ireland with an ICD-9 diagnosis of schizophrenia or AI. Personal interviews were conducted with 88% of traceable, living probands, a mean of 16 years after onset, and 86% of traceable, living first-degree relatives. Best-estimate diagnoses were made at follow-up. Schizophreniform disorder, DD and PD-NOS constituted 6.4%, 2.8% and 7.5%, respectively, of all probands with a registry diagnosis of schizophrenia. Probands with schizophreniform disorder had prominent positive psychotic symptoms, negligible negative symptoms and a good outcome, comparable to that seen in AI probands. Their relatives had an excess risk of schizophrenia spectrum illness but not AI. Probands with DD had prominent delusions but no other psychotic symptoms, few negative symptoms, fair to good outcome and an increased risk in relatives for alcoholism. Probands with PD-NOS had both moderate positive and negative psychotic symptoms, a poor to fair outcome and a substantially elevated risk in relatives of schizophrenia and schizophrenia spectrum disorders but not AI. These results suggest that i) DSM-III-R criteria for schizophreniform disorder define a good outcome disorder with prominent positive psychotic symptoms that probably has a familial relationship to schizophrenia, but not AI; ii) DD is a rare, monosymptomatic psychosis that may have a modest etiologic relationship with alcoholism, but probably not with schizophrenia or AI and iii) PD-NOS is probably heterogeneous but, of these 3 disorders, most closely resembles schizophrenia with respect to symptoms, outcome and familial psychopathology. These results should be seen as tentative given the small number of probands and relatives evaluated.     

Lifetime positive symptoms in patients with schizophrenia and cannabis abuse are partially explained by co-morbid addiction

Recent prospective findings have shown that cannabis use by young people could be a risk factor for psychotic symptoms in adulthood, but the long-term impact of cannabis abuse on the clinical features of declared schizophrenia remains to be explored. We assessed the independent influence of cannabis abuse on the clinical symptoms of schizophrenia, after controlling for frequently co-occurring addictive disorders. Patients with schizophrenia, and with (N=66), or without (N=139) cannabis abuse, were compared for lifetime positive and negative symptoms, taking into account presence of any other addictive disorders. The incidence of the abuse of drugs other than cannabis was nearly five times greater amongst patients with both schizophrenia and cannabis abuse. When the analyses were limited to subjects with no other abuse, less avolution and fewer apathy symptoms were still detected in patients with schizophrenia and cannabis abuse than in those with no abuse (p=0.0001). In contrast, between-group differences for positive symptoms were abolished when multiple substance abuses were taken into account. The strong association between cannabis abuse and fewer negative symptoms in schizophrenia was thus replicated in this sample, but once co-morbid addictive disorders had been controlled no influence of cannabis abuse on hallucinations was detected. Distinguishing the effects of co-occurring addictive disorder(s) in patients with schizophrenia and cannabis dependence may thus be important when attempting to analyse the impact of cannabis abuse.     

Prevalence of substance abuse in schizophrenia: demographic and clinical correlates

Methodological issues involved in assessing the prevalence of substance abuse in schizophrenia are discussed, and previous research in this area is comprehensively reviewed. Many studies suffer from methodological shortcomings, including the lack of diagnostic rigor, adequate sample sizes, and simultaneous assessment of different types of substance abuse (e.g., stimulants, sedatives). In general, the evidence suggests that the prevalence of substance abuse in schizophrenia is comparable to that in the general population, with the possible exceptions of stimulant and hallucinogen abuse, which may be greater in patients with schizophrenia. Data are presented on the association of substance abuse with demographics, diagnosis, history of illness, and symptoms in 149 recently hospitalized DSM-III-R schizophrenic, schizophreniform, and schizoaffective disorder patients. Demographic characteristics were strong predictors of substance abuse, with gender, age, race, and socioeconomic status being most important. Stimulant abusers tended to have their first hospitalization at an earlier age and were more often diagnosed as having schizophrenia, but did not differ in their symptoms from nonabusers. A history of cannabis abuse was related to fewer symptoms and previous hospitalizations, suggesting that more socially competent patients were prone to cannabis use. The findings show that environmental factors may be important determinants of substance abuse among schizophrenic-spectrum patients and that clinical differences related to abuse vary with different types of drugs.     

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.     

Precipitation and determination of the onset and course of schizophrenia by substance abuse--a retrospective and prospective study of 232 population-based first illness episodes

Onset and lifetime prevalence of substance abuse were assessed retrospectively using the IRAOS interview in a population-based, controlled sample of 232 first episodes of schizophrenia (ABC sample). Subjects with schizophrenia were twice as likely as controls to have a lifetime history of substance abuse at the age of first admission (alcohol abuse: 23.7 versus 12.3%; drug abuse: 14.2 versus 7.0%). 88% of the patients with drug abuse took cannabis. The sequence of substance abuse and schizophrenia was studied on the timing of abuse onset and illness onset, the latter as based on various definitions: first sign of the disorder, first psychotic symptom and first admission. 62% of the patients with drug abuse and 51% of those with alcohol abuse began the habit before illness onset (=first sign of the disorder). Abuse onset and illness onset occurred highly significantly within the same month (drug abuse in 34.6%, alcohol abuse in 18.2%). Unexpectedly, no temporal correlation was found between abuse onset and the onset of the first psychotic episode. We concluded that a small proportion of schizophrenias might have been precipitated by substance--mainly cannabis--abuse. Long-term effects of early substance abuse were studied prospectively at six cross-sections over five years from first admission on in a subsample of 115 first episodes of schizophrenia. Abusers showed significantly more positive symptoms and a decrease in affective flattening compared with controls. Five-year outcome as based on treatment compliance, utilization of rehabilitative measures and rate of employment was also poorer for patients with than without early substance abuse.     

Cannabis and schizophrenia: demographic and clinical correlates

The high prevalence of psychoactive substance abuse or dependence among schizophrenic patients has now been well established. Mueser et al. stressed the need to assess the abuse of specific classes of substances and analyse the data accordingly. The objective of this study was to compare the socio-demographic correlates and the clinical features in a group of schizophrenic patients with a lifetime cannabis abuse or dependence according to the DSM III-R with a group of schizophrenic patients who had never presented any abuse or dependence. SUBJECTS AND METHODS: The study included 124 subjects with diagnoses of schizophrenia or schizoaffective disorders according to the DSM III-R. Inclusion criteria for participation in the study were age 18 years or older and willingness to provide consent to participate in the study. The inpatients were evaluated when their condition was stabilised. Assessment tools were the psychoactive substance use disorder section of the Composite International Diagnostic Interview (CIDI), the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning Scale (GAF). Subjects with cannabis abuse or dependence during their lifetime were compared with subjects without abuse or dependence, using chi(2) test for categorical variables and analyses of covariance (ANCOVA) for quantitative variables. RESULTS: Forty-nine subjects (42,6%) presented lifetime abuse or dependence on one or more substances. Since 19 patients with alcohol, stimulant, sedative or opiate abuse or dependence were excluded, the study finally included 96 subjects including a first group of schizophrenic patients with cannabis abuse (n=6) or dependence (n=24) and a second group without any psychoactive substance abuse (n=66). Thirteen (11.3%) patients presented cannabis abuse or dependence within the 6 months prior to the assessment. The mean SD age of onset of cannabis abuse or dependence was 19.6 +/- 3.0 years. Cannabis abuse/dependence preceded the first psychiatric treatment in 70% of the subjects (n=21). 83.3% of the schizophrenic patients with cannabis abuse or dependence were male (n=25) compared to 62.1% in the group without substance abuse (n=41) (chi(2)=4.32, df=1, p=0.04). Schizophrenic patients with cannabis abuse were significantly younger (mean age: 28.9 +/- 6.3 vs 37.0 +/- 12.7, ANCOVA, F=7.2, df=1,96 p=0.009). There was no significant difference between the two groups for marital status, (chi(2)=5.34, df=2, p=0.07), level of education, (chi(2)=0.93, df=2, p=0.62) professional status, (chi(2)=8.7, df=5, p=0.11), on PANSS total score (ANCOVA, F=0.42, df=1,93, p=0.52), GAF score (ANCOVA, F=0.06, df=1,92, p=0.80), mean number of hospitalizations (ANCOVA, F=3.25, df=1,85, p=0.08), mean age of first psychiatric contact (ANCOVA, F=0.74, df=1,93, p=0.39), and neuroleptic dosages (ANCOVA, F=0.03, df=1,90, p=0.87). In contrast, the total duration of hospitalization was significantly longer for the group with cannabis abuse. Patients with cannabis abuse were more likely to have an history of suicide attempts than subjects without substance abuse (chi(2)=11.52, df=1, p=0.0007). DISCUSSION: The prevalence rates for substance abuse and the socio-demographic characteristics of the population of our study are consistent with findings of previous studies. Male gender and age were significantly related to history of cannabis abuse or dependence. Cannabis abuse frequently preceded the onset of psychiatric treatment. However, both schizophrenia and substance abuse tend to develop gradually, with no clear demarcation for the onset of schizophrenia. The absence of any link between the scores for the subscales of the PANSS and cannabis abuse, both in our study and in some retrospective previous studies, is not suggestive of cannabis abuse as a self-medication of positive or negative symptoms of schizophrenia. Self-medication could concern other symptoms, such as cognitive deficits. In addition, the hypothesis of self-medication has especially been suggested in cocaine abuse or dependence. Some limitations to this study can be discussed. First, although the recruitment was systematic and done in a public mental health service, the patients of our study are not necessarily representative of all schizophrenic patients. Secondly, as in any retrospective study, the prevalence of lifetime substance abuse may have been under-estimated. Urinary toxicology tests may have been able to improve the sensitivity of the diagnosis of recent substance abuse, but structured interviews are more appropriate for the diagnosis of lifetime substance abuse in schizophrenic patients than urinary toxicology tests. CONCLUSION: The socio-demographic characteristics of cannabis abuse or dependence in schizophrenia are similar to those found in general population. Cannabis using schizophrenic patients were more likely to be younger and male than non users. The duration of hospitalization was significantly longer for the group with cannabis abuse. Prevalence of suicide attempts in schizophrenia is closely correlated to cannabis abuse.     

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.     

Obstetric complications and Apgar score in early-onset schizophrenic patients with prominent positive and prominent negative symptoms

The objective of the study was to find associations between obstetric complications (OCs) history and schizophrenia course and symptoms. We analysed the obstetric and psychiatric history of 50 DSM IV schizophrenic subjects who experienced their first schizophrenia episode in adolescence, and 30 healthy controls. Obstetrical data and Apgar scores were obtained from medical records and evaluated with the Lewis and Murray Scale. Based on patients' documentation [including longitudinal evaluation with Positive and Negative Syndrome Scale (PANSS)] the symptom profile and the course of schizophrenia were determined. Results: we distinguished two major groups of patients: with prominent negative and prominent positive symptoms. Schizophrenics with prominent negative symptoms and a chronic schizophrenia course had significantly more definite OCs and lower Apgar scores than patients with prominent positive symptoms and controls. Subjects who had a positive OCs history were more than four times likely to develop schizophrenia in adolescence than those without such a history (OR=4.64; 95% CI=1.29-17.51) with the likelihood of developing schizophrenia with prominent negative symptoms especially high (OR=7.31; 95% CI=1.80-29.65). An Apgar score of between 0 and 3 after birth was associated with an increased risk for developing schizophrenia (OR=2.25; 95% CI=0.56-9.12), especially with prominent negative symptoms (OR=3.71; 95% CI=0.84-16.32). The findings support the hypothesis of a role of OCs in developing early-onset schizophrenia and suggest the associations of the OCs history with a specific symptoms profile (prominent negative symptoms) and a chronic course of schizophrenia.     

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.     

Drug abuse in schizophrenic patients: clinical correlates and reasons for use

OBJECTIVE: This study aimed to 1) determine substance abuse prevalence and preference in a diverse sample of schizophrenic, schizoaffective, and schizophreniform inpatients, 2) compare drug-abusing and non-drug-abusing patients on demographic and clinical variables during the acute and stabilization phases of their hospital course, and 3) obtain data from patients on reasons for drug abuse and on acute state-related changes during periods of intoxication. METHOD: Eighty-three psychotic inpatients consecutively admitted to a New York City teaching hospital were evaluated. Sixty-eight had schizophrenia, 12 had schizoaffective disorder, and three had schizophreniform disorder diagnosed according to the Structured Clinical Interview for DSM-III-R. Each patient received ratings on the Brief Psychiatric Rating Scale, the Global Assessment Scale, and the Scale for the Assessment of Negative Symptoms at admission and at discharge, an evaluation of premorbid adjustment, and an extensive interview on drug and alcohol use. RESULTS: Forty (48%) of the patients received diagnoses of drug or alcohol abuse or dependence. The drug-abusing patients primarily used cannabis (N = 26), alcohol (N = 21), and cocaine (N = 14) and reported that they abused drugs to get "high," to relieve depression, and to relax. They had significantly fewer positive and negative symptoms at discharge, better sexual adjustment and worse school performance during adolescence, and more family histories of drug abuse than the non-drug-abusing patients. CONCLUSIONS: Schizophrenic patients who abuse drugs may represent a subgroup of patients with better prognoses and less severe clinical characteristics of schizophrenia, but their drug abuse may adversely affect global outcome.     

Lower negative symptom scores among cannabis-dependent patients with schizophrenia-spectrum disorders: preliminary evidence from an African American first-episode sample

Substance use disorders, especially cannabis abuse and dependence, are common comorbid diagnoses among patients in the early course of schizophrenia. Some prior research suggests that individuals with schizophrenia and related disorders and comorbid substance abuse may have fewer negative symptoms than those without substance abuse. This pilot study examined the association between cannabis dependence and negative symptoms in a relatively homogenous sample of 18 African American first-episode, first-hospitalization patients. Those with cannabis dependence had significantly lower Positive and Negative Syndrome Scale (PANSS) negative subscale scores compared to those without cannabis dependence (p<0.012). The two groups did not differ on PANSS positive and general psychopathology subscale scores. Additional research is needed on the correlates of substance abuse among first-episode patients, including socially disadvantaged African American patients.     

Predictors of abnormal involuntary movement in an african schizophrenia population

As little is known about the risk factors for abnormal involuntary movements in African patients with schizophrenia, 170 Xhosa participants with schizophrenia were rated with the abnormal involuntary movement scale. Abnormal involuntary movements occurred in 19.4% of this group. Modeling of the data set showed that combining age at interview, age-squared, cannabis use or abuse, and anhedonia successfully identified 82.35% of cases of involuntary movements overall. Abnormal involuntary movements increased with increasing age (in a nonlinear manner), the presence of a cannabis use or abuse history seems to be protective against involuntary movements, and anhedonia is associated with the group that displayed fewer involuntary movements.     

Cannabis abuse and brain morphology in schizophrenia: a review of the available evidence

Substance abuse is the most prevalent comorbid psychiatric condition associated with schizophrenia, and cannabis is the illicit drug most often abused. Apart from worsening the course of schizophrenia, frequent cannabis use especially at an early age seems to be an important risk factor for developing schizophrenia. Although a large body of neuroimaging studies gives evidence for structural alterations in many different brain regions in schizophrenia patients, there is still limited knowledge of the impact of cannabis abuse on brain structure in schizophrenia. We performed a systematic review including structural magnetic resonance imaging studies comparing high-risk and schizophrenia patients with and without cannabis abuse and found inconclusive results. While there is some evidence that chronic cannabis abuse could alter brain morphology in schizophrenia in patients continuing their cannabis consumption, there is no convincing evidence that this alteration takes place before the onset of schizophrenia when looking at first-episode patients. There is some weak evidence that cannabis abuse could affect brain structures in high-risk subjects, but replication of these studies is needed.     

Effects of cannabis and familial loading on subcortical brain volumes in first-episode schizophrenia

Schizophrenia is a severe neuropsychiatric disorder with familial loading as heritable risk factor and cannabis abuse as the most relevant environmental risk factor up to date. Cannabis abuse has been related to an earlier onset of the disease and persisting cannabis consumption is associated with reduced symptom improvement. However, the underlying morphological and biochemical brain alterations due to these risk factors as well as the effects of gene-environmental interaction are still unclear. In this magnetic resonance imaging (MRI) study in 47 first-episode schizophrenia patients and 30 healthy control subjects, we investigated effects of previous cannabis abuse and increased familial risk on subcortical brain regions such as hippocampus, amygdala, caudate nucleus, putamen, thalamus and subsegments of the corpus callosum (CC). In a subsequent single-volume ¹H-magnetic resonance spectroscopy study, we investigated spectra in the left hippocampus and putamen to detect metabolic alterations. Compared to healthy controls, schizophrenia patients displayed decreased volumes of the left hippocampus, bilateral amygdala and caudate nucleus as well as an increased area of the midsagittal CC1 segment of the corpus callosum. Patients fulfilling the criteria for cannabis abuse at admission showed an increased area of the CC2 segment compared to those who did not fulfill the criteria. Patients with a family history of schizophrenia combined with previous cannabis abuse showed lower volumes of the bilateral caudate nucleus compared to all other patients, implicating an interaction between the genetic background and cannabis abuse as environmental factor. Patients with cannabis abuse also had higher ratios of N-acetyl aspartate/choline in the left putamen, suggesting a possible neuroprotective effect in this area. However, antipsychotic medication prior to MRI acquisition and gender effects may have influenced our results. Future longitudinal studies in first-episode patients with quantification of cannabis abuse and assessment of schizophrenia risk genes are warranted.

     

Effect of comorbid substance use on neuropsychological performance in subjects with psychotic or mood disorders

Objective - Patients presenting with psychotic or mood disorders present with neuropsychological deficits such as executive and memory disturbance. Deficits of these functions have also been reported in patients presenting with alcohol use or substance use disorders. A large percentage of patients with non-affective psychotic or mood disorders present with a comorbid substance use disorder. These subjects are often a priori excluded from most neuropsychological studies. However, using such an exclusion criterion may induce a selection bias linked to the high prevalence of this dual diagnosis. It is therefore necessary to further explore the impact of substance abuse on neuropsychological performance in subjects with psychotic or mood disorders. Method - Patients consecutively hospitalized for a non-affective psychotic disorder or a mood disorder were included. A standardised method was used to collect information on addictive behaviour, clinical and social characteristics. DSM IV diagnoses, including those of substance use, were made using a structured diagnostic interview and all other available clinical and historical information collected during the hospital stay. Memory performance was tested using the Batterie d'Efficience Mnésique 84 (Battery of memory efficiency 84 items, BEM 84). Executive abilities were explored using the Wisconsin Card Sorting Test (WCST) and the Stroop test. ANCOVAs with cannabis use disorder or alcohol use disorder as main factor were used to examine associations with neuropsychological test scores. Results - We have included 77 patients fulfilling the diagnostic criteria for non-affective psychotic disorders (schizophrenia, schizoaffective disorder, delusional disorder, other psychotic disorder, n=35) or mood disorders (n=42). Among these patients, 27.3% presented with a lifetime history of alcohol abuse/dependence (current prevalence: 14.3%) and 23.4% presented with a lifetime history of cannabis abuse/dependence (current prevalence: 11.7%). We have assessed the specific impact of alcohol and cannabis use on neuropsychological performance. No significant differences on memory and executive performance were found between patients presenting with and without a lifetime history of alcohol abuse/dependence. These results were not modified after adjustement for potential confounding factors (age, gender, educational level, age at onset, diagnosis, current versus past addictive behaviour). Patients with a lifetime history of cannabis abuse/dependence had significantly higher (i.e. better performance) general BEM 84 score (F=3.89, df=1, p=0.05), higher complex figure delayed recall scores (F=6.62, df=1, p=0.01) and higher recognition scores (F=3.9, df=1, p=0.05) than patients presenting without a lifetime history of cannabis use. After adjustment on covariables (age, gender, educational level, age at onset, diagnosis, current versus past addictive behaviour), the differences on memory performance between the two groups were no longer significant, the differences found before adjustment were mainly explained by the confounding effect of age. Patients presenting with a lifetime history of cannabis abuse/dependence had significantly lower interference scores on the Stroop test than subjects without cannabis use (F=5.67, df=1, p=0.02). This finding was not modified after adjustment for confounding factors. Information on substance use was collected by interviewing the patient and was completed by using all other available source of information, but no urine testing was performed. Thus, substance use could have been underestimated or unrecognized in some patients. We did not distinguish patients who presented with substance abuse from those who presented with dependence because there were few of the latter. Distinguishing these two populations would be of interest because dependence may have a more deleterious effect than abuse in neuropsychological performances. Finally, we did not included normal control subjects so we can not assess if our cohort present with memory and executive deficits compared to normal subjects. Conclusion - Comorbid alcohol or cannabis abuse/dependence has limited effects on memory and executive abilities in subjects with psychotic or mood disorder. The only significant difference between subjects with and without a dual diagnosis was that subjects with cannabis use disorder performed poorly on the Stroop test. No other significant difference in executive and memory performance was found after adjustment for confounding factors. Since there is a high prevalence of a comorbid substance use disorder in subjects with psychotic or mood disorder, the exclusion of these patients in neuropsychological studies may not be systematically justified.