Influence of CRTC1 polymorphisms on body mass index and fat mass in psychiatric patients and the general adult population.

IMPORTANCE: There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE: To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS: Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123,865). INTERVENTION: Noninterventional studies. MAIN OUTCOME AND MEASURE: Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS: Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (P(adjusted) = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m² lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87-kg/m² lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r² = 0.7) was associated with lower BMI (sample 5, n = 123,865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE: These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.

Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population.

PURPOSE: To describe the weight gain-related side-effects of psychotropic drugs and their consequences on metabolic complications (hypercholesterolemia, obesity) in a Swiss cohort of psychiatric patients. METHOD: This cross-sectional observational study was performed in an out-patient psychiatric division with patients having received for more than 3 months the following drugs: clozapine, olanzapine, quetiapine, risperidone, lithium, and/or valproate. Clinical measures and lifestyle information (smoking behaviour, physical activity) were recorded. RESULTS: 196 inclusions were completed. Weight gain (≥10% of initial weight) following drug treatment was reported in 47% of these patients. Prevalence of obesity (BMI ≥ 30), hypercholesterolemia (≥6.2 mmol/L) and low HDL-cholesterol (<1.0 mmol/L in men, <1.3 mmol/L in women) were present in 38%, 21%, and 27% of patients, respectively. A higher standardised dose, an increase of appetite following medication introduction, the type of medication (clozapine or olanzapine > quetiapine or risperidone > lithium or valproate), and the gender were shown to be significantly associated with evolution of BMI. CONCLUSION: High prevalence of obesity and hypercholesterolemia was found in an out-patient psychiatric population and confirms drug-induced weight gain complications during long-term treatment. The results support the recently published recommendations of monitoring of metabolic side-effects during treatment with atypical antipsychotics. Moreover, the weight gain predictors found in the present study could help to highlight patients with special health care management requirement.

Testing the Cigarette Dependence Scale in 4 samples of daily smokers: psychiatric clinics, smoking cessation clinics, a smoking cessation website and in the general population.

AIM: To assess the properties of the Cigarette Dependence Scale (CDS-12) in various samples of daily smokers and to provide reference scores in a general population sample. METHODS: Surveys in 4 samples of daily cigarette smokers: psychiatric out-patients in Geneva, Switzerland (n=226), clients of smoking cessation clinics in France (n=370), visitors of a French-language smoking cessation website (n=13,697) and a representative sample of the general population of Geneva (n=292). RESULTS: In all 4 samples, Cronbach's alpha coefficients were >0.87 and factor analyses indicated that CDS-12 was unidimensional. CDS-12 was slightly skewed towards higher values, and it was associated with expired carbon monoxide, but this association was not strong (9% of variance explained, p<0.001). CDS-12 scores were highest in clients of smoking cessation clinics (mean=47.7, SD=10.2), followed by psychiatric patients (mean=44.4, SD=8.4), visitors of smoking cessation websites (mean=43.3, SD=11.6) and the general population sample (mean=36.9, SD=12.3). Except for tolerance, each element in the DSM-IV and ICD-10 definitions of dependence is reflected by at least one item in CDS-12, even though the match with these definitions is sometimes indirect. CONCLUSIONS: This paper presents reference scores and validity and reliability tests for CDS-12 in a diversity of samples of daily smokers. This information should be useful to clinicians and researchers.

Acceptability and impact of a partial smoking ban followed by a total smoking ban in a psychiatric hospital.

OBJECTIVE: To assess the impact of a partial smoking ban followed by a total smoking ban in a psychiatric hospital in Switzerland. METHODS: In 2003, smoking was allowed everywhere in psychiatric units. In 2004, smoking was prohibited everywhere except in smoking rooms. In 2006, smoking rooms were removed and smoking was totally prohibited indoors. Patients and staff were surveyed in 2003 (n=106), 2004 (n=108), 2005 (n=119) and 2006 (n=134). RESULTS: Exposure to environmental tobacco smoke (ETS) decreased after the partial ban and further decreased after the total ban. Among patients, after the total ban, more smokers attempted to quit smoking (18%) relative to before the total ban (2%, odds ratio=10.1, p=0.01). More smokers said that hospital staff gave them nicotine replacement products after the total ban (52%), compared with before (13%, odds ratio=7.6, p<0.001). Many participants (55%) commented that the total ban was too strict, and most (64%) preferred the partial ban. CONCLUSIONS: The partial ban decreased exposure to ETS and the total ban further improved the situation and increased the proportion of smokers who attempted to quit smoking and received nicotine medications. The total ban was loosely enforced and was overall acceptable, but most participants preferred a partial ban.

Acceptability and impact of a partial smoking ban in a psychiatric hospital.

OBJECTIVE: The acceptability and impact of partial smoking bans in psychiatric hospitals are not well documented. We assessed the impact of a partial smoking ban in a psychiatric hospital in Switzerland. METHODS: Before the intervention, smoking was not allowed in bedrooms and dining rooms, but this ban was not enforced. The intervention consisted of banning smoking everywhere, except in dedicated smoking rooms. Patients and staff were surveyed before (October 2003, 49 patients and 57 staff) and 2 months after the smoking ban (April 2004, 54 patients and 54 staff). Analyses included both patients and staff. RESULTS: Compared with baseline, after the intervention twice as many non-smokers reported that they were "never" exposed to environmental tobacco smoke (ETS) in bedrooms (before=25.0%, after=54.5%, p=0.046), dining rooms (35.5 vs. 65.5%, p=0.037), corridors (10.4 vs. 30.9%, p=0.001) and meeting rooms (36.8 vs. 75.0%, p=0.012). The smoking ban was loosely enforced; although the ban reduced ETS, substantial exposure to ETS remained after it was introduced. Most participants (87%) rejected the idea of a total smoking ban. CONCLUSION: The partial smoking ban was well accepted and was associated with less exposure to ETS. However, even a partial ban proved difficult to enforce in this hospital.

[Prevalence and characteristics of neuroleptic association in a patient cohort with psychotic disorders]. / Prévalence et caractéristiques de l'association de neuroleptiques chez une cohorte de patients souffrant de troubles psychotiques.

OBJECTIVES: Combined antipsychotic drugs are often prescribed, despite a lack of objective supporting data. Therefore, it is especially important to determine the scope of this practice and to better understand the characteristics of affected patients to identify which associations to study first. METHOD: We studied patients with psychotic disorders followed for at least 1 year at an outpatient psychiatric clinic in Geneva (n = 253). We collected data on prescriptions given at baseline and during that period, as well as sociodemographic and clinical data. RESULTS: During the follow-up period, 36% of patients were prescribed a neuroleptic. These patients differ by negative changing characteristics: less activity, financial assistance, nursing home placement, and numerous admissions with earlier onset of disorder. Three-quarters of patients did not change treatment during that period. Treatment stability is associated with treatment compliance and lack of hospital admission during the follow-up period. CONCLUSION: Without any scientific substantiation, patients with negative changing characteristics are often prescribed neuroleptics. Such treatment options are likely relatively inefficient strategies. Moreover, this practice risks further complicating patients who are already characterized by negative elements.

[The role of the primary care physician in the care of the psychotic patient]. / Rôle du médecin de premier recours dans la prise en charge du patient psychotique.

The primary care physician (PCP) plays an important role in the outpatient care of psychotic patients, particularly in the early detection of these disorders. Through the PCP's status as a trusted individual who knows the patient and his/her family, his/her opinion and attitude influence treatment acceptance and, consequently, the prognosis. By ensuring the continuity of care, in collaboration with a psychiatrist, the PCP helps prevent relapse and the evolution towards chronicity and long-term handicaps. A high incidence of cardiopulmonary disease and concomitant substance abuse in the population of chronic psychotic patients, as well as the monitoring of potential somatic side effects of psychotropic medication, require regular somatic follow-up by the PCP.

Stages of change in smokers with schizophrenia or schizoaffective disorder and in the general population.

This study compared smoking behavior and motivation to quit smoking, assessed with a "stages of change" questionnaire, in outpatients with schizophrenia or schizoaffective disorder and in a representative sample of the general population. We conducted a mail survey in a representative sample of the general population of Geneva, Switzerland, in 1996 (n = 742); and a survey of 151 patients with schizophrenia (84%) or schizoaffective disorder (16%) who attended a Geneva ambulatory psychiatric clinic in 2000. There were more smokers (70% vs. 28%, p < 0.001) in patients with schizophrenia or schizoaffective disorder than in the general population, and fewer ex-smokers (15% vs. 52%, p < 0.001). Patients with schizophrenia or schizoaffective disorder smoked more than smokers in the general population (22 vs. 16 cigarettes per day, p < 0.001). Among current smokers, the distribution of stages of change was similar in patients with schizophrenia or schizoaffective disorder (precontemplation 79%, contemplation 18%, preparation 3%) and in the general population sample (74%, 22%, and 4%, p = 0.6). In both samples, similar proportions of smokers had made an attempt to quit in the previous year (27% vs. 22%, p = 0.3). These results suggest that a substantial minority of smokers with schizophrenia or schizoaffective disorder are motivated to quit smoking, try to quit, and succeed in quitting.

Alcohol consumption and the CAGE test in outpatients with schizophrenia or schizoaffective disorder and in the general population.

We conducted a survey of 151 outpatients with schizophrenia or schizoaffective disorder in Geneva, Switzerland, in 2000, and a mail survey in a representative sample of the general population of Geneva in 1996 (n = 742), to compare alcohol consumption and alcoholism in these two samples. Fewer patients with schizophrenia than participants in the general population drank alcohol daily (9.9% vs. 18.3%, p < 0.001). Excluding participants who said they currently never drank, alcohol consumption was similar in both groups (3 vs. 4 glasses/week, p = 0.22). However, more patients with schizophrenia than participants in the population sample had a CAGE score > or = 2 (21.2% vs. 10.1%, p < 0.001), indicating a suspicion of alcoholism. Thus, asking about alcohol consumption produced different results from assessing hidden alcoholism with the CAGE. Either patients with schizophrenia under-reported their alcohol consumption, or the CAGE produced higher scores in these patients, for any given level of alcohol consumption. Previous research has shown, however, that the CAGE is a valid test in patients with schizophrenia, which suggests that in Geneva, alcoholism is more prevalent in patients with schizophrenia than in the general population.