Psychiatric comorbidities in bipolar disorders: An examination of the prevalence and chronology of onset according to sex and bipolar subtype.

OBJECTIVES: Bipolar Disorder (BD) is frequently comorbid with other psychiatric disorders. However, few studies systematically examine which disorders are more likely to occur pre- or post-BD onset. We examine the prevalence and Age At Onset (AAO) of psychiatric conditions in adults with BD. METHODS: A structured clinical interview was used to assess lifetime history and AAO of alcohol and cannabis misuse, suicide attempts, anxiety and eating disorders in a French sample of euthymic patients with BD (n = 739). Regression analyses were used to test for statistically significant associations between rates and AAO of comorbidities in BD groups stratified by sex or subtype. RESULTS: Prevalence of alcohol and cannabis misuse was associated with male sex and BD-I subtype; whilst most anxiety and eating disorders were associated with female sex. The AAO of most comorbid conditions preceded that of BD, except for panic disorder, agoraphobia and alcohol misuse. Few variations were observed in AAO of comorbidities according to groups. LIMITATIONS: All assessments were retrospective, so estimates of prevalence rates and especially exact AAO of some comorbidities are at risk of recall bias. CONCLUSIONS: Sex and BD subtype are associated with different rates of comorbid disorders. However, there were minimal between group differences in median AAO of comorbidities. By describing the chronological sequence of comorbidities in BD we were able to demonstrate that a minority of comorbidities typically occurred post-onset of BD. This is noteworthy as these disorders might be amenable to interventions aimed at early secondary prevention.

[Characteristics of cannabis users in a French family practice]. / Caractéristiques des usagers de cannabis dans un cabinet de médecine générale en France.

AIM: Cannabis use, as well as the prevalence of cannabis use disorder, are not known among the population attending general practices in France. We wanted to describe the characteristics of current cannabis users, estimate cannabis use disorder and self-rating of cannabis dependence, and describe medical conditions associated with cannabis use in a general practice in Paris. METHODS: An anonymous questionnaire was proposed to every patient aged 18-65 in a general practice during three months from June to August 2014. Cannabis use in the last six months was recorded and cannabis use disorder was assessed according to three different means: answering yes to the question: do you feel like you are dependent on cannabis? or answering yes to the question: do you smoke cannabis in the first 5minutes after awakening? or CUDIT score≥8 points. RESULTS: Two hundred and fifty-eight questionnaires were analyzed. Cannabis use in the past six months was found in 54 subjects (21%). Subjective feeling of cannabis dependence was endorsed by 18 subjects (6.9%). Cannabis use in the first 5minutes after awakening was found in five subjects (1.9%) and 23 (8.9%) had a CUDIT score≥8 points. Cannabis smokers had more often addictive and psychiatric associated medical conditions. CONCLUSION: General practitioners could ask about cannabis use and self-rated cannabis use disorder because it is frequent and patients with cannabis use disorder deserve specific care.

Gender-specific study of recurrent suicide attempts in outpatients with multiple substance use disorders.

BACKGROUND: people suffering from substance use disorders (SUD) often die by suicide, so that the prevention of suicide attempts (SA) remains a top priority in this population. SA recurrence is common and is associated with suicide death, but this phenotype has been overlooked in SUD populations. Thus, we aimed at identifying the risk factors of SA recurrence in SUD, controlling for both gender and levels of exposure to addictive substances, including tobacco. METHODS: we consecutively recruited 433 treatment-seeking outpatients with either opiate or cocaine use disorder and assessed their lifetime history of addictive and suicidal symptoms by standardized questionnaires. They were reliably classified as never, single or recurrent (≥ 2) suicide attempters, whose characteristics were identified by multinomial regression, stratified by gender; and compared to our previous work on serious SA in order to identify common or different risk profiles. RESULTS: 86/140 (61%) suicide attempters reported recurrence. The mean number of SA was 3.1. Recurrence was independently associated with psychiatric hospitalization in both genders, with nicotine dependence in men and with sedative use disorders in women. LIMITATIONS: psychiatric diagnoses were derived from the current medication regimen. CONCLUSION: specific and possibly avoidable/treatable risk factors for the recurrence of SA in SUD have been identified for the first time, opening new avenues for research and prevention in this high-risk population. Apart from nicotine dependence, these risk factors were very similar to those of serious SA. Although this comparison is indirect for now, it suggests a common liability towards suicidal behavior.

Serious suicide attempts in outpatients with multiple substance use disorders.

BACKGROUND: Suicide is a major public health concern and suicide attempts (SA) are frequent and burdensome in people suffering from substance use disorders (SUDs). In particular, serious SAs are a preoccupying form of attempt, which remain largely overlooked in these populations, especially regarding basic risk factors such as gender, addictive comorbidity and substance use patterns. Thus, we undertook a gender-specific approach to identify the risk factors for serious SAs in outpatients with multiple SUDs. MATERIAL AND METHODS: 433 Treatment-seeking outpatients were consecutively recruited in specialized care centers and reliably classified as serious, non-serious and non-suicide attempters. We also characterized lifetime exposure to SUDs, including tobacco smoking, with standardized instruments. Current medication, including psychotropic treatments were collected, which informed psychiatric diagnoses. Multinomial regression identified independent factors specifically associated with serious SAs in each gender, separately. RESULTS: 32% Participants (N=139, 47% Women and 27% Men) reported lifetime SA. There were 82 serious attempters (59% of attempters), without significant gender difference. Sedative dependence was an independent risk factor for serious SA compared to non-SA in Women and compared to non-serious SA in Men, respectively. Other risk factors included later onset of daily tobacco smoking in Men and history of psychiatric hospitalizations in Women, whose serious SA risk was conversely lower when reporting opiate use disorder or mood disorder, probably because of treatment issues. CONCLUSIONS: Despite several study limitations, we identified subgroups for a better-tailored prevention of serious SAs among individuals with SUDs, notably highlighting the need to better prevent and treat sedative dependence.

[Emotional and impulsive dimensions in bipolar disorder and borderline personality disorder]. / Dimensions affectives et impulsives dans le trouble bipolaire et le trouble de la personnalité borderline.

BACKGROUND: Studies have shown that patients with borderline personality disorder are often misdiagnosed to have bipolar disorder and conversely. Indeed, a number of characteristics common to both disorders could explain this problem: emotional instability as well as impulsivity represent confounding factors and contribute to the risk of misdiagnosis. However, it appears that these characteristics manifest themselves in different ways according to the pathology. The aim of the study is to show differences between affective lability, emotional intensity and impulsivity dimensions. The clinical aim is to refine bipolar disorder and borderline personality disorder diagnosis, to improve psychological care for these patients in the long-term. METHOD: We compared the emotional and impulsive dimensions in two groups of patients: a group of 21 patients with bipolar disorder and a group of 19 patients with borderline personality disorder. Tools: ALS, a self-report questionnaire to evaluate affective lability, AIM, a self-report questionnaire to see affective intensity, and UPPS, a self-report questionnaire to measure impulsivity according to several dimensions. RESULTS: The results indicate that borderline patients scored significantly higher than bipolar patients at the ALS and AIM scales. Regarding the UPPS, borderline patients scored significantly higher than bipolar patients for the dimensions "lack of premeditation" and "lack of perseverance"; however, bipolar patients had significantly higher scores than borderline patients for the dimension "negative emergency". CONCLUSION: This study shows that bipolar disorder and borderline personality can be differentiated thanks to emotional dimensions as well as different dimensions of impulsivity: borderline patients appear to have an affective lability and intensity more important than bipolar patients; it also appears that impulsivity manifests itself differently according to the disorder.

The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens.

Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulation of reward and addiction are still unknown. In this study, we showed that disruption of the gene that encodes VGLUT3 (Slc17a8) markedly increased cocaine self-administration in mice. Concomitantly, the amount of dopamine (DA) release was strongly augmented in the NAc of VGLUT3(-/-) mice because of a lack of signaling by metabotropic glutamate receptors. Furthermore, dendritic spines and glutamatergic synaptic transmission on medium spiny neurons were increased in the NAc of VGLUT3(-/-) mice. Increased DA and glutamate signaling in the NAc are hallmarks of addiction. Our study shows that TANs use glutamate to reduce DA release and decrease reinforcing properties of cocaine in mice. Interestingly, we also observed an increased frequency of rare variations in SLC17A8 in a cohort of severe drug abusers compared with controls. Our findings identify VGLUT3 as an unexpected regulator of drug abuse.

[Comorbidity in 207 cannabis users in a specific outpatient setting]. / Comorbidités chez 207 usagers de cannabis en consultation jeunes consommateurs.

BACKGROUND: Health care seeking for a problematic use of cannabis is in progress in France. OBJECTIVES: The aim is to assess the addictive and psychiatric comorbidity in cannabis users seen in the specific setting at the Lariboisière hospital. METHOD: Two hundred and seven cannabis users were included from January 2004 to December 2009. Twelve-month and lifetime diagnosis of abuse and dependence (cannabis, alcohol, cocaine/crack) (DSM-IV), current and lifetime mood disorders, anxiety disorders, eating disorders and psychotic disorders were assessed (Mini-International Neuropsychiatric Interview). Logistic regression analyses identified adjusted odds ratios associated with the gender and the health care seeking (P=0.01). RESULTS: One hundred and forty-seven men (71%) and 60 women (29%), 29.3±8.6 years (15.2-51.6 years). Most of the outpatients ask for health care themselves (59.7%), whereas 19.4% are asked to seek health care by relatives (19.4%) or because of an academic, health or justice injunction (20.4%). In total, 49.3% of the outpatients are single, 35.7% are cohabitating, 9.3% are married and 6.3% are separated/divorced. About 20.4% of the outpatients are students, 35.7% have a professional activity, 19% are jobless, 2.4% are impaired, 0.5% are retired, at home and 12.1% do not have an official income. Twelve-month and lifetime prevalence of abuse/dependence are: cannabis (10.1/82.1% and 8.7/88.4%), alcohol (9.7/8.7% and 19.3/18.8%), cocaine/crack (2.4/3.4% and 4.8/11.6%). The mean duration of cannabis dependence for the current dependent users is 8.4±5.8 years. The mean number of "joints" during the last 6 months is 6±4.3, the mean amount of cannabis per week is 12.5±11.3g. About 51.3% of the dependent users report externalized and/or internalized disorders at school during childhood and adolescence. In total, 19.4% of the dependent users have a suicide attempt history and 18.9% have a psychiatric hospitalisation history, more frequently women (P<0.01 and P=0.02). About 73.8% have a psychologist or psychiatrist care history. In total, 38.1% of users have at least one current mood disorder, females more frequently than males (P<0.001). Current and lifetime prevalence of mood disorders are: major depressive disorder (MDD) (29.1% and 57.1%); current dysthymia (20.3%); hypomania (1.9 and 6.7%); mania (2.9 and 12.8%). Females have more frequently than males current and lifetime MDD (P<0.001). About 53.2% of users have at least one current anxiety disorder, females more frequently than males (P<0.001). Current and lifetime prevalence of anxiety disorders are: panic disorder (10 and 16.4%); agoraphobia (13.9 and 17.4%); social phobia (26.9 and 32.8%); obsessive-compulsive disorder (9.5 and 12.9%); post-traumatic stress disorder (PTSD) (6.5 and 16.4%); current generalized anxiety disorder (26.8%). Females have more frequently current and lifetime: agoraphobia (P=0.01 and P<0.001); PTSD (P<0.001); current social phobia (P=0.049). Current and lifetime eating disorders prevalence are: anorexia (0 and 1.5%); bulimia (4 and 8%); females more frequently have bulimia (P=0.02 and P<0.001). In total, 4.8% have a psychotic disorder. Adjusted odds ratios of associated variables to gender (women/men) are lifetime MDD OR=4.71 [2.1-10.61] (P<0.001) and later age of onset of cannabis abuse OR=1.1 [1.04-1.17] (P=0.002). Adjusted odds ratios associated with personal health care seeking compared to a non personal motivated health care seeking are the numbers of criteria of 12-month cannabis dependence OR=1.26 [1.06-1.51] (P=0.009) and age OR=1.07 [1.03-1.12] (P=0.002). CONCLUSION: Our survey confirms the high mood and anxiety disorders comorbidity in cannabis dependent users seen in a specific setting and underlines the need to evaluate those disorders.

Alteration of glutamate/GABA balance during acute alcohol withdrawal in emergency department: a prospective analysis.

AIMS: Animal studies suggest that in alcohol withdrawal the balance of neurotransmitters gamma aminobutyric acid (GABA) and glutamate is altered. To test this in humans, we aimed to measure plasma levels of glutamate, GABA and glutamate/GABA ratio in alcoholic patients presenting with complicated AWS with the same values in non-alcohol abuser/dependent controls and to determine prognostic factors for severe withdrawal. METHODS: 88 patients admitted to the emergency room for acute alcohol intoxication (DSM-IV) were prospectively included. Measurements of GABA and glutamate were performed on admission (Time 1, T1) and after 12 ± 2 h (T2). The experimental group (EG) was composed of 23 patients who presented at T2 with a severe AWS. The control group (CG) consisted of healthy subjects paired with the EG (gender and age). Logistic regression was performed in order to compare associated clinical and biological variables that could predict severe withdrawal. RESULTS: The concentration of GABA in the EG at T1 was significantly lower than that in the CG. The concentration of glutamate in the EG at T1 was significantly higher than that in the CG. The glutamate/GABA ratio in the EG at T1 was significantly higher than the ratio in the CG. With a multivariate logistic regression model, glutamate level at admission remained the only criterion identified as a predictor of AWS at 12 h. CONCLUSION: Decreased synthesis of GABA and increased synthesis of glutamate might be related to withdrawal symptoms experienced on brutal cessation of chronic alcohol intake.

[Cannabis withdrawal syndrome in patients with cannabis dependence only, and in patients with cannabis and opioid dependence]. / Syndrome de sevrage au cannabis dans une population de patients mono- et polydépendants (cannabis et opiacés).

BACKGROUND: The cannabis withdrawal syndrome occurs after cannabis cessation in more than 50% of dependent smokers. But although opioid-dependent patients are more frequently cannabis users and cannabis-dependent than the general population, the frequency and phenomenology of cannabis withdrawal symptoms in this specific population is unknown. Our hypothesis was that cannabis-dependent patients with current opioid dependence would experience the same withdrawal syndrome after cannabis cessation. OBJECTIVE: To describe cannabis withdrawal symptoms in cannabis-only dependent patients and in cannabis-dependent patients with current opioid dependence. METHODS: Using retrospective interviews, we evaluated the number and duration of six cannabis withdrawal symptoms in two groups: 56 cannabis-dependent patients without and 43 cannabis dependent patients with current opioid dependence. Cannabis and opioid dependence diagnoses were defined with DSM IV criteria using the MINI structured interview. RESULTS: The two groups were not different in terms of age of onset of cannabis use, and number of cannabis joints smoked at the time of the cannabis cessation attempt. The frequency of a cannabis withdrawal syndrome (defined as at least two different symptoms) did not differ in the two groups (65%). Neither was the proportion of subjects with the following symptoms: appetite or weight loss (30.8%), irritability (45.1%), anxiety (56%), aggression (36.3%) and restlessness (45.1%). Patients with cannabis dependence and current opioid dependence were more likely to report sleep disturbances (79.1 vs. 53.6%, chi(2)=6.91, P=0.007). The median duration of this cannabis withdrawal syndrome was 20 days post-cessation. CONCLUSION: This is, to our knowledge, the first study describing cannabis withdrawal syndrome in cannabis-dependent patients with current opioid dependence. These patients experience a cannabis withdrawal syndrome as often as cannabis-only dependent subjects, but describe more frequently sleep disturbances. This high rate of sleep disturbances may cause relapse to cannabis use.

Could the inter-individual variability in cocaine-induced psychotic effects influence the development of cocaine addiction? Towards a new pharmacogenetic approach to addictions.

Cocaine addiction is a chronic disease marked by relapses, co-morbidities and the importance of psychosocial consequences. The etiology of cocaine addiction is complex and involves three types of factors: environmental factors, factors linked to the specific effects of cocaine and genetic factors. The latter could explain 40-60% of the risk for developing an addiction. Several studies have looked for a link between cocaine addiction and the genes of the dopaminergic system: the genes DRD2, COMT, SLC6A3 (coding for the dopamine transporter DAT) and DBH (coding for the dopamine beta hydroxylase) but unfortunately very few well established results. Pharmacogenetic approach could be an interesting opportunity for the future. The gene DBH has particularly been linked with the psychotic effects caused by cocaine. This so-called cocaine-induced psychosis (CIP) or cocaine-induced paranoia may influence the development of cocaine addiction. Indeed, these psychotic symptoms during cocaine exposure could cause an aversive effect limiting the development of an addiction. Several functional alterations caused by different mutations of the genes involved in dopaminergic transmission (principally-1021C>T of the gene DBH, but also Val158Met of the gene COMT, TaqI A of the gene DRD2 and VNTR 9 repeat of the DAT) could result in a cocaine-induced psychosis prone phenotype. We are hypothesising that the appearance of CIP during the first contact with cocaine is associated with a lower risk of developing cocaine addiction. This protective effect could be associated with the presence of one or more polymorphisms associated with CIP. A pharmacogenetic approach studying combination of polymorphism could isolate a sub-group of patients at risk for CIPs but more favorably protected from developing an addiction. This theory could enable a better understanding of the protective factors against cocaine addiction and offer new therapeutic or preventive targets in vulnerable sub-groups exposed to cocaine.

[Sociodemographic profiles, addictive and mental comorbidity in cannabis users in an outpatient specific setting]. / Facteurs sociodémographiques, conduites addictives et comorbidité psychiatrique des usagers de cannabis vus en consultation spécialisée.

CONTEXT: In the 1990s, cannabis consumption in France increased considerably. So, in 10 years, the number of adolescents reporting regular cannabis use (10 or more times during the last 12 months) tripled. In 2004, an official program to address problems related to cannabis addiction was implemented. As part of this program, specific outpatient settings for cannabis use disorders were created. OBJECTIVE: We present the sociodemographic characteristics, the prevalence of cannabis, alcohol and others psychoactive substances and the prevalence of mental disorders in 90 cannabis users seen at an outpatient specific setting for cannabis use disorders in the Lariboisière hospital (a university hospital in Paris). MEASURES: Twelve months prevalence of substance abuse and dependence, psychiatric diagnoses based on the DSM-IV and the Mini-International Neuropsychiatric Interview (MINI) results are described. RESULTS: The study population had the following characteristics: 67% male, mean age 27.5 (S.D.=8.4) years and 59% single or divorced. Approximately, two-thirds of the users (67%) were students or currently working and 32% were unemployed. Twenty-two percent of the cannabis users received unemployment, welfare or disability benefits and 11% declared no source of revenue. Most of the users (63%) decided on their own to seek care at the setting. Seventy-three percent of the subjects had seen a psychologist or a psychiatrist in the past, with or without relation to cannabis use. By far, most of the users were cannabis dependent (82%) and 9% cannabis abusers in the last 12 months according to DSM-IV criteria prior to their visit. Seven percent of the cannabis users had alcohol dependence and 7% were abusers. The 12 months prevalence of cocaine or ecstasy dependence was 2% and the prevalence of benzodiazepines, heroin or stimulants dependence 1%. The main substances used over lifetime were tobacco (99%); alcohol (96%); cocaine (41%); benzodiazepines and hypnotics (41%); ecstasy (40%) and heroin (23%). Four percent of cannabis users had a history of intravenous drug use. The main consumption mode of cannabis in France is the blunt. About three-quarters of the consumption is in the form of resin (hashish) and one-quarter as marijuana (grass). The average consumption of cannabis in the last six months was equivalent to 5.8 blunts per day (S.D.=4.4) and 12 g per week (S.D.=10.5), and the average monthly cost was 159 euro (S.D.=133) (234 USD, S.D.=196). The prevalence of psychiatric disorders according to DSM-IV criteria in the sample is high. A current mood disorder was present in 48% and an anxiety disorder in 55% of the cannabis users in the last 12 months. The prevalence of affective disorders in the last 12 months was major depressive disorder (38%), dysthymia (19%), hypomania (3%) and mania (1%). The prevalence of anxiety disorders in the last 12 months was social phobia (29%); generalised anxiety disorder (17%); panic disorder with or without agoraphobia (16%); obsessive compulsive disorder (12%); agoraphobia without panic disorder (9%) and post-traumatic stress disorder (5%). The prevalence of schizophrenia was 4%. The prevalence of bulimia was 4% and no anorexia. Women are more likely to report an affective disorder (64% versus 41%; p=0.04) or a post-traumatic stress disorder (17% versus 0%; p<0.001) in the last 12 months. The prevalence of family history for psychiatric disorders was 52% and for addiction, 59%. CONCLUSIONS: The cannabis users seen in our specific setting are a fairly homogeneous group and for the most part addicted to cannabis only, but with very high rates of dependence. Indeed, other than tobacco dependence, 80% of the users were only dependent on, or abused on cannabis in the last 12 months. In comparison with the cohort of French cannabis users (n=4202) seen at specific outpatient settings for marijuana users in 2005, cannabis users seen in Lariboisière Hospital are older, the percentage of females is greater, they are more dependent on marijuana and have a high prevalence of affective and anxiety disorders.

Smoking ban in a psychiatry department: are nonsmoking employees less exposed to environmental tobacco smoke?

Staff members of psychiatric facilities are at high risk of secondhand smoking. Smoking exposure was assessed in 41 nonsmoking employees of a psychiatry department before and after a ban. Subjective exposure measures decreased in 76% of the subjects. Salivary cotinine decreased in the subsample of seven subjects with high pre-ban levels (32+/-8 vs 40+/-17 ng/ml, p=.045).