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Background: It is unclear whether the normative sequence of drug use initiation, beginning with tobacco and alcohol, progressing to cannabis and then other illicit drugs, is due to causal effects of specific earlier drug use promoting progression, or to influences of other variables such as drug availability and attitudes. One way to investigate this is to see whether risk of later drug use in the sequence, conditional on use of drugs earlier in the sequence, changes according to time-space variation in use prevalence. We compared patterns and order of initiation of alcohol, tobacco, cannabis, and other illicit drug use across 17 countries with a wide range of drug use prevalence.Method: Analyses used data from World Health Organization (WHO) World Mental Health (WMH) Surveys, a series of parallel community epidemiological surveys using the same instruments and field procedures carried out in 17 countries throughout the world.Results: Initiation of "gateway" substances (i.e. alcohol, tobacco and cannabis) was differentially associated with subsequent onset of other illicit drug use based on background prevalence of gateway substance use. Cross-country differences in substance use prevalence also corresponded to differences in the likelihood of individuals reporting a non-normative sequence of substance initiation.Conclusion: These results suggest the "gateway" pattern at least partially reflects unmeasured common causes rather than causal effects of specific drugs on subsequent use of others. This implies that successful efforts to prevent use of specific "gateway" drugs may not in themselves lead to major reductions in the use of later drugs. [ABSTRACT FROM AUTHOR]

Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity., Methods: Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately., Results: Cocaine dependence (p occurrence = 6.18 × 10 -5 , p severity = 9.25 × 10 -8 ), number of cocaine dependence DSM IV-Tr criteria (p occurrence = 1.22 × 10 -7 , p severity = 5.09 × 10 -6 ), and frequency of intake during the worst period of misuse (p occurrence = 8.51 × 10 -04 , p severity = 0.04) were associated with greater occurrence and higher severity of CIH. The genetic associations did not yield significant results after correction for multiple tests. However, some nominal associations of SNPs mapped to the VMAT2, DBH, DRD1, and DRD2 genes were significant. In the multivariate model, the significant variables were the number of cocaine dependence criteria, lifetime alcohol dependence, and the nominally associated SNPs., Conclusion: Our study shows that CIH occurrence and severity are two distinct phenotypes, with shared clinical risk factors; however, they likely do not share the same genetic background., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Suicide attempts have been associated with both cocaine use disorder (CocUD) and childhood trauma. We investigated how childhood trauma is an independent risk factor for serious and recurrent suicide attempts in CocUD. Method : 298 outpatients (23% women) with CocUD underwent standardized assessments of substance dependence (Diagnostic and Statistical Manual-mental disorders, fourth edition, text revised), impulsiveness, resilience, and childhood trauma, using validated tools. Suicide attempts history was categorized as single vs. recurrent or non-serious vs. serious depending on the lifetime number of suicide attempts and the potential or actual lethality of the worst attempt reported, respectively. Bivariate and multinomial regression analyses were used to characterize which childhood trauma patterns were associated with the suicide attempts groups. Results : 58% of CocUD patients reported childhood trauma. Recurrent and serious suicide attempts clustered together and were thus combined into "severe SA." Severe suicide attempt risk increased proportionally to the number of childhood traumas (test for trend, p  = 9 × 10 -7 ). Non-severe suicide attempt risk increased with impulsiveness and decreased with resilience. In multinomial regression models, a higher number of traumas and emotional abuse were independently and only associated with severe vs. non-severe suicide attempts (effect size = 0.82, AUC = 0.7). The study was limited by its cross-sectional design. Conclusion : These preferential associations between childhood trauma and severe suicide attempts warrant specific monitoring of suicide attempts risk in CocUD, regardless of the severity of addiction profiles.

Suicide attempts (SA), especially recurrent SA or serious SA, are common in substance use disorders (SUD). However, the genetic component of SA in SUD samples remains unclear. Brain-derived neurotrophic factor (BDNF) alleles and levels have been repeatedly involved in stress-related psychopathology. This investigation uses a within-cases study of BDNF and associated factors in three suicidal phenotypes ('any', 'recurrent', and 'serious') of outpatients seeking treatment for opiate and/or cocaine use disorder. Phenotypic characterization was ascertained using a semi-structured interview. After thorough quality control, 98 SNPs of BDNF and associated factors (the BDNF pathway) were extracted from whole-genome data, leaving 411 patients of Caucasian ancestry, who had reliable data regarding their SA history. Binary and multinomial regression with the three suicidal phenotypes were further performed to adjust for possible confounders, along with hierarchical clustering and compared to controls (N = 2504). Bayesian analyses were conducted to detect pleiotropy across the suicidal phenotypes. Among 154 (37%) ever suicide attempters, 104 (68%) reported at least one serious SA and 96 (57%) two SA or more. The median number of non-tobacco SUDs was three. The BDNF gene remained associated with lifetime SA in SNP-based (rs7934165, rs10835210) and gene-based tests within the clinical sample. rs10835210 clustered with serious SA. Bayesian analysis identified genetic correlation between 'any' and 'serious' SA regarding rs7934165. Despite limitations, 'serious' SA was shown to share both clinical and genetic risk factors of SA-not otherwise specified, suggesting a shared BDNF-related pathophysiology of SA in this population with multiple SUDs.

The study aimed to examine the age of onset of stages of alcohol use in the general population, and to estimate the association of cohort use with the probability of transitioning from alcohol use to alcohol use disorder (AUD) and remission. French data (N = 2,894) from the European Study of the Epidemiology of Mental Disorders Survey and collected in 2000 were used. Data on lifetime history of alcohol use and DSM-IV alcohol use disorders, and remission were collected. Nearly every adult has consumed alcohol at least once in their lifetime (92.8%), and among users, 88.3% developed regular use, 6.0% met criteria for abuse and 1.7% for dependence. One-third of the population (32.8%) had used alcohol by the age of 15. Over 85% of cases of regular use were established prior to age 25, as were 61.1% of abuse and 39.4% of dependence cases. The proportion of people in an individual's age and sex cohort who had already used alcohol by a given age was positively and significantly associated with increased odds of transitioning to each stage examined. The findings highlight sensitive periods of life where persons are at greater risk for transitioning to a higher level of alcohol use, and underscore the importance of cohort use in transition risk.

Aims: To examine cross-national patterns of 12-month substance use disorder (SUD) treatment and minimally adequate treatment (MAT), and associations with mental disorder comorbidity., Design: Cross-sectional, representative household surveys., Setting: Twenty-seven surveys from 25 countries of the WHO World Mental Health Survey Initiative., Participants: A total of 2446 people with past-year DSM-IV SUD diagnoses (alcohol or illicit drug abuse and dependence)., Measurements: Outcomes were SUD treatment, defined as having either received professional treatment or attended a self-help group for substance-related problems in the past 12 months, and MAT, defined as having either four or more SUD treatment visits to a health-care professional, six or more visits to a non-health-care professional or being in ongoing treatment at the time of interview. Covariates were mental disorder comorbidity and several socio-economic characteristics. Pooled estimates reflect country sample sizes rather than population sizes., Findings: Of respondents with past-year SUD, 11.0% [standard error (SE) = 0.8] received past 12-month SUD treatment. SUD treatment was more common among people with comorbid mental disorders than with pure SUDs (18.1%, SE = 1.6 versus 6.8%, SE = 0.7), as was MAT (84.0%, SE = 2.5 versus 68.3%, SE = 3.8) and treatment by health-care professionals (88.9%, SE = 1.9 versus 78.8%, SE = 3.0) among treated SUD cases. Adjusting for socio-economic characteristics, mental disorder comorbidity doubled the odds of SUD treatment [odds ratio (OR) = 2.34; 95% confidence interval (CI) = 1.71-3.20], MAT among SUD cases (OR = 2.75; 95% CI = 1.90-3.97) and MAT among treated cases (OR = 2.48; 95% CI = 1.23-5.02). Patterns were similar within country income groups, although the proportions receiving SUD treatment and MAT were higher in high- than low-/middle-income countries., Conclusions: Few people with past-year substance use disorders receive adequate 12-month substance use disorder treatment, even when comorbid with a mental disorder. This is largely due to the low proportion of people receiving any substance use disorder treatment, as the proportion of patients whose treatment is at least minimally adequate is high., (© 2019 Society for the Study of Addiction.)

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., (Copyright © 2018. Published by Elsevier B.V.)

Aims: A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders., Methods: In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18-100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction., Results: An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6-17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both., Conclusions: CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.

Background: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection., Methods: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ., Results: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls., Conclusions: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.

Little is known regarding between-subject variability in the subjective effects of first cocaine use. This study retrospectively assesses the subjective effects of first cocaine use in 160 current treatment-seeking cocaine use disorder patients. Subjective effects of first cocaine use were evaluated with an ad-hoc questionnaire used for cannabis effects. A principal component analysis (PCA) was performed, with resulting factors correlated with clinical variables (α = 0.05). Four factors emerged in the PCA, namely Anxiety (accounting for 21.5% of questionnaire variance), Disinhibition (17.3%), Tachypsychia (16%) and Calmness (13%). Male gender was associated with Disinhibition and Tachypsychia. Cocaine severity factors were associated with Disinhibition, Tachypsychia and Calmness. Opiate, sedative and poppers uses were associated with Anxiety, Tachypsychia and Calmness. The retrospective assessment of the subjective effects of first cocaine use shows significant variability. The different dimensions of subjective first effects are influenced by age, gender and previous substance use history, as well as characteristics of first cocaine use and cocaine-related outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

High-dose baclofen is prescribed as a maintenance treatment to reduce alcohol use in patients with alcohol use disorder. Nevertheless, some patients still have massive alcohol intakes and require inpatient alcohol withdrawal. To compare the oral dose of benzodiazepine prescribed to manage alcohol withdrawal symptoms in patients with vs. without steady-state pretreatment with high-dose baclofen. Retrospective chart review study. Prescribed benzodiazepine dose expressed in diazepam-equivalent was compared between groups. Thirty-one patients were assessed in the high-dose maintenance baclofen group and compared to 31 matched patients not receiving baclofen. No statistically significant difference was evident between groups regarding levels of benzodiazepines prescribed. The mean diazepam-equivalent dose during the first 7 days was 294 ± 149 mg in the baclofen group vs. 310 ± 133 mg (t-test = 0.440, P = 0.661) in matched controls. Steady-state high-dose baclofen before an inpatient alcohol cessation hospitalization does not lower the needed benzodiazepine dose in the management of alcohol withdrawal symptoms., (© 2017 Société Française de Pharmacologie et de Thérapeutique.)

Purpose: Understanding the effects of war on mental disorders is important for developing effective post-conflict recovery policies and programs. The current study uses cross-sectional, retrospectively reported data collected as part of the World Mental Health (WMH) Survey Initiative to examine the associations of being a civilian in a war zone/region of terror in World War II with a range of DSM-IV mental disorders., Methods: Adults (n = 3370) who lived in countries directly involved in World War II in Europe and Japan were administered structured diagnostic interviews of lifetime DSM-IV mental disorders. The associations of war-related traumas with subsequent disorder onset-persistence were assessed with discrete-time survival analysis (lifetime prevalence) and conditional logistic regression (12-month prevalence)., Results: Respondents who were civilians in a war zone/region of terror had higher lifetime risks than other respondents of major depressive disorder (MDD; OR 1.5, 95% CI 1.1, 1.9) and anxiety disorder (OR 1.5, 95% CI 1.1, 2.0). The association of war exposure with MDD was strongest in the early years after the war, whereas the association with anxiety disorders increased over time. Among lifetime cases, war exposure was associated with lower past year risk of anxiety disorders (OR 0.4, 95% CI 0.2, 0.7)., Conclusions: Exposure to war in World War II was associated with higher lifetime risk of some mental disorders. Whether comparable patterns will be found among civilians living through more recent wars remains to be seen, but should be recognized as a possibility by those projecting future needs for treatment of mental disorders.

Background: Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors., Methods: The WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD., Results: 20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2-0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66-55% v. 43%) and later-recovery (75-68% v. 39%)., Conclusions: We found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Current treatments of opioid addiction include primarily maintenance medications such as methadone. Chronic exposure to opiate and/or long-lasting maintenance treatment induce modulations of gene expression in brain and peripheral tissues. There is increasing evidence that epigenetic modifications underlie these modulations. This review summarizes published results on opioid-induced epigenetic changes in animal models and in patients. The epigenetic modifications observed with other drugs of abuse often used by opiate abusers are also outlined. Specific methadone maintenance treatment induced epigenetic modifications at different treatment stages may be combined with the ones resulting from patients' substance use history. Therefore, research comparing groups of addicts with similar history and substances use disorders but contrasting for well-characterized treatment phenotypes should be encouraged.

Objective: Schizophrenia and bipolar disorder are associated with cognitive impairment leading to social disruption. While previous studies have focused on the effect of individual infectious exposure, namely, Herpesviridae viruses or Toxoplasma gondii (T gondii), on cognitive functioning, the objective of the present study was to examine the effect of multiple infections on cognitive functioning in patients with schizophrenia and bipolar disorder and in healthy controls., Methods: Seropositivity to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), and T gondii was related to cognitive status among 423 participants (recruited between 2008 and 2014; 138 patients with bipolar disorder, 105 patients with schizophrenia [DSM-IV criteria], and 180 healthy controls) for episodic verbal memory (California Verbal Learning Test), working memory (Wechsler Adult Intelligence Scale, third edition), and premorbid intelligence quotient (National Adult Reading Test)., Results: Seropositivity to and antibody levels of HSV-1 were significantly associated with working memory, which persisted after correction (backward digit span: β = -0.10 [0.05], χ² = 33.89, P = .0001) in the overall sample. This association was particularly strong in the control group (β = -0.18 [0.08], P = .04, Z = -3.55, P = .0008; corrected P = .012). Further, cumulative exposure to HSV-1, HSV-2, and CMV viruses and T gondii parasite was also associated with lower scores on working memory as measured by backward digit span in the overall sample (Z = 2.86, P = .004; Z = 2.47, P = .01; and Z = 3.35, P = .01, respectively)., Conclusions: Exposures to Herpesviridae and T gondii parasite seem to impact cognitive functioning. Because infections caused by Herpesviridae and/or T gondii parasite are quite common in the (general) population, assessing and confirming the cognitive impairment among those who have cumulative exposures is useful and of interest., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Benzodiazepines should be prescribed on a short-term basis, but a significant proportion of patients (%) use them for more than 6 months, constituting a serious public health issue. Indeed, few strategies are effective in helping patients to discontinue long-term benzodiazepine treatments. The aim of this study was to assess the feasibility and the impact of a program including cognitive behavioural therapy, psychoeducation, and balneotherapy in a spa resort to facilitate long-term discontinuation of benzodiazepines. We conducted a prospective multicentre cohort study. Patients with long-term benzodiazepine use were recruited with the aim of anxiolytic withdrawal by means of a psychoeducational program and daily balneotherapy during 3 weeks. The primary efficacy outcome measure was benzodiazepine use 6 months after the program, compared to use at baseline. A total of 70 subjects were enrolled. At 6 months, overall benzodiazepine intake had decreased by 75.3%, with 41.4% of patients completely stopping benzodiazepine use. The results also suggest a significantly greater improvement in anxiety and depression symptoms among patients who discontinued benzodiazepines compared to patients who only reduced their use. Our findings suggest that balneotherapy in association with a psychoeducative program is efficient in subjects with benzodiazepine addiction., Competing Interests: Dr. O. Dubois is President of the French Society of Thermal Medicine.

Background: The presence of cocaine dependence is under-recognized by cocaine users and requires a careful standardized interview to be ascertained by clinicians., Objective: To test if past experiences of cue-induced physical symptoms of craving (nausea, vomiting, sweating, shaking, nervousness) before cocaine use could be a useful way to boost the diagnosis of cocaine dependence., Methods: A cross-sectional study of 221 cocaine users from several outpatient addiction treatment services in France, addressing the most severe period of cocaine use. DSM-IV cocaine dependence was determined with the MINI International Neuropsychiatric Interview (MINI). Physical symptoms before using cocaine were retrospectively assessed with a single item rated on a 0-5 scale., Results: The prevalence of DSM-IV cocaine dependence was 84.6%. The mean score on the physical symptoms item was 1.3 (SD 1.3). A cut-off score of ≥ 1 on this item alone resulted in a sensitivity of 62%, a specificity of 88.2%, a positive predictive value of 96.6% and a negative predictive value of 29.7% to detect DSM IV cocaine dependence in this sample. Adding this item to a model with the frequency of cocaine use significantly increased the predictive power: Nagelkerke's R(2) increased from .149 to .326 (p < .001)., Discussion and Conclusion: Recalling past experiences of cue-induced physical signs of cocaine craving is associated with a clinical diagnosis of lifetime cocaine dependence and could be a simple way to improve its detection in clinical settings., (© American Academy of Addiction Psychiatry.)

Background and Objectives: The burden of opiate dependence not only relies on somatic complications such as infectious diseases or acute intoxication but also on frequent psychiatric events such as major depressive disorder (MDD) and suicidal behavior (SB). Given the preclinical and clinical evidence regarding the associations between cannabinoid systems and both opiate dependence and psychiatric disorders, we chose to address whether one single nucleotide polymorphism (SNP) of the cannabinoid receptor type 1 gene (CNR1) named rs2023239 would be associated with lifetime MDD and SB in a population of opiate-dependent outpatients remitted under stable methadone treatment., Methods: Sociodemographic and clinical data were included as independent factors in two logistic regression models aimed at predicting SB and MDD, respectively, performed with 85 Caucasian individuals., Results: The minor C allele of rs2023239 showed an independent protective effect against lifetime MDD after adjustment for potential confounders. It was not associated with variables related to suicidal behavior., Conclusions and Scientific Significance: Despite limitations due to the modest sample size, our results are consistent with previous research on the endocannabinoid system and suggest new leads for detecting subjects at risk of MDD, which remains insufficiently diagnosed and treated in patients suffering from severe addictive disorders., (© American Academy of Addiction Psychiatry.)

A personal history of childhood trauma has been associated with the severity of psychotic symptoms in several disorders. We evaluated retrospectively cocaine-induced psychotic symptoms with the SAPS-CIP and childhood trauma with the CTQ in a clinical sample of 144 cocaine users. The SAPS-CIP score was not statistically associated with the presence or number or intensity of trauma, but was associated with rapid routes of administration (intravenous and smoked) and with frequent cocaine use., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

This study examined the prevalence of traumatic events and the conditional probability of posttraumatic stress disorder (PTSD) associated with both specific and broad classes of events in a nationally representative sample from France. The sample (N = 1,436) was a part of the European Study of the Epidemiology of Mental Disorders Survey (ESEMeD), under the WHO World Mental Health Surveys-2000 initiative. Overall, exposure to any traumatic event was 72.7%, which appeared to be lower than what has been reported in Sweden (80.8%), similar to data from the Netherlands (71.1%), and higher than what has been reported in Spain (54.0%), Italy (56.1%), Northern Ireland (60.6%) or the U.S (55.9%). Lifetime prevalence of PTSD was 3.9%, lower than in the United States (7.8%), Sweden (5.6%), or Northern Ireland (8.8%), but higher than in Spain (2.2%) or Italy (2.4%). Being beaten up by a romantic partner (25.0%), having a child with serious illness (23.5%), and rape (21.5%) were associated with the highest risk of PTSD. The average duration of PTSD was 5.3 years (0.2-28.1). The burden of PTSD in France appeared to come from the consequences of violence and social network events suggesting that prevention efforts might focus on limiting the occurrence of exposure to avoidable events such as violence as well as provide support for persons exposed to social network events., (Copyright © 2015 International Society for Traumatic Stress Studies.)

Background: Cognitive deficits are present in a large majority of Bipolar Disorder (BD) patients and known to be a marker of bad prognosis. Because, these deficits encompass several domains and no specific medical treatment seems to be effective, it is important to better understand the mechanisms underlying cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of pro-inflammatory cytokines such as IL-6, we will explore here the possible role of T. gondii in the cognitive decline observed in BD., Methods: 42 euthymic BD patients and 36 controls were assessed for episodic verbal memory using the CVLT and for working memory and verbal ability using the WAIS III. Patients and controls were also screened for seropositivity to T. gondii and evaluated for the levels of IL-6 transcripts., Results: The seropositivity for T. gondii was significantly higher in BD patients as compared to controls (p=0.005). The cognitive deterioration index (DI) was higher in BD patients (p=5.10(-6)) and correlated to high IL-6 mRNA expression only among those infected by T. gondii (rho=0.43, p=0.01). Among deteriorated patients (defined by scores above 0.10 according to Weschler׳s definition), the IL-6 mRNA expression was twice greater (p=0.01)., Limitations: Our results are to be interpreted with caution because of our small sample size and the cross-sectional design., Conclusions: A long-term exposure to inflammation, measured here with IL-6 mRNA expression in T. gondii infected BD may alter cognitive functioning. IL-6 could thus be a useful predictive marker of cognitive deterioration in BD and may help to design personalized treatment., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Whether the Brain Derived Neurotrophic Factor (BDNF) Val66Met polymorphism can predict antidepressant drug efficacy in depressed patients remains unclear, suggesting that it may depend on antidepressant classes. We assessed the impact of Val66Met polymorphism on antidepressant response and remission depending on antidepressant classes., Methods: In a 6-month prospective, real-world setting, treatment study, 345 Caucasian depressed patients requiring a new or different drug treatment with a selective serotonin reuptake inhibitor (SSRI), a serotonin and noradrenalin reuptake inhibitor (SNRI) or a tricyclic antidepressant (TCA), were genotyped and assessed for response and remission., Results: 231 (67%) patients were homozygous for the Val66 allele (Val/Val) and 114 (33%) were carriers of Met allele (Met). 152 (44.1%) patients were treated with SSRI, the others with SNRI/TCA. Both response and remission were explained by interactions between the Val66Met polymorphism and antidepressant drug classes (multivariate models adjusted for propensity-scores: p=0.02 and p=0.03 respectively). With SSRI, Val/Val patients had a higher response rate 3 months post-treatment than Met patients (68.1% versus 44%; adjusted-OR: 3.04, IC95% [1.05; 9.37], p=0.04). With SNRI/TCA, Val/Val patients had a lower remission rate 6 months post-treatment than Met patients (33.3% versus 60.9%, adjusted-OR: 0.27, IC95% [0.09; 0.76], p=0.02)., Limitations: Limited sample size., Conclusions: This study argues for a personalized prescription of antidepressants in Caucasian patients with major depressive disorder, based on the BDNF Val66Met polymorphism: SSRI should be preferred for Val/Val patients and SNRI/TCA for Met patients. Further studies are required to confirm these data., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The co-occurrence of substance use disorders (SUDs) and anxiety disorders has been now well established. This association is frequent and can be explained by three models: the shared vulnerability factors model, the self-medication model, and the substance-induced model. General population epidemiological studies provide strong evidence of the frequency of the association for the most used substances: tobacco, alcohol, cannabis, and to a lesser extent sedatives, opiates, and cocaine. For substances that are less commonly used in the general population, the frequency of the co-occurrence can more precisely be studied in clinical samples. We provide the most recent literature results on the association of SUDs and anxiety, and evidence for one explicative model or the other when available. For substances with sedative properties (alcohol, benzodiazepines, cannabis, opioids), both evidence for a self-medication and for a toxic effect exist. For substances with psychostimulant properties (tobacco, cocaine, and amphetamines), the literature favors the toxic hypothesis to explain the association with anxiety disorders. We give practical steps for the recognition of these dual diagnoses and present therapeutic issues, although the strategies are rarely evidence based.

Background and Objectives: Associations between asthma and anxiety and mood disorders are well established, but little is known about their temporal sequence. We examined associations between a wide range of DSM-IV mental disorders with adult onset of asthma and whether observed associations remain after mental comorbidity adjustments., Methods: During face-to-face household surveys in community-dwelling adults (n = 52,095) of 19 countries, the WHO Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Asthma was assessed by self-report of physician's diagnosis together with age of onset. Survival analyses estimated associations between first onset of mental disorders and subsequent adult onset asthma, without and with comorbidity adjustment., Results: 1860 adult onset (21 years+) asthma cases were identified, representing a total of 2,096,486 person-years of follow up. After adjustment for comorbid mental disorders several mental disorders were associated with subsequent adult asthma onset: bipolar (OR = 1.8; 95%CI 1.3-2.5), panic (OR = 1.4; 95%CI 1.0-2.0), generalized anxiety (OR = 1.3; 95%CI 1.1-1.7), specific phobia (OR = 1.3; 95%CI 1.1-1.6); post-traumatic stress (OR = 1.5; 95%CI 1.1-1.9); binge eating (OR = 1.8; 95%CI 1.2-2.9) and alcohol abuse (OR = 1.5; 95%CI 1.1-2.0). Mental comorbidity linearly increased the association with adult asthma. The association with subsequent asthma was stronger for mental disorders with an early onset (before age 21)., Conclusions: A wide range of temporally prior mental disorders are significantly associated with subsequent onset of asthma in adulthood. The extent to which asthma can be avoided or improved among those with early mental disorders deserves study., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

An association between serotonin 2A receptor (5-HT2AR), encoded by HTR2A gene, and major depressive disorder (MDD) has been suggested. Here, we combined preclinical and ecological clinical approaches to explore the impact of impaired 5-HT2AR-mediated transmission on MDD or anxio-depressive-like phenotype in mice. Htr2a knock-out mice (Htr2a(-/-)) and wild-type mice were compared for the ability of chronic corticosterone to elicit some anxio-depressive-like phenotype in three behavioral paradigms (elevated plus maze, tail suspension test and splash test). Accordingly, two single nucleotide polymorphisms of the HTR2A gene (rs6314 ie His452Tyr and rs6313 ie 102C/T), which specific allelic variants may decrease 5-HT2AR-mediated transmission (as in Htr2a(-/-)mice), were studied in a sample of 485 Caucasian patients with MDD. In response to chronic corticosterone exposure, Htr2a(-/-) mice displayed more pronounced anxiodepressive-like phenotype than wild-type mice, as shown by a significant higher "emotionality score" (p<0.01). In patients, the C allele of rs6313 was more frequent in depressed patients (p=0.019) and was also associated with a more severe major depressive episode (p=0.03). This translational and ecological study involving constitutive Htr2a(-/-) knock-out mice and related SNPs in depressed patients suggests that a lower neurotransmission at the 5-HT2AR may favor the susceptibility and severity of MDE. It also suggests that specific allelic variants of the rs6313 and rs6314 may reduce 5-HT2AR-mediated transmission., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: The burden of health problems, including mental disorders, can be assessed in several ways such as through healthcare costs or loss of productivity. Their impact on daily activities as a whole has received much less attention, especially in France. Therefore, we undertook the analysis of the French general population data from the World Mental Health (WMH) surveys promoted by the World Health Organization (WHO) assessing the number of days out of role due to common mental and physical disorders., Methods: Face-to-face interviews were carried out with 2894 respondents (45.9% pooled response rate). Presence of ten chronic physical disorders and nine mental disorders was assessed for each respondent along with information about the number of days in the past month each respondent reported being totally unable to work or carry out their other normal daily activities because of problems with either physical or mental health. Multiple regression analysis was used to estimate associations of specific conditions and comorbidities with days out of role, after controlling for basic socio-demographics., Results: One thousand four hundred and thirty-six subjects reporting at least one core-symptom of a mental disorder underwent the whole assessment. The mean annual number of days out of role was high among those with at least one mental disorder (24.2±8.3). The population attributable risk proportion (PARP), i.e. the proportion of days out of role that would have been avoided if the considered disorder had remitted, was also estimated. Mental disorders as a whole accounted for 49.5% of the PARP., Discussion: French data on days out of role from the WHO WMH surveys showed the high burden of mental illness in the general population. These results may have been underestimated, taking into account that subjects who were hospitalized at the time of recruitment, whose disorders might also account for a high proportion of days out of role, could not be assessed with our design., Conclusion: Common health conditions, especially mental disorders, make up a large proportion of the number of days out of role. Such data should be considered to design more efficient public health strategies., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Many drugs increase the duration of the QT interval of patients, potentially leading to harmful effects such as polymorphic ventricular arrhythmias. Most of these drugs do so by inhibiting the rapid component IKr of the delayed rectifier potassium current IK. Methadone is the most prescribed heroin maintenance treatment and is known to inhibit the cardiac potassium channel hERG, which recapitulates IKr. In order to evaluate if any polymorphism of potassium channels' genes could explain some of the "idiosyncratic" QT prolongations observed in patients treated with methadone, we tested the association between KCNE1, KCNE2, and KCNH2 polymorphism and the QT interval prolongation in those patients, controlling for other variables associated with a decrease of the repolarizing reserve., Methods: A cohort of 82 patients treated with stable dosage of methadone (mean dosage 65 mg/d) for at least three months was genotyped for five polymorphisms in KCNE1, KCNE2 and KCNH2 genes and had their corrected QT (QTc) assessed., Results: The mean QTc interval was 415±34ms. In a linear regression model, longer QTc interval was associated with methadone dosage and with one genetic factor. Each copy of a Lys allele at codon 897 of KCNH2, the gene that encodes the cardiac potassium voltage-gated channel hERG, was associated with a 15.4ms longer QTc (95% CI [4.6-26.2]; p=0.001)., Conclusion: KCNH2 genotyping may be relevant in the analysis of cumulative risk factors for QT prolongation in patients on methadone maintenance treatment., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Methadone maintenance treatment is the most widely prescribed treatment for opiate dependence with proven benefits for patients. In naïve users or in case of recreational misuse, methadone can be a source of potentially lethal intoxications, resulting in fatal overdoses. A few cases of infantile intoxications have been described in the literature, some of which resulted in death. Nowadays, more than 50,000 bottles are used every day in France, most of which are thrown away in the bin. Relatives at home, especially children, can have access to these empty bottles. This study aims to determine whether the residual quantity of methadone in the bottles is associated with a risk of intoxication for someone who has a low tolerance to opiates, such as a child., Methods: The methadone dosage left in a sample of 175 bottles recapped after use by the patients taking their maintenance treatment in an addiction treatment program centre was analysed during a 2-week period in March 2013., Results: The mean residual quantity of methadone left in each bottle after use is 1.9 ± 1.8 mg and 3.3 ± 2.4 mg in the sample of 60 mg bottles., Conclusions: There is a potential danger of accidental overdose with empty bottles of methadone syrup, especially for children. To take into account this hazard, several harm reduction strategies can be proposed, such as favouring the taking of the treatment within the delivery centres rather than the 'take home' doses, asking methadone users to bring back their used bottles, and raising patients' awareness of the intoxication risks and the necessary everyday precautions. For stable patients with take home methadone, the use of capsules could be considered.

Background: Major Depressive Disorder (MDD) is the 3rd source for burden worldwide according to the World Health Organization (WHO). This comes partly from unsatisfactory response rates after usual treatment, highlighting the need for early indicators such as early improvement of depressive symptoms to adapt treatment strategies, especially for severe inpatients. Thus our objective was to assess the predictive value of baseline partial resistance in early antidepressant response (EAR), hypothesizing that previous treatment failures would decrease the probability of early response., Methods: We included 122 consecutive inpatients with current unipolar MDE. The Mini-Neuropsychiatric Interview was used to ascertain DSM-IV diagnoses of MDD as well as psychiatric comorbidities, and to exclude patients with a history of bipolar disorder. A specifically designed questionnaire was used to collect data on previous treatment trials for the current episode so as to generate scores on the five existing methods for quantifying treatment resistance. We prospectively assessed EAR, defined as a 50% decrease in MADRS after 14 days of steady regimen of antidepressant., Results: In the per protocol sample (N=76), multivariate analyses showed that psychotic features at baseline remained an independent predictor of absence of EAR (p<.01), unlike baseline partial resistance, which may rather be associated with a lack of any improvement., Limitations: Lack of data about further response and non-randomized treatment allocation., Conclusion: Available methods for quantifying treatment resistance are heterogeneous and do not predict short-term response among severely depressed inpatients, despite potential usefulness in predicting a lack of early improvement., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: The associations between mental disorders and cancer remain unclear. It is also unknown whether any associations vary according to life stage or gender. This paper examines these research questions using data from the World Mental Health Survey Initiative., Methods: The World Health Organization Composite International Diagnostic Interview retrospectively assessed the lifetime prevalence of 16 DSM-IV mental disorders in face-to-face household population surveys in nineteen countries (n = 52,095). Cancer was indicated by self-report of diagnosis. Smoking was assessed in questions about current and past tobacco use. Survival analyses estimated associations between first onset of mental disorders and subsequently reported cancer., Results: After adjustment for comorbidity, panic disorder, specific phobia and alcohol abuse were associated with a subsequently self-reported diagnosis of cancer. There was an association between number of mental disorders and the likelihood of reporting a cancer diagnosis following the onset of the mental disorder. This suggests that the associations between mental disorders and cancer risk may be generalised, rather than specific to a particular disorder. Depression is more strongly associated with self-reported cancers diagnosed early in life and in women. PTSD is also associated with cancers diagnosed early in life., Conclusion: This study reports the magnitude of the associations between mental disorders and a self-reported diagnosis of cancer and provides information about the relevance of comorbidity, gender and the impact at different stages of life. The findings point to a link between the two conditions and lend support to arguments for early identification and treatment of mental disorders., Competing Interests: The authors have no competing interests to report., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Previous single country research has raised concerns that: (1) the DSM-IV diagnosis of alcohol abuse (AA) is met primarily through the hazardous use criterion related to drinking and driving and (2) that the hazardous use and social consequences AA criteria primarily reflect varying socioeconomic and cultural factors rather than psychiatric disorder., Methods: Using representative cross-national data from the 21 countries in the World Mental Health surveys, adults meeting DSM-IV lifetime criteria for AA but not dependence from 10 developed (n=46,071) and 11 developing (n=49,761) countries were assessed as meeting AA with the hazardous use or the social consequences criteria., Results: Between 29.3% (developed) and 16.2% (developing) of respondents with AA met only the hazardous use criterion. AA cases with and without hazardous use were similar in age-of-onset, course, predictors, and psychopathological consequences in both developed and developing countries., Discussion and Conclusions: Despite some associations of the AA criteria with socioeconomic factors, the hazardous use and social consequences criteria were significantly associated with psychiatric predictors and sequelae. The findings indicate that these criteria reflect psychiatric disorder and are appropriate for inclusion as DSM-5 Alcohol Use Disorder criteria., Scientific Significance: These findings support a psychiatric rather than a sociocultural view of the hazardous use and social consequences symptoms and provide evidence that they are appropriate diagnostic criteria cross-nationally with utility in a wide range of socioeconomic environments. This suggests consideration for their adoption by ICD-11. Further research is needed on the implications of these results for prevention and treatment., (Copyright © American Academy of Addiction Psychiatry.)

Objectives: Acute chest pain and myocardial infarction are frequent complications of cocaine use. Indeed, these represent 40% of emergency department visits associated with cocaine use and 2% to 7% of all patients attending the emergency department for chest pain. Nevertheless, the prevalence of past cocaine-associated chest pain has never been evaluated in an outpatient facility for addiction. Our objective was to assess lifetime episodes of cocaine-associated chest pain in current cocaine users in an outpatient facility., Methods: Fifty consecutive, nonselected current cocaine users were retrospectively evaluated with a standardized interview and a medical assessment. The patients and the pain characteristics are described, and clinical and biological factors associated with experiencing cocaine-associated chest pain are studied with univariate and logistic regressions analyses., Results: Twenty-six subjects (52%) reported a history of chest pain associated with cocaine use. This pain was frequently described as oppressive (28%) and located in the retrosternal area (61.5%). The mean (±SD) time between cocaine use and the occurrence of the pain was 8 (±8) minutes and the mean duration was 22 (±236) minutes. Subjects who reported cocaine-associated chest pain reported an average of 12 (±7) distinct episodes. Patients describing chest pain could be predicted with one independent factor in our sample: age of onset of cocaine use (P = 0.042)., Conclusions: Transient cocaine-associated chest pains are frequent in current cocaine users attending specialized addiction facilities. Cardiological explorations and monitoring and risk-reduction interventions need to be provided to this specific population.

People who suffer from substance use disorders (SUDs) frequently report to have undergone childhood adversity that is often associated with father or mother dysfunction, or both. Yet that issue has been barely addressed in opiate dependent patients. Therefore we sought to evaluate parent-specific dysfunctional styles perceived during childhood in a clinical sample from an outpatient addiction treatment program using the Measure Of Parental Styles (MOPS) questionnaire. DSM-IV diagnoses of substance use disorders and history of suicide attempts, family structure and changes of caregiver during childhood were obtained from 159 consecutive outpatients, along with their perception of parental bonding with the MOPS, in which mother and father scores are separate. Mother neglect dimension was significantly correlated with an earlier age at onset of several substances' use, the number of prior hospitalizations and of lifetime suicide attempts. Most of these associations remained significant in multivariate models. This was the first assessment of a representative sample of outpatients with SUDs by the MOPS questionnaire. Given its excellent acceptance and its association with several key correlates of SUDs, it should be used to design specific interventions targeted at attachment and familial management as well as in research models on gene × environment interactions., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Prior studies on the depression-heart disease association have not usually used diagnostic measures of depression, or taken other mental disorders into consideration. As a result, it is not clear whether the association between depression and heart disease onset reflects a specific association, or the comorbidity between depression and other mental disorders. Additionally, the relative magnitude of associations of a range of mental disorders with heart disease onset is unknown., Methods: Face-to-face household surveys were conducted in 19 countries (n=52,095; person years=2,141,194). The Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Heart disease was indicated by self-report of physician's diagnosis, or self-report of heart attack, together with their timing (year). Survival analyses estimated associations between first onset of mental disorders and subsequent heart disease onset., Results: After comorbidity adjustment, depression, panic disorder, specific phobia, post-traumatic stress disorder and alcohol use disorders were associated with heart disease onset (ORs 1.3-1.6). Increasing number of mental disorders was associated with heart disease in a dose-response fashion. Mood disorders and alcohol abuse were more strongly associated with earlier onset than later onset heart disease. Associations did not vary by gender., Conclusions: Depression, anxiety and alcohol use disorders were significantly associated with heart disease onset; depression was the weakest predictor. If confirmed in future prospective studies, the breadth of psychopathology's links with heart disease onset has substantial clinical and public health implications., (© 2013.)

Background: We examined the extent to which disability mediates the observed associations of common mental and physical conditions with perceived health., Methods and Findings: WHO World Mental Health (WMH) Surveys carried out in 22 countries worldwide (n = 51,344 respondents, 72.0% response rate). We assessed nine common mental conditions with the WHO Composite International Diagnostic Interview (CIDI), and ten chronic physical with a checklist. A visual analog scale (VAS) score (0, worst to 100, best) measured perceived health in the previous 30 days. Disability was assessed using a modified WHO Disability Assessment Schedule (WHODAS), including: cognition, mobility, self-care, getting along, role functioning (life activities), family burden, stigma, and discrimination. Path analysis was used to estimate total effects of conditions on perceived health VAS and their separate direct and indirect (through the WHODAS dimensions) effects. Twelve-month prevalence was 14.4% for any mental and 51.4% for any physical condition. 31.7% of respondents reported difficulties in role functioning, 11.4% in mobility, 8.3% in stigma, 8.1% in family burden and 6.9% in cognition. Other difficulties were much less common. Mean VAS score was 81.0 (SD = 0.1). Decrements in VAS scores were highest for neurological conditions (9.8), depression (8.2) and bipolar disorder (8.1). Across conditions, 36.8% (IQR: 31.2-51.5%) of the total decrement in perceived health associated with the condition were mediated by WHODAS disabilities (significant for 17 of 19 conditions). Role functioning was the dominant mediator for both mental and physical conditions. Stigma and family burden were also important mediators for mental conditions, and mobility for physical conditions., Conclusions: More than a third of the decrement in perceived health associated with common conditions is mediated by disability. Although the decrement is similar for physical and mental conditions, the pattern of mediation is different. Research is needed on the benefits for perceived health of targeted interventions aimed at particular disability dimensions.

Background: Prenatal exposure to viruses or parasites with tropism for the central nervous system is one of the risk factors for psychotic disorders. However, the relationship between past exposure to Toxoplasma gondii (T. gondii) and incidence of bipolar disorders (BD) is poorly documented across populations., Methods: We explored the potential association between T. gondii exposure and BD in France, a country of high prevalence of Toxoplasmosis, comparing the prevalence of serological markers (IgG/IgM class antibodies) for T. gondii infection in 110 BD patients and 106 healthy controls all living in France. In a subgroup of 42 patients and 42 controls we also evaluated the levels of interleukin 6 (IL-6) transcripts, an adjunct marker of inflammation., Results: We found that the sero-positive group for IgG antibodies to T. gondii had a 2.7 fold odds of having BD as compared to the sero-negative group (OR=2.17 CI 95%=1.09-4.36, p=0.028). Despite the fact that BD patients had significantly higher levels of IL-6 than the non-patient controls, no notable association between T. gondii status and IL-6 transcript levels was found. We did not find any clinical or demographic correlates of Toxoplasma exposure in the study population., Limitations: Our results are to be interpreted with caution because of our small sample size., Results: We confirm the association between seropositive status to T. gondii and bipolar disorders reported in other populations and extend it to French patients. Our data strengthen the importance of early detection of T. gondii infected patients in order to propose specific and adequate treatments., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Although irritability is a core symptom of DSM-IV major depressive disorder (MDD) for youth but not adults, clinical studies find comparable rates of irritability between nonbipolar depressed adults and youth. Including irritability as a core symptom of adult MDD would allow detection of depression-equivalent syndromes with primary irritability hypothesized to be more common among males than females. We carried out a preliminary examination of this issue using cross-national community-based survey data from 21 countries in the World Mental Health (WMH) Surveys (n = 110,729)., Methods: The assessment of MDD in the WHO Composite International Diagnostic Interview includes one question about persistent irritability. We examined two expansions of the definition of MDD involving this question: (1) cases with dysphoria and/or anhedonia and exactly four of nine Criterion A symptoms plus irritability; and (2) cases with two or more weeks of irritability plus four or more other Criterion A MDD symptoms in the absence of dysphoria or anhedonia., Results: Adding irritability as a tenth Criterion A symptom increased lifetime prevalence by 0.4% (from 11.2 to 11.6%). Adding episodes of persistent irritability increased prevalence by an additional 0.2%. Proportional prevalence increases were significantly higher, but nonetheless small, among males compared to females. Rates of severe role impairment were significantly lower among respondents with this irritable depression who did not meet conventional DSM-IV criteria than those with DSM-IV MDD., Conclusion: Although limited by the superficial assessment in this single question on irritability, results do not support expanding adult MDD criteria to include irritable mood., (© 2013 Wiley Periodicals, Inc.)