Evidence That Nine Autistic Women Out of Ten Have Been Victims of Sexual Violence.

Background: Research indicates that sexual violence affects about 30% of women in the general population and between two to three times as much for autistic women. Materials and Methods: We investigated prevalence of sexual abuse, autistic traits and a range of symptoms, using an online survey addressed to the women of the French autistic community (n = 225). We assessed victimization through an open question and through a specific questionnaire, derived from the Sexual Experiences Survey-Short Form Victimization. Results: Both case identification methods yielded high figures: 68.9% victimization (open question) compared to 88.4% (standardized questionnaire). Two thirds of the victims were very young when they were first assaulted: among 199 victims, 135 were aged 18 or below and 112 participants were aged 15 or below. 75% of participants included in our study reported several aggressions. Analyses indicate that primo-victimization was highly correlated to revictimization and that being young increased that risk. Young victims were also at higher risk of developing post-traumatic stress disorder. A third of the victims reported the assault. 25% of those were able to file a complaint (n = 12) and/or receive care (n = 13). For the remainder 75%, reporting did not lead to action. Discussion: Those findings indicate a very large proportion of victims of sexual assault among autistic women, consistently with previous research. The World Health Organization states unambiguously that sexual violence is systemic and that vulnerable individuals are preferably targeted by offenders. We therefore postulate that it would be erroneous to consider that victimization of autistic women is mainly due to autism. On the contrary, autism seems to be just a vulnerability factor. Some authors propose that educating potential victims to better protect themselves would help preventing abuse. We reviewed this proposition in the light of our results and found it to be impossible to apply since more than half of the victims were below or at the age of consent. Literature about sexual violence is discussed. Large-scale prevention programs proposed by World Health Organization and the Center for Disease Control aim at cultural changes in order to diminish gender inequality, that they identify as the very root of sexual violence.

Factors Associated With a Higher Score of Burnout in a Population of 860 French Psychiatrists.

Burnout rates are estimated to be twice as high among healthcare professionals as in the general working population, and studies indicate rising incidence. The present study aimed to identify the contextual factors associated with self-reported burnout rates among French psychiatrists. A total of 860 French or French-speaking psychiatrists completed an online questionnaire when they registered for a major psychiatric conference. The Copenhagen Burnout Inventory, a validated scale that independently appraises personal, work- and patient-related dimensions, was used to assess the degree of perceived burnout. Respondents were divided into lower risk and higher risk groups. The latter contained the 25% of individuals who scored the highest on each of the three dimensions of the CBI scale. Univariate analysis showed that private practice was associated with lower levels of risk on the personal and work-related dimensions. Working for the public sector and long hours were both associated with a higher score on the work-related dimension. Interestingly, none of the variables we investigated, except from poor atmosphere at work, correlated with the patient-related dimension. Among public-sector psychiatrists, female gender, longer hours, and more consultations per week were associated with a higher score on the work-related dimension. Working four or more night shifts per month was significantly associated with a higher score of burnout risk on all three dimensions. Private- and public-sector practitioners who mainly treated patients with schizophrenia had a higher score of burnout risk. Multivariate analysis showed that a poor atmosphere at work, longer hours, and working four or more night shifts were significantly associated with higher score of burnout risk. A nonreassuring working environment and more stressors while treating patients each had a possibly negative impact. Although this study only examined the factors that distinguish between clinicians with the lowest versus highest CBI burnout risk scores, it opens up important avenues for research and development of programs to reduce burnout risk within the French healthcare system.

Variable individual sensitivity to cannabis in patients with schizophrenia.

There is now compelling evidence that cannabis consumption might precipitate psychosis onset. The objective of the present study was to assess the role of individual sensitivity to the psychotogenic effect of cannabis in male patients with schizophrenia. The lifetime diagnosis, disease and substance-use history were determined using a standardized interview in 190 patients with schizophrenia. Of patients with lifetime cannabis use (n=121), 44 were characterized as Cannabis-sensitive (CS) patients if the onset of psychotic symptoms occurred within 1 month following the initiation of cannabis consumption, or following a marked rise of cannabis consumption, or marked aggravation of psychotic symptoms each time the subject used cannabis. Age at onset of psychosis was not different in patients with lifetime cannabis use compared to non-users. By contrast, the first psychotic episode occurred 2.6 yr earlier in CS compared to Non-cannabis-sensitive (NCS) patients (p=0.006). Moreover, a specific excess of family history of psychotic disorder was found in CS patients, but not of any other psychiatric disorder, as well as an earlier age at exposure to cannabis (16.7+/-2.5 yr, p=0.03). Sensitivity to psychotogenic effects of cannabis in schizophrenia patients could be related to both genetic vulnerability to schizophrenia and the influence of cannabis on brain maturation and could modulate the influence of cannabis on the onset of schizophrenia.

Milnacipran and venlafaxine at flexible doses (up to 200 mg/day) in the outpatient treatment of adults with moderate-to-severe major depressive disorder: a 24-week randomized, double-blind exploratory study.

The objective of this exploratory, multicenter, randomized, double-blind study, was to evaluate the efficacy and safety/tolerability of milnacipran and venlafaxine administered at flexible doses (100, 150 or 200 mg/day, bid administration) for 24 weeks (including 4 weeks up titration period) in the outpatient treatment of adults presenting with a moderate or severe episode of major depressive disorder (MDD) without high suicidal risk (MINI-DSM IV-TR). Of the 195 patients included, 134 (68.7%) completed the study. At baseline the two groups were similar, except there was a higher proportion of patients whose episode was severe-DSM IV in the milnacipran group (63.3% versus 54.0% in the venlafaxine group). The initial MADRS score (mean 31.0) decreased progressively during the study, and this decrease was in the two treatment groups (n = 177: 90 milnacipran; 87 venlafaxine) at week 24 (observed case/OC, mean change -23.1 milnacipran; -22.4 venlafaxine). The rate of MADRS response (reduction >/= 50%) at week 8 and week 24-last observation carried forward/LOCF was similar in the two groups (week 8: 64.4% milnacipran; 65.5% venlafaxine; week 24: 70% milnacipran; 77% venlafaxine), as was the rate of MADRS remission (score

Neurological soft signs in patients with schizophrenia and their unaffected siblings: frequency and correlates in two ethnic and socioeconomic distinct populations.

Recent studies have suggested that ethnicity and socioeconomic status may have an impact on the frequency and significance of neurological soft signs (NSS). However, this impact has not been adequately assessed. The objectives were to determine the NSS scores in patients with schizophrenia and their unaffected siblings and to examine the clinical and therapeutic correlates of NSS in two ethnic and socioeconomic distinct populations. Two independent replicate studies were carried out: (1) a French Caucasian sample of 69 patients with schizophrenia, 43 of their unaffected siblings and 108 control subjects; (2) a Tunisian sample of 66 patients with schizophrenia, 31 of their unaffected siblings and 60 control subjects. NSS were assessed with a multidimensional scale, previously validated in drug-naïve and treated samples of patients with schizophrenia. Both patient groups were assessed with the positive and negative syndrome scale (PANSS), the clinical global impressions (CGI) and the global assessment of functioning. NSS total scores were significantly higher in patients with schizophrenia comparatively to siblings and to controls in both studies. The two sibling groups had also higher NSS scores than controls. In addition, NSS total scores were correlated to the PANSS negative and disorganization sub-scores, to the CGI-severity of illness and to a low educational level in both studies. These studies provide a confirmation in two distinct samples of the high prevalence of NSS in patients with schizophrenia, and in their biological relatives, independently of their respective ethnic and socioeconomic origins.

Early environment and major depression in young adults: a longitudinal study.

Post-natal incubator care represents an early specific environment that may affect the risk for major depression later in life. A subsample of 1212 young adults from the French-speaking general population of the region of Quebec were selected from an ongoing longitudinal study that started during their kindergarten years. Information on peri-natal condition, obstetrical complications and incubator care was collected by consulting hospital medical records. Participants were evaluated using DSM III-R based psychiatric assessment when they were 15 and 21 years old. Incubator care predicted an approximate two- to three-fold decreased risk for depressive disorder at age 21. Results from three different logistic models adjusting for family adversity and for maternal depression confirmed this relationship. Analyses were replicated for depression at age 15, showing the same association in female adolescents. This study suggests that post-natal incubator care may paradoxically decrease the occurrence of major depression later in life. This protective effect might be direct (through optimized biological, physiological and sensory parameters) or indirect (induction of specific parent-child interactions due to the perception of their infant's vulnerability). This study could enhance understanding of the links between early post-natal environment and affective disorders later in life.

Bipolar disorders and quality of life: the impact of attention deficit/hyperactivity disorder and substance abuse in euthymic patients.

Patients with bipolar disorders (BPD) display high rates of comorbidities, especially substance abuse (20-40%) and attention deficit/hyperactivity disorder (ADHD) (6%-20%). However, there are virtually no data evaluating the role of current ADHD on the global functioning of patients with BPD. The recent literature suggests that impairments in quality of life are a key prognostic feature for predicting the long course of BPD. The aim of this study was to investigate the intrinsic impact of adult ADHD and substance abuse in patients with BPD on levels of social adaptation, functioning and vitality. Seventy-three outpatients with BPD I or II, all euthymic and being treated with mood stabilizers, were evaluated using the following measures: 1) the Diagnostic Interview of Genetics Study for DSM-IV criteria; 2) the ADHD Self-Report Scale (ASRS) (screening of adult ADHD); 3) measures of quality of life: social adaptation (Social Adjustment Scale Self-Report (SAS-SR)), well-being (Short Form 36 (SF-36) Health Survey), and the Brief Psychiatric Rating Scale. In this clinical sample, 30% met the ADHD criteria and 22% were substance abusers. The results showed that the presence of ADHD in BPD patients significantly predicted a low social functioning and adaptation by comparison with BPD patients without ADHD. By contrast, we failed to detect a significant impact of substance abuse on those functional outcomes. This is the first step towards improved screening for comorbidities and an understanding of their crucial role in the prognosis of the disorder, as well as in defining new multilevel therapeutic strategies.

Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia.

BACKGROUND: Approximately 40% to 70% of neuroleptic-resistant schizophrenic patients are nonresponders to clozapine. Several clozapine augmentation strategies have come into clinical practice although often without evidence-based support. Among these strategies, the combined use of clozapine with another antipsychotic has been reported for up to 35% of patients receiving clozapine. OBJECTIVE: The purposes of the present work were to (1) review the available literature on the efficacy and safety of the clozapine augmentation with another antipsychotic using a MEDLINE search of the literature from 1978 to December 2005 and (2) to propose an operational definition of schizophrenia refractory to clozapine ("ultraresistant schizophrenia") for the implementation and homogenization of future therapeutic trials. CONCLUSION: Case controls and open clinical trials largely dominate the literature, and there are only 4 double-blind studies of clozapine augmentation with antipsychotics. The results of these studies are somewhat discrepant. Moreover, the heterogeneity of definitions of resistance to clozapine, of outcome measures and of dose and duration of pharmacological trials is a major limitation for drawing conclusions.

Somatic augmentation strategies in clozapine resistance--what facts?

BACKGROUND: Polypharmacy without evidence-based support is sometimes needed for patients treated with 40% to 70% clozapine who are clozapine nonresponders. Several somatic augmentation strategies are proposed in the scientific literature, with different levels of evidence for safety and efficacy. OBJECTIVES: The purpose of the present study is to review the available literature on the efficacy and safety of clozapine augmentation with somatic agents other than antipsychotics. The following classes of agents are considered: (1) mood stabilizers, (2) antidepressants, (3) electroconvulsive therapy and repetitive transcranial magnetic stimulation, (4) glutamatergic agents, (5)fatty acids supplements, and (6) benzodiazepines. RESULTS: Case controls and small-size clinical trials largely dominate the literature, limiting the power to draw conclusions concerning safety issues and the meaning of negative studies. Moreover, variable definitions of clozapine resistance, heterogeneous outcome measures, and short duration of treatment trials are additional limitations. CONCLUSION: Generally, adjunctive strategies for clozapine-resistant patients remain based on scarce evidence of efficacy and significant safety concerns. Low-frequency repetitive transcranial magnetic stimulation, fatty acids supplements, and mirtazapine showed good tolerability and some efficacy, but the results need replication.

[Physiological adolescence, pathological adolescence]. / Adolescences physiologiques, adolescences pathologiques.

The uncertainties of looming adulthood, nostalgia for childhood, and a general malaise explain the crisis of adolescence. Rebellion, conflict, occasional failure at school or in society, and at-risk behaviors are not always signs of future psychiatric illness. In contrast, the physician must be in a position to identify tell-tale signs such as dysmorphophobia, existential anxiety, a feeling of emptiness, and school or social breakdown. Most psychiatric disorders that begin in adolescence are only diagnosed several years after onset. Yet early diagnosis is of utmost importance, as treatment becomes less effective and the long-term prognosis worsens with time. Suicide is the second cause of death during adolescence. All signs of suicidal behavior require hospitalization and evaluation in a psychiatric unit. Antidepressants may be necessary in adolescence. The recent controversy concerning a possible increase in the suicidal risk during antidepressant treatment should not mask the fact that the real public health issue is depression, and not antidepressants. Eating disorders are especially frequent among adolescent girls; it is important to identify psychiatric comorbidities such as schizophrenia, depression and obsessive-compulsive disorders, and to assess the vital risk. Illicit drug and alcohol consumption are frequent during adolescence; for example, close to half of all French adolescents have tried cannabis at least once. Once again, it is important to detect psychiatric comorbidities in substance-abusing adolescents. Phobia is an underdiagnosed anxiety disorder among adolescents; it may become chronic if proper treatment is not implemented, leading to suffering and disability. Finally, two major psychiatric disorders--schizophrenia and bipolar disorder--generally begin in adolescence. Treatment efficacy and the long-term prognosis both depend on early diagnosis. Treatment must be tailored to the individual patient. "Borderline" states are over-diagnosed, hindering more precise diagnosis and delaying appropriate treatment.

Age at onset of schizophrenia: interaction between brain-derived neurotrophic factor and dopamine D3 receptor gene variants.

One of the main features of schizophrenia is its age at onset in early adulthood. Dopaminergic dysregulation is the most documented neurobiological factor that may be involved in triggering schizophrenia. Recent findings on neurodevelopmental processes show that the brain-derived neurotrophic factor plays a critical role in the development of mesolimbic dopaminergic-related systems and regulates the expression of dopamine D3 receptors. In this study, we examine whether an interaction between dopamine D3 receptors and brain-derived neurotrophic factor gene variants influences age at onset in patients with schizophrenia. Our findings show that this gene-gene interaction was significantly associated with an earlier emergence of psychosis by 3 years.

Population-based and family-based association study of 5'UTR polymorphism of the reelin gene and schizophrenia.

Reelin is a glycoprotein involved in the migration and positioning of proliferating neurons and synaptic connectivity during neurodevelopment. It may also modulate neuronal plasticity throughout life. Therefore, the reelin gene is a candidate gene for schizophrenia. We examined the association of the CGG repeat polymorphism in the 5'-untranslated region of the reelin gene with schizophrenia in 266 unrelated French Caucasian patients, 156 of their parents, and 103 controls. We found no difference in the allele distribution between patients and controls although there was a significant higher prevalence of the genotype 8-8 in controls (CLUMP T3: chi(2) = 6.3, P = 0.035). There was no significant transmission disequilibrium in intrafamilial analysis. To refine our phenotypic characterization and in accordance with converging evidence suggesting that treatment resistance is associated with indices of abnormal neurodevelopment, we studied the association between reelin gene polymorphism and response to antipsychotics. Patients who responded to antipsychotics had a higher frequency of both the (CGG)(10) allele and (CGG)(10)-containing genotypes (P = 0.02; P = 0.006, respectively), with an odd ratio for genotypes of 4.2 (CI = [1.4;12.4]). Our results weakly support an association of reelin gene variants with schizophrenia as a whole, yet suggest that reelin could be associated with treatment-resistant schizophrenia.

Cerebellum development and schizophrenia: an association study of the human homeogene Engrailed 2.

Epidemiological data and family studies in schizophrenia show that genetic factors contribute to the vulnerability to this disorder. The homeogene Engrailed 2 (EN2) is specifically involved in patterning the region that gives rise to the cerebellum and controls the plasticity of midbrain dopaminergic neurons. We carried out an association study for a CA repeat polymorphism located in the 3' region of the homeogene EN2. The subjects consisted of 165 patients with schizophrenia and 97 controls matched for age and ethnicity from a French Caucasian population. We found no significant association of schizophrenia with this bi-nucleotide repeat polymorphism of the EN2 gene.

Minor physical anomalies in patients with schizophrenia and their parents: prevalence and pattern of craniofacial abnormalities.

The frequency of minor physical anomalies (MPAs) in patients with schizophrenia suggests an early disturbance in the development of the neuroectoderm. To improve the phenotypic delimitation of this disorder, we used a comprehensive scale of MPAs (41 items) in patients with schizophrenia and their first-degree relatives. This scale, adapted from a revised version of the Waldrop Scale (Ismail et al. Minor physical anomalies in schizophrenic patients and their siblings, American Journal of Psychiatry 155, 1998a, 1695-1702), introduced new items assessing facial and limbs asymmetry. The interrater reliability between two examiners was good: intraclass correlation coefficient: 0.68 (0.42-0.92). Patients with schizophrenia (n=40; mean=5.8, S.D.=4) and their non-psychotic parents (n=45; mean=4.7, S.D.=2.8) had significantly more MPAs than healthy comparison subjects (n=42; mean=2.2, S.D.=1.2). A logistical regression model showed the ability of several items to predict group status, including facial asymmetry, cleft palate, hair whorls and abnormal palmar crease. The high prevalence of facial asymmetry in patients with schizophrenia and their first-degree relatives provides new insights into the underlying dysembryogenic processes. This revised scale thus appears to be a useful complementary tool in pathophysiological studies aiming at the identification of developmental factors in schizophrenia.

Neurological soft-signs and minor physical anomalies in schizophrenia: differential transmission within families.

Markers of vulnerability have been identified in schizophrenia, and among them, neurological soft-signs (NSS) and minor physical anomalies (MPAs) also seem to occur in biological relatives. The similarities of these developmental markers within families may depend on either genetic or non-genetic factors. The aim of the study was to investigate the intra-familial similarities of NSS and MPAs within 18 nuclear families (18 probands with schizophrenia and 36 of their non-psychotic parents). A general linear model showed similarities within families for NSS (intra-class coefficient [ICC] = 0.64; F = 2.6; df = 17.17; p = 0.02) but not for MPAs (ICC = -0.10; F = 0.7; df = 17.17; ns). We thus found a direct evidence for the intra-familial transmission of NSS but not of MPAs, suggesting that this morphological phenotypic trait could be more dependent on epigenetic influences.

Test-retest reliability of the Temperament and Character Inventory in patients with opiate dependence.

We examined the test-retest reliability of the Temperament and Character Inventory (TCI) in a clinical sample of 29 inpatients with opiate dependence disorder (DSM-IV). The previously validated French translation of the TCI was administered at baseline and again four weeks later. Intraclass correlation coefficients (ICCs) were used to estimate stability of the TCI over time for the 15 patients who completed the study. For all ICCs, the TCI showed satisfactory to excellent stability across all factors (ICC= 0.66-0.82). Stability was lower for the two temperamental traits of 'persistence' (ICC=0.51) and 'reward dependence' (ICC=0.63), possibly reflecting both clinical instability and measurement errors. These results highlighted the overall stability of the TCI in patients with opiate dependence and provided evidence for the usefulness of this questionnaire, which was originally designed to explore genetic and environmental factors underlying normal and abnormal personality dimensions. Further studies are required to confirm these results on larger clinical samples.