[Temporary approval for intranasal naloxone: Setting up in a French addiction center]. / Pratique de l'ATU de cohorte de la naloxone intranasale (Nalscue®) : mise en place dans un CSAPA parisien.

Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients' as well as peers' and families' education is needed.

Angiotensin I-converting enzyme I/D polymorphism and suicidal behaviors.

Suicide is one of the ten most common causes of death in Western countries. It involves genetic vulnerability factors and is often associated with major depression. A Japanese team reported an association between the insertion allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with completed suicide. The ACE I/D polymorphism was investigated in two independent case-control studies, one involving 64 suicide completers and 90 controls who all underwent forensic investigations, the second one consisting of 588 suicide attempters and 639 controls. In the two population samples studied a statistically significant risk of suicidal behavior was observed for subjects bearing the DD genotype. These results suggest a possible role of the renin-angiotensin system in suicidal behavior.

Prevalence of Metabolic Syndrome and Associated Factors in a Cohort of Individuals With Treatment-Resistant Depression: Results From the FACE-DR Study.

BACKGROUND: The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its components in a cohort of French patients with treatment-resistant depression (TRD) and to determine correlations with sociodemographic, clinical, and treatment-related factors. METHODS: From 2012 to 2018, 205 patients who met DSM-IV criteria for major depressive episode with moderate-to-severe symptoms (Montgomery-Asberg Depression Rating Scale score ≥ 20), and at least Stage II resistance according to Thase and Rush criteria were enrolled in the FondaMental Advanced Centers of Expertise in Resistant Depression (FACE-DR) cohort. Data on sociodemographic and clinical characteristics, lifestyle information, and treatment and comorbidities were collected, and a blood sample was drawn. MetS was defined according to the criteria of the International Diabetes Federation. RESULTS: Overall, 38% of individuals with TRD met criteria for MetS. The frequency of MetS was significantly higher in men than in women only for patients aged 40 years or older (46.3% vs 35.2%, P = .0427). Moreover, whereas the management for diabetes was good, less than one-third of the patients with high blood pressure or dyslipidemia were treated for these conditions. Multivariate analysis showed that individuals with abnormal plasma c-reactive protein levels had a 3-fold increased risk (95% CI, 1.5-5.2) of having MetS, independent of other potential confounders. CONCLUSION: The prevalence of MetS is higher in patients with TRD than in those with other psychiatric disorders and characterized by a considerable undertreatment of some components of MetS in this population. Diagnosis and treatment of the components of MetS should be systematically performed to prevent the occurrence of cardiovascular diseases in patients with TRD. These findings highlight the need for integrated care, with more interaction and coordination between psychiatrists and primary care providers.

Left superior temporal gyrus activation during sentence perception negatively correlates with auditory hallucination severity in schizophrenia patients.

The left superior temporal cortex, which supports linguistic functions, has consistently been reported to activate during auditory-verbal hallucinations in schizophrenia patients. It has been suggested that auditory hallucinations and the processing of normal external speech compete for common neurophysiological resources. We tested the hypothesis of a negative relationship between the clinical severity of hallucinations and local brain activity in posterior linguistic regions while patients were listening to external speech. Fifteen right-handed patients with schizophrenia and daily auditory hallucinations for at least 3 months were studied with event-related fMRI while listening to sentences in French or to silence. Severity of hallucinations, assessed using the auditory hallucination subscales of the Psychotic Symptom Rating Scales (PSYRATS) and of the Scale for the Assessment of Positive Symptoms (SAPS-AH), negatively correlated with activation in the left temporal superior region in the French minus silence condition. This finding supports the hypothesis that auditory hallucinations compete with normal external speech for processing sites within the temporal cortex in schizophrenia.

"Where do auditory hallucinations come from?"--a brain morphometry study of schizophrenia patients with inner or outer space hallucinations.

Auditory verbal hallucinations are a cardinal symptom of schizophrenia. Bleuler and Kraepelin distinguished 2 main classes of hallucinations: hallucinations heard outside the head (outer space, or external, hallucinations) and hallucinations heard inside the head (inner space, or internal, hallucinations). This distinction has been confirmed by recent phenomenological studies that identified 3 independent dimensions in auditory hallucinations: language complexity, self-other misattribution, and spatial location. Brain imaging studies in schizophrenia patients with auditory hallucinations have already investigated language complexity and self-other misattribution, but the neural substrate of hallucination spatial location remains unknown. Magnetic resonance images of 45 right-handed patients with schizophrenia and persistent auditory hallucinations and 20 healthy right-handed subjects were acquired. Two homogeneous subgroups of patients were defined based on the hallucination spatial location: patients with only outer space hallucinations (N=12) and patients with only inner space hallucinations (N=15). Between-group differences were then assessed using 2 complementary brain morphometry approaches: voxel-based morphometry and sulcus-based morphometry. Convergent anatomical differences were detected between the patient subgroups in the right temporoparietal junction (rTPJ). In comparison to healthy subjects, opposite deviations in white matter volumes and sulcus displacements were found in patients with inner space hallucination and patients with outer space hallucination. The current results indicate that spatial location of auditory hallucinations is associated with the rTPJ anatomy, a key region of the "where" auditory pathway. The detected tilt in the sulcal junction suggests deviations during early brain maturation, when the superior temporal sulcus and its anterior terminal branch appear and merge.

Social phobia is associated with suicide attempt history in bipolar inpatients.

OBJECTIVES: In an attempt to reduce the phenotypical heterogeneity in an ongoing genetic study of suicidal behavior, we investigated the impact of comorbid anxiety disorders on suicidal behavior in bipolar disorder (BD) patients. METHODS: Anxiety disorders were compared in 406 BD I and BD II patients with or without lifetime history of suicide attempt. RESULTS: Among anxiety disorders, only social phobia (SP) was significantly associated with history of suicide attempt in BD [p<0.001, odds ratio 4.26 (2.284-7.946)]. Moreover, onset of SP was found to precede onset of BD. CONCLUSIONS: This result suggests that SP is an important risk factor for suicidal behavior in BD. Further studies are required to determine whether comorbid SP may help to identify a more homogeneous BD sub-group, especially when studies of suicidal behavior are conducted. A second question is whether SP identifies a sub-group of subjects with BD who have a more severe illness course and whether treatment of SP with selective serotonin reuptake inhibitor (SSRI) antidepressants is associated with improvement or worsening of the course of BD.

Expression and genetic variability of PCDH11Y, a gene specific to Homo sapiens and candidate for susceptibility to psychiatric disorders.

Synaptogenesis, the formation of functional synapses, is a crucial step for the development of the central nervous system. Among the genes involved in this process are cell adhesion molecules, such as protocadherins and neuroligins, which are essential factors for the identification of the appropriate partner cell and the formation of synapses. In this work, we studied the expression and the genetic variability of two closely related members of the protocadherin family PCDH11X/Y, located on the X and the Y chromosome, respectively. PCDH11Y is one of the rare genes specific to the hominoid lineage, being absent in other primates. Expression analysis indicated that transcripts of the PCDH11X/Y genes are mainly detected in the cortex of the human brain. Mutation screening of 30 individuals with autism identified two PCDH11Y polymorphic amino acid changes, F885V and K980N. These variations are in complete association, appeared during human evolution approximately 40,000 years ago and represent informative polymorphisms to study Y chromosome variability in populations. We studied the frequency of these variants in males with autism spectrum disorders (n = 110), attention deficit hyperactivity disorder (ADHD; n = 61), bipolar disorder (n = 61), obsessive-compulsive disorder (n = 51), or schizophrenia (n = 61) and observed no significant differences when compared to ethnically-matched control populations. These findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders.

No association between DUP25 and anxiety disorders.

Gratacos et al. [2001: Cell 106:367-379] described an interstitial duplication dup(15)q24q26 (DUP25) in patients with anxiety disorders; this duplication was found in approximately 90% of patients and in 7% of controls. In order to determine if DUP25 is present in additional individuals susceptible to panic attacks, we tested 44 patients with anxiety disorders, using probes 251c23 and 216c14 mapping in the 15q24 and 15q26 region. We have not detected any DUP25. Our results suggest that DUP25 is not common in people with anxiety disorders in the population tested here.