Family and twin studies have shown that both common genetic variants and environmental factors contribute to vulnerability to suicide behaviour. Interactions between several candidate genes and environmental factors have been reported. In order to discover new candidate gene using an agnostic method we examined the association between common genome-wide variations and lifetime suicide behaviour (suicide attempt, SA, and completion, SC) (genome-wide association study, GWAS).

In the first, discovery, analysis allele frequencies of the common non-imputed 282'738 single nucleotide polymorphisms (SNPs) were compared between 833 SA, 235 SC and 1360 controls from the French-Swiss collaboration, genotyped with the Illumina Human 660W-Quad bead chips and HumanHap300 BeadChipsSNPs platforms respective. Thirty SNPs were associated at level p<10-5 for SA and 5 for SC. Strongest evidence of association for SA was observed 150kb from PLXNA2 (rs10779481, p=4×10-8) and for SC in the DROSHA locus (rs7726209, p=9.9 ×10-6). The combined sample of suicide attempters and completers, identified two SNPs (rs9038 and rs2574852) located at chromosome 17q25.3 within a gene encoding the septin 9 (SEPT9) that showed a trend for an association with SB (p=2.04×10-7 and 7.52×10-7).

Replication studies are now in progress by analysing existing comparable samples, a second new French-Swiss sample, and imputation. These results suggest that GWAS could identify new candidate genes involved in new candidate pathways involved in vulnerability to SA and SC.

La stimulation magnétique transcrânienne répétitive (SMTr) appliquée sur le cortex préfrontal dorso-latéral (CPFDL) a prouvé son efficacité dans le traitement de la dépression résistante [1]. En plus d’une amélioration sur la symptomatologie, des études rapportent des effets positifs sur le fonctionnement cognitif [2], dont la mémoire de travail. Cependant, cet effet ne semble pas être retrouvé chez des sujets sains [3] lors d’une tâche de N-back sans leurre. L’objectif de notre étude est donc d’évaluer l’impact de la SMTr sur le CPFDL, région plus sensible à une tâche de N-back avec leurre [4].

Une étude randomisée en double insu a été menée chez 30 participants sains. Une stimulation de type iTBS (intermittent theta burst stimulation) a été effectuée pendant 5 jours à raison de 2 séances/jour appliquée au niveau du CPFDL gauche ciblé par neuro-navigation sur les coordonnées MNI (X, Y, Z = –50,30,36). Nous avons observé l’impact de la SMTr sur le comportement des participants durant la tâche de N-back. Pour cela, les participants ont effectué cette tâche, composée de blocs de 0-back, 3-back et 3-back contenant des leurres, lors de deux sessions d’IRMf (une avant et une après la semaine de stimulation active ou placebo). La performance, le temps de réaction ainsi que les données d’imageries ont été recueillis.

Les 2 groupes ne montrent pas de différence au niveau de l’âge ou du genre. Au niveau comportemental, les premières analyses sur la performance ainsi que sur le temps de réaction ne montrent pas d’effet d’interaction Groupe (actif/placebo) * Temps (avant/après SMTr). Au niveau des données de neuro-imagerie, une analyse d’interaction Groupe * Temps en prenant en compte la condition leurre nous permettra de mieux comprendre l’impact de la SMTr sur la mémoire de travail impliquant le CPFDL.

Recent research on late-life depression (LLD) pathophysiology suggests the implication of abnormalities in cerebral white matter [1] and particularly in interhemispheric transfer [2]. Corpus callosum (CC) is the main brain interhemispheric commissure [3]. Hence, we investigated the association between baseline CC measures and risk of LDD.

We studied 467 non-demented individuals without LLD at baseline from a cohort of community-dwelling people aged 80 years or younger (the ESPRIT study). LLD was assessed at year 2, 4, 7 and 10 of the study follow-up. At baseline, T1-weighted magnetic resonance images were manually traced to measure the mid-sagittal areas of the anterior, mid and posterior CC. Multivariate Cox proportional hazards models stratified by sex were used to predict LLD incidence over 10 years.

A significant interaction between gender and CC size was found (P = 0.02). LLD incidence in elderly women, but not in men, was significantly associated with smaller anterior (HR 1.37 [1.05–1.79] P = 0.017), mid (HR 1.43 [1.09–1.86] P = 0.008), posterior (HR1.39 [1.12–1.74] P = 0.002) and total (HR 1.53 [1.16–2.00] P = 0.002) CC areas at baseline in Cox models adjusted for age, education, global cognitive impairment, ischemic pathologies, left-handedness, white matter lesion, intracranial volume and past depression.

The main limitation was the retrospective assessment of major depression.

Smaller CC size is a predictive factor of incident LLD over 10 years in elderly women. Our finding suggests a possible role of CC and reduced interhemispheric connectivity in LLD pathophysiology. Extensive explorations are needed to clarify the mechanisms leading to CC morphometric changes in mood disorders.

Studies of normal aging have shown age-related decreases in functional connectivity (FC) within the default mode network (DMN), particularly involving the posterior cingulate cortex (PCC). Although psychiatric conditions are common and underdiagnosed, none of these studies have combined psychiatric structured interview and neuropsychological evaluation to select the sample.

to characterize age-related changes in PCC-FC connectivity in adults carefully screened to rule out neuropsychiatric disorders.

neuropsychiatric disorders were excluded by the Structured Clinical Interview for DSM-IV and neuropsychological evaluation. Restingstate functional MRI was acquired from 40, young, middle-age and elderly participants. After preprocessing, whole-brain, seed-based FC was estimated using a PCC seed. The relationship between age and PCC-FC was assessed using partial least squares.

age was positively associated with PCC-FC in the left dorsolateral prefrontal cortex, bilateral supplementary motor area, right insula and left cerebellum; PCC-FC in these regions was negative or close to zero in young adults. PCC-FC of the medial part of the ventral prefrontal cortex was negatively associated with age; this region presented high positive PCC-FC in young adults (see figure).

age-related increases in PCC-FC were found in regions which are anti-correlated with the DMN, suggesting a decrease in the magnitude of anti-correlation. This may reflect a dedifferentiation process or weaker inter-network interactions. The careful sample selection prevents confounds related to neuropsychiatric disorders.

Il existe de fortes présomptions théoriques et cliniques en faveur d’une relation entre certaines formes de Trouble obsessionnel compulsif (TOC) et des événements traumatiques [1]. De nombreuses études épidémiologiques ont aussi montré une association entre des traumatismes ou un ESPT et TOC[2]. L’ESPT et le TOC présentent certaines similitudes. Cette relation peut-elle être expliquée par une confusion de symptômes ? Existe-t-il une vulnérabilité commune ou un lien causal d’un trouble à l’autre ? La description d’une forme spécifiquement post-traumatique de TOC pourrait aussi être envisagée sur des arguments phénoménologiques[3].

Étude descriptive psychométrique de l’association de l’ESPT au Trouble obsessionnel compulsif. Les données présentées ont été recueillies auprès de patients venus consulter à l’hôpital de la Pitié-Salpétrière courant 2012 pour leur TOC (n = 43). Quinze patients TOC + ESPT appariés à 28 patients TOC sans ESPT ont été évalués cliniquement et à l’aide d’échelles psychométriques (YBOCS, HAD, EPN 31, EGF, Sheehan Disability Scale, Liste des Pensées Obsessives, TCI-R de Cloninger).

Identifier des différences dans le profil psychométrique des patients TOC + ESPT par rapport aux patients TOC ; afin de pouvoir discuter l’existence d’une forme de TOC post-traumatique.

L’analyse dimensionnelle des patients présentant un TOC associé à un ESPT retrouve des scores plus élevés pour la dimension de Transcendance (questionnaire TCI-R de Cloninger) que chez les patients souffrant d’un TOC seul. Aucune différence symptomatique, émotionnelle et de personnalité n’est retrouvée.

Cette étude souligne l’importance de rechercher systématiquement l’existence d’un traumatisme devant un TOC afin d’adapter la prise en charge. Il serait également intéressant de poursuivre les investigations afin d’identifier l’existence ou non d’une forme spécifique de TOC post-traumatique.

There is paucity of published literature on antidepressants in a cost-consequence study design.

Measuring clinical outcomes of pharmacotherapy.

Costs and consequences determination in depressive episode acute medical care.

Cost-consequence analysis;Setting-Serbian tertiary university clinic(2010-2012). Patient visits to attending psychiatrists:baseline, 3,8 weeks. HDRS-17 and Q-LES-Q-SF scale were applied in each of control visits. Resource use patterns and costs were evidenced for up to 14 weeks from study entry. Micro-costing approach allowed for most direct and indirect costs measurement. Costs were expressed in national currency-Central Serbian Dinar(1€≈115.85CSD;2012). Societal perspective and 14 weeks time horizon were adopted. Random selection of 65 depressive patients was based on clinical criteria and their assignment to either one of three different treatment protocols.5 patients were lost to follow up.

There was no statistically significant difference in terms of therapeutic response by the HDRS scores before and after introducing treatment groups(χ2=4.339; ?=0.362). QALY value increased by 11.77(SSRI group);8.93(SNRI)and 12.54 (heterocyclics). Mean cost per QALY was 9,937.51 CSD for SSRI; 7,138.27 CSD in SNRI; and 6,164.96 CSD for heterocyclics. There were 28.69 depression with free days in SSRI, 21.78 days in SNRI, and 30.59 days in heterocyclic group. Cost-effectiveness assessment was was 346.38 CSD per day(SSRI); 327.74 CSD(SNRI), and 201.54 CSD(heterocyclics).

Heterocyclic antidepressants provide highest'value for money' in terms of QALY in depressive episode treatment and its treatment is most cost effective. Cost-consequence evaluations have heavier impact to clinical decision making with regards to major depressive disorder treatment in the absence of clear clinical superiority of any major pharmacological protocol.

Catechol-O-methyltransferase (COMT) play an important role in modulating cortical dopaminergic catabolism and has been associated with schizophrenia. However, it remains unclear that if the variations in dopamine signaling affect the gray matter (GM) structural maturation in typically developing individuals, and whether such effect are disrupted in schizophrenia patients. This study aims (1) to explore the relationship between the functional polymorphisms Val158Met of COMT gene and GM volume in first-episode treatment-naïve patients with schizophrenia and healthy controls, (2) to investigate the influence of COMT Val158Met on TMT performance, (3) to investigate the relationship among GM volume, cognitive deficit and psychiatric symptoms.

Whole GM volume which was computed by an automated SPM and clinical performances were evaluated in 150 first-episode treatmentnaïve patients with schizophrenia and 100 healthy controls. In addition, 2-sample t-tests was used to explore the main effect of diagnostic group, a full factorial model was used to obtain genotype-by-diagnostic interaction in the volume of GM according to genotypes of above the polymorphism, and multiple regression was used to explore the correlation whole GM volume with TMT measurements and clinical syndromes, with age and sex as covariance.

A significant GM volume reduced in the right precentral gyrus [MNI: 37 -16 70], right cerebellum anterior lobe [MNI: 6 -56 26] and left Postcentral gyrus [MNI: -8 -36 80] (P < .05, FWE corrected) in schizophrenia. There was also a strong for a group× genotype interaction on the right precuneus (P < .001, uncorrected). A significant negative correlation of the GM volume over the cluster located at cerebellum anterior lobe with TMT-A and TMT-B within schizophrenic patients (P < .05, FDR corrected). A significant positive correlation of the GM volume over the cluster located at middle frontal gyrus [MNI: 36 60 15] with PANSS subscales for general psychopathological symptoms within schizophrenic patients, the negative correlation of the GM volume over the cluster located at parahippocampa gyrus [MNI: 27 -10 -25] with PANSS subscales for negative symptoms within schizophrenic patients (FDR correction at p < 0.05).

These findings suggest that COMT Metvariant was associated with disruption of dopaminergic in?eunces on GM maturation and may be the pathogenesis of schizophrenia, and maybe that the abnormal GM structure were association with cognitive function and clinical syndromes.

La rTMS est une technique non invasive modulant l’excitabilité corticale. Elle peut améliorer les performances mnésiques des patients âgés souffrant de troubles cognitifs. L’objectif est de présenter l’évolution des fonctions mnésiques de patients traités par rTMS. Sujet 1 : 73 ans, patient inclus dans une étude ayant pour but d’évaluer l’impact de la rTMS sur les troubles cognitifs. Le critère principal est l’évolution de la MoCA.

Stimulation du cortex préfrontal dorso-latéral droit à 1 Hz. Le patient reçoit 20 séances sur 4 semaines, 8 séances le 2e mois, 4 séances le 3e mois puis 6 séances les 3 derniers mois.

MoCA pré-inclusion : 25/30. Augmentation progressive jusqu’à M6 pour atteindre 30/30 puis diminution entre M6 et M12 jusqu’à 27/30. Sujet 2 : 81 ans, patient atteint de la maladie d’Alzheimer depuis 5 ans, traité par Donepezil. Méthode : protocole iTBS, 600 pulses, sur cortex dorso-latéral préfrontal gauche, à 80 % du seuil moteur gauche. Quarante séances sur 4 semaines. Le MMSE initial est de 16/30. Le MMSE post-rTMS immédiat s’élève à 20/30 et le MMSE à 3 mois à 24/30. Sujet 3 : 73 ans, patiente présentant des plaintes mnésiques à type d’atteinte isolée de la mémoire épisodique verbale. Elle est traitée par Duloxétine 30 mg/j et Rivastigmine patch 4,6 mg/. Méthode : 30 séances d’iTBS, 600 pulses, à 80 % du seuil moteur appliqué sur le cortex dorso-latéral préfrontal gauche, sur 3 semaines, répétée à M3. La MoCA pré-stimulation est à 15/30 et augmente à 19/30 après la seconde série.

La rTMS a montré des résultats positifs et encourageants pouvant être une piste pour la future prise en charge des troubles mnésiques chez le sujet âgé.

The discharge letter is the principal means of communication between the inpatient and the primary care physicians in the UK health care system. Good-quality correspondence between specialist services and general practitioners (GPs) is fundamental to patient care and makes transition from secondary to primary care as smooth as possible for patients

The aim of this study was to assess and improve the quality of discharge communication from the specialist substance misuse inpatient unit to general practitioners

This study was carried out in North Staffordshire Combined Healthcare NHS Trust in July 2013, UK. Fifty three Patients who were admitted to the inpatient unit between March & May 2013 were randomly selected from the Health Informatics Service. A proforma was designed based on approved mental health discharge summary headings from the Royal College of Psychiatrists UK and the results were compared against a previous audit done in 2012 which only looked into some of the component included in the present study

The study showed that most components of GP details, Patient Demographics, Admission Details, Clinical Details and discharge recommendations were well documented in the discharge letters analysed. The sub components where documentation were not adequate included Gender (0% documented), discharge destination (34% documented), mental capacity (1% documented), allergies (0% documented), Risk assessment (68% documented). However the findings were significant better than the previous audit in most areas.

This re-audit revealed that the quality and standards achieved for most aspects of discharge summaries were high. However not all aspects met the standards, some very important aspects including risk assessment, drug allergy, details of care coordinator and discharge destinations recordings were poor. There may be reasons for failure to meet the standards; Gender was never recorded in the discharge letters but one could easily assume the gender of the patients from the narrative of the discharge letters. It was noted that discharge destinations were more likely to be recorded if patients were not discharged home. Mental Capacity was not recorded in 98% of cases, as most admissions to the Inpatient unit are planned and patients come on a voluntary basis and have capacity regarding the admission and treatment

Les troubles dépressifs concernent près de deux fois plus de femmes que d’hommes [1]. Cette prévalence pourrait être due à une sensibilité accrue des femmes aux émotions négatives [2]. Peu d’études d’imagerie cérébrale ont comparé l’activité cérébrale des hommes et des femmes lors de la présentation de stimuli émotionnels.

Notre objectif était d’étudier les activations cérébrales des hommes et des femmes lors d’une tâche émotionnelle. Nous avons émis l’hypothèse que le pattern d’activations cérébrales diffère selon le sexe des individus et la valence des stimuli.

Nous avons mené une étude en imagerie par résonance magnétique fonctionnelle (IRMf) chez 30 participants sains (15 hommes et 15 femmes). Des stimuli à valence positive, négative et neutre étaient présentés aux sujets. Les participants ont évalué subjectivement la valence et l’intensité des stimuli.

Nous observons une activité plus importante chez les femmes que chez les hommes dans plusieurs régions clés du traitement des émotions lors de la présentation de stimuli négatifs. Aucune différence significative entre les hommes et les femmes n’a été relevée concernant l’évaluation subjective des stimuli en termes de valence et d’intensité.

Les résultats suggèrent qu’il existe bien une différence de patterns d’activation entre les hommes et les femmes lors de la perception des émotions négatives, qui irait dans le sens d’une sensibilité accrue chez les femmes. Celle-ci pourrait expliquer leur plus grande vulnérabilité aux troubles dépressifs. Il pourrait être intéressant de répliquer cette étude chez des patients qui souffrent de troubles de l’humeur.

Decreased vesicular glutamate transporter type 2 (VGLUT2) in schizophrenic brain indicates the deficit of glutamatergic function which may produce cognitive impairment in the patients. Bacopa monnieri (Brahmi), a traditional Indian Ayurvedic medicinal plant and popularly known as a cognitive enhancer might be a novel therapeutic agent for the cognitive deficit treatment in schizophrenia by changing cerebral VGLUT2 density.

To study effects of Brahmi on attenuation at cognitive deficit and cerebral VGLUT2 density in sub-chronic phencyclidine (PCP) rat model of schizophrenia.

Rats were administered PCP or vehicle. Half of the PCP-group was treated with Brahmi. Discrimination ratio (DR) representing cognitive ability was obtained from novel object recognition test. VGLUT2 immunodensity was measured in the prefrontal cortex, striatum, cornu ammonis 1 (CA1) and cornu ammonis 2/3 (CA2/3) of hippocampus using immunohistochemistry.

DR in PCP-group was significantly decreased compared with control. This occurred alongside reduced VGLUT2 density in the prefrontal cortex, but not in striatum, CA1 and CA2/3. PCP with Brahmi showed a significant increase in DR score compared with PCP alone. This occurred alongside significant increase in VGLUT2 density in the prefrontal cortex.

Cognitive deficit observed in PCP-administered rats was mediated by VGLUT2 reduction in the prefrontal cortex. Interestingly, Brahmi could recover this cognitive deficit by increasing VGLUT2 in the prefrontal cortex to normal. Conclusively, Brahmi could be a new frontier of cognitive deficit treatment in schizophrenia.