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The spatial functional chronnectome is an innovative mathematical model designed to capture dynamic features in the organization of brain function derived from resting-state functional magnetic resonance imaging data. Measurements of dynamic functional connectivity have been developed from this model to quantify the brain dynamical self-reconfigurations at different spatial and temporal scales. This study examined whether two spatiotemporal dynamic functional connectivity quantifications were linked to late adolescence-onset major depressive disorder (AO-MDD), and scaled with depression and symptom severity measured with the Montgomery-Åsberg Depression Rating Scale.Thirty-five patients with AO-MDD (21 ± 6 years of age) and 53 age- and sex-matched healthy young participants (20 ± 3 years of age) underwent 3T magnetic resonance imaging structural and resting-state functional magnetic resonance imaging acquisitions. The chronnectome here comprised seven individualized functional networks portrayed along 132 temporal overlapping windows, each framing 110 seconds of resting brain activity.Based on voxelwise analyses, patients with AO-MDD demonstrated significantly reduced temporal variability within the bilateral prefrontal cortex in five functional networks including the limbic network, default mode network, and frontoparietal network. Furthermore, the limbic network appeared to be particularly involved in this sample and was associated with Montgomery-Åsberg Depression Rating Scale scores, and its progressive dynamic inflexibility was linked to sadness. Default mode network and frontoparietal network dynamics scaled with negative thoughts and neurovegetative symptoms, respectively.This triple-network imbalance could delay spatiotemporal integration, while across-subject symptom variability would be network specific. Therefore, the present approach supports that brain network dynamics underlie patients' symptom heterogeneity in AO-MDD.

Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions.

Changing sleep rhythms in adolescents often lead to sleep deficits and a delay in sleep timing between weekdays and weekends. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n = 101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationships between sleep habits, assessed with self-reports, and regional grey matter volumes, and psychological functioning, assessed with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and externalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development. publishedVersion

Background Although treatment-resistant and nontreatment-resistant depressed patients show structural brain anomalies relative to healthy controls, the difference in regional volumetry between these two groups remains undocumented. Methods A whole-brain voxel-based morphometry (VBM) analysis of regional volumes was performed in 125 participants’ magnetic resonance images obtained on a 1.5 Tesla scanner; 41 had treatment-resistant depression (TRD), 40 nontreatment-resistant depression (non-TRD), and 44 were healthy controls. The groups were comparable for age and gender. Bipolar/unipolar features as well as pharmacological treatment classes were taken into account as covariates. Results TRD patients had higher gray matter (GM) volume in the left and right amygdala than non-TRD patients. No difference was found between the TRD bipolar and the TRD unipolar patients, or between the non-TRD bipolar and non-TRD unipolar patients. An exploratory analysis showed that lithium-treated patients in both groups had higher GM volume in the superior and middle frontal gyri in both hemispheres. Conclusions Higher GM volume in amygdala detected in TRD patients might be seen in perspective with vulnerability to chronicity, revealed by medication resistance.

BACKGROUND: Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. METHODS: 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. RESULTS: The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. CONCLUSIONS: We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity.

Resume Objectif La consommation de benzodiazepines en France est un probleme de sante publique qui a fait, ces dernieres annees, l’objet de nombreux rapports nationaux (HAS, INPES, OPEPS, ANSM…). Depuis les annees 1990, de nombreux travaux ont signale le niveau excessivement eleve de la consommation de benzodiazepines en France. En 2009, la France etait le deuxieme pays europeen consommateur d’anxiolytiques et d’hypnotiques. Chaque annee, un Francais sur cinq consomme au moins une benzodiazepine ou une molecule apparentee. Cette consommation des anxiolytiques est majoritairement feminine et augmente avec l’âge. On sait egalement que l’introduction d’un traitement par benzodiazepines entraine une consommation moyenne continue de sept mois et, pour 52 % de ces patients, une exposition moyenne de deux ans consecutifs. Le rapport de la HAS d’octobre 2007 rappelle que la prise de benzodiazepines expose plus specifiquement a des risques de chutes (grade B), a des alterations cognitives (grade C) et a des accidents de la voie publique (grade C), alors que l’arret progressif et encadre des benzodiazepines peut ameliorer certaines fonctions cognitives. Materiel et methode Face a ce probleme, il existe peu de strategies therapeutiques efficaces pour le sevrage et le maintien de l’arret de cette consommation de medicaments. Dans des etudes recentes, la balneotherapie a montre son efficacite dans le traitement du trouble anxieux generalise. Par ailleurs, des programmes de psychoeducation se sont montres efficaces en addictologie dans la prevention de la rechute. Ainsi, est apparu credible le projet d’associer une cure thermale de trois semaines, un programme psycho-educatif de type therapie cognitive et comportementale valide par un groupe d’experts. Ce programme a ete constitue et mis en place dans quatre des cinq stations thermales psychiatriques francaises. Le programme consistait en l’association de techniques a base de therapie cognitive et comportementale, d’entretien motivationnel et de seances de relaxation. Chaque equipe a ete formee par un psychologue clinicien, specialiste en therapie cognitive et comportementale. Soixante-dix patients, d’un âge moyen de 54 ans et 9 mois, ont integre ce protocole. Ils ont ete repartis en 9 groupes de 6 a 12 patients sur les quatre centres. L’objectif de l’etude consistait a assurer le sevrage durable des benzodiazepines. Resultats A l’issue de la cure, un suivi longitudinal sur six mois etait assure a J5, J30, J60, J100 et J180. L’evaluation methodologique de l’etude a ete realisee par l’ISPED de Bordeaux II. Les resultats sont en cours d’analyse, mais il est permis des a present de conclure en la faisabilite de la mise en place d’un tel programme en station thermale et en l’obtention de resultats tres encourageants dans l’objectif d’un sevrage a six mois des benzodiazepines. Conclusions La medecine thermale, qui peut s’associer a une prise en charge en therapie cognitive et comportementale, pourrait se reveler etre une solution therapeutique adaptee pour la prise en charge de la consommation chronique et stable de benzodiazepines. Cette etude est le premier essai clinique evaluant l’efficacite de la balneotherapie associee a un modele psycho-educatif specifique sevrage de benzodiazepines.

Neuroimaging studies investigating dopamine (DA) function widely support the hypothesis of presynaptic striatal DA hyperactivity in schizophrenia. However, published data on the striatal DA transporter (DAT) appear less consistent with this hypothesis, probably partly due to methodological limitations. Moreover, DAT in extrastriatal regions has been very poorly investigated in the context of schizophrenia. In order to address these issues, we used a high resolution positron emission tomograph and the selective DAT radioligand [11C]PE2I, coupled with a whole brain voxel-based analysis method to investigate DAT availability in striatal but also extra-striatal regions in 21 male chronic schizophrenia patients compared to 30 healthy male controls matched by age. We found higher DAT availability in schizophrenia patients in midbrain, striatal, and limbic regions. DAT availability in amygdala/hippocampus and putamen/pallidum was positively correlated with hallucinations and suspiciousness/persecution, respectively. These results are consistent with an increase of presynaptic DA function in patients with schizophrenia, and support the involvement of both striatal and extrastriatal DA dysfunction in positive psychotic symptoms. The study also highlights the whole brain voxel-based analysis method to explore DA dysfunction in schizophrenia.

Objective Repetitive transcranial magnetic stimulation (rTMS) over the left temporo-parietal region has been proposed as a treatment for resistant auditory verbal hallucinations (AVH), but which patients are more likely to benefit from rTMS is still unclear. This study sought to assess the effects of rTMS on AVH, with a focus on hallucination phenomenology. Method Twenty-seven patients with schizophrenia and medication-resistant AVH participated to a randomized, double-blind, placebo-controlled, add-on rTMS study. The stimulation targeted a language-perception area individually determined using functional magnetic resonance imaging and a language recognition task. AVH were assessed using the hallucination subscale of the Scale for the Assessment of Positive Symptoms (SAPS). The spatial location of AVH was assessed using the Psychotic Symptom Rating Scales. Results A significant improvement in SAPS hallucination subscale score was observed in both actively treated and placebo-treated groups with no difference between both modalities. Patients with external AVH were significantly more improved than patients with internal AVH, with both modalities. Conclusions A marked placebo effect of rTMS was observed in patients with resistant AVH. Patients with prominent external AVH may be more likely to benefit from both active and placebo interventions. Cortical effects related to non-magnetic stimulation of the auditory cortex are suggested.

Benzodiazepines are widely used in France: 11.5 million of consumers (22% with 2 benzodiazepines simultaneously), 131 million of boxes of benzodiazepines were sold in 2012. Annual length of use: anxiolytic 5 months, hypnotic 3.9 months. Risk of fall, Road accident, risk of Abuse and dependence & possible increase risk of Alzheimer disease. Using the fact that spa center are an institutional place not as stigmatizing and less regressing than being in hospital and are able to reduce anxiety disorders (STOP TAG study).

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.

Objectives: Cerebral abnormalities have been detected in patients with bipolar disorder (BD). In comparison to BD with a later onset, early-onset BD has been found to have a poorer outcome. However, it is yet unknown whether neuroanatomical abnormalities differ between age-at-onset subgroups of the illness. We searched for cortical folding differences between early-onset (before 25 years) and intermediate-onset (between 25 and 45 years) BD patients. Methods: Magnetic resonance images of 22 early-onset BD patients, 14 intermediate-onset BD patients, and 50 healthy participants were analyzed using a fully automated method to extract, label, and measure the sulcal area in the whole cortex. Cortical folding was assessed by computing global sulcal indices (the ratio between total sulcal area and total outer cortex area) for each hemisphere, and local sulcal indices for 12 predefined regions in both hemispheres. Results: Intermediate-onset BD patients had a significantly reduced local sulcal index in the right dorsolateral prefrontal cortex in comparison to both early-onset BD patients and healthy subjects, and lower global sulcal indices in both hemispheres in comparison to healthy subjects (p