Depression and obesity, data from a national administrative database study: Geographic evidence for an epidemiological overlap.

BACKGROUND: Depression and obesity are two major conditions with both psychological and somatic burdens. Some data suggest strong connections between depression and obesity and more particularly associated prevalence of both disorders. However, little is known about the geographical distribution of these two diseases. This study aimed to determine if there is spatial overlap between obesity and depression using data from the entire French territory. METHODS: Data for 5,627 geographic codes for metropolitan France were collected from the two national hospital databases (PMSI-MCO and RIM-P) for the year 2016. We identified people who were depressed, obese or both registered in the two public medico-administrative databases, and we assessed their location. In addition, a multivariable analysis was performed in order to determine geographic interactions between obesity and depression after controlling for age, sex, environmental and socio-economic factors (social/material deprivation, urbanicity/rurality). RESULTS: 1,045,682 people aged 18 years and older were identified. The mapping analysis showed several cold and hot regional clusters of coinciding obesity and depression. The multivariable analysis demonstrated significant geographic interactions, with an increasing probability of finding a high prevalence of obesity in regions with major depression (OR 1.29 95% CI 1.13-1.49, p = 0.0002) and an increased probability of finding a high prevalence of depression in regions with a high ration of obesity (OR 1.32, 95% CI 1.15-1.52, p<0.0001). CONCLUSION: Our study confirms the significant bidirectional relationships between obesity and depression at a group level. French geographic patterns reveal a partial overlap between obesity and depression, suggesting these two diseases can be included in a common approach. Further studies should be done to increase the understanding of this complex comorbidity.

Distinct Expression Pattern of Epigenetic Machinery Genes in Blood Leucocytes and Brain Cortex of Depressive Patients.

In major depressive disorder (MDD), altered gene expression in brain cortex and blood leucocytes may be due to aberrant expression of epigenetic machinery coding genes. Here, we explore the expression of these genes both at the central and peripheral levels. Using real-time quantitative PCR technique, we first measured expression levels of genes encoding DNA and histone modifying enzymes in the dorsolateral prefrontal cortex (DLPFC) and cingulate cortex (CC) of MDD patients (n = 24) and healthy controls (n = 12). For each brain structure, transcripts levels were compared between subject groups. In an exploratory analysis, we then compared the candidate gene expressions between a subgroup of MDD patients with psychotic characteristics (n = 13) and the group of healthy subjects (n = 12). Finally, we compared transcript levels of the candidate genes in blood leucocytes between separate samples of MDD patients (n = 17) and healthy controls (n = 16). In brain and blood leucocytes of MDD patients, we identified an overexpression of genes encoding enzymes which transfer repressive transcriptional marks: HDAC4-5-6-8 and DNMT3B in the DLPFC, HDAC2 in the CC and blood leucocytes. In the DLPFC of patients with psychotic characteristics, two genes (KAT2A and UBE2A) were additionally overexpressed suggesting a shift to a more transcriptionally permissive conformation of chromatin. Aberrant activation of epigenetic repressive systems may be involved in MDD pathogenesis both in brain tissue and blood leucocytes.

[Biopsychosocial approach to caregiving burden: Why should we care about caregivers' health?] / Impact biopsychosocial de la charge des aidants : pourquoi faut-il porter une attention spécifique envers la santé des aidants ?

There are 11 million family caregivers in France and some estimates indicate that there will be 17 million in 2020. Caregiving is a source of chronic stress that requires adaptation and coping strategies. Caregiving may benefit the health of a caregiver with a positive coping style and altruistic goals. However, the caregiver's burden is frequently associated with negative effects in terms of biopsychosocial imbalance and medical conditions, with frequent anxiety and depression. The management of the caregiving burden starts with the recognition of health professionals - caregivers may benefit from consultation-liaison psychiatry and multidisciplinary medico-social strategies, in addition to constant support from their GPs.

Effects of Transcranial Magnetic Stimulation on the Hypothalamic-Pituitary Axis in Depression: Results of a Pilot Study.

Some studies have reported that repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) is able to induce changes in the hypothalamic-pituitary axis in subjects with major depression. The causes of these neuroendocrine effects are unknown and deserve to be studied. The authors monitored neuroendocrine hormones in 15 subjects with major depression treated by 1-Hz rTMS on the right DLPFC and explored a correlation with mood improvement. Unlike previous studies, no changes in serum cortisol, prolactin, and thyroid hormone levels were found. However, the authors did observe short-term changes in growth hormone levels in nonresponsive subjects.

Stress, anxiety and depression in heart disease patients: A major challenge for cardiac rehabilitation.

Cardiovascular events and emotional disorders share a common epidemiology, thus suggesting fundamental pathways linking these different diseases. Growing evidence in the literature highlights the influence of psychological determinants in somatic diseases. A patient's socio-economic aspects, personality traits, health behavior and even biological pathways may contribute to the course of cardiovascular disease. Cardiac events often occur suddenly and the episode can be traumatic for people not prepared for such an event. In this review of the literature, the authors tackle the question of psychobiological mechanisms of stress, in a pathophysiological approach to fundamental pathways linking the brain to the heart. Various psychological, biological and genetic arguments are presented in support of the hypothesis that various etiological mechanisms may be involved. The authors finally deal with biological and psychological strategies in a context of cardiovascular disease. Indeed, in this context, cardiac rehabilitation, with its global approach, seems to be a good time to diagnose emotional disorders like anxiety and depression, and to help people to cope with stressful events. In this field, cardiac rehabilitation seems to be a crucial step in order to improve patients' outcomes, by helping them to understand the influence of psychobiological risk factors, and to build strategies in order to manage daily stress.

Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial.

BACKGROUND: Approximately 15 million persons in the European Union and 10 million persons in the USA are alcohol-dependent. The global burden of disease and injury attributable to alcohol is considerable: worldwide, approximately one in 25 deaths in 2004 was caused by alcohol. At the same time, alcohol use disorders remain seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation may play a prominent role. The early results of studies using transcranial direct current stimulation found that stimulations delivered to the dorsolateral prefrontal cortex result in a significant reduction of craving and an improvement of the decision-making processes in various additive disorders. We, therefore, hypothesize that transcranial direct current stimulation can lead to a decrease in alcohol consumption in patients suffering from alcohol use disorders. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial, to evaluate the efficacy of transcranial direct current stimulation on alcohol reduction in patients with an alcohol use disorder. The study will be conducted in 14 centers in France and Monaco. Altogether, 340 subjects over 18 years of age and diagnosed with an alcohol use disorder will be randomized to receive five consecutive twice-daily sessions of either active or placebo transcranial direct current stimulation. One session consists in delivering a current flow continuously (anode F4; cathode F3) twice for 13 minutes, with treatments separated by a rest interval of 20 min. Efficacy will be evaluated using the change from baseline (alcohol consumption during the 4 weeks before randomization) to 24 weeks in the total alcohol consumption and number of heavy drinking days. Secondary outcome measures will include alcohol craving, clinical and biological improvements, and the effects on mood and quality of life, as well as cognitive and safety assessments, and, for smokers, an assessment of the effects of transcranial direct current stimulation on tobacco consumption. DISCUSSION: Several studies have reported a beneficial effect of transcranial direct current stimulation on substance use disorders by reducing craving, impulsivity, and risk-taking behavior, and suggest that transcranial direct current stimulation may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm the hypothesis. Results from this large randomized controlled trial will give a better overview of the therapeutic potential of transcranial direct current stimulation in alcohol use disorders. TRIAL REGISTRATION: Clinical Trials Gov, NCT02505126 (registration date: July 15 2015).

Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial.

BACKGROUND: Further evidence suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is an effective method to reduce tobacco craving among smokers. HYPOTHESIS: As relapse is common within a few days after smoking cessation, we hypothesized that combining the anti-craving effects of rTMS with Nicotine replacement therapy (NRT) to attenuate withdrawal symptoms could increase abstinence rates in smokers with severe nicotine dependence who quit smoking. METHODS: Thirty-seven smokers who failed to quit with the usual treatments were randomly assigned to two treatment groups to receive either active (n = 18) or sham (n = 19) 1-Hz rTMS of the right dorsolateral prefrontal cortex. The day after quitting smoking, each patient combined NRT (21-mg patch) with active or sham rTMS (10 sessions) for 2 weeks. Cessation support was then continued with NRT alone using lower-dose patches. Abstinence rates and self-report craving scales were used to assess the therapeutic results during the combined treatment and for up to 12 weeks after quitting. RESULTS: At the end of the combined treatment, there were significantly more abstinent participants in the active rTMS group (n = 16) than in the sham rTMS group (n = 9) (P = 0.027). The craving scales analysis revealed that active rTMS (P = 0.011) but not sham rTMS (P = 0.116) led to a significant decrease in the compulsive factor. However, no lasting rTMS effect was found. CONCLUSIONS: 1-Hz rTMS combined with NRT improved the success rate of abstinence in smokers during tobacco cessation. The stimulation-induced reduction in compulsivity may explain this result.

Metacognitive training for schizophrenia: a multicentre randomised controlled trial.

A psychotherapeutic approach for schizophrenia is now recommended as an adjuvant for psychopharmacology, since antipsychotic medications only have a partial impact especially as regards positive symptoms and insight. In addition, cognitive distortions and the lack of metacognitive skills might increase positive symptoms leading to poor social functioning. This underlines the need for specific approaches which target cognitive processes relevant for insight, and abilities in metacognition. Metacognitive training (MCT) is a structured group intervention, which enhances a patient's reflection on cognitive biases and improves problem-solving. The aim of our study was to assess MCTs' short term impact on insight, symptoms and quality of life. Fifty patients with schizophrenia or schizoaffective disorders and persistent positive symptoms (delusions or hallucinations) were enrolled in the study. After baseline assessment participants were randomised either to supportive therapy or MCT. Both groups used the same design (1h-session twice a week during 8weeks) although the basic knowledge given to participants was different between interventions. Participants were assessed at eight weeks based on the Scale to Assess Unawareness of Mental Disorder, Positive and Negative Syndrome Scale (PANSS), Psychotic Symptom Rating Scales, the Calgary Depression Scale for Schizophrenia and the Quality of Life Scale. Between-group differences were significant in favour of MCT on the PANSS positive scale. Between-group differences in post- and pre-test values showed a trend in favour of MCT for insight on hallucinations. Results of our study indicate that the MCT has an effect on reducing positive symptomatology, and a trend impact on insight and social functioning.

Interest of targeting either cortical area Brodmann 9 or 46 in rTMS treatment for depression: a preliminary randomized study.

OBJECTIVE: To assess the interest of specifically targeting Brodmann Areas (BA) 9 or 46 for rTMS treatment of depression. METHODS: Patients with Treatment-Resistant Depression were randomly assigned to two treatment groups to receive either rTMS on BA 9 or on BA 46. Each patient underwent 10 sessions of 1Hz-rTMS for 2weeks. The Hamilton and Montgomery-Asberg Depression Rating Scales (HDRS, MADRS) were used under blind conditions to assess the therapeutic response (50% improvement). A Wilcoxon signed-rank test was used to compare the depression rating scales scores obtained before and after the 10 rTMS sessions for each of the two groups. The therapeutic results in the two groups were compared using the Mann-Whitney-Wilcoxon test. We also reported the effect sizes using Hedges's g. RESULTS: Fifteen patients were included. Stimulation of both BA 9 (n=7) and BA 46 (n=8) led to similar therapeutic responses in the two groups (with moderate effect size), such as the mean decrease in HDRS (BA 9: p=0.015; BA 46: p=0.010) and MADRS (BA 9: p=0.042; BA 46: p=0.038) scores. CONCLUSION: Our results do not come out in favor of one or the other BA. SIGNIFICANCE: Stimulation of BA 9 and BA 46 appears to be equally effective in the treatment of depression.

Longitudinal study of alexithymia and multiple sclerosis.

OBJECTIVE: The aim of this study was to investigate the course of alexithymia and its relation with anxiety and depression in patients with multiple sclerosis (MS), over a period of 5 years. METHODS: Sixty-two MS patients were examined at two timepoints, 5 years apart, and they answered questionnaires collecting socio-demographic, medical, and psychological data (depression, anxiety, alexithymia). RESULTS: Our data show that emotional disorders remain stable over time in patients with MS, particularly as regards alexithymia and anxiety. Conversely, the rate of depression decreased between the two evaluations, falling from 40% to 26%. The two dimensions of alexithymia (i.e., difficulty describing and difficulty identifying feelings) were correlated with anxiety and depression, whereas the third component of alexithymia (externally oriented thinking) was independent, and was the only component to change over time, with a significant fall observed at 5 years. CONCLUSION: Alexithymia was associated with increased severity of anxiety and attack relapses.

Leukocyte telomere length in mastocytosis: correlations with depression and perceived stress.

BACKGROUND: Mastocytosisis a rare disease associated with chronic symptoms related to mast cell mediator release. Patients with mastocytosis display high level of negative emotionality such as depression and stress sensibility. Brain mast cells are mainly localized in the diencephalon, which is linked to emotion regulatory systems. Negative emotionality has been shown to be associated with telomere shortening. Taken together these observations led us to hypothesize that mast cells activity could be involved in both negative emotionality and telomere shortening in mastocytosis. OBJECTIVE: To demonstrate a possible relationship between negative emotionality in mastocytosis and leukocytes telomere length. METHODS: Leukocyte telomere length and telomerase activity were measured among mastocytosis patients and were correlated with perceived stress and depression assessed by the Beck Depression Inventory revised and the Perceived Stress Scale. RESULTS: Mild-severe depression scores were frequent (78.9%) as well as high perceived stress (42.11%). Telomere length was correlated to perceived stress (r=0.77; p=0.0001) but not to depression in our population. Patients displaying Wild-type KIT significantly presented higher perceived stress levels. Patients with the D816VC KIT mutation who had high perceived stress scores displayed significantly shorter telomere but not if they had high depression scores. CONCLUSION: These findings suggest that high perceived stress in mastocytosis could accelerate the rate of leukocytes telomere shortening. Since mastocytosis is, by definition, a mast cell mediated disease; these cells could be involved in this phenomenon. Mechanistic causal relationships between these parameters need to be investigated.

Correlative gene expression pattern linking RNF123 to cellular stress-senescence genes in patients with depressive disorder: implication of DRD1 in the cerebral cortex.

BACKGROUND: The expression level of the RNF1213 gene in blood cells has been identified as a disease risk marker, more than ten years before the diagnosis of depression (Glahn et al., 2012). To explore the status of this gene in the acute depressive state we have quantified the expression of RNF123 in the blood leukocytes (N=17), dorsolateral prefrontal and cingulate cortex (N=24) of patients with diagnosed depression and of matched controls. We have measured the expression of the DRD1 gene as a "neuronal probe". We have also quantified the mRNA of six genes previously identified as markers of the biopsychological stress associated with major depression: FOS, DUSP1, OGG1, STMN1, p16(INK4a) and TERT. METHODS: The steady state of mRNA has been quantified by the real-time quantitative PCR technique. RESULTS: RNF123 was overexpressed by 45% in the cingulate cortex of patients with psychotic depression. There were distinct co-expression patterns of RNF123 and stress-related genes in the blood cells and brain cortex of patients, demonstrating a transcriptional regulatory shift. In both the prefrontal and cingulate cortex of these patients a strong correlation interlinked STMN1, TERT and DRD1 pointing to a role of these genes in dopamine signaling. LIMITATIONS: The two groups of patients were clinically heterogeneous. All the patients had received antidepressant treatment, details of which were not available. CONCLUSION: We did not identify RNF123 as a clinically relevant, peripheral state marker of depression, but our study probably lacked statistical power to detect small effect size. It is likely to be involved in distinct pleiotropic molecular pathways at peripheral (blood) and central (brain) level.

Review on depression and coronary heart disease.

The impact of psychological factors on somatic disorders - and vice versa - and the involvement of biological mechanisms in psychic disorders have generated considerable interest in recent years, notably thanks to cutting-edge investigation techniques (immunohistochemistry, functional imaging, genetics, etc.). In the field of psychosomatics, coronary heart disease (CHD) is a frequent co-morbidity of mental disorders, particularly mood disorders. Indeed, there is a bidirectional relationship between CHD and mood disorders, with a strong co-occurrence of the two diseases accompanied by a reciprocal worsening of the prognosis for the two conditions. Various epidemiological studies have shown that depression is a psychic risk factor for CHD and that CHD is present in almost 30% of patients with affective disorders. In this review of the literature, we tackle the crucial question of the diagnosis of depression during myocardial infarction. This clinical approach is essential given the underevaluation of this psychic problem. Then, various psychological, biological and genetic arguments are presented in support of the hypothesis that various aetiological mechanisms of the two disorders are partly shared. We finally deal with the treatment of depression in the context of CHD with its pharmacological and psychological specificities. In conclusion, this review reiterates the need for a multidisciplinary approach, which is necessary to understand, diagnose and then treat this frequent co-morbid condition of heart disease and depression.

Up-regulation of leucocytes genes implicated in telomere dysfunction and cellular senescence correlates with depression and anxiety severity scores.

BACKGROUND: Major depressive disorder (MDD) is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to evaluate the somatic impact of MDD. METHODOLOGY: To address this issue we have measured in the blood leucocytes of MDD patients (N=17) and controls (N=16) the expression of two genes identified as robust biomarkers of human aging and telomere dysfunction: p16(INK4a) and STMN1. We have also quantified the transcripts of genes involved in the repair of oxidative DNA damage at telomeres (OGG1), telomere regulation and elongation (TERT), and in the response to biopsychological stress (FOS and DUSP1). RESULTS: The OGG1, p16(INK4a), and STMN1 gene were significantly up-regulated (25 to 100%) in the leucocytes of MDD patients. Expression of p16(INK4a) and STMN1 was directly correlated with anxiety scores in the depression group, and that of p16(INK4a), STMN and TERT with the depression and anxiety scores in the combined sample (MDD plus controls). Furthermore, we identified a unique correlative pattern of gene expression in the leucocytes of MDD subjects. CONCLUSIONS: Expression of p16(INK4) and STMN1 is a promising biomarker for future epidemiological assessment of the somatic impact of depressive and anxious symptoms, at both clinical and subclinical level in both depressive patients and general population.

Factors influencing French medical students towards a career in psychiatry.

BACKGROUND: There is a need to increase the recruitment to psychiatry in France. Our aim in this study was to compare factors influencing career choice between French medical students considering and not considering psychiatry as a specialty. SUBJECTS AND METHODS: Quantitative cross-sectional online survey on 145 French students in their last year of medical school. RESULTS: 22.7% of our sample considered choosing a career in psychiatry. A preference for a career in psychiatry was associated with more frequent history of personal/familial mental illness, higher ratings of psychiatric teaching, more weeks of compulsory psychiatry teaching and placement, during which students had more often met patients in recovery and been asked their opinion on patients. Students considering psychiatry as a career also emphasized more the need for a good work-life balance, and presented better attitudes toward psychiatry. CONCLUSIONS: Improving opportunities of interactions between students and psychiatrists or psychiatric patients might help to improve recruitment in psychiatry.

[Bipolar disorders and somatic comorbidities: a focus on metabollic syndrome, diabetes and cardiovascular disease]. / Trouble bipolaire et comorbidités somatiques : diabète et troubles cardiométaboliques Données physiopathologiques.

Bipolar Disorders (BD) are currently regarded as a multidimensional disease involving both psychological and physical determinants. If mood dimension and thymic instability have usually been considered as the « core ¼ aspect of bipolar disorders, it's crucial to note that somatic problems frequently occur in BD, deeply worsening the prognosis of this affection. Indeed, comorbid somatic illnesses of bipolar disorder are mainly represented by cardiovascular and metabolic disorders, which are shortening life expectancy by 25 to 30 years as compared to the general population. In this review, the authors examine epidemiological data about this comorbidity, then they attempt to provide etiologic and physiopathologic hypotheses about the links between bipolar disorders and metabolic diseases. Despite the absence of strong scientific explanation for this link, its existence highlights the need for more integrated care and interdisciplinary collaboration in order to improve patients'outcome.

Stroke with neuropsychiatric sequelae after cannabis use in a man: a case report.

INTRODUCTION: The outcome of cerebral ischemic stroke associated with cannabis use is usually favorable. Here we report the first case of cannabis-related stroke followed by neuropsychiatric sequelae. CASE PRESENTATION: A 24-year-old Caucasian man was discovered in a deeply comatose non-reactive state after cannabis use. A magnetic resonance imaging scan of his brain showed bilateral multiple ischemic infarcts. The patient remained deeply comatose for four days, after which time he developed other behavioral impairments and recurrent seizures. CONCLUSION: Stroke related to cannabis use can be followed by severe neuropsychiatric sequelae. Concomitant alcohol intoxication is essential neither to the occurrence of this neurologic event nor to its severity.