Habenular volume changes after venlafaxine treatment in patients with major depression.

BACKGROUND: Habenula, a hub brain region controlling monoaminergic brain center, has been implicated in major depressive disorder (MDD) and as a possible target of antidepressant response. Nevertheless, the effect of antidepressant drug treatment on habenular volumes remains unknown. The objective of the present research was to study habenular volume change after antidepressant treatment in patients with MDD, and assess whether it is associated with clinical improvement. METHODS: Fifty patients with a current major depressive episode (MDE) in the context of MDD, and antidepressant-free for at least 1 month, were assessed for habenula volume (3T MRI with manual segmentation) before and after a 3 months sequence of venlafaxine antidepressant treatment. RESULTS: A 2.3% significant increase in total habenular volume (absolute volume: P = 0.0013; relative volume: P = 0.0055) and a 3.3% significant increase in left habenular volume (absolute volume: P = 0.00080; relative volume: P = 0.0028) were observed. A significant greater variation was observed in male patients (4.8%) compared to female patients. No association was observed between habenular volume changes and response and remission. Some habenula volume changes were associated with improvement of olfactory pleasantness. CONCLUSION: Habenular volumes increased after 3 months of venlafaxine treatment in depressed patients. Further studies should assess whether cell proliferation and density or dendritic structure variations are implied in these volume changes.

Four- and sixteen-month clinical status of a cohort of patients following hospitalization for COVID-19.

BACKGROUND AND OBJECTIVES: Although many symptoms of post-COVID syndrome have been described, a comprehensive evaluation of their prevalence is lacking. We aimed to describe symptoms at 16 months from hospitalization for COVID-19. METHODS: A telephone assessment was performed one year later in a cohort of COVID-19 survivors hospitalized between March and May 2020 and already evaluated four months after discharge. Patients with relevant symptoms at 16 months, patients who presented symptoms at four months, and all intensive care unit patients were invited for assessment at an outpatient facility. At telephone consultation, respiratory, cognitive, and functional symptoms were assessed. Patients underwent pulmonary function tests, lung CT scans, and psychometric and cognitive tests at the outpatient facility. RESULTS: Among 478 patients evaluated four months after discharge, 317 (67 %) were assessed at telephone consultation and 124 at ambulatory assessment. At telephone assessment, ≥1 new symptom was reported by 216 patients (68 %), mainly fatigue (53 %), dyspnea (37 %), and memory difficulties (24 %). Seventy-nine patients (25 %) were asymptomatic at four months but declared ≥1 symptom one year later. In patients evaluated twice, the prevalence of cognitive impairment was 45 % at four months and 40 % at 16 months. Depression and post-traumatic symptoms prevalence remained stable, and the prevalence of anxiety significantly decreased. Dysfunctional breathing was detected in 32 % of patients. At 16 months after discharge, lung CT-scan exhibited abnormalities in 30/80 patients (38 %), compared to 52/85 patients (61 %) at four months. CONCLUSION: At 16 months after hospitalization for COVID-19, 68 % of patients declared symptoms, including patients whose symptoms appeared between 4 and 16 months. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04704388.

Psychotic and Somatic Symptoms Are Frequent in Refugees With Posttraumatic Stress Disorder: A Narrative Review.

OBJECTIVE: In 2021, 89.3 million refugees were vulnerable to posttraumatic stress disorder (PTSD) after exposure to multiple and repeated traumatic experiences. The recent war in Ukraine provoked 7 million refugees to flee their homes. Specific clinical presentations of PTSD in refugee populations may not be familiar to most physicians. The goal of this review is to describe the diagnosis and specific clinical features of PTSD in refugees. METHODS: This narrative review of 263 articles explores 3 PTSD diagnoses that are frequently described in refugee populations and that have been observed in our clinical practices: complex PTSD, PTSD with psychotic symptoms, and PTSD with somatic symptoms. RESULTS: While complex PTSD does not seem to be related to individuals' culture and origin, the other 2 diagnoses have been specifically described in refugee populations. PTSD with somatic manifestations appears to be the most frequently described and commonly acknowledged form in refugee populations, whereas PTSD with psychotic symptoms remains more controversial due to its clinical variability and association with comorbid disorders. CONCLUSIONS: The difficulty of identifying PTSD with psychotic symptoms and PTSD with somatic symptoms in refugee populations may lead to misdiagnosis and explain the moderate effectiveness of care delivered to these populations. Appropriate diagnosis is essential to provide optimal psychiatric care to refugee populations.

Assisted reproductive technologies could be associated with higher risk of parenting difficulties in women with postpartum major depression.

No increased risk of postpartum major depression (PPMD) was reported in women conceiving through assisted reproductive technologies (ART). However, ART may be associated with a higher risk of parenting difficulties in women with PPMD. In 359 women with a PPMD admitted to a Mother-Baby Unit (MBU), ART-women (4.2%) showed a 5-fold higher rate of parenting difficulties than those with spontaneous pregnancy (73.33% vs. 35.17%, multivariate ORa = 5.09 [1.48-17.48] p = 0.01). Specific support for mother-child relationship should be implemented in ART-women with PPMD.

Lower risk of hospitalisation for depression following hospitalisation for COVID-19 versus for another reason.

INTRODUCTION: Although hospitalisation for COVID-19 is associated with a higher post-discharge risk of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), this risk has not been compared to that following hospitalisation for a reason other than COVID-19. METHODS: Using data from France's National Health Data System (SNDS) database, we compared patients hospitalised for mood disorders in the 12 months following COVID-19/another reason hospitalisation. RESULTS: 96,313 adult individuals were hospitalised for COVID-19, and 2,979,775 were hospitalised for another reason. In the 12 months post-discharge, 110,976 (3.83 %) patients were hospitalised for mood disorders. In unadjusted analyses, patients initially hospitalised for COVID-19 (versus another reason) were more likely to be subsequently hospitalised for a mood disorder (4.27 % versus 3.82 % versus, respectively, p < 0.0001). These patients were also more likely to have a history of mood disorders, especially depressive disorders (6.45 % versus 5.77 %, respectively, p < 0.0001). Women, older age, lower social deprivation, a history of mood disorders, longer initial hospitalisation (COVID-19 or other), and a higher level of clinical care during initial hospitalisation were all significantly associated with the risk of subsequent hospitalisation for MDD and BD. In contrast, after adjusting for all these factors, persons initially hospitalised for COVID-19 were less likely to be subsequently hospitalised for MDD (OR = 0.902 [0.870-0.935]; p < 0.0001). No difference between both groups was observed for BD. LIMITATIONS: Other reasons were not separately studied. CONCLUSIONS: After adjusting for confounding factors, initial hospitalisation for COVID-19 versus for another reason was associated with a lower risk of hospitalisation for a mood disorder.

Impact of paternal psychiatric disorders on parents-baby separation after mother-baby unit care.

BACKGROUND: Paternal mental health may have an impact on parenthood especially in case of maternal postpartum severe psychiatric illness. OBJECTIVE: The aim of this study was to search for an association between paternal psychiatric disorder and parents-baby separation after a maternal joint hospitalization for a severe postpartum psychiatric episode. PARTICIPANTS AND SETTINGS: In an observational, naturalist and multicentric study, 787 fathers whose partner was hospitalized in a mother-baby unit were included. METHODS: Fathers were assessed for psychiatric diagnoses associated with parents-baby separation. RESULTS: 25 % of the fathers had a psychiatric disorder. 69 babies (8.77 %) were separated from their parents at the end of the joint hospitalization. In multivariate analysis, parents-baby separation was associated with a paternal diagnosis of addictive disorder (OR = 8.35, 95 % CI [3.45-30.30]) and psychotic disorder (OR = 5.76, 95 % CI [1.97-16.78]), independently from potential confounding variables including maternal psychiatric diagnosis. CONCLUSIONS: This study shows the major impact of a paternal psychiatric disorder in the outcome of a joint hospitalization. A paternal mental illness should be systematically looked for in case of a severe maternal postpartum psychiatric episode, considering it is predictive of parenthood difficulties.

Metabolomic profiles of 38 acylcarnitines in major depressive episodes before and after treatment.

BACKGROUND: Major depression is associated with changes in plasma L-carnitine and acetyl-L-carnitine. But its association with acylcarnitines remains unclear. The aim of this study was to assess metabolomic profiles of 38 acylcarnitines in patients with major depression before and after treatment compared to healthy controls (HCs). METHODS: Metabolomic profiles of 38 plasma short-, medium-, and long-chain acylcarnitines were performed by liquid chromatography-mass spectrometry in 893 HCs from the VARIETE cohort and 460 depressed patients from the METADAP cohort before and after 6 months of antidepressant treatment. RESULTS: As compared to HCs, depressed patients had lower levels of medium- and long-chain acylcarnitines. After 6 months of treatment, increased levels of medium- and long-chain acyl-carnitines were observed that no longer differed from those of controls. Accordingly, several medium- and long-chain acylcarnitines were negatively correlated with depression severity. CONCLUSIONS: These medium- and long-chain acylcarnitine dysregulations argue for mitochondrial dysfunction through fatty acid ß-oxidation impairment during major depression.

[Burnout, anxiety, insomnia and depressive symptoms among French outpatient physicians in the second wave of COVID-19: Comparison between general practitioners and specialists]. / Santé mentale des médecins libéraux français pendant la deuxième vague de COVID 19.

INTRODUCTION: The 2019 coronavirus (COVID-19) pandemic has caused a public health crisis worldwide. Concerns have been expressed about the rapid deterioration of mental health among primary care physicians among whom burnout already had a high prevalence prior to the pandemic. However, there is little data on private doctors during the pandemic. France experienced a second wave with a second lockdown. We aimed to assess and compare physicians' burnout, anxiety and depression symptoms and insomnia between general practitioners (GP) and all other private specialists during the second Covid-19 wave. METHODS: We conducted an online survey of private practitioners registered on Doctolib® (n=32,655), the interface software most used by private practitioners for booking medical appointments in France. Doctors were invited by email to complete an online survey in November 2020. Inclusions were closed on 1st December. The 2nd lockdown lasted from 30th October to 15th December 2020. We used the Copenhagen Burnout Inventory (CBI) to assess burnout syndrome. A mean score of>50 in at least one subscale defined burnout. The Hospital Anxiety and Depression Scale assessed anxiety and depression symptoms. We used two cut-offs, 8 (>7) and 11 (>10), as both are validated in the ability to find cases. The Insomnia Severity Index (ISI) measures sleep-related complaints among physicians (cut-off >7). To link variations in the psychological scales to the COVID-19 pandemic, one of the items asked explicitly whether participants considered that "the COVID-19 epidemic we are currently experiencing is a source of excess stress, psychological suffering or burnout". Approval for this study was obtained from the local institutional review board of the University of Paris-Saclay, France. The questionnaires were collected anonymously. Statistical significance was tested using the chi-square test and student's t-test to compare the prevalence between GPs and other specialities. Subsequently, logistic regression models were run for statistically significant associations. RESULTS: 1992 physicians replied, a response rate of 12.8% of those who received the invitation email. Among them, 79.4% suffered from psychological distress (symptoms of anxiety or depression or burnout), of which 71.3% suffered from burnout, 26.7% from depressive symptoms, 58.9% from anxiety symptoms and 45.8% from insomnia. There was no difference in gender between GPs and specialists, but there was an age difference (P<0.001). GPs had a higher prevalence of burnout (OR=1.33 CI95 [1.09;1.63]) and took more psychotropic drugs (1.38 CI95 [1.05;1.81]). They were also more likely to perceive their stress as work-related (OR=1.50 CI95 [1.23;1.81]) or COVID-19-related (OR=1.43 CI95 [1.16;1.77]). CONCLUSION: Our study is the first to assess the mental health of private practitioners in the second wave in association with COVID-19 stress. Firstly, GPs who provide primary care have a significantly higher burnout rate than other doctors. Secondly, COVID-19 stress is associated with more significant psychological distress. Thirdly, almost 80% of the private doctors surveyed suffer from psychological pain, and 71% suffer from burnout. This study has strengths and limitations. Firstly, this study assesses mental health and stress related to its COVID-19 association. Second, this is the largest population of private physicians during the COVID-19 pandemic. The low response rate is the main limit of this study. The alarming rates of psychological distress among private doctors and, in particular, GPs should lead to intervention to help doctors reduce stress, burnout and other mental disorders. This study gives a picture of the situation during the second wave and the lock-in, and we need to be cautious with the next waves.

[Ketamine and suicidal behavior: Contribution of animal models of aggression-impulsivity to understanding its mechanism of action]. / Kétamine et suicidalité : modèles animaux pour comprendre son mécanisme d'action.

More than two-thirds of suicides occur during a major depressive episode. Acting out prevention measures and therapeutic options to manage the suicidal crisis are limited. The impulsive-aggressive dimensions are vulnerability factors associated with suicide in patients suffering from a characterized depressive episode: this can be a dimension involved in animals. Impulsive and aggressive rodent models can help analyze, at least in part, the neurobiology of suicide and the beneficial effects of treatments. Ketamine, a glutamatergic antagonist, by rapidly improving the symptoms of depressive episodes, would help reduce suicidal thoughts in the short term. Animal models share with humans impulsive and aggressive endophenotypes modulated by the serotonergic system (5-HTB receptor, MAO-A enzyme), neuroinflammation or the hypothalamic-pituitary-adrenal axis and stress. Significant effects of ketamine on these endophenotypes remain to be demonstrated.

The risk of hospitalization for psychotic disorders following hospitalization for COVID-19: a French nationwide longitudinal study.

COVID-19, like other infectious diseases, may be a risk factor for psychotic disorders. We aimed to compare the proportions of hospitalizations for psychotic disorders in the 12 months following discharge from hospital for either COVID-19 or for another reason in the adult general population in France during the first wave of the pandemic. We conducted a retrospective longitudinal nationwide study using the national French administrative healthcare database. Psychotic disorders were first studied as a whole, and then chronic and acute disorders separately. The role of several adjustment factors, including sociodemographics, a history of psychotic disorder, the duration of the initial hospitalization, and the level of care received during that hospitalization, were also analyzed. Between 1 January 2020 and 30 June 2020, a total of 14,622 patients were hospitalized for psychotic disorders in the 12 months following discharge from hospital for either COVID-19 or another reason. Initial hospitalization for COVID-19 (vs. another reason) was associated with a lower rate of subsequent hospitalization for psychotic disorders (0.31% vs. 0.51%, odds ratio (OR) = 0.60, 95% confidence interval (CI) [0.53-0.67]). This was true for both chronic and acute disorders, even after adjusting for the various study variables. Importantly, a history of psychotic disorder was a major determinant of hospitalization for psychotic disorders (adjusted OR = 126.56, 95% CI [121.85-131.46]). Our results suggest that, in comparison to individuals initially hospitalized for another reason, individuals initially hospitalized for COVID-19 present a lower risk of hospitalization for first episodes of psychotic symptoms/disorders or for psychotic relapse in the 12 months following discharge. This finding contradicts the hypothesis that there is a higher risk of psychotic disorders after a severe COVID-19.

Precarious Young Adults' Mental Health during the Pandemic: The Major Impact of Food Insecurity Independently of COVID-19 Diagnosis.

The COVID-19 pandemic had a major impact on mental health across populations, especially young and precarious people. Furthermore, COVID-19 diagnosis itself has been associated with psychiatric symptoms. However, only a few studies have assessed the mental health of precarious youth, and examined a possible association with food insecurity, while including COVID-19 diagnosis in their analyses. We aimed to determine the prevalence of poor mental health in precarious youth during the COVID-19 pandemic, and to investigate its possible association with food insecurity, independently of COVID-19 diagnosis. In a cross-sectional study conducted in the context of an employment program for precarious youth (18-25 years) living in Paris, France, 823 individuals were assessed for depression, anxiety, subjective distress and food insecurity during the second lockdown of 2020. A directed acyclic graph (DAG)-based approach was used to identify confounders for inclusion in a multivariate regression model. Of the 823 precarious youth, 45.93% reported significant symptoms of depression, 36.69% anxiety, 39% distress and 25.39% suicidal ideation. In the multivariate analysis based on DAG, food insecurity (less than one meal per day) was associated with depression (OR = 2.30; CI%: 1.19-4.51), anxiety (OR = 2.51; CI%: 1.29-4.88), distress (OR = 2.36; CI%: 1.23-4.57) and suicidal ideation (OR = 4.81; CI%: 2.46-9.44), independently of age, gender, education, COVID-19 contact and COVID-19 diagnosis. This study highlights the importance of food insecurity on mental health among young precarious people during the COVID-19 pandemic. Reducing food insecurity is essential to help reduce psychological distress.

A complex relation between levels of adult hippocampal neurogenesis and expression of the immature neuron marker doublecortin.

We investigated the mechanisms underlying the effects of the antidepressant fluoxetine on behavior and adult hippocampal neurogenesis (AHN). After confirming our earlier report that the signaling molecule ß-arrestin-2 (ß-Arr2) is required for the antidepressant-like effects of fluoxetine, we found that the effects of fluoxetine on proliferation of neural progenitors and survival of adult-born granule cells are absent in the ß-Arr2 knockout (KO) mice. To our surprise, fluoxetine induced a dramatic upregulation of the number of doublecortin (DCX)-expressing cells in the ß-Arr2 KO mice, indicating that this marker can be increased even though AHN is not. We discovered two other conditions where a complex relationship occurs between the number of DCX-expressing cells compared to levels of AHN: a chronic antidepressant model where DCX is upregulated and an inflammation model where DCX is downregulated. We concluded that assessing the number of DCX-expressing cells alone to quantify levels of AHN can be complex and that caution should be applied when label retention techniques are unavailable.

Male Victims of Sexual Abuse: Impact and Resilience Processes, a Qualitative Study.

The increasing prevalence of sexual abuse calls for exceptional awareness of its multidimensional impact on the mental, sexual, and social wellbeing of male adults. This study aims to deepen the overall understanding of sexual abuse consequences; to highlight some common resilience factors; and to strengthen therapeutic and social support. In this qualitative research, we conducted seven semi-structured interviews with male victims of sexual violence. The data were analysed with the interpretative phenomenological analysis. They shed light on the great suffering linked to sexual violence, and on seven themes which are seemingly pillars of resilience: bond to others, bond to the body, making sense of things, expression, rediscovering oneself, institutions, and finally, learning and commitment. The exploration of these themes reveals several avenues for adjusting care, most of which imply the importance of raising awareness so that spaces receiving the victims' word can emerge.

[Post-COVID-19 syndrome]. / Syndrome post-COVID-19.

In the aftermath of acute infection with the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a large number of symptoms persist or appear, constituting a real syndrome called "long COVID-19" or "post-COVID- 19" or "post-acute COVID-19 syndrome". Its incidence is very high, half of patients showing at least one symptom at 4-6 months after Coronarovirus infectious disease 2019 (COVID-19). They can affect many organs. The most common symptom is persistent fatigue, similar to that seen after other viral infections. Radiological pulmonary sequelae are relatively rare and not extensive. On the other hand, functional respiratory symptoms, primarily dyspnoea, are much more frequent. Dysfunctional breathing is a significant cause of dyspnoea. Cognitive disorders and psychological symptoms are also very common, with anxiety, depression and post-traumatic stress symptoms being widely described. On the other hand, cardiac, endocrine, cutaneous, digestive or renal sequelae are rarer. The symptoms generally improve after several months, even if their prevalence at two years remains significant. Most of the symptoms are favored by the severity of the initial illness, and the psychic symptoms by the female sex. The pathophysiology of most symptoms is poorly understood. The influence of the treatments used in the acute phase is also important. Vaccination, on the other hand, seems to reduce their incidence. The sheer number of affected patients makes long-term COVID-19 syndrome a public health challenge.

A systematic review of the factors associated with suicide attempts among sexual-minority youth

Background and objectives: Recent literature reported a higher risk of suicide attempts among sexual minority youth. Discovering the risk and protective factors of suicide attempts among this vulnerable population can play a key role in reducing the suicide rate. Our research aims to systematically search for the risk and protective factors for suicide attempts among sexual minority youth.MethodsWe have conducted a systematic review of published studies of associated factors for suicide attempts in sexual minority youth. Four databases up to 2020 were searched to find relevant studies.ResultsTwelve articles were included. For sexual minority youth, the identified risk factors associated with suicide attempts are early coming out, being unacceptable by families, dissatisfaction with sexual minority friendships, too few friends, physical abuse, sexual abuse, and bullying. The identified protective factors for suicide attempts are feeling safe at school, teacher support, anti-bullying policy, and other adult support.ConclusionBoth risk and protective factors for suicide attempts stem directly from the environments in which youth grew up: family, school, and the internet. Effective preventive measures among sexual minority youth need to be developed and implemented. Societal-level anti-stigma interventions are needed to reduce the risk of victimization and awareness should be raised among family and friends. (AU)

Intrahippocampal injection of a selective blocker of NMDA receptors containing the GluN2B subunit, Ro25-6981, increases glutamate neurotransmission and induces antidepressant-like effects.

Major depressive disorder (MDD) is a serious public health problem, as it is the most common psychiatric disorder worldwide. Antidepressant drugs increase adult hippocampal neurogenesis, which is required to induce some behavioral effects of antidepressants. Adult-born granule cells in the dentate gyrus (DG) and the glutamate receptors subunits 2 (GluN2B) subunit of N-methyl-D-aspartate (NMDA) ionotropic receptors play an important role in these effects. However, the precise neurochemical role of the GluN2B subunit of the NMDA receptor on adult-born GCs for antidepressant-like effects has yet to be elucidated. The present study aims to explore the contribution of the GluN2B-containing NMDA receptors in the ventral dentate gyrus (vDG) to the antidepressant drug treatment using a pharmacological approach. Thus, (αR)-(4-hydroxyphenyl)-(ßS)-methyl-4-(phenylmethyl)-1-piperidinepropanol (Ro25-6981), a selective antagonist of the GluN2B subunit, was acutely administered locally into the ventral DG (vDG, 1 µg each side) following a chronic fluoxetine (18 mg/kg/day) treatment-known to increase adult hippocampal neurogenesis-in a mouse model of anxiety/depression. Responses in a neurogenesis-dependent task, the novelty suppressed feeding (NSF), and neurochemical consequences on extracellular glutamate and gamma-aminobutyric acid (GABA) levels in the vDG were measured. Here, we show a rapid-acting antidepressant-like effect of local Ro25-6981 administration in the NSF independent of fluoxetine treatment. Furthermore, we revealed a fluoxetine-independent increase in the glutamatergic transmission in the vDG. Our results suggest behavioral and neurochemical effects of GluN2B subunit independent of serotonin reuptake inhibition.

Association between car driving and successful ageing. A cross sectional study on the "S.AGES" cohort.

BACKGROUND: Assessing successful ageing (SA) is essential to identify modifiable factors in order to enforce health promotion and prevention actions. SA comprises 3 dimensions: an active engagement with life, a low probability of disease and disease-related disability, and a high cognitive and physical functional capacity. Driving seems to be linked to SA as it is a mean to preserve social interactions and requires preserved functional and cognitive status. This study aims to investigate whether driving status can be considered a proxy of SA, by describing determinants associated with driving status in the 65+. METHODS: This cross-sectional study is ancillary to the S.AGES (Sujets AGÉS-Aged Subjects) study, an observational prospective cohort study which included patients suffering from chronic pain, type-2 diabetes mellitus or atrial fibrillation from 2009 to 2014. SA was defined by the success of three dimensions: physiological comprised of comorbidity and autonomy scores, psychological comprised of cognitive status and emotional state, and a social dimension. RESULTS: 2,098 patients were included of whom 1,226 (58.4%) reported being drivers. 351/2,092 (16.7%) were classified as successful agers: 292/1,266 (23.8%) in the driver group vs. 59/872 (6.8%) in the non-driver group; p < .001. In the final logistic model, after adjustment for relevant variables, SA was associated with driver status OR 1.94 [1.36-2.77]. CONCLUSION: Driving may be considered as a proxy to SA: it reflects elders' independence, cognitive ability and a means to maintain social interactions. To preserve their mobility and enable them to achieve SA, regular screening of driving skills, specific rehabilitation programs are needed. Moreover development and communication on special transports services, communal rides or even driverless car to avoid apprehension around older adults driving could be solutions.