Childhood maltreatment and clinical severity of treatment-resistant depression in a French cohort of outpatients (FACE-DR): One-year follow-up.

BACKGROUND: Childhood maltreatment is associated with major depressive disorder (MDD). It not only increases the risk of lifetime MDD, but it also aggravates its course. Among depressed patients, 20-30% of them experience treatment-resistance depression (TRD). We aimed to assess the association between childhood maltreatment, severity of depression in a unipolar TRD sample, and patient outcomes after one-year of follow-up. METHODS: Patients were recruited for a prospective cohort from the French network of TRD expert centers. Depressive symptom severity was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology self-report (QIDS-SR). Childhood maltreatment was evaluated with the Childhood Trauma Questionnaire (CTQ). RESULTS: In total, 256 patients filled in the CTQ at baseline between 2012 and 2019. At baseline, the MADRS score was associated with CTQ score (ß = .185; p = .004). QIDS was also associated with CTQ scores (ß = .27; p < .001). Regarding the different subtypes of childhood maltreatment, MADRS was associated with physical (ß = .21; p = .005) and sexual abuse (ß = .22; p = .002), while QIDS with physical abuse (ß = .304; p < .001) and physical neglect (ß = .254; p < .001). However, we did not find any significant association focusing on the other types of traumas. During a 1-year follow-up focusing on remission, CTQ scores (baseline) were less important in remittent patients [n = 38; CTQ score = 39.26 (9.68)] than in nonremittent ones [n = 92; CTQ score = 46.02 (17.53)] (p = .027). There was no significant difference among remitters and nonremitters based on trauma subtypes. At baseline, CTQ scores had a significant influence on remission at 1 year (χ2 (1) = 5.57; p < .05). We lost this influence adding MADRS scores at baseline in the model (p = .063). CONCLUSION: We highlighted a significant association between the severity of depressive disorders and childhood maltreatment in the TRD population. Information about a history of childhood maltreatment helps in identifying individuals who could be less likely to go into remission after treatment.

Attitudes of family physicians towards adolescent cannabis users: a qualitative study in France.

BACKGROUND: GPs are the health professionals most frequently consulted by adolescents. However, discussion between GPs and adolescents regarding cannabis use does not occur spontaneously. OBJECTIVE: To identify obstacles to the identification and management of cannabis use by adolescents based on GPs' experiences. METHODS: We conducted a qualitative study using focus groups of GPs from the Auvergne area (France). The GPs were selected according to descriptive and strategic variables. Three researchers--an anthropologist, a psychiatrist with expertise in addiction and a GP--performed a thematic analysis. RESULTS: Twenty-four GPs participated in three consecutive focus groups. The GPs were aware of the health risks of cannabis, yet ambivalent about its use by adolescents. The GPs also reported a lack of patient questioning during consultation. The obstacles to the identification and treatment of cannabis use by adolescents identified included lack of GP knowledge about cannabis (e.g. consumption patterns and laws); difficulties in addressing the issue with adolescents, evaluating adolescents' consumption and its impact and proposing support and follow-up and the presence of parents. The GPs were aware that their role lies at the intersection between the medical, personal, familial and social fields. CONCLUSION: Despite these barriers, GPs are willing to ask adolescents about their cannabis use. An adolescent's awareness, environment and receptiveness favour a sustainable therapeutic relationship. Brief intervention is a tool that may be of assistance in this relationship and allow GPs to take the initiative.

Predictors of relapse in a study of duloxetine treatment for patients with generalized anxiety disorder.

OBJECTIVE: Data from a relapse prevention study of duloxetine treatment for adults with generalized anxiety disorder (GAD) were examined to identify predictors of relapse. METHODS: Patients responding to 6 months of open-label duloxetine treatment were randomized to continuation with duloxetine or withdrawal to placebo for a 6-month double-blind continuation phase (duloxetine, N= 216; placebo, N= 213). Post hoc analyses compared time to GAD relapse during continuation phase by using predictor variables that included patient demographics, symptom severity measures (Hamilton Anxiety Scale Scores [HAMA], Hospital Anxiety and Depression Scale), functional outcomes, and visual analogue scale (VAS) pain measures. Univariate and multivariate analyses were performed using predictor variables from time of randomization into the continuation, withdrawal phase. RESULTS: Severity of anxiety symptoms, degree of functional impairment, and severity of pain at time of randomization were significantly predictive of likelihood of relapse during the continuation phase. Multivariate backwards elimination analysis of significant univariate predictors identified HAMA item one (anxious mood) ≥ 1 and severity of pain while awake (≥ 30 on VAS) as the strongest predictors of GAD relapse. CONCLUSIONS: For patients with GAD responding to open-label treatment with duloxetine, residual symptoms related to anxious mood, pain severity, and psychosocial function were associated with increased relapse risk, although the greatest risk was associated with anxious mood and increased severity of pain while awake.

Influence of Clinical Markers of Dopaminergic Behaviors on Depressive Symptoms During Withdrawal in Cocaine Users.

Background: During cocaine withdrawal, transient depressive symptoms that do not meet the criteria for depression, but promote relapse, are frequently observed. Their temporality could evoke a role of dopamine, especially since the underlying mechanism of these depressive symptoms is not well understood. We hypothesized that variation in the dopaminergic activity profile, modeled from clinical markers, could be implicated in the development of depressive symptoms during cocaine withdrawal. Methods: We compared patients reporting depressive symptoms (RDS+) or not (RDS-) during cocaine withdrawal. We evaluated dopaminergic activity through indirect clinical markers based on the known dopaminergic behaviors. A combined criterion was constructed for hyper and hypo dopaminergic models according to the O'Brien method and illustrated by the Hedges' effect-size and forest-plot graph. A multidimensional factorial analysis was carried out to determine which parameters discriminate RDS+/RDS- patients. Results: 313 patients were included, and 77% reported depressive symptoms during cocaine withdrawal. Hyperdopaminergic variables used to discriminate the two groups had a large overall effect size (-0.669) and included psychotic symptoms (-0.524), hallucinations (-0.548), and delusions (-0.528). The overall effect of the hypodopaminergic component was considerable (-0.604) with a large effect size for the severity of dependence (-0.616), withdrawal symptoms (-0.578), and anhedonia (-0.528). The combined model including hyperdopaminergic and hypodopaminergic components had the largest effect size (-0.785). Conclusion: The dopaminergic activities profile, assessed by indirect clinical markers, seems to characterize patients with depressive symptoms very well during cocaine withdrawal. RDS+ patients reported moreover higher levels of psychotic symptoms and more severe cocaine use disorder than RDS-.

Motivational properties of D2 and D3 dopamine receptors agonists and cocaine, but not with D1 dopamine receptors agonist and L-dopa, in bilateral 6-OHDA-lesioned rat.

Dopamine dysregulation syndrome in Parkinson's disease (PD) has been attributed to dopamine replacement therapy (DRT). We hypothesize that DRT can induce a potential rewarding effect in an animal model of PD. Using the conditioned place preference (CPP) paradigm, we investigated the motivational effects of L-dopa, dopamine receptor agonists (DRAs), and cocaine in rat with a bilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. In 6-OHDA animals, D1 receptors agonist (SKF81297) revealed significantly a conditioned place aversion (CPA) at 3 mg/kg and 9 mg/kg doses. D2 receptors agonist (bromocriptine) induced both CPP and CPA at 1 mg/kg and 10 mg/kg doses respectively. D3 receptors agonist (PD128907) induced a CPP only at 1 mg/kg, comparable to that of cocaine. Sham animals revealed biphasic CPP curves, with significant dose effect, for the intermediate dose of the 3 DRAs. However, L-dopa induced no significant effect while cocaine induced CPP in both lesioned and sham animals. In conclusion, this study confirms the predominant roles of D2R class, and most specifically D3R subtypes, in rewarding properties of DRT.

GC-MS determined cotinine in an epidemiological study on smoking status at delivery.

The objective of this study was to measure the plasma cotinine levels in pregnant women and their newborns using a gas chromatography-mass spectrometry (GC-MS) method in an epidemiological-delivered population with a wide range of tobacco intakes. Nearly 1000 pregnant women from regional maternity wards (n=1007) were selected for the study. Each patient kept a tobacco diary and underwent a blood test to assess cotinine levels and at the same time that the newborns' cordonal plasma was taken. These values were then cross-checked. Cotinine was estimated using a selected-ion monitoring mode with a 1.5 ng/ml quantification limit. The cotinine levels in mothers and newborns were highly correlated, whatever the mother's smoking status, with a calculated cut-off for cotinine levels in active smokers of 21.5 ng/ml. Finally, the cotinine determined through this GC-MS method offered a sensitive and accurate measure of tobacco exposition of the pregnant women and their babies.