Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used psychopharmaceutical treatment for major depressive disorder (MDD), but individual responses to SSRIs vary greatly. CYP2C19 is a key enzyme involved in the metabolism of several drugs, including SSRIs. Variations in the CYP2C19 gene are associated with differential metabolic activity, and thus differential SSRI exposure; accordingly, the CYP2C19 genotype may affect the therapeutic response and clinical outcomes, though existing evidence of this link is not entirely consistent. Therefore, we analysed data from the UK Biobank, a large, deeply phenotyped prospective study, to investigate the effects of CYP2C19 metaboliser phenotypes on several clinical outcomes derived from primary care records, including multiple measures of antidepressant switching, discontinuation, duration, and side effects. In this dataset, 24,729 individuals were prescribed citalopram, 3012 individuals were prescribed escitalopram, and 12,544 individuals were prescribed sertraline. Consistent with pharmacological expectations, CYP2C19 poor metabolisers on escitalopram were more likely to switch antidepressants, have side effects following first prescription, and be on escitalopram for a shorter duration compared to normal metabolisers. CYP2C19 poor and intermediate metabolisers on citalopram also exhibited increased odds of discontinuation and shorter durations relative to normal metabolisers. Generally, no associations were found between metabolic phenotypes and proxies of response to sertraline. Sensitivity analyses in a depression subgroup and metabolic activity scores corroborated results from the primary analysis. In summary, our findings suggest that CYP2C19 genotypes, and thus metabolic phenotypes, may have utility in determining clinical responses to SSRIs, particularly escitalopram and citalopram, though further investigation of such a relationship is warranted.

Psychiatric disorder management is based on the prescription of psychotropic drugs. Response to them remains often insufficient and varies from one patient to another. Pharmacogenetics explain part of this variability. Pharmacogenetic testing is likely to optimize the choice of treatment and thus improve patients’ care, even if concerns and limitations persist. This practice of personalized medicine is not very widespread in France. We conducted a national survey to evaluate the acceptability of this tool by psychiatrists and psychiatry residents in France, and to identify factors associated with acceptability and previous use. The analysis included 397 observations. The mean acceptability score was 10.70, on a scale from 4 to 16. Overall acceptability score was considered as low for 3.0% of responders, intermediate for 80.1% and high for 16.9%. After regression, the remaining factors influencing acceptability independently of the others were prescription and training history and theoretical approach. The attitude of our population seems to be rather favorable, however, obvious deficiencies have emerged regarding perceived skills and received training. Concerns about the cost and delays of tests results also emerged. According to our survey, one of the keys to overcoming the barriers encountered in the integration of pharmacogenetics seems to be the improvement of training and the provision of information to practitioners.

Advances in genetic applications within psychiatry offer promising benefits in diagnosis, treatment personalization, and risk prediction. However, ethical concerns-such as fear of discrimination and eugenics-and limited awareness hinder their widespread adoption. This review aims to evaluate the attitudes of psychiatric patients and their relatives toward genetics in psychiatry and to identify the key factors that influence these perceptions. A systematic review and meta-analysis adhering to PRISMA guidelines was performed across databases including PubMed, Scopus, and CINAHL up to February 2024. Studies exploring attitudes toward genetics in psychiatry among patients and relatives were included; their quality was assessed using the Quality Assessment Tool for Diverse Studies tool. A qualitative meta-synthesis identified themes, whereas a meta-analysis estimated favorable attitudes. Seventy studies examined applications such as predictive testing, pharmacogenetics, and genetic counseling. Overall, 80% (95% CI = 0.72 to 0.87) expressed favorable attitudes toward genetic testing. Notable barriers included concerns about discrimination, limited knowledge, and ethical issues related to prenatal testing. Although genetic counseling was positively received, its use remained limited due to lack of awareness. Despite the promise genetics holds for psychiatry, addressing technical, ethical, and educational challenges is essential for wider acceptance. Future research should focus on underserved populations and prioritize enhancing genetic counseling and professional education to support the responsible integration of genetic advancements.

Background: Adults with mood and/or anxiety disorders have increased risks of comorbidities, chronic treatments and polypharmacy, increasing the risk of drug–drug interactions (DDIs) with antidepressants. Aims: To use primary care records from the UK Biobank to assess DDIs with citalopram, the most widely prescribed antidepressant in UK primary care. Method: We classified drugs with pharmacokinetic or pharmacodynamic DDIs with citalopram, then identified prescription windows for these drugs that overlapped with citalopram prescriptions in UK Biobank participants with primary care records. We tested for associations of DDI status (yes/no) with sociodemographic and clinical characteristics and with cytochrome 2C19 activity, using univariate tests, then fitted multivariable models for variables that reached Bonferroni-corrected significance. Results: In UK Biobank primary care data, 25 508 participants received citalopram prescription(s), among which 11 941 (46.8%) had at least one DDI, with an average of 1.96 interacting drugs. The drugs most commonly involved were proton pump inhibitors (40% of co-prescription instances). Individuals with DDIs were more often female and older, had more severe and less treatment-responsive depression, and had higher rates of psychiatric and physical disorders. In the multivariable models, treatment resistance and markers of severity (e.g. history of suicidal and self-harm behaviours) were strongly associated with DDIs, as well as comorbidity with cardiovascular disorders. Cytochrome 2C19 activity was not associated with the occurrence of DDIs. Conclusions: The high frequency of DDIs with citalopram in fragile groups confirms the need for careful consideration before prescribing and periodic re-evaluation.

Bien que la turbulence soit connue pour sa capacité à disperser efficacement la matière, des particules inertielles transportées par un écoulement turbulent n’explorent pas toutes ses régions de manière homogène. Au cours de cette thèse, deux études expérimentales ont ainsi permis d’aborder le problème de l’exploration préférentielle de particules plus denses que le fluide porteur.Dans un premier dispositif expérimental, la distribution spatiale de billes en polyamide ou en polyacétal de tailles comparables à l’échelle intégrale de la turbulence, transportées par un écoulement tourbillonnaire fermé à grands nombres de Reynolds, a été étudiée. Ces particules étant plus denses que le fluide porteur, leur dynamique est pilotée par la compétition entre l’agitation turbulente et l’effet de la gravité. Lorsque la fréquence de rotation du disque qui engendre l’écoulement est faible, la sédimentation des billes domine leur resuspension par la turbulence de telle sorte qu’elles restent confinées en bas de la cuve. À partir d’une certaine fréquence de rotation, les fluctuations turbulentes surpassent l’effet de la gravité et les particules explorent l’entièreté de la boîte. Cependant, deux comportements extrêmement différents apparaissent en fonction de la taille des billes. Alors que les plus petites sont distribuées de façon presque homogène, les plus grosses se trouvent préférentiellement dans la partie supérieure, comme si la gravité avait été inversée. Ce piégeage trouve son origine dans le fait que ces dernières sont trop grosses pour atteindre les zones descendantes de l’écoulement situées dans les coins et ne retombent donc que très rarement vers le bas.Un second dispositif expérimental a été construit dans lequel un écoulement turbulent est généré dans une tour par un réseau de jets orientés vers le haut, s’allumant et s’éteignant de façon aléatoire. Un tel forçage permet de minimiser l’existence d’un écoulement moyen tout en garantissant d’importantes fluctuations de vitesse, mais une décroissance spatiale de la turbulence est observée en s’éloignant des jets. Cet écoulement a permis l’étude de l’altération de la vitesse de sédimentation de particules en verre de tailles légèrement supérieures à l’échelle dissipative par la turbulence. En s’appuyant sur une mesure simultanée des propriétés de l’écoulement et des trajectoires des particules inertielles au cours de leur chute, il a été possible de mettre directement en évidence que les billes explorent préférentiellement les régions descendantes de la turbulence. Il en résulte que leur vitesse de sédimentation est accrue d’autant plus fortement que l’intensité de la turbulence est grande et que la taille de la particule est petite.

Background: Sensory processing difficulties are increasingly recognized in major depressive disorder (MDD), with patients often exhibiting heightened sensitivity, avoidance, and low registration. However, the temporal stability of these patterns—trait vs. state—remains unclear. Methods: In this longitudinal study, 45 adult inpatients with MDD were assessed using the Adolescent/Adult Sensory Profile (AASP) at admission and 3 months later; 34 completed both assessments. Clinical variables included depression (Hamilton Depression Rating Scale [HDRS‐17]), anxiety (Hamilton Anxiety Rating Scale [HARS]), anhedonia (Snaith‐Hamilton Pleasure Scale [SHAPS]), self‐esteem (Rosenberg Self‐Esteem Inventory [RSEI]), and psychomotor retardation (Clinical Outcomes in Routine Evaluation [CORE]). Nonparametric tests examined sensory changes and associations with clinical outcomes. Results: At follow‐up, 61.8% of participants showed clinical improvement and 44.1% achieved remission. Significant decreases in low registration and sensory sensitivity, along with increased sensation seeking, indicated that sensory processing is dynamic and partially state‐dependent. Sensory avoidance remained stable and was more pronounced in recurrent MDD. Patients with clinical improvement or remission had sensory profiles closer to normative ranges. Higher sensitivity and avoidance correlated with more severe depression, anxiety, and lower self‐esteem, while greater sensation seeking was associated with better outcomes. Conclusions: Sensory processing profiles in MDD are state‐dependent and linked to clinical changes. These findings support the relevance of sensory traits as potential clinical markers and therapeutic targets. Personalized interventions addressing sensory processing may contribute to improved treatment outcomes. Further longitudinal and multimodal research is needed to clarify their predictive value. Trial Registration: ClinicalTrials.gov identifier: NCT05686668