A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking

Neuroendocrine studies in schizophrenia An approach to pathophysiological mechanisms

SIGLEAvailable from British Library Lending Division - LD:D53268/85 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Thioridazine and sudden unexplained death in psychiatric patients

Background Sudden death has been linked to antipsychotic therapy, but the relative risk associated with specific drugs is unknown. Aims To assess the risk of sudden unexplained death associated with antipsychotic drug therapy and its relation to drug dose and individual agents. Method A case—control study of psychiatric in-patients dying suddenly in five hospitals in the north-east of England and surviving controls matched for age, gender and mental disorder. Logistic regression analysis was used to identify significant risk factors, and odds ratios were calculated. Results Sixty-nine case—control clusters were identified. Probable sudden unexplained death was significantly associated with hypertension, ischaemic heart disease and current treatment with thioridazine (adjusted odds ratio=5.3, 95% CI 1.7-16.2, P=0.004). There was no significant association with other individual antipsychotic drugs. Conclusions Thioridazine alone was associated with sudden unexplained death, the likely mechanism being drug induced arrythmia

Processing of Facial Emotion in Bipolar Depression and Euthymia

Previous studies of facial emotion processing in bipolar disorder (BD) have reported conflicting findings. In independently conducted studies, we investigate facial emotion labeling in euthymic and depressed BD patients using tasks with static and dynamically morphed images of different emotions displayed at different intensities. Study 1 included 38 euthymic BD patients and 28 controls. Participants completed two tasks: labeling of static images of basic facial emotions (anger, disgust, fear, happy, sad) shown at different expression intensities; the Eyes Test (Baron-Cohen, Wheelwright, Hill, Raste, & Plumb, 2001), which involves recognition of complex emotions using only the eye region of the face. Study 2 included 53 depressed BD patients and 47 controls. Participants completed two tasks: labeling of “dynamic” facial expressions of the same five basic emotions; the Emotional Hexagon test (Young, Perret, Calder, Sprengelmeyer, & Ekman, 2002). There were no significant group differences on any measures of emotion perception/labeling, compared to controls. A significant group by intensity interaction was observed in both emotion labeling tasks (euthymia and depression), although this effect did not survive the addition of measures of executive function/psychomotor speed as covariates. Only 2.6–15.8% of euthymic patients and 7.8–13.7% of depressed patients scored below the 10th percentile of the controls for total emotion recognition accuracy. There was no evidence of specific deficits in facial emotion labeling in euthymic or depressed BD patients. Methodological variations—including mood state, sample size, and the cognitive demands of the tasks—may contribute significantly to the variability in findings between studies. (JINS, 2015, 21, 709–721

DISC1 exon 11 rare variants found more commonly in schizoaffective spectrum cases than controls

We previously performed a linkage study using families identified through probands meeting criteria for DSM-IV schizoaffective disorder, bipolar type (SABP) and observed a genome-wide significant signal (LOD = 3.54) at chromosome 1q42 close to DISC1. An initial sequencing study of DISC1 using 14 unrelated DSM-IV SABP samples from the linkage study identified 2 non-synonymous coding SNPs in exon 11 in 2 separate individuals. Here we provide evidence of additional rare coding SNPs within exon 11. In sequencing exon 11 in 506 cases and 1,211 controls for variants that occurred only once, 4 additional rare variants were found in cases (P-value = 0.008, Fisher's exact trend test)