Social contexts of depression

This thesis documents the meaning of depression for 80 people living in the inner Western suburbs of Sydney in the late 1980’s. It also documents the views of 20 general practitioners who practised in those suburbs. Accounts of depression have always been controversial. Different disciplines put forward varied explanations and prescriptions about treatment. Despite the apparent proliferation of research into the area of depression, limited attention has been given to the social context of depressed respondents’ lives. In this Sydney study, however, a combination of clinical and social criteria were used to make sense of the 80 respondents’ experience of depression. The meaning of social context and the notion, ‘impaired social functioning’, were analysed in terms of a mixture of respondents’ positive and negative experiences at work, in relationships and with reference to social conditions. For all 80 respondents, role performance was impaired in at least one area. The label ‘no relief in sight’ describes those respondents who felt that work, relationships and social conditions contributed to their depression. The notion ‘highly vulnerable’ draws together the experiences of 43 (54%) whose role performance was impaired in two out of three areas. The term ‘not so vulnerable’ identifies the 31 (39%) who had been functioning, in their terms, ‘below par’, or ‘at a low ebb’ in one specific area. General practitioners’ views of depression and of the conditions which affected their ability to treat depressed people were examined. These doctors’ adherence to a View of their practice as a scientific endeavour, and the fee-for-service arrangement for paying doctors discouraged them from considering social issues. From the 80 respondents’ perspective, issues raised about treatment, both medical and non-medical, ranged from apparent willingness to seek medical help to reluctance to do so and a reliance on self-remedies. Respondents’ accounts of non-medical treatment ranged from confiding in one key person to collective social endeavours, from physical activities to self-medication. Although respondents’ experiences of depression were rooted in the constraints of context, their remedies were individualised attempts to help them ‘feel better’. Social problems were as difficult for respondents to remedy, - hence the reliance on individual solutions, as they were for doctors to discuss, let alone treat. The non-medical professionals’ response, as identified by these respondents, was also of the ‘quick fix’ nature. Individuals were regarded as responsible for their condition, a point of view which did not match the respondents’ experiences of depression. They explained depression as a response not only to personal difficulties but also to the consequences of what they saw as debilitating social and economic policies. In any future deliberations about the nature of depression, it would be helpful to conceptualise ‘treatment’ in terms of an educational experience. The reconstruction of that experience would produce a contrast to individualised remedies and a real alternative to traditional forms of medical intervention

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Selective Manganese-Catalyzed Semihydrogenation of Alkynes with in-situ Generated H2 from KBH4 and Methanol

The selective semihydrogenation of alkynes with the Mn(I) alkyl catalyst fac-[Mn(dippe)(CO)3(CH2CH2CH3)] (dippe = 1,2-bis(di-iso-propylphosphino)ethane) as pre-catalyst is described. Hydrogen gas required for the hydrogenation is generated in situ upon alcoholysis of KBH4 with methanol. A series of aryl-aryl, aryl-alkyl, alkyl-alkyl and terminal alkynes were readily hydrogenated to yield E-alkenes in good to excellent isolated yields. The reaction proceeds at 90°C with catalyst loadings of 0.5 -2 mol%. The implemented protocol tolerates a variety of electron donating and electron withdrawing functional groups including halides, phenols, nitriles, unprotected amines and heterocycles. The reaction can be upscaled to the gram scale. Mechanistic investigations including deuterium labelling studies and DFT calculations were undertaken to provide a reasonable reaction mechanism showing that initially formed Z-isomer undergoes fast isomerization to afford the thermodynamically more stable E-isomer

PASCAL versus MitraClip-XTR edge-to-edge device for the treatment of tricuspid regurgitation: a propensity-matched analysis

Background!#!Transcatheter tricuspid valve repair (TTVR) is a promising technique for the treatment of tricuspid regurgitation (TR). Data comparing the performance of novel edge-to-edge devices (PASCAL and MitraClip-XTR) are scarce.!##!Methods!#!We identified 80 consecutive patients who underwent TTVR using either the PASCAL or MitraClip-XTR system to treat symptomatic TR from July 2018 to June 2020. To adjust for baseline imbalances, we performed a propensity score (PS) 1:1 matching. The primary endpoint was a reduction in TR severity by at least one grade at 30 days.!##!Results!#!The PS-matched cohort (n = 44) was at high-surgical risk (EuroSCORE II: 7.5% [interquartile range (IQR) 4.8-12.1%]) with a mean TR grade of 4.3 ± 0.8 and median coaptation gap of 6.2 mm [IQR 3.2-9.1 mm]. The primary endpoint was similarly observed in both groups (PASCAL: 91% vs. MitraClip-XTR: 96%). Multiple device implantation was the most common form (59% vs. 82%, p = 0.19), and the occurrence of SLDA was comparable between the PASCAL and MitraClip-XTR system (5.7% [2 of 35 implanted devices] vs. 4.4% [2 of 45 implanted devices], p = 0.99). No periprocedural death or conversions to surgery occurred, and 30-day mortality (5.0% vs. 5.0%, log-rank p = 0.99) and 3-month mortality (10.0% vs. 5.0%, log-rank p = 0.56) were similar between both groups. During follow-up, functional NYHA class, 6-min walking distance, and health status improved in both groups.!##!Conclusions!#!Both TTVR devices, PASCAL and MitraClip-XTR, appeared feasible and comparable for an effective TR reduction. Randomized head-to-head comparisons will help to further define the appropriate scope of application of each system