First-episode affective psychoses: exploring specific clinical features in order to adapt early intervention strategies

Backgroung: Affective psychosis is a conceptual grouping used in clinical practice that lacks strong scientific basis. It includes patients who, in addition to psychosis, have a mood disorder. While early intervention has shown great efficacy, it mainly focuses on schizophrenia spectrum disorders, neglecting the affective forms of psychosis. Thus, this PhD thesis aims to study the relevance of the concept of affective psychosis in early intervention and its usefulness in developing stratification strategies. Method: These aims are addressed in two ways through four chapters, first through a literature review and then in the frame of three prospective studies conducted in a sample a first episode psychosis patients treated at the Treatment and early intervention in psychosis programme (TIPP) in Lausanne (Switzerland). The first chapter investigates literature on first-episode affective psychoses, outlining its specific clinical features and challenges. The second chapter explores the differences between affective and non-affective psychosis patients. The third chapter explores to which degree the various diagnostic categories included in the affective psychosis subgroup have sufficient commonalities to justify this grouping. Finally, the fourth chapter explores premorbid-based stratification strategies within affective psychoses to identify subgroups of patients that may require specific early intervention strategies. Results: Studies 1, 2, and 3 confirm the relevance of using the conceptual grouping of affective psychoses. Study 4 shows that the concept of affective psychoses regroups patients with various premorbid profiles that may require specific pharmacological and psychosocial treatment adjustment. Conclusion: This PhD thesis provides further evidence for the need of developing research in early intervention using the concept of affective psychosis, and points out clinical characteristics that may be used as therapeutic targets to develop adapted early intervention strategies for these patients

Evidence of mediation of severity of anxiety and depressive symptoms between abuse and positive symptoms of psychosis

Considerable evidence on general population suggests that an "Affective pathway to psychosis", involving depression and anxiety dimensions, mediates the abuse-psychosis association. However, this has never been tested in Early Psychosis (EP) patients. We aim at testing whether severity of depressive and anxiety mediates the abuse-positive symptoms dyad in an EP prospective sample. 330 EP subjects aged 18-35 were assessed for psychopathology after 2, 6, 12, 18, 24, 30, and 36 months of treatment. Abuse was considered as facing at least one experience of physical, sexual, or emotional abuse before age 16. Positive psychotic symptoms and anxiety were measured with the Positive and Negative Syndrome Scale and depressive symptoms with the Montgomery-Asberg Depression Rating Scale. Mediation analyses were performed to study whether the abuse-positive symptom's link was mediated by depressive, anxiety, and a combination of anxiety/mood symptoms. Among the 330 EP patient included, 104 (31.5% of the total) were exposed to abuse. Analyses across the 36 months of follow-up showed that depression and anxiety partially mediated 26.7% of the total effect of the abuse-positive symptoms association (indirect effects (IE) = 0.392 and 0.421 respectively), while the combined anxiety/mood model mediated 28.9% (IE = 0.475). Subanalyses at two and 36 months revealed a consistent role of depression, while that of anxiety was only present at baseline. Our work confirms a mediating role of mood and anxiety in the association between abuse and positive symptoms during the first three years of treatment

MOSPD2 is an endoplasmic reticulum–lipid droplet tether functioning in LD homeostasis

International audienceMembrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER–anchored proteins, such as MOSPD2, that function as major ER–organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain. In this study, we show that MOSPD2 forms ER–lipid droplet (LD) contacts, thanks to its CRAL-TRIO domain. MOSPD2 ensures the attachment of the ER to LDs through a direct protein–membrane interaction. The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Remarkably, the absence of MOSPD2 markedly disturbs the assembly of lipid droplets. These data show that MOSPD2, in addition to being a general ER receptor for inter-organelle contacts, possesses an additional tethering activity and is specifically implicated in the biology of LDs via its CRAL-TRIO domain