Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor BDNF] and nerve growth factor NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs.

The objective of this study is to investigate cognitive performance in a first-episode psychosis
sample, when stratifying the interaction by cannabis use and familial or non-familial psychosis.
Hierarchical-regression models were used to analyse this association in a sample of
268 first-episode psychosis patients and 237 controls. We found that cannabis use was
associated with worse working memory, regardless of family history. However, cannabis
use was clearly associated with worse cognitive performance in patients with no family history
of psychosis, in cognitive domains including verbal memory, executive function and
global cognitive index, whereas cannabis users with a family history of psychosis performed
better in these domains. The main finding of the study is that there is an interaction between
cannabis use and a family history of psychosis in the areas of verbal memory, executive
function and global cognition: that is, cannabis use is associated with a better performance
in patients with a family history of psychosis and a worse performance in those with no family
history of psychosis. In order to confirm this hypothesis, future research should explore
the actual expression of the endocannabinoid system in patients with and without a family
history of psychosis., The Spanish Ministry of Economy and Competitiveness (Ref. ISCIII 2009-2011:PI 080208), the Instituto de Salud Carlos III-European Fund for Regional Development (PI10/01430, PI10/01746, PI11/01977, PI11/02708, 2011/1064, PI12/02077, PI13/02252, PI13/00451 and PI14/01900, PI11/02831), the Centre for Biomedical Research in the Mental Health Network (CIBERSAM), the Health Department of the Government of Navarre (11/101 and 87/2014), the Government of Catalonia, Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2014SGR441), the Contract FI-DGR-2013 from the Agència de Gestió d'Ajuts Universitaris i de Recerca, AGAUR (2015 FI_B2 00100 to GM), the Esther Koplowitz Centre (Barcelona), local grants from the Department of Education, Linguistic Policy and Culture of the Basque Country Government, the Basque Foundation for Health Innovation and Research (BIOEF), Madrid Regional Government (S2010/BMD-2422 AGES), European Union Structural Funds and European Union Seventh Framework Program under grant agreements FP7-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7-HEALTH-2009-2.2.1-3-242114 (Project OPTiMISE), FP7- HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN) and FP7-HEALTH-2013-2.2.1-2-602478 (Project METSY); Alicia Koplowitz Foundation, Mutua Madrileña Foundation and the University of the Basque Country (GIC10/80, GIC12/84). The psychiatric research department at Araba University Hospital is supported by the Stanley Research Foundation (03-RC-003).

The objective of this study is to investigate cognitive performance in a first-episode psychosis sample, when stratifying the interaction by cannabis use and familial or non-familial psychosis. Hierarchical-regression models were used to analyse this association in a sample of 268 first-episode psychosis patients and 237 controls. We found that cannabis use was associated with worse working memory, regardless of family history. However, cannabis use was clearly associated with worse cognitive performance in patients with no family history of psychosis, in cognitive domains including verbal memory, executive function and global cognitive index, whereas cannabis users with a family history of psychosis performed better in these domains. The main finding of the study is that there is an interaction between cannabis use and a family history of psychosis in the areas of verbal memory, executive function and global cognition: that is, cannabis use is associated with a better performance in patients with a family history of psychosis and a worse performance in those with no family history of psychosis. In order to confirm this hypothesis, future research should explore the actual expression of the endocannabinoid system in patients with and without a family history of psychosis.