Winter birth: A factor of poor functional outcome in a Swiss early psychosis cohort.

OBJECTIVE: Winter birth has consistently been identified as a risk factor for schizophrenia. This study aimed to determine whether individuals born during this season are also at higher risk for early psychosis and whether this is associated with distinct functional and clinical outcomes. METHODS: We conducted a prospective study on 222 patients during their early phase of psychosis in Switzerland, nested in the Treatment and Early Intervention in Psychosis (TIPP) cohort. We compared the birth trimesters of these patients with those of the general Swiss population. Additionally, we evaluated the Global Assessment of Functioning scale (GAF) and the Positive and Negative Syndrome Scale (PANSS) scores among patients born in winter (January to March) versus those born during the rest of the year during a three-year follow-up period. RESULTS: A significantly higher proportion of patients experiencing early psychosis were born in winter compared to the general Swiss population. Patients born in winter had significantly lower GAF scores at 6 months, 24 months, and 36 months of follow-up, compared to patients born during the rest of the year. They also manifested fewer positive symptoms, as indicated by the PANSS positive subscale. CONCLUSION: Birth in winter appears to be associated with a lower functional outcome and potentially distinct symptomatology in the early phase of psychosis.

Low protein-induced intrauterine growth restriction as a risk factor for schizophrenia phenotype in a rat model: assessing the role of oxidative stress and neuroinflammation interaction.

A large body of evidence suggests that intrauterine growth restriction (IUGR) impedes normal neurodevelopment and predisposes the offspring to cognitive and behavioral deficits later in life. A significantly higher risk rate for schizophrenia (SZ) has been reported in individuals born after IUGR. Oxidative stress and neuroinflammation are both involved in the pathophysiology of SZ, particularly affecting the structural and functional integrity of parvalbumin interneurons (PVI) and their perineuronal nets (PNN). These anomalies have been tightly linked to impaired cognition, as observed in SZ. However, these pathways remain unexplored in models of IUGR. New research has proposed the activation of the MMP9-RAGE pathway to be a cause of persisting damage to PVIs. We hypothesize that IUGR, caused by a maternal protein deficiency during gestation, will induce oxidative stress and neuroinflammation. The activation of these pathways during neurodevelopment may affect the maturation of PVIs and PNNs, leading to long-term consequences in adolescent rats, in analogy to SZ patients. The level of oxidative stress and microglia activation were significantly increased in adolescent IUGR rats at postnatal day (P)35 as compared to control rats. PVI and PNN were decreased in P35 IUGR rats when compared to the control rats. MMP9 protein level and RAGE shedding were also increased, suggesting the involvement of this mechanism in the interaction between oxidative stress and neuroinflammation. We propose that maternal diet is an important factor for proper neurodevelopment of the inhibitory circuitry, and is likely to play a crucial role in determining normal cognition later in life, thus making it a pertinent model for SZ.