Psychotic disorders present a significant lifetime risk for suicide. Past estimates suggest that up to 25-50% of individuals with schizophrenia (SCZ) may attempt suicide during their lifetime. A growing body of literature indicates that the level of cognitive performances may be associated with a differing level of lifetime suicide attempts, albeit inconsistently depending on the diagnostic category and study setting. However, the vast majority of the literature in the field is composed of cross-sectional studies, limiting the overall interpretation of the available evidence.

In the present study, we probed the possible association of BDNF plasma levels, cognitive functions assessed through the Brief Assessment of Cognition in Schizophrenia (BACS) and lifetime suicide ideation and/or attempts (LSI+LSA). More specifically, we tested whether such association would persist during the 2 years follow-up divided in 5 different timepoints at 6-month intervals, if present.

The present study represents a secondary analysis of a previously described cohort (Manchia et al. Brain Sci. 2022 Dec 4;12(12):1666). The sample comprised 105 subjects with SZC or schizoaffective disorder. We employed the 1) Wilcoxon test for non-parametric data 2) linear modelling to test the possible association of BACS-defined cognitive task performances with LSI+LSA. We also investigated if either BDNF plasma levels or four tested BDNF SNP genes would mediate this association.

From a total of 105 subjects, data relevant to the analysis were available for 89 subjects. We observed a significant association between BACS-Letter fluency task (BACS-LF) with LSI+LSA, persisting even when adjusting for gender, duration of untreated psychosis, total Positive and Negative Syndrome Scale score, age, chlorpromazine equivalents of antipsychotic therapy and for the effect of time. The association remained significant even when adjusting with the Bonferroni-Holms method for multiple comparisons (p=0.002). No association was found either for BDNF plasma levels or the tested BDNF genes for the tested outcomes.

In our sample, higher BACS-LF performances appeared to be associated with a higher lifetime risk of LSI+LSA. This report adds to the previous literature suggesting that different cognitive performance levels may represent one of the many chronic risk factors associated with LSI+LSA, and that may ultimately complexly interact with more proximal ones.

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Schizophrenia spectrum disorders are among the most debilitating mental disorders and evidence on its pathophysiological underpinnings is scant. The brain-derived neurotrophic factor (BDNF) appears to be involved in the pathophysiology of these complex psychiatric disorders.

The present study investigates the longitudinal variation of serum BDNF levels in a 24-month observational cohort study of Sardinian psychotic patients (LABSP). This study assessed the variation in BDNF serum levels and its relationship with psychopathological and cognitive changes. Further, we also examined if genetic variations within the BDNF gene could moderate these relationships.

Every six months 105 LABSP patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and drug-related measures. Four tag single nucleotide polymorphisms (SNPs) within the BDNF gene were selected and analyzed using Polymerase Chain Reaction (PCR). Longitudinal data were analyzed using mixed-effects linear regression models (MLRM).

Analysis showed significantly lower peripheral BDNF levels in psychotic patients with depressive and negative symptoms. BDNF levels were also decreased in patients scoring lower in cognitive measures such as symbol coding and semantic fluency. In addition, Val66Met polymorphism within the BDNF gene significantly moderated the relationship between the severity of negative symptoms and BDNF levels.

Our findings are consistent with previous literature suggesting that peripheral BDNF levels are associated with some cognitive domains and mood disruption in major psychosis. The results also suggest the lack of association between most BDNF genetic variants, except Val66Met polymorphism, with the severity of negative symptoms.

No significant relationships.