Symptomatic remission and recovery in major psychosis: Is there a role for BDNF? A secondary analysis of the LABSP cohort data.

Remission, relapse prevention, and clinical recovery are crucial areas of interest in schizophrenia (SCZ) research. Although SCZ is a chronic disorder with poor overall outcomes, years of research demonstrated that recovery is possible. There are considerable data linking brain-derived neurotrophic factor (BDNF) to SCZ, however, evidence on the role of BDNF in remission in SCZ is scarce. This secondary analysis of the Longitudinal Assessment of BDNF in Sardinian patients (LABSP) data aimed to investigate the relationship between serum BDNF levels and symptomatic remission, simultaneous clinical and functional remission, and recovery in patients with SCZ. A total of 105 patients with SCZ or schizoaffective disorder were recruited for a longitudinal assessment of BDNF levels over 24 months. Longitudinal data were analyzed using mixed-effects linear regression models. The study found significant associations between use of long acting injectables (χ2 = 7.075, df = 1, p = 0.008), baseline serum BDNF levels (U = 701, z = -2.543, p = 0.011), and "childhood" (U = 475, z = -2.124, p = 0.034) and "general" (U = 55, z = -2.014, p = 0.044) subscales of the Premorbid Adjustment Scale (PAS) with patients maintaining remission and recovery. The diagnosis of SCZ was significantly associated with lower BDNF levels for patients with simultaneous clinical and functional remission (Z = 2.035, p = 0.0419) and recovery (Z = 2.009, p = 0.0445) compared to those without. There were no significant associations between remission in the entire sample and longitudinal serum BDNF levels or genetic variants within the BDNF gene. These findings provide further insight into the complex relationship between BDNF and SCZ.

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies.

The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison.

Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders.

Brain-derived neurotrophic factor (BDNF) is a key modulator of neuroplasticity and has an important role in determining the susceptibility to severe psychiatric disorder with a significant neurodevelopmental component such as major psychoses. Indeed, a potential association between BDNF serum levels and schizophrenia (SCZ) and schizoaffective disorder (SAD) has been tested in diverse studies and a considerable amount of them found reduced BDNF levels in these disorders. Here, we aimed at testing the association of BDNF serum levels with several demographic, clinical, and psychometric measures in 105 patients with SCZ and SAD, assessing the moderating effect of genetic variants within the BDNF gene. We also verified whether peripheral BDNF levels differed between patients with SCZ and SAD. Our findings revealed that BDNF serum levels are significantly lower in patients affected by SCZ and SAD presenting more severe depressive symptomatology. This finding awaits replication in future independent studies and points to BDNF as a possible prognostic indicator in major psychoses.

Exploring the association between brain-derived neurotrophic factor levels and longitudinal psychopathological and cognitive changes in Sardinian psychotic patients.

BACKGROUND AND HYPOTHESIS: Schizophrenia spectrum disorders are among the most debilitating mental disorders and has complex pathophysiological underpinnings. There is growing evidence that brain-derived neurotrophic factor (BDNF) can play a role in its pathogenesis. The present study investigated the longitudinal variation of serum BDNF levels in a 24-month observational prospective cohort study of Sardinian psychotic patients and its relationship with psychopathological and cognitive changes. Furthermore, we examined whether genetic variation within the BDNF gene could moderate these relationships. STUDY DESIGN: Every 6 months, 105 patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and social measures. We performed a targeted analysis of four tag single nucleotide polymorphisms within the BDNF gene that were selected and analyzed using polymerase chain reaction. Longitudinal data were analyzed using mixed-effects linear regression models. STUDY RESULTS: We observed a declining longitudinal trajectory of BDNF levels in psychotic patients in general, and in relation to the severity of depressive and negative symptoms. BDNF serum levels also declined in patients scoring lower in cognitive measures such as attention and speed of information processing and verbal fluency. The rs7934165 polymorphism moderated the significant association between verbal fluency and BDNF levels. CONCLUSIONS: These findings in patients from real-world settings suggest a plausible role of peripheral BDNF levels as a marker of illness burden in schizophrenia spectrum disorders.