Improvement in verbal memory following SSRI augmentation of antipsychotic treatment is associated with changes in the expression of mRNA encoding for the GABA-A receptor and BDNF in PMC of schizophrenic patients

Abstract

Verbal memory impairment in schizophrenia is associated with abnormalities in gamma-aminobutyric acid (GABA)-ergic and brain-derived neurotrophic factor (BDNF) systems. Recent evidence from animal and clinical studies that adding fluvoxamine to antipsychotics alters the expression of transcripts encoding for the GABA-A receptor and BDNF led us to postulate that fluvoxamine augmentation may improve memory in schizophrenia. To test this, we examined the effect of add-on fluvoxamine on verbal memory and other cognitive functions and related it to the expression of mRNA coding for the GABA-A receptor and BDNF in peripheral mononuclear cells (PMC) of schizophrenic patients. Twenty-nine patients completed a 6-week study in which fluvoxamine (100 mg/day) was added to ongoing antipsychotic treatment. Verbal memory, abstraction working memory, object and face recognition, and psychomotor speed and clinical symptoms were assessed at baseline and after 3 and 6 weeks of treatment. Blood samples were taken at baseline and weeks 1, 3, and 6 and PMC was assayed for the GABA-A beta3 receptor and BDNF mRNA by quantitative real-time reverse transcription-PCR. Associative and logical verbal memory improved significantly and showed a significant correlation with changes in PMC BDNF and GABA-A beta3 receptor mRNA, which increased during treatment. Abstraction and object recognition improved, but this did not correlate with PMC measures. Negative and positive symptoms improved significantly; the latter showed significant correlations with changes in PMC measures. Addition of fluvoxamine to antipsychotics improves verbal memory. It is postulated that the mechanism involves enhanced GABA-A receptor/BDNF-dependent synaptic plasticity in the hippocampus.

Increased serum brain-derived neurotrophic factor levels following electroconvulsive therapy or antipsychotic treatment in patients with schizophrenia

“…Our results are consistent with recent reports demonstrating that serum BDNF levels are lower in schizophrenia patients with deficit syndrome [8] and that BDNF mRNA expression is downregulated in various cortical areas in schizophrenia [18][19][20]. Some clinical studies recently reported a significant increase in BDNF transcript levels in peripheral mononuclear cells of schizophrenia patients following fluvoxamine augmentation of antipsychotics [21,22]. Here we found a significant negative correlation between serum BDNF level and PANSS score after ECT and medication.…”

Diverging functional connectivity timescales: Capturing distinct aspects of cognitive performance in early psychosis

“…Although (small) positive effects of APs on cognition have consistently been reported (Baldez et al, 2021; Keefe et al, 2007), our findings suggest that pharmacological interventions specifically aimed at noradrenergic and/or serotonergic systems might proof beneficial in terms of improving specific aspects of cognition in PSD and related disorders. While some evidence exists in that regard (Mancini et al, 2021; Silver et al, 2015), no clinical relevance of antidepressants in general was reported in a recent metanalysis of chronic SCZ patients (Vernon et al, 2014). However, the included studies were small, and cognitive outcomes were grouped within a-priori cognitive domains (EF, language, etc.)…”

7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders

“…Caution therefore needs to be taken when assessing serum BDNF as a reflection of brain BDNF in patients and ideally should be corroborated with other measures such as correlation with symptomology and changes in level in response to medication. However, despite some studies failing to find differences in serum BDNF levels between schizophrenia patients and controls (T. L. Huang and Lee, 2006;Shimizu et al, 2003), the majority consensus suggests palpable dysfunction in BDNF-TrkB signalling as being a fundamental aspect of pathophysiology in schizophrenia (Green et al, 2011). The common BDNF Val66Met polymorphism has also been found to be linked with aspects of schizophrenia symptomology e for example, the detrimental Met allele is associated with earlier disease onset (Chao et al, 2008).…”

“…G. Lee et al, 2010). The antidepressant fluvoxamine, when added as an adjunct treatment to antipsychotics in a recent study, improved associative and logical verbal memory and this improvement was correlated with increases in BDNF mRNA (Silver et al, 2015). Exercise has been shown to have beneficial effects on both positive and negative symptoms (Behere et al, 2011;Scheewe et al, 2013;Vancampfort et al, 2011) and memory performance in schizophrenia (Kimhy et al, 2015;Pajonk et al, 2010) as well as increasing BDNF (Kimhy et al, 2015;Kuo et al, 2013).…”