Effect of antipsychotics on the focal adhesion pathway.

Abstract

Focal adhesions and their dynamic nature are essential for various physiological processes, including the formation of neurites, synaptic function and plasticity. Alterations in these processes have been associated with schizophrenia and bipolar disorder.

Objectives: This study aimed to explore the impact of pharmacological treatments used for bipolar disorder and schizophrenia on the expression of genes involved in the focal adhesion pathway, addressing a gap in understanding the interaction between medication effects and disease pathophysiology.

Methods: NT2-N (neuron-like) cells were exposed to treatment with amisulpride, aripiprazole, chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone, or vehicle for 24 h. Genome-wide mRNA expression was analysed using gene set enrichment analysis.

Results: The analysis revealed that seven out of the eight drugs widely prescribed for bipolar disorder and schizophrenia downregulate the expression of genes associated with the focal adhesions pathway. Focal adhesion was the pathway with the most negative normalised enrichment score across all treatments.

Conclusions: Our results support the hypothesis that focal adhesion pathways may play a role in the pathophysiology of bipolar disorder and schizophrenia. Moreover, the data underscore the importance of differentiating medication effects from disease mechanisms in psychiatric research, a challenge compounded by the medicated state of most study participants.