ROLE OF PREFRONTAL CORTEX IN THE PATHOPHYSIOLOGY AND TREATMENT OF DEPRESSION AND SCHIZOPHRENIA

The prefrontal cortex represents the brain region with the highest hierarchical level among the association cortices and stands as the most evolved cortex, responsible of the superior mental functions. The representation, planning and execution of actions, cognition, behavior and emotional control, adaptation to the environment and the working memory are dependent on the integrity of the prefrontal cortex and its interconnections with cortical and subcortical areas. Schizophrenia and depression generate profound changes in the patient’s behavior, disabling them for a normal adaptation to society. In addition, treatments are far from being optimal for both illnesses; their effectiveness has a high degree of variation, and severe secondary effects usually emerge. Alterations of higher brain functions can be observed, thus indicating that depression and schizophrenia have in common a damage or dysfunction of the prefrontal cortex circuitry. Particularly, disruption of prefrontal neurotransmission of serotonin and dopamine is a shared feature. Furthermore, both psychiatric diseases present marked mood alterations. Hence, the characteristic negative symptoms of schizophrenia (apathy, lack of motivation) are key features of depression.In the present chapter we review the changes and alterations observed in the prefrontal cortex of patients of depression and schizophrenia in terms of cytoarchitecture, connections and functions, and how they are disrupted in both disorders. Some important preclinical findings are also reviewed. We also discuss how different treatments normalize the altered cortical neurotransmission and how this could be reflected by an improvement of the patient’s symptomatology.

Keywords: Orbital (oPFC), medial (mPFC) and lateral (lPFC) prefrontal cortex, depression, schizophrenia, deep brain stimulation (DBS), NMDA receptor, antidepressant and antipsychotic drugs, glutamate, γ-aminobutyric acid (GABA).