Research SummaryExploring brain connectivity, neuroprophic and clinical correlates of treatment response to electro convulsive therapy in refractory schizophrenia
Schizophrenia is a disabling condition. Though antipsychotic medications are effective, nearly 30% do not improve with antipsychotics. Clozapine is effective in such treatment-resistant patients. However, around 50% of patients remain refractory even to clozapine. With electroconvulsive therapy (ECT) nearly 50% of clozapine-resistant schizophrenia patients improved in a recent study. Determinants of improvement with ECT are not known. Brain-connectivity within the default mode network (DMN) and blood levels of a neurochemical called BDNF have been investigated as mediators of ECT response in depression. In this proposal, we plan to examine the association between change in functional and structural connectivity within the DMN and change in serum BDNF levels with treatment response to ECT in clozapine-refractory schizophrenia patients. This research has potential to unravel the mechanisms of action of ECT in this clinically challenging population.
Joint write up:
Having been discovered as a treatment for schizophrenia, Electroconvulsive therapy (ECT) in current day finds its place only in treatment refractory schizophrenia. Being most effective treatment in the field of psychiatry among all severe mental illnesses, mechanism of its action still remains enigmatic. Many theories have been proposed based on animal as well as human studies. Increase in neurotrophic factors, neurogenesis at hippocampus, altered neurotransmitter levels in brain being some of them. In a recent study, patients with severe depression who responded to ECT had altered connectivity in default mode network (DMN). Also many studies have revealed increase in BDNF (Brain Derived Neurotrophic Factor) levels in depression patients who responded to ECT. One of the RCTs showed up to 50% response with ECT among clozapine refractory schizophrenia patients.
Schizophrenia patients, who are refractory/intolerant to clozapine, pose a tremendous clinical challenge. Treatment options are very limited and ECT is one of the last resorts that may be considered. A hyperconnected DMN and low BDNF blood levels have been recognized as markers of poor treatment response in preliminary studies. In this study, we aim to leverage this neurobiological knowledge within a clinical setting. We will study resting state fMRI- & DTI-measured connectivity of DMN along with BDNF levels before and after a trial with electroconvulsive therapy to see whether changes in these parameters explain treatment response in schizophrenia. We will also follow up patients till 3 months looking for clinical and cognitive profiles. The study has the potential to reveal novel information regarding the mechanisms of ECT and take us a step closer as clinicians, to predict response to ECT among schizophrenia patients.