F92. “EFFECT OF CLOZAPINE ON FRONTAL ACTIVITY IN TREATMENT RESISTANT SCHIZOPHRENIA - A PROSPECTIVE STUDY USING FUNCTIONAL NEAR INFRARED SPECTROSCOPY”

Clozapine is the only antipsychotic proven to be of definitive higher efficacy than any other drug in patients with treatment resistant schizophrenia. In particular, it is the first line treatment for treatment-resistant schizophrenia. There is evidence that abnormalities in regional blood flow and perfusion are associated with impaired brain functions in patients with schizophrenia. A few studies have reported the hemodynamic changes in antipsychotic response. However, conflicting observations are reported with regards to the impact of clozapine on prefrontal neurohemodynamics (i.e. both increase as well as decreased activations have been described). The current study aimed at evaluating the changes in neurohemodynamic response to n-Back task using functional near infrared spectroscopy (fNIRS) in patients on clozapine.

23 patients with treatment resistant schizophrenia were recruited with written informed consent after institutional ethical committee approval. Psychopathology was assessed on scale for assessment of negative symptoms (SANS) and scale for assessment of positive symptoms (SAPS) were done. Assessment of hemodynamic state using 8x8 bifrontal fNIRS montage during computerized n-Back (0-, 1- & 2- back) task which was presented in block design and was conducted before initiation of clozapine and after 3 months of initiation of clozapine. Data was processed using the SPM for NIRS software for topographic analysis and GLM computations on fNIRS time-series data. Changes in oxy-hemoglobin concentration (HbO) were used to report the results. Excluding 4 dropouts and 2 patients’ data due to technical reasons, in 18 patients were finally included for the analysis.

On paired sample t-test a significant improvement was noted in positive (t=3.7, p=0.002) as well as negative (t=2.76, p=0.006) symptoms after clozapine. As the n-Back was not distributed normally, Wilcoxon-signed rank test was used to compare the difference in n-Back performance and frontal neurohemodynamic activity. A significant improvement in 0-back accuracy was noted (z=2.02, p=0.04) and a trend level improvement in accuracy of 1-back (z=1.76, p=0.08) and 2-back (z=1.71, p=0.09).

The percentage difference in 0-back reaction time positively correlated with percentage difference in activation at left BA8 (r=0.562, p=0.024) during 0-Back test using Spearman’s correlation. Also, increased activation at left BA10 (r=0.541, p=0.03) and left BA47 (r=0.727, p<0.003) during 2-back>1-back contrast positively correlated with improvement in 2-back performance (reaction time and accuracy, respectively).

Patients with schizophrenia showed significant improvement in psychopathology as well as performance in tasks evaluating attention and processing speeds after 3 months of clozapine treatment. A trend towards improvement was noted in working memory tasks. The improvement in processing speed in zero back was associated with reduction in activation at left superior frontal gyrus and the improvement in working memory with increase in the hemodynamic activity at left superior and inferior frontal gyrus. Thus, clozapine seems to improve cognitive functions in patients with treatment resistant schizophrenia which are related to changes in activity at the prefrontal cortical regions.

Acknowledgements: This study is supported by as the Department of Science and Technology [DST] (Government of India) Research Grant (DST/SJF/LSA-02/2014–15) to GV.