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S071-2

Effect of Antipsychotic Treatment on White Matter Abnormalities in Previously
Antipsychotic-Naïve/ Antipsychotic-Free Patients with Schizophrenia

Sri Mahavir Agarwal1, Sunil Kalmady1, Venkataram Shivakumar1, Amaresha Anekal1, Anushree
Bose1, Vijay Danivas1, Janardhanan Narayanaswamy1, Ganesan Venkatasubramanian1, Bangalore
Gangadhar1, Matcheri Keshavan2

1National Institute of Mental Health And Neurosciences (NIMHANS), India 2Beth Israel Deaconess Medical Center
and Harvard Medical School, USA

Background/Objective: We examined antipsychotic-naïve/antipsychotic-free DSM-IV
schizophrenia patients (SCZ) for white matter abnormalities at baseline and after 3-6 months of
antipsychotic treatment.

Method: Diffusion tensor imaging (DTI; 64-directions) was performed on right handed patients
[N=79; 56 antipsychotic-naïve; age=30.9±6.7 years, 45 male, duration of illness 4.1±3.9 years] and
age, sex and handedness matched HC [N=79, age=30.0±4.9 years, 45 male] in a 3-Tesla MRI. A
subset of patients [N=30; age=30.9±6.5 years, 19 male] was rescanned after 4.4±0.6 months of
antipsychotic therapy [all patients were on oral atypical agents; additionally two patients were on
fluphenazine depot injections]. Psychopathology was assessed using the Scale for Assessment of
Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). DTI
images were processed using Tract Based Spatial Statistics implemented in FSL to analyse fractional
anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) with
multiple comparison correction using threshold-free cluster enhancement [5000 permutations,
p<0.05].

Result: SCZ had significantly greater FA (Figure-1) and lesser AD (Figure-2), RD (Figure-3) and
MD (Figure-4) at baseline compared to HC in multiple bilateral tracts including superior and inferior
longitudinal fasciculi, corticospinal tract, corpus callosum, and thalamic radiation. Patients at
baseline had significantly greater FA (Figure-5) and lesser RD (Figure-6) than at follow-up. There
was no significant difference in diffusivity measures between patients at follow-up and HC. SAPS
total score reduced significantly from 27.9±11.2 to 7.8±9.4 (t=9.3, p<0.001). SANS total score
reduced significantly from 27.9±23.4 to 18.5±14.2 (t=2.1, p=0.040). Change in diffusivity measures
did not correlate with change in psychopathology, age of onset, duration of illness or duration
between scans.

Conclusion: Findings suggest that SCZ have lesser AD, and even lesser RD compared to HC
resulting in higher FA at baseline. “Normalization” in FA following antipsychotic treatment is
probably due to increase in RD which may occur through glia mediated mechanisms.