Acute Lithium Therapy Increases Cortical Thickness in Patients with Bipolar Disorder Noha AbdelGawad1, Tomas Melicher1,2,3, Bo Cao1, Benson Mwangi1, Salih Selek1, Marsal Sanches1, Giovana B.Zunta-Soares1, Jair C. Soares1 1Department of Psychiatry and Behavioral Sciences University of Texas Medical School, Houston, Texas, USA, 2 National IT System of Mental Health and Brain Monitoring, National Institute of Mental Health, Klecany, Chezch Republic, 3 Psychiatry and Neuroscience, 3rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic Abstract Study Design Discussion Background Lower cortical thickness in patients with bipolar disorder (BD) has been reported1, with some reports of lithium treatment being associated with reversal of these abnormalities2. Little is known about the regional specificity of this effect. In this study we aimed to identify the effect of lithium on cortical thickness in BD patients after four weeks of treatment. Methods 22 patients with BD and 21 healthy controls underwent MRI scanning using a 3.0T Siemens scanner at baseline and after four weeks. During the 4 weeks, patients were treated with lithium monotherapy at therapeutic concentrations. Subjects were drug free for 2 weeks before the initial scan and had no psychiatric, neurologic, or medical comorbidities. Regional cortical thickness measurements were extracted using Freesurfer 5.3.0. We used multivariate testing of the effect of time x treatment group in general linear model to test statistical significance. HAM-D & YMRS were administered at baseline and after 4 weeks. Results Of 70 examined regions, five frontal cortical regions showed statistically significant increase in cortical thickness following lithium treatment: right pars orbitalis, right & left frontal poles, left pars opercularis, and left superior frontal gyrus. Left superior frontal gyrus showed the most significant increase in lithium treated BP patients versus healthy controls (2.75±0.17 to 2.8±0.16 versus 2.72±0.14 to 2.74±0.15, p=0.007). Conclusion Our study revealed five frontal cortical regions that increased in thickness following four weeks of lithium treatment. To our knowledge, this is the first longitudinal study examining the effects of lithium on cortical thickness measures in bipolar disorder. Five frontal cortical regions appear to have increased in thickness following lithium treatment. Left superior frontal gyrus showed the most significant increase. These findings are consistent with previous studies2,3,4 and are substantial considering the short duration of treatment. Our findings strengthen the case for lithium as a neuro-protective agent capable of reversing the pathological findings in brains of patients with BD. Results Cortical Thickness (mm)   Healthy Controls Patients Regions of Interest Baseline 4 weeks Right pars orbitalis 2.66 ± 0.16 2.61 ± 0.18 2.64 ± 0.19 2.73 ± 0.22 p = 0.03 Right frontal pole 2.88 ± 0.18 2.70 ± 0.25 2.86 ± 0.25 2.88 ± 0.24 p = 0.045 Left frontal pole 2.79 ± 0.31 2.66 ± 0.24 2.75 ± 0.24 2.82 ± 0.26 p = 0.017 Left pars opercularis 2.54 ± 0.15 2.51 ± 0.15 2.57 ±0.18 2.6 ± 0.15 p = 0.033 Left superior frontal gyrus 2.72 ± 0.14 2.74 ± 0.15 2.75 ±0.17 2.8 ± 0.16 p = 0.007 References *p-values uncorrected LAN, M. J. et al. Cortical thickness differences between bipolar depression and major depressive disorder. Bipolar Disord, v. 16, n. 4, p. 378-88, Jun 2014. HAFEMAN, D. M. et al. Effects of medication on neuroimaging findings in bipolar disorder: an updated review. Bipolar Disord, v. 14, n. 4, p. 375-410, Jun 2012. GIAKOUMATOS, C. I. et al. Effects of lithium on cortical thickness and hippocampal subfield volumes in psychotic bipolar disorder. J Psychiatr Res, v. 61, p. 180-7, Feb 2015. ISSN 1879-1379. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/25563516 BEARDEN, C. E. et al. Greater cortical gray matter density in lithium-treated patients with bipolar disorder. Biol Psychiatry, v. 62, n. 1, p. 7-16, Jul 2007. ISSN 0006-3223. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/17240360 >. Baseline Demographics Mood Scores   Healthy Controls (n=21) Patients (n=22) Mean age ± SD 37.24 ± 12.57 31.48 ± 10.53 % females (n) 52% (11) 50% (11)   Baseline 4 weeks HAM-D (mean ± SD) 17.14 ± 7.25 10.36 ± 7.59 YMRS (mean ± SD) 3.43 ± 2.60 3.64 ± 4.38