Volumetric MRI Analysis of The Prefrontal Cortex in

Volumetric MRI Analysis of The Prefrontal Cortex in Patients With Major Depressive Disorder Hussain G. 1 , Zoleta C. 1 , Huang Y. 1 , Coupland N. 3, Carter R. , 3, Seres P. 1, and Malykhin N. 1, 2 1 Biomedical Engineering, 2 Centre for Neuroscience, 3 Department of Psychiatry, University of Alberta, Edmonton, AB, Canada 1 INTRODUCTION • Click to Severe forms of depression affect 2 -5% of the population, ranking as one of the top ten causes of disability (. Discovering the cause of major depressive disorder (MDD) is a challenging task for society. Most of the structural MRI studies in depression have focused on limbic structures-- particularly the hippocampus, amygdala, and cingulate gyrus (Hajek et al. , 2009; Malykhin et al. , 2010). However, only a few studies have examined the prefrontal cortex (Steingard et al. , 2002; Botteron et al. , 2002), where the abnormalities have consistently been reported using functional MRI. In addition, in post- mortem studies the volume reduction, dendrite retraction, and spine loss have been well demonstrated in the subgenual prefrontal cortex (PFC) of the depressed patients (Hajek et al. , 2008). 1 Age, Healthy Controls MDD patients 1 Number of subjects 23 25 Age (years), mean ± SD 31. 7 ± 7. 8 35. 1 ± 8. 1 Male/Female 6/17 4/21 sex, and education-matched controls to MDD patients 4 a MATERIALS AND METHOD Data acquisition and analysis: MRI datasets were acquired using a MPRAGE sequence on a 1. 5 Tesla scanner (Siemens) with a high resolution 3 -D MPRAGE sequence (TR=1800 ms, TE=3. 82 ms, TI=1100 ms, 1 average, flip angle=15 degrees, FOV=256 mm, image matrix=256 x 256, 128 coronal slices, 1. 5 mm slice 1 a thickness, Fig. scan time 9 minutes, resolution 1. 5 x 1 x 1 mm. The high resolution 3 D MPRAGE volume was used for volumetric measurements of frontal cortex and intracranial volume (ICV) using software DISPLAY. ICV was calculated manually as previously described (Malykhin et al. , 2007). A manual FC parcellation method was developed by incorporating a posterior and anterior boundary to separate the PFC into four regions: the dorsolateral PFC, medial PFC, lateral OFC and medial OFC (fig. 1). The left and right PFC regions were measured separately. All cortical volumes were adjusted for ICV: normalized volume=(raw volume/ICV)x 1, 000 cm 3. Statistics: Groups were compared using ANOVA. The data were analyzed by using SPSS 18. 0 for Windows. Fig 1 - b Fig 2 Fig 3 Fig. 1 - Sample parcellation of the 4 major frontal sub-regions of the PFC divided into right and left hemispheres, coronal view Fig. 2 - Sagittal view Fig. 3 - Axial view 3 RESULTS Figure 4: Comparison of normalized structural volumes between healthy controls and MDD patients Gray Matter (cm 3) Subjects: 25 patients with major depressive disorder (15 medicated, 10 unmedicated, table 1) and 23 age and sex matched healthy controls were recruited for the study. MDD patients were recruited who met DSM-IV criteria for moderate or severe MDD, on the basis of full clinical assessment and the Structured Clinical Interview for Diagnosis for DSM-IV (SCID). Medicated MDD patients had received continuous antidepressant treatment for ≥ 6 months. Unmedicated MDD patients were medication free for ≥ 12 months. CONCLUSION This is one of the first volumetric study in MDD showing no regional differences in the prefrontal cortex among healthy controls and MDD patients. This preliminary cross-sectional study suggests that prefrontal cortical volumes are not altered in major depression. The present study has several goals. The initial goal was to develop a manual PFC parcellation method to separate the PFC into four regions. The second goal was to determine whether these specific prefrontal areas are affected with patients with MDD. 2 Inter- and intra-rater reliability for the parcellation protocol of the subregions was achieved for all cortical measures (all ICCs > 0. 9). We found that global prefrontal grey matter volume and intracranial volume did not differ between depressed patients and healthy patients (both p>0. 05, Fig. , Tab 2). Further analysis of the prefrontal sub-regions did not reveal significant difference in any of the studied regions (all p>0. 05, Tab 2 ). Medicated an unmedicated patients with major depression also did not differ (all p>0. 05). Table 1: Demographics of the study’s participants 5 REFERENCES 1) Botteron KN, Raichle ME, et al (2002) Volumetric reduction in left subgenual prefrontal cortex in early onset depression. Biological Psychiatry 51: 342 -344. 2) Hajek T, Kozeny J, Kopecek M, Alda M, Höschl C. (2008) Reduced subgenual cingulate volumes in mood disorders: a meta-analysis. J Psychiatry Neurosci 33: 91 -9. 3) Hajek T, Kopecek M, Kozeny J, Gunde E, Alda M, Höschl C. (2009) Amygdala volumes in mood disorders--meta-analysis of magnetic resonance volumetry studies. J Affect Disor 115: 395 -410. 4) Malykhin NV, Bouchard TP, et al (2007) Three- dimensional volumetric analysis and reconstruction of amygdala and hippocampal head, body and tail. Psychiatry Research: Neuroimaging 155: 155– 165. 5) Malykhin NV, Carter R, Seres P, Coupland N (2010) Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment. " Journal of Psychiatry and Neuroscience 35(5): 337 -43. 6) Steingard RJ, Renshaw PF, et al (2002) Small Frontal Lobe White matter volumes in depressed adolescents. Biological Psychiatry 52: 413 -417. 6 ACKNOWLEDGEMENTS ¹MDD – Includes pooled data from both unmedicated and medicated subjects Table 2: ANOVA significance levels between all ¹MDD patients and healthy volunteers Left Hemisphere Right Hemisphere MOFC 0. 66 0. 82 LOFC 0. 90 0. 93 MPFC 0. 62 0. 87 DLPFC 0. 84 0. 99 Total Frontal 0. 83 0. 98 Canadian Institutes of Health Research (CIHR); Office of the Provost and VP (Academic), University of Alberta.