Childhood Sexual Abuse and Cortical Thinning in Adults With Major Depressive Disorder

Objective@#A growing body of evidence reports on the effect of different types of childhood abuse on the structural and functional architecture of the brain. In the present study, we aimed to investigate the differences in cortical thickness according to specific types of childhood abuse between patients with major depressive disorder (MDD) and healthy controls (HCs). @*Methods@#A total of 61 patients with MDD and 98 HCs were included in this study. All participants underwent T1-weighted magnetic resonance imaging, and the occurrence of childhood abuse was assessed using the Childhood Trauma Questionnaire. We investigated the association between whole-brain cortical thickness and exposure to any type of childhood abuse and specific type of childhood abuse in the total sample using the FreeSurfer software. @*Results@#No significant difference was reported in the cortical thickness between the MDD and HC groups nor between the “any abuse” and “no abuse” groups. Compared to no exposure to childhood sexual abuse (CSA), exposure to CSA was significantly associated with cortical thinning in the left rostral middle frontal gyrus (p=0.00020), left (p=0.00240), right fusiform gyri (p=0.00599), and right supramarginal gyrus (p=0.00679). @*Conclusion@#Exposure to CSA may lead to cortical thinning of the dorsolateral prefrontal cortex, which is deeply involved in emotion regulation, to a greater extent than other types of childhood abuse.

Cerebral Cortex Changes in Basketball Players

Background@#Plastic changes to brain structure and function have been reported in elite athletes of various sports. Interestingly, different regions of the brain were engaged according to the type of sports analyzed. Our laboratory reported no difference in total cerebellar volume of basketball players compared to that in the control group using the manual segmentation method. Further detailed analyses showed that elite basketball players had increased volume of the striatum and vermian lobules VI–VII of the cerebellum. We analyzed the brain magnetic resonance imaging (MRI) of basketball players to understand their cerebral cortical plasticity through automatic analysis tools for MRI. @*Methods@#Brain MRI data were collected from 19 male university basketball players and 20 age-, sex-, and height-matched control groups. In order to understand the changes in the cerebral cortices of basketball players, we employed automated MRI brain analysis techniques, including voxel-based morphometry (VBM) and surface-based morphometry (SBM). @*Results@#VBM showed increased gray and white matter volume in both precentral gyri, paracentral lobules and increased gray matter volume in the right anterior superior temporal gyrus. SBM revealed a left dominant increase in both pericentral gyri. Fractal dimensional analysis showed an increase in the area of both precentral gyri, the left subcallosal gyrus, and the right posterior cingulate gyrus. These results suggest a significant role not only for the primary motor cortex, but also for the cingulate gyrus during basketball. @*Conclusion@#Plastic changes of both precentral gyri, the pericentral area, paracentral lobules, and the right superior temporal gyrus were observed in elite basketball players. There was a strong increase of fractal complexity in both precentral gyri and a weak increase in the right posterior cingulate gyrus and left collateral gyrus. In this study, plastic regions linked to functional neuroanatomy were related to the competence required to play basketball.

Cortical Thickness and Surface Area Abnormalities in Bipolar I and II Disorders

Objective@#Although bipolar II disorder (BD II) is not simply a mitigated form of bipolar I disorder (BD I), their neurobiological differences have not been elucidated. The present study aimed to explore cortical thickness (CT) and surface area (SA) in patients with BD I and BD II and healthy controls (HCs) to investigate the shared and unique neurobiological mechanisms of BD subtypes. @*Methods@#We enrolled 30 and 44 patients with BD I and BD II, respectively, and 100 HCs. We evaluated CT and SA using FreeSurfer and estimated differences in CT and SA among the three groups (BD I vs. BD II vs. HC). We adjusted for age, sex, educational level, and intracranial volume as confounding factors. @*Results@#We found widespread cortical thinning in the bilateral frontal, temporal, and occipital regions; cingulate gyrus; and insula in patients with BD. Alterations in SA, including increased SA of the pars triangularis and decreased SA of the insula, were noted in patients with BD. Overall, we found BD II patients demonstrated decreased SA in the right long insula compared to BD I patients. @*Conclusion@#Our results suggest that decreased SA in the right long insula is crucial for differentiating BD subtypes.

Association of Prefrontal Cortex Thinning with High Impulsivity in Healthy Adults

Objective@#Studies have been conducted to identify brain structural alterations related to high impulsivity in psychiatric populations. However, research on healthy subjects is relatively less extensive. Therefore, we aimed to investigate the correlation between the cortical thickness of whole brain regions and the impulsivity level in a healthy population. @*Methods@#We included 100 healthy participants aged 19–65 years. Their T1-weighted magnetic resonance images and the 23-item Barratt Impulsiveness Scale (BIS) score were obtained. The patients were divided into high and low impulsivity groups according to the 75th percentile score of the BIS in the sample. The thickness of each cortical region was calculated using the FreeSurfer, and the difference in cortical thickness of the whole brain between the high and low impulsivity groups was analyzed using one-way analysis of covariance including age, sex, education level, and total intracranial cavity volume as covariates. @*Results@#The high impulsivity group showed significant cortical thinning in the left pars opercularis. The cortical thickness of the left pars opercularis significantly correlated negatively with the total, attention, and motor scores of the BIS scale. @*Conclusion@#Our findings suggest that prefrontal cortex thinning may play an important role in the development of high impulsivity in healthy adults.

Cortical Thickness and Surface Area Abnormalities in Bipolar I and II Disorders

Objective@#Although bipolar II disorder (BD II) is not simply a mitigated form of bipolar I disorder (BD I), their neurobiological differences have not been elucidated. The present study aimed to explore cortical thickness (CT) and surface area (SA) in patients with BD I and BD II and healthy controls (HCs) to investigate the shared and unique neurobiological mechanisms of BD subtypes. @*Methods@#We enrolled 30 and 44 patients with BD I and BD II, respectively, and 100 HCs. We evaluated CT and SA using FreeSurfer and estimated differences in CT and SA among the three groups (BD I vs. BD II vs. HC). We adjusted for age, sex, educational level, and intracranial volume as confounding factors. @*Results@#We found widespread cortical thinning in the bilateral frontal, temporal, and occipital regions; cingulate gyrus; and insula in patients with BD. Alterations in SA, including increased SA of the pars triangularis and decreased SA of the insula, were noted in patients with BD. Overall, we found BD II patients demonstrated decreased SA in the right long insula compared to BD I patients. @*Conclusion@#Our results suggest that decreased SA in the right long insula is crucial for differentiating BD subtypes.

Association of Prefrontal Cortex Thinning with High Impulsivity in Healthy Adults

Objective@#Studies have been conducted to identify brain structural alterations related to high impulsivity in psychiatric populations. However, research on healthy subjects is relatively less extensive. Therefore, we aimed to investigate the correlation between the cortical thickness of whole brain regions and the impulsivity level in a healthy population. @*Methods@#We included 100 healthy participants aged 19–65 years. Their T1-weighted magnetic resonance images and the 23-item Barratt Impulsiveness Scale (BIS) score were obtained. The patients were divided into high and low impulsivity groups according to the 75th percentile score of the BIS in the sample. The thickness of each cortical region was calculated using the FreeSurfer, and the difference in cortical thickness of the whole brain between the high and low impulsivity groups was analyzed using one-way analysis of covariance including age, sex, education level, and total intracranial cavity volume as covariates. @*Results@#The high impulsivity group showed significant cortical thinning in the left pars opercularis. The cortical thickness of the left pars opercularis significantly correlated negatively with the total, attention, and motor scores of the BIS scale. @*Conclusion@#Our findings suggest that prefrontal cortex thinning may play an important role in the development of high impulsivity in healthy adults.

Alterations in the Occipital Cortex of Drug-Naïve Adults With Major Depressive Disorder: A Surface-Based Analysis of Surface Area and Cortical Thickness

Objective@#Advances in surface-based morphometric methods have allowed researchers to separate cortical volume into cortical thickness (CTh) and surface area (SA). Although CTh alterations in major depressive disorder (MDD) have been observed in numerous studies, few studies have described significant SA alterations. Our study aimed to measure patients’ SAs and to compare it with their CTh to examine whether SA exhibits alteration patterns that differ from those of CTh in drug-naïve patients with MDD. @*Methods@#A total of 71 drug-naïve MDD patients and 111 healthy controls underwent structural magnetic resonance imaging, and SA and CTh were analyzed between the groups. @*Results@#We found a smaller SA in the left superior occipital gyrus (L-SOG) in drug-naïve patients with MDD. In the CTh analysis, the bilateral fusiform gyrus, left middle occipital gyrus, left temporal superior gyrus, and right posterior cingulate showed thinner cortices in patients with MDD, while the CTh of the bilateral SOG, right straight gyrus, right posterior cingulate, and left lingual gyrus were increased. @*Conclusion@#Compared with the bilateral occipito-temporal changes in CTh, SA alterations in patients with MDD were confined to the L-SOG. These findings may improve our understanding of the neurobiological mechanisms of SA alteration in relation to MDD.

Shape Analysis of the Subcortical Nuclei in Amyotrophic Lateral Sclerosis without Cognitive Impairment

Background@#and Purpose: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that mainly affects the pyramidal motor system. However, recent studies have suggested that degeneration of the extramotor system plays a role in the disability experienced by patients with ALS. We investigated the local shape changes and mean volumes of the subcortical nuclei in sporadic ALS patients with preserved cognition. @*Methods@#The participants comprised 32 patients with ALS and 43 age- and sex-matched healthy controls. Three-dimensional T1-weighted structural images were acquired. Surfacebased vertex analysis was performed with fully automated segmentation of both amygdalae, hippocampi, caudate nuclei, nuclei accumbens, putamina, pallida, and thalami, and the brainstem. The scalar distances from the mean surfaces of the individual subcortical nuclei were compared between groups, and correlations of the local shape distances with initial Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALS-FRS-R) scores and the delta FRS-R and with the disease duration were analyzed. @*Results@#ALS patients showed regional shape contractions on the lateral surfaces of both pallida, the lateroposterior surface of the right putamen, and the anterior basal surface of the right accumbens. Delta FRS-R scores were negatively correlated with local shape distances in the right hippocampus and the putamina. However, the initial ALS-FRS-R score and disease duration were not correlated with local shape distances. @*Conclusions@#Subcortical gray-matter structures are involved in the neurodegenerative process of ALS before cognitive impairment becomes evident.

Shape and Volumetric Differences in the Corpus Callosum between Patients with Major Depressive Disorder and Healthy Controls

Objective@#This study aimed to investigate the morphometric differences in the corpus callosum between patients with major depressive disorder (MDD) and healthy controls and analyze their relationship to gray matter changes. @*Methods@#Twenty female MDD patients and 21 healthy controls (HCs) were included in the study. To identify the difference in the regional gray matter concentration (GMC), VBM was performed with T1 magnetic resonance imaging. The shape analysis of the corpus callosum was processed. Diffusion tensor imaging (DTI) fiber-tracking was performed to identify the regional tract pathways in the damaged corpus callosal areas. @*Results@#In the shape analysis, regional shape contractions in the rostrum and splenium were found in the MDD patients. VBM analysis showed a significantly lower white matter concentration in the genu and splenium, and a significantly lower GMC in the frontal, limbic, insular, and temporal regions of the MDD patients compared to the HCs. In DTI fiber-tracking, the fibers crossing the damaged areas of the genu, rostrum, and splenium were anatomically connected to the areas of lower GMC in MDD patients. @*Conclusion@#These findings support that major depressive disorder may be due to disturbances in multiple neuronal circuits, especially those associated with the corpus callosum.

Shape Deformation in the Brainstem of Medication-Naïve Female Patients with Major Depressive Disorder

Objective@#Although neuroimaging studies have shown volumetric reductions, such as the anterior cingulate, prefrontal cortices, and hippocampus in patients with major depressive disorder (MDD), few studies have investigated the volume of or shape alterations in the subcortical regions and the brainstem. We hypothesized that medication-naïve female adult patients with MDD might present with shape and volume alterations in the subcortical regions, including the brainstem, compared to healthy controls (HCs). @*Methods@#A total of 20 medication-naïve female patients with MDD and 21 age-matched female HCs, underwent 3D T1-weighted structural magnetic resonance scanning. We analyzed the volumes of each subcortical region and each brainstem region, including the midbrain, pons, and medulla oblongata. We also performed surface-based vertex analyses on the subcortical areas and brainstem. @*Results@#Female patients with MDD showed non-significant volumetric differences in the subcortical regions, whole brainstem, and each brainstem region compared to the HCs. However, in the surface-based vertex analyses, significant shape contractions were observed in both cerebellar peduncles located on the lateral wall of the posterior brainstem [threshold-free cluster enhancement, corrected for family-wise error (FWE) at p<0.05] in patients with MDD. @*Conclusion@#We revealed shape alterations in the posterior brainstem in female patients with MDD.

Neuroanatomical Predictors of Dysphagia after Stroke: Voxel-Based Lesion Symptom Mapping Study / 대한연하장애학회지

OBJECTIVE: Dysphagia is a common consequence of stroke with a negative effect on the clinical outcome. Given these potential outcomes, it is important to identify the precursors to dysphagia after stroke. The aims of this study were to identify lesions associated with dysphagia after an ischemic supratentorial stroke using voxel-based lesion symptom mapping (VLSM) and compare the difference in the lesion pattern between the oral and pharyngeal phase dysphagia. METHODS: Stroke patients who met the following inclusion criteria were screened retrospectively between January 2012 and November 2014: a first-ever stroke, supratentorial lesion and who underwent brain MRI and functional dysphagia scale (FDS) from videofluoroscopic swallowing study (VFSS). Finally, the MRI data of 83 patients were analyzed. Statistical maps of the lesion contribution related to dysphagia were generated using VLSM. RESULTS: VLSM showed that FDS was associated with damage to the putamen, caudate, insula, frontal precentral gyrus, and inferior frontal gyrus. The lesions were distributed more widely in the left than right hemisphere. Lesions correlated with the FDS oral score were distributed mainly in the frontal lobe and insula. Otherwise, the associated lesion with the FDS pharyngeal score was mainly the basal ganglia. CONCLUSION: In these results, lesions that correlated with dysphagia were distributed more widely in the left hemisphere, reflecting the possibility of lateralization of the swallowing function. Oral phase dysphagia was associated with left frontal lobe and insula; the lesion correlated with the cognitive function or apraxia. On the other hand, VLSM revealed the lesions associated with pharyngeal dysphagia to be the basal ganglia, which is a structure that plays a role in the automatic motor control network.

Erratum: Morphologic Alterations in Amygdala Subregions of Adult Patients with Bipolar Disorder

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Morphologic Alterations in Amygdala Subregions of Adult Patients with Bipolar Disorder

OBJECTIVES: Previous studies have revealed inconsistent results on amygdala volume in adult bipolar disorder (BD) patients compared to healthy controls (HC). Since the amygdala encompasses multiple subregions, the subtle volume changes in each amygdala nucleus might have not been fully reflected in the measure of the total amygdala volume, causing discrepant results. Thus, we aimed to investigate volume changes in each amygdala subregion and their association with subtypes of BD, lithium use and clinical status of BD. METHODS: Fifty-five BD patients and 55 HC underwent T1-weighted structural magnetic resonance imaging. We analyzed volumes of the whole amygdala and each amygdala subregion, including the anterior amygdaloid area, cortico-amygdaloid transition area, basal, lateral, accessory basal, central, cortical, medial and paralaminar nuclei using the atlas in the FreeSurfer. The volume difference was analyzed using a one-way analysis of covariance with individual volumes as dependent variables, and age, sex, and total intracranial volume as covariates. RESULTS: The volumes of whole right amygdala and subregions including basal nucleus, accessory basal nucleus, anterior amygdaloid area, and cortico-amygdaloid transition area in the right amygdala of BD patients were significantly smaller for the HC group. No significant volume difference between bipolar I disorder and bipolar II disorder was found after the Bonferroni correction. The trend of larger volume in medial nucleus with lithium treatment was not significant after the Bonferroni correction. No significant correlation between illness duration and amygdala volume, and insignificant negative correlation were found between right central nucleus volume and depression severity. CONCLUSIONS: Significant volume decrements of the whole amygdala, basal nucleus, accessory basal nucleus, anterior amygdaloid area, and cortico-amygdaloid transition area were found in the right hemisphere in adult BD patients, compared to HC group. We postulate that such volume changes are associated with altered functional activity and connectivity of amygdala nuclei in BD.

Changes in the Volume and Cortical Thickness of the Specific Regions of Cerebellum of Patients with Major Depressive Disorder

OBJECTIVES: A growing body of evidence has suggested that morphologic changes in cerebellum may be implicated with pathophysiology of major depressive disorder (MDD). The aim of this study is to investigate a difference in the volume and cortical thickness of the specific region of cerebellum between patients with MDD and healthy controls (HC). METHODS: A total of 127 patients with MDD and 105 HC participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed volume and cortical thickness of each twelve cerebellum regions divided by left and right and the volume and cortical thickness of the whole cerebellum from T1-weigted image of participants. One-way analysis of covariance was used to investigate the volume and cortical thickness difference of total and specific regions between two groups adjusting for age, gender, medication, and total intracranial cavity volume. RESULTS: We found that the patients with MDD had significantly greater volume in the left cerebellum lobule III region [false discovery rate (FDR)-corrected p = 0.034] compared to HC. Also, our findings indicate that cortical thickness of left lobule VIIB (FDR-corrected p = 0.032) and lobule VIIIB (FDR-corrected p = 0.032) are significantly thinner in the patients with MDD compared with the HC. No significant volume and cortical thickness differences were observed in other sub-regions of the cerebellum. The volumes and cortical thickness of whole cerebellum between patients with MDD and HC did not differ significantly. CONCLUSIONS: We observed the region-specific volume and cortical thickness difference in cerebellum between the patients with MDD and HC. The results of our study implicate that the information about structural alterations in cerebellum with further replicative studies might provide a stepping stone toward a specific marker to diagnose MDD.

Current Clinical Applications of Diffusion-Tensor Imaging in Neurological Disorders

Diffusion-tensor imaging (DTI) is a noninvasive medical imaging tool used to investigate the structure of white matter. The signal contrast in DTI is generated by differences in the Brownian motion of the water molecules in brain tissue. Postprocessed DTI scalars can be used to evaluate changes in the brain tissue caused by disease, disease progression, and treatment responses, which has led to an enormous amount of interest in DTI in clinical research. This review article provides insights into DTI scalars and the biological background of DTI as a relatively new neuroimaging modality. Further, it summarizes the clinical role of DTI in various disease processes such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's dementia, epilepsy, ischemic stroke, stroke with motor or language impairment, traumatic brain injury, spinal cord injury, and depression. Valuable DTI postprocessing tools for clinical research are also introduced.

Neuroanatomical Mechanism of Cerebellar Mutism After Stroke

Cerebellar mutism (CM) is a rare neurological condition characterized by lack of speech due to cerebellar lesions. CM is often reported in children. We describe a rare case of CM after spontaneous cerebellar hemorrhage. The patient showed mutism, irritability, decreased spontaneous movements and oropharyngeal apraxia. Diffusion tensor imaging revealed significant volume reduction of medial frontal projection fibers from the corpus callosum. In Tracts Constrained by UnderLying Anatomy (TRACULA) analysis, forceps major and minor and bilateral cingulum-angular bundles were not visualized. Cerebello-frontal pathway reconstructed from the FMRIB Software Library showed continuity of fibers, with decreased number of fibers on qualitative analysis. These results suggest that cerebello-frontal disconnection may be a neuroanatomical mechanism of CM. Damage of brain network between occipital lobe, cingulate and cerebellum caused by hemorrhage may also have role in the mechanism of CM in our case.

Effect of MRI Scanner Noise on Blood Oxygen Level-Dependent Activation of Cortical and Subcortical Auditory Centers / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: We compared functional MRI acquisition methods of sparse temporal acquisition (STA) and continuous acquisition (CA) to estimate the effect of MRI scanner background noise (SBN) on blood oxygen level-dependent (BOLD) activation of cortical and subcortical auditory centers during auditory stimulation. SUBJECTS AND METHOD: Fourteen healthy subjects (eight males, age 30.6+/-4.7 years) were presented with classical music in a block paradigm (36 s on/off) in two STA [repitition time (TR)=12 s, 60 volumes] and two CA (TR=2 s, 360 volumes) functional MRI sessions. To account for the sample size difference, an additional volume-matched continuous dataset (CAm) was generated by matching CA to 60 volumes of STA. A group-level analysis based on BOLD activation maps was performed. Percent signal change (PSC), T-statistic values and signal variability in cortical and subcortical auditory regions of interest (ROIs) were calculated from individual activation maps and compared between the STA, CA, and CAm. RESULTS: The group analysis showed activation in the primary and secondary auditory cortices in all datasets. However, the activation of subcortical auditory centers above the accepted threshold was only observed in STA. STA (less SBN) showed higher PSCs and T-statistic values in all ROIs except planum temporale when compared to CAm. However, there was no difference in signal variability among the datasets. CONCLUSION: Our results suggest that SBN should be considered as a significant confounder in auditory-evoked functional MRI studies particularly in the activation of subcortical auditory centers, and that STA can be an effective imaging method for reducing the effect of SBN.

Evaluation of Hippocampal Volume Based on Various Inversion Time in Normal Adults by Manual Tracing and Automated Segmentation Methods

PURPOSE: To investigate the value of image post-processing software (FreeSurfer, IBASPM [individual brain atlases using statistical parametric mapping software]) and inversion time (TI) in volumetric analyses of the hippocampus and to identify differences in comparison with manual tracing. MATERIALS AND METHODS: Brain images from 12 normal adults were acquired using magnetization prepared rapid acquisition gradient echo (MPRAGE) with a slice thickness of 1.3 mm and TI of 800, 900, 1000, and 1100 ms. Hippocampal volumes were measured using FreeSurfer, IBASPM and manual tracing. Statistical differences were examined using correlation analyses accounting for spatial interpretations percent volume overlap and percent volume difference. RESULTS: FreeSurfer revealed a maximum percent volume overlap and maximum percent volume difference at TI = 800 ms (77.1 +/- 2.9%) and TI = 1100 ms (13.1 +/- 2.1%), respectively. The respective values for IBASPM were TI = 1100 ms (55.3 +/- 9.1%) and TI = 800 ms (43.1 +/- 10.7%). FreeSurfer presented a higher correlation than IBASPM but it was not statistically significant. CONCLUSIONS: FreeSurfer performed better in volumetric determination than IBASPM. Given the subjective nature of manual tracing, automated image acquisition and analysis image is accurate and preferable.

Reduced Gray Matter Volume of Auditory Cortical and Subcortical Areas in Congenitally Deaf Adolescents: A Voxel-Based Morphometric Study

PURPOSE: Several morphometric studies have been performed to investigate brain abnormalities in congenitally deaf people. But no report exists concerning structural brain abnormalities in congenitally deaf adolescents. We evaluated the regional volume changes in gray matter (GM) using voxel-based morphometry (VBM) in congenitally deaf adolescents. MATERIALS AND METHODS: A VBM8 methodology was applied to the T1-weighted magnetic resonance imaging (MRI) scans of eight congenitally deaf adolescents (mean age, 15.6 years) and nine adolescents with normal hearing. All MRI scans were normalized to a template and then segmented, modulated, and smoothed. Smoothed GM data were tested statistically using analysis of covariance (controlled for age, gender, and intracranial cavity volume). RESULTS: The mean values of age, gender, total volumes of GM, and total intracranial volume did not differ between the two groups. In the auditory centers, the left anterior Heschl's gyrus and both inferior colliculi showed decreased regional GM volume in the congenitally deaf adolescents. The GM volumes of the lingual gyri, nuclei accumbens, and left posterior thalamic reticular nucleus in the midbrain were also decreased. CONCLUSIONS: The results of the present study suggest that early deprivation of auditory stimulation in congenitally deaf adolescents might have caused significant underdevelopment of the auditory cortex (left Heschl's gyrus), subcortical auditory structures (inferior colliculi), auditory gain controllers (nucleus accumbens and thalamic reticular nucleus), and multisensory integration areas (inferior colliculi and lingual gyri). These defects might be related to the absence of general auditory perception, the auditory gating system of thalamocortical transmission, and failure in the maturation of the auditory-to-limbic connection and the auditorysomatosensory-visual interconnection.

Regional Gray Matter Volume Reduction Associated with Major Depressive Disorder: A Voxel-Based Morphometry

BACKGROUND AND PURPOSE: The association between the low emotional regulation and the brain structural change of major depressive disorder (MDD) has been proposed, but the voxel-based morphometry (VBM) studies on female MDD are rare. The purpose of the present study was to show the regional volume changes of gray matter (GM) in female patients with MDD by optimized VBM. METHODS: To control subjects homogeneity, twenty female MDD patients and age, sex matched 21 normal controls were included for the VBM analysis. To identify the change of regional gray matter volume (GMV), the optimized VBM was performed with T1 MRIs. The amounts of gray/white matter and intracranial cavity volumes (ICV) were measured. The analysis of covariance (ANCOVA) and partial correlation analyses covariate with age and ICV were applied for VBM. RESULTS: The age and ICV distributions were similar between the two groups. In the ANCOVA, the total GMV of MDD was smaller than that of normal controls. In the VBM, regional GMV was relatively decreased in the limbic system (amygdalae, ambient gyri, hippocampi heads, subiculum, posterior parahippocampal gyri, pulvinar nuclei, dorsal posterior cingulate gyri, and left pregenual cingulate gyrus). The lingual gyri, short insular gyri, right fusiform gyrus, and right inferior frontal gyrus were also showed decreased regional GMV. CONCLUSION: The results of this study indicate that the female MDD is mainly associated with the structural deficits of the limbic system and limbic system related cortices, which were known to the center of emotions.