Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder.

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder.

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.

Abnormal resting-state functional connectivity of the insula in medication-free patients with obsessive-compulsive disorder.

BACKGROUND: The function of the insula has been increasingly mentioned in neurocircuitry models of obsessive-compulsive disorder (OCD) for its role in affective processing and regulating anxiety and its wide interactions with the classic cortico-striato-thalamo-cortical circuit. However, the insular resting-state functional connectivity patterns in OCD remain unclear. Therefore, we aimed to investigate characteristic intrinsic connectivity alterations of the insula in OCD and their associations with clinical features. METHODS: We obtained resting-state functional magnetic resonance imaging data from 85 drug-free OCD patients and 85 age- and sex-matched healthy controls (HCs). We performed a general linear model to compare the whole-brain intrinsic functional connectivity maps of the bilateral insula between the OCD and HC groups. In addition, we further explored the relationship between the intrinsic functional connectivity alterations of the insula and clinical features using Pearson or Spearman correlation analysis. RESULTS: Compared with HCs, patients with OCD exhibited increased intrinsic connectivity between the bilateral insula and bilateral precuneus gyrus extending to the inferior parietal lobule and supplementary motor area. Decreased intrinsic connectivity was only found between the right insula and bilateral lingual gyrus in OCD patients relative to HC subjects, which was negatively correlated with the severity of depression symptoms in the OCD group. CONCLUSION: In the current study, we identified impaired insular intrinsic connectivity in OCD patients and the dysconnectivity of the right insula and bilateral lingual gyrus associated with the depressive severity of OCD patients. These findings provide neuroimaging evidence for the involvement of the insula in OCD and suggest its potential role in the depressive symptoms of OCD.

Temporal variability of regional intrinsic neural activity in drug-naïve patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) displays alterations in regional brain activity represented by the amplitude of low-frequency fluctuation (ALFF), but the time-varying characteristics of this local neural activity remain to be clarified. We aimed to investigate the dynamic changes of intrinsic brain activity in a relatively large sample of drug-naïve OCD patients using univariate and multivariate analyses. We applied a sliding-window approach to calculate the dynamic ALFF (dALFF) and compared the difference between 73 OCD patients and age- and sex-matched healthy controls (HCs). We also utilized multivariate pattern analysis to determine whether dALFF could differentiate OCD patients from HCs at the individual level. Compared with HCs, OCD patients exhibited increased dALFF mainly within regions of the cortical-striatal-thalamic-cortical (CSTC) circuit, including the bilateral dorsal anterior cingulate cortex, medial prefrontal cortex and striatum, and right dorsolateral prefrontal cortex (dlPFC). Decreased dALFF was identified in the bilateral inferior parietal lobule (IPL), posterior cingulate cortex, insula, fusiform gyrus, and cerebellum. Moreover, we found negative correlations between illness duration and dALFF values in the right IPL and between dALFF values in the left cerebellum and Hamilton Depression Scale scores. Furthermore, dALFF can distinguish OCD patients from HCs with the most discriminative regions located in the IPL, dlPFC, middle occipital gyrus, and cuneus. Taken together, in the current study, we demonstrated a characteristic pattern of higher variability of regional brain activity within the CSTC circuits and lower variability in regions outside the CSTC circuits in drug-naïve OCD patients.

Alterations in hippocampal subfield and amygdala subregion volumes in posttraumatic subjects with and without posttraumatic stress disorder.

The hippocampus and amygdala are important structures in the posttraumatic stress disorder (PTSD); however, the exact relationship between these structures and stress or PTSD remains unclear. Moreover, they consist of several functionally distinct subfields/subregions that may serve different roles in the neuropathophysiology of PTSD. Here we present a subregional profile of the hippocampus and amygdala in 145 survivors of a major earthquake and 56 non-traumatized healthy controls (HCs). We found that the bilateral hippocampus and left amygdala were significantly smaller in survivors than in HCs, and there was no difference between survivors with (n = 69) and without PTSD (trauma-exposed controls [TCs], n = 76). Analyses revealed similar results in most subfields/subregions, except that the right hippocampal body (in a head-body-tail segmentation scheme), right presubiculum, and left amygdala medial nuclei (Me) were significantly larger in PTSD patients than in TCs but smaller than in HCs. Larger hippocampal body were associated with the time since trauma in PTSD patients. The volume of the right cortical nucleus (Co) was negatively correlated with the severity of symptoms in the PTSD group but positively correlated with the same measurement in the TC group. This correlation between symptom severity and Co volume was significantly different between the PTSD and TCs. Together, we demonstrated that generalized smaller volumes in the hippocampus and amygdala were more likely to be trauma-related than PTSD-specific, and their subfields/subregions were distinctively affected. Notably, larger left Me, right hippocampal body and presubiculum were PTSD-specific; these could be preexisting factors for PTSD or reflect rapid posttraumatic reshaping.

Data-driven clustering differentiates subtypes of major depressive disorder with distinct brain connectivity and symptom features.

BACKGROUND: Major depressive disorder (MDD) is a clinically and biologically heterogeneous syndrome. Identifying discrete subtypes of illness with distinguishing neurobiological substrates and clinical features is a promising strategy for guiding personalised therapeutics. AIMS: This study aimed to identify depression subtypes with correlated patterns of functional network connectivity and clinical symptoms by clustering patients according to a weighted linear combination of both features in a relatively large, medication-naïve depression sample. METHOD: We recruited 115 medication-naïve adults with MDD and 129 matched healthy controls, and evaluated all participants with magnetic resonance imaging. We used regularised canonical correlation analysis to identify component mapping relationships between functional network connectivity and symptom profiles, and K-means clustering was used to define distinct subtypes of patients. RESULTS: Two subtypes of MDD were identified: insomnia-dominated subtype 1 and anhedonia-dominated subtype 2. Subtype 1 was characterised by abnormal hyperconnectivity within the ventral attention network and sleep maintenance insomnia. Subtype 2 was characterised by abnormal hypoconnectivity in the subcortical and dorsal attention networks, and prominent anhedonia symptoms. CONCLUSIONS: Our study identified two distinct subtypes of patients with specific neurobiological and clinical symptom profiles. These findings advance understanding of the biological and clinical heterogeneity of MDD, offering a pathway for defining categorical subtypes of illness via consideration of both biological and clinical features.

Anatomic alterations across amygdala subnuclei in medication-free patients with obsessive-compulsive disorder.

Background: The amygdala has been implicated in obsessive-compulsive disorder (OCD), a common, disabling illness. However, the regional distribution of anatomic alterations in this structure and their association with the symptoms of OCD remains to be established. Methods: We collected high-resolution 3D T1-weighted images from 81 untreated patients with OCD and no lifetime history of comorbid psychotic, affective or anxiety disorders, and from 95 age- and sex-matched healthy controls. We extracted the volume of the central nucleus of the amygdala (CeA) and the basolateral complex of the amygdala (BLA) and compared them across groups using FreeSurfer 6.0. In exploratory analyses, we evaluated other subnuclei, including the cortical medial nuclei, the anterior amygdaloid area, and the corticoamygdaloid transition area. Results: Patients with OCD had reduced amygdala volume bilaterally compared with healthy controls (left, p = 0.034; right, p = 0.002). Volume reductions were greater in the CeA (left: -11.9%, p = 0.002; right: -13.3%, p < 0.001) than in the BLA (left lateral nucleus: -3.3%, p = 0.029; right lateral nucleus: -3.9%, p = 0.018; right basal nucleus: -4.1%, p = 0.017; left accessory basal nucleus: -6.5%, p = 0.001; right accessory basal nucleus: -9.3%, p < 0.001). Volume reductions in the CeA were associated with illness duration. Exploratory analysis revealed smaller medial (left: -15.4%, p < 0.001, η2 = 0.101) and cortical (left: -9.1%, p = 0.001, η2 = 0.058; right: -15.4%, p < 0.001, η2 = 0.175) nuclei in patients with OCD compared with healthy controls. Limitations: Although the strict exclusion criteria used in the study helped us to identify OCD-specific alterations, they may have limited generalizability to the broader OCD population. Conclusion: Our results provide a comprehensive anatomic profile of alterations in the amygdala subnuclei in untreated patients with OCD and highlight a distinctive pattern of volume reductions across subnuclei in OCD. Based on the functional properties of the amygdala subnuclei established from preclinical research, CeA impairment may contribute to behavioural inflexibility, and BLA disruption may be responsible for altered fear conditioning and the affective components of OCD.

Quantitative tractography reveals changes in the corticospinal tract in drug-naïve children with attention-deficit/hyperactivity disorder

Background: The specific role of the corticospinal tract with respect to inattention and impulsive symptoms in children with attention-deficit/hyperactivity disorder (ADHD) has been explored in the past. However, to our knowledge, no study has identified the exact regions of the corticospinal tract that are affected in ADHD. We aimed to determine comprehensive alterations in the white matter microstructure of the corticospinal tract and underlying neuropsychological substrates in ADHD. Methods: We recruited 38 drug-naïve children with ADHD and 34 typically developing controls. We employed a tract-based quantitative approach to measure diffusion parameters along the trajectory of the corticospinal tract, and we further correlated alterations with attention and response inhibition measures. Results: Compared with controls, children with ADHD demonstrated significantly lower fractional anisotropy and higher radial diffusivity at the level of cerebral peduncle, and higher fractional anisotropy at the level of the posterior limb of the internal capsule in the right corticospinal tract only. As well, increased fractional anisotropy in the posterior limb of the internal capsule was negatively correlated with continuous performance test attention quotients and positively correlated with reaction time on the Stroop Colour­Word Test; increased radial diffusivity in the right peduncle region was positively correlated with omissions in the Stroop test. Limitations: The sample size was relatively small. Moreover, we did not consider the different subtypes of ADHD and lacked sufficient power to analyze subgroup differences. Higher-order diffusion modelling is needed in future white matter studies. Conclusion: We demonstrated specific changes in the right corticospinal tract in children with ADHD. Correlations with measures of attention and response inhibition underscored the functional importance of corticospinal tract disturbance in ADHD.

White matter disruption in obsessive-compulsive disorder revealed by meta-analysis of tract-based spatial statistics.

BACKGROUND: Exploring white matter (WM) microstructural alterations is a momentous step for gaining insights about underlying mechanisms of obsessive-compulsive disorder (OCD) and improving the efficacy of therapies for this condition. Many tract-based spatial statistics (TBSS) studies have revealed abnormalities of fractional anisotropy (FA; an index of WM integrity) in OCD. However, research works have not drawn robust conclusions. Therefore, we integrated the findings of TBSS studies to identify the most consistent FA changes in OCD using meta-analytical approach. METHODS: Online databases were systematically searched for all TBSS studies comparing FA between patients with OCD and controls. A coordinate-based meta-analysis was performed using anisotropic effect size version of the seed-based d mapping software. Meanwhile, meta-regression was used to explore the potential association of clinical characteristics with regional FA abnormalities. RESULTS: Our meta-analysis included 488 OCD patients and 519 controls across 17 datasets. FA reductions were identified in the genu of the corpus callosum and the left orbitofrontal WM in OCD patients relative to controls. Metaregression analyses showed that the FA in the left orbitofrontal WM was negatively and independently correlated with symptom severity and illness duration in patients with OCD. CONCLUSIONS: The current study provides a quantitative overview of TBSS findings in OCD and demonstrates the most prominent and replicable WM abnormalities in OCD are in the anterior part of the brain including interhemispheric connection and orbitofrontal region. Additionally, our findings suggest that FA reduction in the orbitofrontal WM might be a potential biomarker in predicting disease severity and progression in patients with OCD.

Abnormalities of hippocampal shape and subfield volumes in medication-free patients with obsessive-compulsive disorder.

In this study, we sought to identify alterations of hippocampal shape and subfield volumes in a relatively large sample of medication-free obsessive-compulsive disorder (OCD) patients without comorbid depression. 3D T1-weighted Magnetic Resonance Imaging scans were collected from 81 medication-free OCD patients and 95 age- and sex-matched healthy controls (HC). Total hippocampal volume and volume of eight bilateral subfields were measured using FreeSurfer software. Subregional shape deformity was examined via FSL software. Volumetric and shape differences between groups and correlations with OCD symptoms were examined. The volume of right hippocampus was significantly reduced in OCD patients (p = .001, η2 = 0.065). Follow-up analysis of right hemisphere subfields showed reduced volume in right subiculum (p < .001, η2 = 0.081), presubiculum (p < .001, η2 = 0.125), CA2/3 (p = .001, η2 = 0.06), and hippocampal tail (p < 0.001, η2 = 0.105), while the volume of right fimbria was increased (p = .001, η2 = 0.058). Shape analysis revealed a bilateral outward bending in the hippocampal body related to a lateral displacement of hippocampus from the body to the tail. Symptom severity was correlated with volumes of presubiculum (with compulsions, r = -0.25, p = .024) and fimbria (with obsessions, r = -0.28, p = .012), and with the lateral shift of middle and posterior hippocampus (with obsessions). Alterations across hippocampal subfields and overall shape may contribute to the distinctive cognitive and affective abnormalities associated with OCD.

Impairments of large-scale functional networks in attention-deficit/hyperactivity disorder: a meta-analysis of resting-state functional connectivity.

Altered resting-state functional connectivity (rsFC) has been noted in large-scale functional networks in attention-deficit/hyperactivity disorder (ADHD). However, identifying consistent abnormalities of functional networks is difficult due to varied methods and results across studies. To integrate rsFC alterations and search for coherent patterns of intrinsic functional network impairments in ADHD, this research conducts a coordinate-based meta-analysis of voxel-wise seed-based rsFC studies comparing rsFC between ADHD patients and healthy controls. A total of 25 datasets from 21 studies including 700 ADHD patients and 580 controls were analyzed. We extracted the coordinates of seeds and between-group effects. Each seed was then categorized into a seed-network by its location within priori 7-network parcellations. Then, pooled meta-analyses were conducted for the default mode network (DMN), frontoparietal network (FPN) and affective network (AN) separately, but not for the ventral attention network (VAN), dorsal attention network (DAN), somatosensory network (SSN) and visual network due to a lack of primary studies. The results showed that ADHD was characterized by hyperconnectivity between the FPN and regions of the DMN and AN as well as hypoconnectivity between the FPN and regions of the VAN and SSN. These findings not only support the triple-network model of pathophysiology associated with ADHD but also extend this model by highlighting the involvement of the SSN and AN in the mechanisms of network interactions that may account for motor hyperactivity and impulsive symptoms.

Altered cortical morphology of visual cortex in adults with monocular amblyopia.

BACKGROUND: The neural mechanism of amblyopia and its impact on the adult brain remain unclear. This hinders effective treatment for adults with this disease. PURPOSE: To investigate neuroanatomical differences in cortical morphometry between amblyopic adults and healthy controls, and to explore the structural covariance of abnormal morphometric changes. STUDY TYPE: Prospective. POPULATION: Twenty-one amblyopic adults and 34 healthy controls. FIELD STRENGTH/SEQUENCE: 3T MRI, T1 -weighted, MPRAGE sequence. ASSESSMENT: All participants completed ophthalmologic exams to confirm the diagnosis of amblyopia or its absence in the healthy controls, including tests of ocular motility and dilation, fundus exam, autorefraction and synoptophore tests. Cortical volume, thickness, and surface area measurements were obtained using FreeSurfer software. STATISTICAL TESTS: Statistical differences of MRI measures between amblyopic adults and healthy controls were identified using a general linear model with intracranial volume and age as covariates. Monte Carlo simulations were used to correct for multiple comparisons. The structural covariance of abnormal morphometric changes and the relationship between morphometric abnormalities and visual acuity of the amblyopic eye were examined. RESULTS: Compared with healthy controls, amblyopic adults showed reduced cortical volume in left lateral occipital cortex, and decreased cortical thickness in bilateral inferior temporal gyrus and left precentral gyrus (P < 0.05; Monte Carlo corrected). Structural covariance between cortical volume of left lateral occipital cortex and cortical thickness of right inferior temporal gyrus in amblyopic adults was significantly less than in healthy controls (z = 1.73; P < 0.05). DATA CONCLUSION: Our study identified morphological abnormalities in occipital cortex and in temporal and frontal cortex which are projection fields of visual cortex important for processing of visual form and object location information, and disrupted structural covariance of visual cortex with other brain regions in amblyopic patients. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1405-1412.

Abnormal Hippocampal Subfields May Be Potential Predictors of Worse Early Response to Antidepressant Treatment in Drug-Naïve Patients With Major Depressive Disorder.

BACKGROUND: Previous studies had proved that hippocampal volume has predictive value for antidepressant response in patients with major depressive disorder (MDD). However, the exact subregion of the hippocampus relevant to the predictive role of antidepressants response is not known. PURPOSE: To explore which hippocampal subfield volumes might predict an early response to first-time use of antidepressants in drug-naïve MDD patients. STUDY TYPE: Prospective. POPULATION: Thirty-eight drug-naïve MDD patients (mean illness duration = 1.6 years) and 55 healthy control subjects (HCS). FIELD STRENGTH/SEQUENCE: 3.0T MRI, T1 -weighted, 3D, SPGR sequence. ASSESSMENT: The hippocampal subfields and total intracranial volume were measured with FreeSurfer. The response to antidepressants was evaluated by the reduction rate of the Hamilton Rating Scale for Depression score (RRS) after a 6-week routine clinical antidepressant treatment. STATISTICAL TESTS: The relationship between hippocampal subfield volumes and RRS was explored using partial correlation analysis. Volume differences among early responding patients (ERP), nonresponding patients (NRP), and HCS were examined by multivariate analysis of covariance. Receiver operating characteristic (ROC) curve analysis was used to evaluate the sensitivity and specificity of volumes as predictors. RESULTS: NRP had significantly larger volumes than both ERP and HCS in bilateral subiculum, cornu ammonis (CA) 1 and left CA2/3, CA4/dentate gyrus (DG) (all P < 0.01, false discovery rate corrected). Significant negative correlations were found between the RRS and volumes of left subiculum (P = 0.004), CA2/3 (P = 0.008), and CA4/DG (P = 0.004) in the whole MDD group. ROC analysis demonstrated that the left subiculum exhibited the highest accuracy for differentiating NRP from ERP, with a sensitivity of 76.9% and specificity of 80%. DATA CONCLUSION: These findings propose that volumes of certain hippocampal subfields may be associated with antidepressant treatment and this has potential use in clinical applications for treatment selection in patients with MDD at an early stage. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:1760-1768.

Anomalous functional connectivity of amygdala subregional networks in major depressive disorder.

OBJECTIVE: Amygdala-based network dysfunction has been found to be centrally implicated in major depressive disorder (MDD). However, relatively little is known about how different forms of effective or cognitive dysfunction are modulated in MDD. Therefore, in the current study, we aimed to examine the alteration of amygdala subregional networks in adult patients with MDD to explore whether different parts of the amygdala that are functionally connected to different regions contribute differently to the cerebral network mechanism of depression. METHODS: Resting-state fMRI scans were obtained from 70 medication-free adults with MDD and 70 age- and sex-matched healthy controls (HC). Functional connectivity maps of four distinct regions of the amygdala, including the amygdalostriatal transition area (AStr) and the basolateral (BLA), centromedial (CM) and superficial (SF) amygdala, were generated and compared between the two groups. RESULTS: Compared with HC, patients with MDD showed hypoconnectivity between the AStr/BLA and the orbitofrontal cortex (OFC), between the CM/SF and the brainstem/cerebellum, and within AStr/CM/SF-thalamic/striatal networks. Hyperconnectivity was observed between the left AStr/BLA and the fusiform gyrus. There was no difference in the gray matter volume of the amygdala or any of its subregions between the two groups. CONCLUSIONS: These findings suggest that amygdala subregional-network dysfunction in MDD is independent of structural changes and, more important, that hypoconnectivity and hyperconnectivity in different subregional networks may reflect imbalanced network function, which may modulate different forms of emotional and cognitive dysfunction in MDD.

[Hippocampal subfield volume alteration in post-traumatic stress disorder: a magnetic resonance imaging study].

In the current study, we aim to investigate whether post-traumatic stress disorder (PTSD) is associated with structural alterations in specific subfields of hippocampus comparing with trauma-exposed control (TC) in a relatively large sample. We included 67 PTSD patients who were diagnosed under Diagnostic and Statistical Manual of Mental Disorders (4th Edition) (DSM-Ⅳ) criteria and 78 age- and sex-matched non-PTSD adult survivors who experienced similar stressors. High resolution T1 weighted images were obtained via a GE 3.0 T scanner. The structural data was automatically segmented using FreeSurfer software, and volume of whole hippocampus and subfield including CA1, CA2-3, CA4-DG, fimbria, presubiculum, subiculum and fissure were extracted. Volume differences between the two groups were statistically compared with age, years of education, duration from the events and intracranial volume (ICV) as covariates. Hemisphere, sex and diagnosis were entered as fixed factors. Relationship between morphometric measurements with Clinician-Administered PTSD Scale (CAPS) score and illness duration were performed using Pearson's correlation with SPSS. Comparing to TC, PTSD patients showed no statistically significant alteration in volumes of the whole hippocampus and all the subfields ( P > 0.05). In male patients, there were significant correlations between CAPS score and volume of right CA2-3 ( R2 = 0.197, P = 0.034), right subiculum ( R2 = 0.245, P = 0.016), and duration statistically correlated with right fissure ( R2 = 0.247, P = 0.016). In female patients, CAPS scores significant correlated with volume of left presubiculum ( R2 = 0.095, P = 0.042), left subiculum ( R2 = 0.090, P = 0.048), and left CA4-DG ( R2 = 0.099, P = 0.037). The main findings of the current study suggest that stress event causes non-selective damage to hippocampus in both PTSD patients and TC, and gender-specific lateralization may underlie PTSD pathology.

Multivariate association between psychosocial environment, behaviors, and brain functional networks in adolescent depression.

BACKGROUND: Adolescent depression shows high clinical heterogeneity. Brain functional networks serve as a powerful tool for investigating neural mechanisms underlying depression profiles. A key challenge is to characterize how variation in brain functional organization links to behavioral features and psychosocial environmental influences. METHODS: We recruited 80 adolescents with major depressive disorder (MDD) and 42 healthy controls (HCs). First, we estimated the differences in functional connectivity of resting-state networks (RSN) between the two groups. Then, we used sparse canonical correlation analysis to characterize patterns of associations between RSN connectivity and symptoms, cognition, and psychosocial environmental factors in MDD adolescents. Clustering analysis was applied to stratify patients into homogenous subtypes according to these brain-behavior-environment associations. RESULTS: MDD adolescents showed significantly hyperconnectivity between the ventral attention and cingulo-opercular networks compared with HCs. We identified one reliable pattern of covariation between RSN connectivity and clinical/environmental features in MDD adolescents. In this pattern, psychosocial factors, especially the interpersonal and family relationships, were major contributors to variation in connectivity of salience, cingulo-opercular, ventral attention, subcortical and somatosensory-motor networks. Based on this association, we categorized patients into two subgroups which showed different environment and symptoms characteristics, and distinct connectivity alterations. These differences were covered up when the patients were taken as a whole group. CONCLUSION: This study identified the environmental exposures associated with specific functional networks in MDD youths. Our findings emphasize the importance of the psychosocial context in assessing brain function alterations in adolescent depression and have the potential to promote targeted treatment and precise prevention.

Distinctive intrinsic functional connectivity alterations of anterior cingulate cortex subdivisions in major depressive disorder: A systematic review and meta-analysis.

Evidence of whether the intrinsic functional connectivity of anterior cingulate cortex (ACC) and its subregions is altered in major depressive disorder (MDD) remains inconclusive. A systematic review and meta-analysis were therefore performed on the whole-brain resting-state functional connectivity (rsFC) studies using the ACC and its subregions as seed regions in MDD, in order to draw more reliable conclusions. Forty-four ACC-based rsFC studies were included, comprising 25 subgenual ACC-based studies, 11 pregenual ACC-based studies, and 17 dorsal ACC-based studies. Specific alterations of rsFC were identified for each ACC subregion in patients with MDD, with altered rsFC of subgenual ACC in emotion-related brain regions, of pregenual ACC in sensorimotor-related regions, and of dorsal ACC in cognition-related regions. Furthermore, meta-regression analysis revealed a significant negative correlation between the pgACC-caudate hypoconnectivity and percentage of female patients in the study cohort. This meta-analysis provides robust evidence of altered intrinsic functional connectivity of the ACC subregions in MDD, which may hold relevance to understanding the origin of, and treating, the emotional, sensorimotor and cognitive dysfunctions that are often observed in these patients.

Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: Alterations in the default mode network (DMN) have been reported in major depressive disorder (MDD), well-replicated robust alterations of functional connectivity (FC) of DMN remain to be established. Investigating the functional connections of DMN at the overall and subsystem level in early MDD patients has the potential to advance our understanding of the physiopathology of this disorder. METHODS: We recruited 115 first-episode drug-naïve patients with MDD and 137 demographic-matched healthy controls (HCs). We first compared FC within the DMN, within/between the DMN subsystems, and from DMN subsystems to the whole brain between groups. Subsequently, we explored correlations between clinical features and identified alterations in FC. RESULTS: First-episode drug-naïve patients with MDD showed significantly increased FC within the DMN, dorsal DMN and medial DMN. Each subsystem showed a distinct FC pattern with other brain networks. Increased FC between the subsystems (core DMN, dorsal DMN) and other networks was associated with more severe depressive symptoms, while medial DMN-related connectivity correlated with memory performance. LIMITATIONS: The relatively large "pure" MDD sample could only be generalized to a limited population. And, atypical asymmetric FCs in the DMN related to MDD might be missed for only left-lateralized ROIs were used to avoid strong correlations between mirrored (right/left) seed regions. CONCLUSION: These findings suggest patients with early MDD showed distinct patterns of FC alterations throughout DMN and its subsystems, which were related to illness severity and illness-associated cognitive impairment, highlighting their clinical significance.

Divergent effects of sex on hippocampal subfield alterations in drug-naive patients with major depressive disorder.

BACKGROUND: The hippocampus is a crucial brain structure in etiological models of major depressive disorder (MDD). It remains unclear whether sex differences in the incidence and symptoms of MDD are related to differential illness-associated brain alterations, including alterations in the hippocampus. This study investigated divergent the effects of sex on hippocampal subfield alterations in drug-naive patients with MDD. METHODS: High-resolution structural MR images were obtained from 144 drug-naive individuals with MDD early in their illness course and 135 age- and sex-matched healthy controls (HCs). Hippocampal subfields were segmented using FreeSurfer software and analyzed in terms of both histological subfields (CA1-4, dentate gyrus, etc.) and more integrative larger functional subregions (head, body and tail). RESULTS: We observed a significant overall reduction in hippocampal volume in MDD patients, with deficits more prominent deficits in the posterior hippocampus. Differences in anatomic alterations between male and female patients were observed in the CA1-head, presubiculum-body and fimbria in the left hemisphere. Exploratory analyses revealed different patterns of clinical and memory function correlations with histological subfields and functional subregions between male and female patients primarily in the hippocampal head and body. LIMITATIONS: This cross-sectional study cannot clarify the causality of hippocampal alterations or their association with illness risk or onset. CONCLUSIONS: These findings represent the first reported sex-specific alterations in hippocampal histological subfields in patients with MDD early in the illness course prior to treatment. Sex-specific hippocampal alterations may contribute to diverse sex differences in the clinical presentation of MDD.