Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder.

BACKGROUND: It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. METHODS: 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. RESULTS: In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. CONCLUSIONS: Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

Large-scale network abnormality in behavioral addiction.

BACKGROUND: Researchers have endeavored to ascertain the network dysfunction associated with behavioral addiction (BA) through the utilization of resting-state functional connectivity (rsFC). Nevertheless, the identification of aberrant patterns within large-scale networks pertaining to BA has proven to be challenging. METHODS: Whole-brain seed-based rsFC studies comparing subjects with BA and healthy controls (HC) were collected from multiple databases. Multilevel kernel density analysis was employed to ascertain brain networks in which BA was linked to hyper-connectivity or hypo-connectivity with each prior network. RESULTS: Fifty-six seed-based rsFC publications (1755 individuals with BA and 1828 HC) were included in the meta-analysis. The present study indicate that individuals with BAs exhibit (1) hypo-connectivity within the fronto-parietal network (FN) and hypo- and hyper-connectivity within the ventral attention network (VAN); (2) hypo-connectivity between the FN and regions of the VAN, hypo-connectivity between the VAN and regions of the FN and default mode network (DMN), hyper-connectivity between the DMN and regions of the FN; (3) hypo-connectivity between the reward system and regions of the sensorimotor network (SS), DMN and VAN; (4) hypo-connectivity between the FN and regions of the SS, hyper-connectivity between the VAN and regions of the SS. CONCLUSIONS: These findings provide impetus for a conceptual framework positing a model of BA characterized by disconnected functional coordination among large-scale networks.

A Multimodal Meta-Analytical Evidence of Functional and Structural Brain Abnormalities Across Alzheimer's Disease Spectrum.

BACKGROUND: Numerous neuroimaging studies have reported that Alzheimer's disease (AD) spectrum have been linked to alterations in intrinsic functional activity and cortical thickness (CT) of some brain areas. However, the findings have been inconsistent and the correlation with the transcriptional profile and neurotransmitter systems remain largely unknown. METHODS: We conducted a meta-analysis to identify multimodal differences in the amplitude of low-frequency fluctuation (ALFF)/fractional ALFF (fALFF) and CT in patients with AD and preclinical AD compared to healthy controls (HCs), using the Seed-based d Mapping with Permutation of Subject Images software. Transcriptional data were retrieved from the Allen Human Brain Atlas. The atlas-based nuclear imaging-derived neurotransmitter maps were investigated by JuSpace toolbox. RESULTS: We included 26 ALFF/fALFF studies comprising 884 patients with AD and 1,020 controls, along with 52 studies comprising 2,046 patients with preclinical AD and 2,336 controls. For CT, we included 11 studies comprising 353 patients with AD and 330 controls. Overall, compared to HCs, patients with AD showed decreased ALFF/fALFF in the bilateral posterior cingulate gyrus (PCC)/precuneus and right angular gyrus, as well as increased ALFF/fALFF in the bilateral parahippocampal gyrus (PHG). Patients with peclinical AD showed decreased ALFF/fALFF in the left precuneus. Additionally, patients with AD displayed decreased CT in the bilateral PHG, left PCC, bilateral orbitofrontal cortex, sensorimotor areas and temporal lobe. Furthermore, gene sets related to brain structural and functional changes in AD and preclincal AD were enriched for G protein-coupled receptor signaling pathway, ion gated channel activity, and components of biological membrane. Functional and structural alterations in AD and preclinical AD were spatially associated with dopaminergic, serotonergic, and GABAergic neurotransmitter systems. CONCLUSIONS: The multimodal meta-analysis demonstrated that patients with AD exhibited convergent functional and structural alterations in the PCC/precuneus and PHG, as well as cortical thinning in the primary sensory and motor areas. Furthermore, patients with preclinical AD showed reduced functional activity in the precuneus. AD and preclinical AD showed genetic modulations/neurotransmitter deficits of brain functional and structural impairments. These findings may provide new insights into the pathophysiology of the AD spectrum.

The effectiveness of vortioxetine on neurobiochemical metabolites and cognitive of major depressive disorders patients: A 8-week follow-up study.

OBJECTIVE: Vortioxetine has been shown to improve cognitive performance in people with depression. This study will look at the changes in neurobiochemical metabolites that occur when vortioxetine improves cognitive performance in MDD patients, with the goal of determining the neuroimaging mechanism through which vortioxetine improves cognitive function. METHODS: 30 depressed patients and 30 demographically matched healthy controls (HC) underwent MCCB cognitive assessment and 1H-MRS. After 8 weeks of vortioxetine medication, MCCB and 1H-MRS tests were retested in the MDD group. Before and after therapy, changes in cognitive performance, NAA/Cr, and Cho/Cr were examined in the MDD group. RESULTS: Compared with the HC group, the MDD group had significant reduced in verbal learning, social cognition, and total cognition (all p < 0.05). And the MDD group had lower NAA/Cr in Right thalamus and Left PFC; the Cho/Cr in Right thalamus was lower than HC; the Cho/Cr in Left ACC had significantly increase (all p < 0.05). The MDD group showed significant improvements in the areas of verbal learning, attention/alertness, and total cognitive function before and after Vortioxetine treatment (all p < 0.05). The NAA/Cr ratio of the right PFC before and after treatment (t = 2.338, p = 0.026) showed significant changes. CONCLUSIONS: Vortioxetine can enhance not just the depression symptoms of MDD patients in the initial period, but also their verbal learning, social cognition, and general cognitive capacities after 8 weeks of treatment. Furthermore, vortioxetine has been shown to enhance cognitive function in MDD patients by altering NAA/Cr and Cho/Cr levels in the frontal-thalamic-ACC.

A multimodal meta-analysis of regional functional and structural brain abnormalities in obsessive-compulsive disorder.

Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed abnormalities in specific brain regions in obsessive-compulsive disorder (OCD), but results have been inconsistent. We conducted a whole-brain voxel-wise meta-analysis on resting-state functional imaging and VBM studies that investigated differences of functional activity and gray matter volume (GMV) between patients with OCD and healthy controls (HCs) using seed-based d mapping (SDM) software. A total of 41 independent studies (51 datasets) for resting-state functional imaging and 42 studies (46 datasets) for VBM were included by a systematic literature search. Overall, patients with OCD displayed increased spontaneous functional activity in the bilateral inferior frontal gyrus (IFG) (extending to the bilateral insula) and bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), as well as decreased spontaneous functional activity in the bilateral paracentral lobule, bilateral cerebellum, left caudate nucleus, left inferior parietal gyri, and right precuneus cortex. For the VBM meta-analysis, patients with OCD displayed increased GMV in the bilateral thalamus (extending to the bilateral cerebellum), right striatum, and decreased GMV in the bilateral mPFC/ACC and left IFG (extending to the left insula). The conjunction analyses found that the bilateral mPFC/ACC, left IFG (extending to the left insula) showed decreased GMV with increased intrinsic function in OCD patients compared to HCs. This meta-analysis demonstrated that OCD exhibits abnormalities in both function and structure in the bilateral mPFC/ACC, insula, and IFG. A few regions exhibited only functional or only structural abnormalities in OCD, such as the default mode network, striatum, sensorimotor areas, and cerebellum. It may provide useful insights for understanding the underlying pathophysiology of OCD and developing more targeted and efficacious treatment and intervention strategies.

Increased functional connectivity between the midbrain and frontal cortex following bright light therapy in subthreshold depression: A randomized clinical trial.

The underlying mechanisms of bright light therapy (BLT) in the prevention of individuals with subthreshold depression symptoms are yet to be elucidated. The goal of the study was to assess the correlation between midbrain monoamine-producing nuclei treatment-related functional connectivity (FC) changes and depressive symptom improvements in subthreshold depression. This double-blind, randomized, placebo-controlled clinical trial was conducted between March 2020 and June 2022. A total of 74 young adults with subthreshold depression were randomly assigned to receive 8-week BLT (N = 38) or placebo (N = 36). Depression severity was measured using the Hamilton Depression Rating Scale (HDRS). The participants underwent resting-state functional magnetic resonance imaging at baseline and after treatment. The dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and habenula seed-based whole-brain FC were analyzed. A multivariate regression model examined whether baseline brain FC was associated with changes in scores on HDRS during BLT treatment. BLT group displayed significantly decreased HDRS scores from pre- to posttreatment compared to the placebo group. BLT increased the FC between the DRN and medial prefrontal cortex (mPFC) and between the left VTA and right superior frontal gyrus (SFG). Altered VTA-SFG connectivity was associated with HDRS changes in the BLT group. Moreover, the baseline FC between DRN and mPFC could predict HDRS changes in BLT. These results suggested that BLT improves depressive symptoms and increases midbrain monoamine-producing nuclei and frontal cortex connectivity in subthreshold depression, which raises the possibility that pretreatment FC of DRN-mPFC could be used as a biomarker for improved BLT treatment in depression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hippocampal Dynamic Functional Connectivity, HPA Axis Activity, and Personality Trait in Bipolar Disorder with Suicidal Attempt.

INTRODUCTION: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. METHODS: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). RESULTS: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. CONCLUSION: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.

Biochemical metabolism in the anterior cingulate cortex and cognitive function in major depressive disorder with or without insomnia syndrome.

BACKGROUND: Major depressive disorder (MDD) and insomnia have been linked to deficiencies in cognitive performance. However, the underlying mechanism of cognitive impairment in MDD patients with insomnia symptoms (IS) remains unclear. This study aimed to explore the effects of IS in patients with MDD by comparing cognitive function indices among those with IS, those without insomnia symptoms (NIS), and healthy controls (HCs). In addition, we assessed whether the dysfunction of central nervous system (CNS) is one of the important pathophysiologic mechanisms of IS in patients with MDD by comparing the biochemical metabolism ratios in the anterior cingulate cortex (ACC). METHOD: Fifty-five MDD with IS, 39 MDD without IS, and 47 demographically matched HCs underwent the MATRICS Consensus Cognitive Battery (MCCB) assessment and proton magnetic resonance spectroscopy (1H-MRS). MCCB cognitive scores and biochemical metabolism in ACC were assessed and compared between groups. RESULTS: Compared to the HCs group, IS and NIS groups scored significantly lower in seven MCCB cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning problem solving and social cognition). IS group showed a lower speed of processing and lower Cho/Cr ratio in the left ACC vs. NIS group and HCs. Also, in IS group, the Cho/Cr ratio in the left ACC was positively correlated with the composite T-score. CONCLUSION: Patients with comorbidity of MDD with IS may exhibit more common MCCB cognitive impairments than those without IS, particularly speed of processing. Also, dysfunction of ACC may underlie the neural substrate of cognitive impairment in MDD with IS.

Functional and structural brain abnormalities in substance use disorder: A multimodal meta-analysis of neuroimaging studies.

INTRODUCTION: Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed that patients with substance use disorder (SUD) may present brain abnormalities, but their results were inconsistent. This multimodal neuroimaging meta-analysis aimed to estimate common and specific alterations in SUD patients by combining information from all available studies of spontaneous functional activity and gray matter volume (GMV). METHODS: A whole-brain meta-analysis on resting-state functional imaging and VBM studies was conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software, followed by multimodal overlapping to comprehensively investigate function and structure of the brain in SUD. RESULTS: In this meta-analysis, 39 independent studies with 47 datasets related to resting-state functional brain activity (1444 SUD patients; 1446 healthy controls [HCs]) were included, as well as 77 studies with 89 datasets for GMV (3457 SUD patients; 3774 HCs). Patients with SUD showed the decreased resting-state functional brain activity in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC). For the VBM meta-analysis, patients with SUD showed the reduced GMV in the bilateral ACC/mPFC, insula, thalamus extending to striatum, and left sensorimotor cortex. CONCLUSIONS: This multimodal meta-analysis exhibited that SUD shows common impairment in both function and structure in the ACC/mPFC, suggesting that the deficits in functional and structural domains could be correlated together. In addition, a few regions exhibited only structural impairment in SUD, including the insula, thalamus, striatum, and sensorimotor areas.

Alterations of insular dynamic functional connectivity and psychological characteristics in unmedicated bipolar depression patients with a recent suicide attempt.

BACKGROUND: Mounting evidence showed that insula contributed to the neurobiological mechanism of suicidal behaviors in bipolar disorder (BD). However, no studies have analyzed the dynamic functional connectivity (dFC) of insular Mubregions and its association with personality traits in BD with suicidal behaviors. Therefore, we investigated the alterations of dFC variability in insular subregions and personality characteristics in BD patients with a recent suicide attempt (SA). METHODS: Thirty unmedicated BD patients with SA, 38 patients without SA (NSA) and 35 demographically matched healthy controls (HCs) were included. The sliding-window analysis was used to evaluate whole-brain dFC for each insular subregion seed. We assessed between-group differences of psychological characteristics on the Minnesota Multiphasic Personality Inventory-2. Finally, a multivariate regression model was adopted to predict the severity of suicidality. RESULTS: Compared to NSA and HCs, the SA group exhibited decreased dFC variability values between the left dorsal anterior insula and the left anterior cerebellum. These dFC variability values could also be utilized to predict the severity of suicidality (r = 0.456, p = 0.031), while static functional connectivity values were not appropriate for this prediction. Besides, the SA group scored significantly higher on the schizophrenia clinical scales (p < 0.001) compared with the NSA group. CONCLUSIONS: Our findings indicated that the dysfunction of insula-cerebellum connectivity may underlie the neural basis of SA in BD patients, and highlighted the dFC variability values could be considered a neuromarker for predictive models of the severity of suicidality. Moreover, the psychiatric features may increase the vulnerability of suicidal behavior.

Cognitive dysfunction and neurometabolic alternations in major depressive disorder with gastrointestinal symptoms.

BACKGROUND: Brain biochemical abnormalities have been associated with major depressive disorder (MDD) and cognitive impairments. However, the cognitive performance and neurometabolic alterations of MDD patients accompanied by gastrointestinal (GI) symptoms remain to be elucidated. We aimed to reveal the features and correlation between cognitive impairments and brain biochemical abnormalities of depressed patients with GI symptoms. METHODS: Fifty MDD patients with GI symptoms (GI group), 46 patients without GI symptoms (NGI group) and 50 demographically matched healthy controls (HCs) underwent Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) assessments. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to obtain ratios of N-acetyl aspartate to creatine (NAA/Cr) and choline-containing compounds to creatine (Cho/Cr) in the thalamus, putamen and anterior cingulate cortex (ACC). Finally, association analysis was conducted to investigate the relationships of these measurements. RESULTS: Compared to HCs, participants in both the GI and NGI groups had significantly reduced performance in the six MCCB cognitive domains (all p < 0.05), except for reasoning and problem solving. Higher Cho/Cr ratios in the right thalamus (p < 0.05) and lower NAA/Cr ratios in the left putamen (p < 0.05) were found in the NGI group than in the GI group. The severity of GI symptoms was negatively correlated with Cho/Cr ratios in the right ACC (r = -0.288, p = 0.037). In addition, the T-scores of visual learning were negatively correlated with NAA/Cr ratios in the right ACC (r = -0.443, p = 0.001) and right thalamus (r = -0.335, p = 0.015). CONCLUSION: Our findings suggest that MDD patients with GI symptoms may exhibit greater neurometabolic alternations than those without GI symptoms, while both show similar cognitive dysfunction. In addition, neurometabolic alterations in the ACC and thalamus may underlie the neural basis of GI symptoms and cognitive impairment in MDD.

Functional and structural brain differences in bipolar disorder: a multimodal meta-analysis of neuroimaging studies.

BACKGROUND: Numerous studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed differences in specific brain regions of patients with bipolar disorder (BD), but the results have been inconsistent. METHODS: A whole-brain voxel-wise meta-analysis was conducted on resting-state functional imaging and VBM studies that compared differences between patients with BD and healthy controls using Seed-based d Mapping with Permutation of Subject Images software. RESULTS: A systematic literature search identified 51 functional imaging studies (1842 BD and 2190 controls) and 83 VBM studies (2790 BD and 3690 controls). Overall, patients with BD displayed increased resting-state functional activity in the left middle frontal gyrus, right inferior frontal gyrus (IFG) extending to the right insula, right superior frontal gyrus and bilateral striatum, as well as decreased resting-state functional activity in the left middle temporal gyrus extending to the left superior temporal gyrus and post-central gyrus, left cerebellum, and bilateral precuneus. The meta-analysis of VBM showed that patients with BD displayed decreased VBM in the right IFG extending to the right insula, temporal pole and superior temporal gyrus, left superior temporal gyrus extending to the left insula, temporal pole, and IFG, anterior cingulate cortex, left superior frontal gyrus (medial prefrontal cortex), left thalamus, and right fusiform gyrus. CONCLUSIONS: The multimodal meta-analyses suggested that BD showed similar patterns of aberrant brain activity and structure in the insula extending to the temporal cortex, fronto-striatal-thalamic, and default-mode network regions, which provide useful insights for understanding the underlying pathophysiology of BD.

Aberrant dynamic functional connectivity in corticostriatal circuitry in depressed bipolar II disorder with recent suicide attempt.

BACKGROUND: The underlying neurobiological mechanisms on suicidal behavior in bipolar disorder remain unclear. We aim to explore the mechanisms of suicide by detecting dynamic functional connectivity (dFC) of corticostriatal circuitry and cognition in depressed bipolar II disorder (BD II) with recent suicide attempt (SA). METHODS: We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 68 depressed patients with BD-II (30 with SA and 38 without SA) and 35 healthy controls (HCs). The whole-brain dFC variability of corticostriatal circuitry was calculated using a sliding-window analysis. Their correlations with cognitive dysfunction were further detected. Support vector machine (SVM) classification tested the potential of dFC to differentiate BD-II with SA from HCs. RESULTS: Increased dFC variability between the right vCa and the right insula was found in SA compared to non-SA and HCs, and negatively correlated with speed of processing. Decreased dFC variability between the left dlPu and the right postcentral gyrus was found in non-SA compared to SA and HCs, and positively correlated with reasoning problem-solving. Both SA and non-SA exhibited decreased dFC variability between the right dCa and the left MTG, and between the right dlPu and the right calcarine when compared to HCs. SVM classification achieved an accuracy of 75.24 % and AUC of 0.835 to differentiate SA from non-SA, while combining the abnormal dFC features between SA and non-SA. CONCLUSIONS: Aberrant dFC variability of corticostriatal circuitry may serve as potential neuromarker for SA in BD-II, which might help to discriminate suicidal BD-II patients from non-suicidal patients and HCs.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Similarities and differences in working memory and neurometabolism of obsessive-compulsive disorder and major depressive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) both showed cognitive impairment, and the altered neurometabolic may associate with cognitive impairment. However, there are limited comparative working memory (WM) and neuroimaging studies on these two disorders. Therefore, we investigated the characteristics of WM and neurometabolic changes in patients with OCD and MDD. METHODS: A total of 64 unmedicated patients (32 OCD and 32 MDD), and 33 healthy controls (HC) were included to conduct WM assessment comprising Digit Span Test (DST), 2-back task and Stroop Color and Word Test (SCWT). Additionally, all subjects underwent protons magnetic resonance spectroscopy (1H-MRS) to collect neurometabolic ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) in the prefrontal cortex (PFC) and lentiform nucleus (LN). Finally, differential and correlation analysis were conducted to investigate their characteristics and relationships. RESULTS: Compared with HC, both OCD and MDD patients exhibited a lower accuracy rate in the 2-back task, and only MDD patients performed worse in DST scores and longer reaction times in SCWT (all p < 0.05). Both OCD and MDD patients had lower NAA/Cr ratios in bilateral PFC (all p < 0.05). And the decreased NAA/Cr ratios in right PFC were positively correlated to DST scores in MDD group (r = 0.518, p = 0.003). CONCLUSIONS: Both OCD and MDD showed WM impairment and neurometabolic alterations in PFC. Besides, MDD performed more severe and broader WM impairment compared to OCD. Moreover, the dysfunction of PFC may underlie the neural basis of WM impairment in MDD.

Shared and specific characteristics of regional cerebral blood flow and functional connectivity in unmedicated bipolar and major depressive disorders.

BACKGROUND: Identifying brain similarities and differences between bipolar disorder (BD) and major depressive disorder (MDD) can help us better understand their pathophysiological mechanisms and develop more effective treatments. However, the features of whole-brain regional cerebral blood flow (CBF) and intrinsic functional connectivity (FC) underlying BD and MDD have not been directly compared. METHODS: Eighty-eight unmedicated BD II depression patients, 95 unmedicated MDD patients, and 96 healthy controls (HCs) underwent three-dimensional arterial spin labeling (3D ASL) and resting-state functional MRI (rs-fMRI). The functional properties of whole brain CBF and seed-based resting-state FC further performed based on those regions with changed CBF were analyzed between the three groups. RESULTS: The patients with BD and MDD showed commonly increased CBF in the left posterior lobe of the cerebellum and the left middle temporal gyrus (MTG) compared with HCs. The CBF of the left MTG was positively associated with 24-items Hamilton Depression Rating Scale scores in MDD patients. Decreased FC between the left posterior lobe of the cerebellum and the left inferior frontal gyrus (IFG) was observed only in patients with BD compared with HCs. CONCLUSION: Patients with BD and those with MDD shared common features of CBF in the posterior lobe of the cerebellum and the MTG. The altered posterior lobe of the cerebellum-IFG FC can be considered as a potential biomarker for the differentiation of patients with BD from those with MDD.

Thyroid hormones disturbances, cognitive deficits and abnormal dynamic functional connectivity variability of the amygdala in unmedicated bipolar disorder.

OBJECTIVE: Accumulating evidence suggests that hypothalamus-pituitary-thyroid (HPT) axis dysfunction is relevant to the neuropsychological and pathophysiology functions of bipolar disorder (BD). However, no research has investigated the inter-relationships among thyroid hormones disturbance, neurocognitive deficits, and aberrant brain function (particularly in the amygdala) in patients with BD. MATERIALS AND METHODS: Data of dynamic resting-state functional connectivity (rs-dFC) were gathered from 59 patients with unmedicated BD II during depressive episodes and 52 healthy controls (HCs). Four seeds were selected (the bilateral lateral amygdala and the bilateral medial amygdala). The sliding-window analysis was applied to investigate dynamic functional connectivity (dFC). Additionally, the serum thyroid hormone (free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4) and thyroid-stimulating hormone (TSH)) levels, and cognitive scores on the MATRICS Consensus Cognitive Battery (MCCB) in patients and HCs were detected. RESULTS: The BD group exhibited increased dFC variability between the left medial amygdala and right medial prefrontal cortex (mPFC) when compared with the HC group. Additionally, the BD group showed lower FT3, TT3, and TSH level, higher FT4 level, and poorer cognitive score. Moreover, a significant negative correlation was observed between the dFC variability of the left medial amygdala-right mPFC and TSH level, or reasoning and problem solving of MCCB score in BD group. Multiple regression analysis showed that the TSH level × dFC variability of the medial amygdala-mPFC was an independent predictor for cognitive processing speed in BD group. CONCLUSIONS: This study revealed patients with BD II depression had excessive variability in dFC between the medial amygdala and mPFC. Moreover, both HPT axis dysfunction and abnormal dFC of the amygdala-mPFC might be implicated in cognitive impairment in the early stages of BD.

Association between resting-state functional connectivity of amygdala subregions and peripheral pro-inflammation cytokines levels in bipolar disorder.

The pathophysiological mechanisms of bipolar disorder (BD) are not completely known, and systemic inflammation and immune dysregulation are considered as risk factors. Previous neuroimaging studies have proved metabolic, structural and functional abnormalities of the amygdala in BD, suggesting the vital role of amygdala in BD patients. This study aimed to test the underlying neural mechanism of inflammation-induced functional connectivity (FC) in the amygdala subregions of BD patients. Resting-state functional MRI (rs-fMRI) was used to delineate the amygdala FC from two pairs of amygdala seed regions (the bilateral lateral and medial amygdala) in 51 unmedicated BD patients and 69 healthy controls (HCs). The levels of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were measured in the serum. The correlation between abnormal levels of pro-inflammatory cytokines and FC values were calculated in BD patients. The BD group exhibited decreased FC between the right medial amygdala and bilateral medial frontal cortex (MFC), and decreased FC between the left medial amygdala and the left temporal pole (TP), right orbital inferior frontal gyrus compared with HCs. The BD patients had higher levels of TNF-α than HCs. Correlation analysis showed negative correlation between the TNF-α level and abnormal FC of the right medial amygdala-bilateral MFC; and negative correlation between TNF-α levels and abnormal FC of the left medial amygdala-left TP in BD group. These findings suggest that dysfunctional and immune dysregulation between the amygdala and the frontotemporal circuitry might play a critical role in the pathogenesis of BD.

Multimodal MRI reveals alterations of the anterior insula and posterior cingulate cortex in bipolar II disorders: A surface-based approach.

BACKGROUND: Bipolar disorder (BD) is a mental disorder with severe implications for those affected and their families. Previous studies detected brain structural and functional alterations in BD patients. However, very few studies conducted a multimodal MRI fusion analysis, and little is known about the role of common anomalies in the connectivity of BD. METHODS: We collected sMRI, rs-fMRI, and DTI data from 56 patients with unmedicated BD-II depression and 72 age-, sex- and handedness-matched healthy controls. We applied data-driven approaches to analyze multimodal MRI data and detected brain areas with significant group differences in cortical thickness (CT), amplitude of low frequency fluctuations (ALFF), and fractional anisotropy (FA) of the superficial white matter. We observed the common abnormal areas and took these areas as seeds to analyze the resting-state functional connectivity (RSFC) patterns in BD patients by overlapping these abnormal areas. RESULTS: The BD patients showed two common abnormal areas: (1) the left anterior insula (AI) with abnormal CT and FA, and (2) the left posterior cingulate cortex (PCC) with abnormal CT and ALFF. Seed-based analyses showed RSFC between the left AI and left occipital sensory cortex, the left AI and left superior and inferior parietal cortex, and the left PCC and right medial prefrontal cortex were uniformly lower in the BD patients than controls. Correlation analyses showed negative correction between AI's FA and disease episodes and between AI's FA and disease duration in depressed BD-II patients. CONCLUSIONS: We observed abnormal brain structural and functional properties in the left AI and left PCC in BD patients. The abnormal RSFC patterns may suggest sensory and cognitive dysfunction in BD.

Reduced myelin density in unmedicated major depressive disorder: An inhomogeneous magnetization transfer MRI study.

OBJECTIVES: To detect the whole-brain reduced myelin density in unmedicated patients with major depressive disorder (MDD) using the inhomogeneous magnetization transfer (ihMT) imaging technology. Compared to other technologies, the ihMT provides high specificity and sensitivity to detect myelin. METHOD: In this prospective study, fifty unmedicated patients (mean age 25.36 years, 40% men) with MDD and 57 age- and sex-matched healthy controls (HCs) (mean age 25.02 years, 53% men) were recruited between January 2019 and December 2019. All participants underwent ihMT imaging, and pseudo-quantitative ihMT (qihMT) and ihMT ratio (ihMTR) were obtained. The mean values of qihMT and ihMTR extracted from the 50 WM masks (extracted from the International Consortium for Brain Mapping, ICBM-152) in each participant were compared between participants in the MDD and HCs groups. The symptoms of patients were evaluated using the 24-item Hamilton Depression Rating scale (HDRS). RESULTS: Compared with the HC group, the MDD group showed significantly decreased qihMT and ihMTR values in the left inferior fronto-occipital fasciculus (IFOF) (t = -4.057, p < 0.001; t = -3.662, p < 0.001) and the left uncinate fasciculus (UF) (t = -4.776, p < 0.001; t = -3.800, p < 0.001) after Bonferroni correction. The correlation analysis displayed a significant negative correlation between qihMT values of the left IFOF and HDRS total scores in patients with MDD (r = -0.390, p = 0.012). LIMITATIONS: This was a cross-sectional study with a relative small sample. CONCLUSIONS: These findings suggest the reduced myelin density in the IFOF and UF in patients with MDD, which might be associated with the pathophysiology of MDD.