Identifying major depressive disorder with associated sleep disturbances through fMRI regional homogeneity at rest.

BACKGROUND: Anomalies in regional homogeneity (ReHo) have been documented in patients with major depressive disorder (MDD) and sleep disturbances (SDs). This investigation aimed to scrutinize changes in ReHo in MDD patients with comorbid SD, and to devise potential diagnostic biomarkers for detecting sleep-related conditions in patients with MDD. METHODS: Patients with MDD and healthy controls underwent resting-state functional magnetic resonance imaging scans. SD severity was quantified using the 17-item Hamilton Rating Scale for Depression. Subsequent to the acquisition of imaging data, ReHo analysis was performed, and a support vector machine (SVM) method was employed to assess the utility of ReHo in discriminating MDD patients with SD. RESULTS: Compared with MDD patients without SD, MDD patients with SD exhibited increased ReHo values in the right posterior cingulate cortex (PCC)/precuneus, right median cingulate cortex, left postcentral gyrus (postCG), and right inferior temporal gyrus (ITG). Furthermore, the ReHo values in the right PCC/precuneus and ITG displayed a positive correlation with clinical symptoms across all patients. SVM classification results showed that a combination of abnormal ReHo in the left postCG and right ITG achieved an overall accuracy of 84.21%, a sensitivity of 81.82%, and a specificity of 87.50% in identifying MDD patients with SD from those without SD. CONCLUSION: We identified disrupted ReHo patterns in MDD patients with SD, and presented a prospective neuroimaging-based diagnostic biomarker for these patients.

Anatomical distance affects functional connectivity at rest in medicine-free obsessive-compulsive disorder.

BACKGROUND: Brain functional abnormalities at rest have been observed in obsessive-compulsive disorder (OCD). However, whether and how anatomical distance influences functional connectivity (FC) at rest is ambiguous in OCD. METHODS: Using resting-state functional magnetic resonance imaging data, we calculated the FC of each voxel in the whole-brain and divided FC into short- and long-range FCs in 40 medicine-free patients with OCD and 40 healthy controls (HCs). A support vector machine (SVM) was used to determine whether the altered short- and long-range FCs could be utilized to distinguish OCD from HCs. RESULTS: Patients had lower short-range positive FC (spFC) and long-range positive FC (lpFC) in the left precentral/postcentral gyrus (t = -5.57 and -5.43; P < 0.05, GRF corrected) and higher lpFC in the right thalamus/caudate, left thalamus, left inferior parietal lobule (IPL) and left cerebellum CrusI/VI (t = 4.59, 4.61, 4.41, and 5.93; P < 0.05, GRF corrected). Furthermore, lower spFC in the left precentral/postcentral gyrus might be used to distinguish OCD from HCs with an accuracy of 80.77%, a specificity of 81.58%, and a sensitivity of 80.00%. CONCLUSION: These findings highlight that anatomical distance has an effect on the whole-brain FC patterns at rest in OCD. Meanwhile, lower spFC in the left precentral/postcentral gyrus might be applied in distinguishing OCD from HCs.

Increased regional homogeneity modulated by metacognitive training predicts therapeutic efficacy in patients with schizophrenia.

Previous studies have demonstrated the efficacy of metacognitive training (MCT) in schizophrenia. However, the underlying mechanisms related to therapeutic effect of MCT remain unknown. The present study explored the treatment effects of MCT on brain regional neural activity using regional homogeneity (ReHo) and whether these regions' activities could predict individual treatment response in schizophrenia. Forty-one patients with schizophrenia and 20 healthy controls were scanned using resting-state functional magnetic resonance imaging. Patients were randomly divided into drug therapy (DT) and drug plus psychotherapy (DPP) groups. The DT group received only olanzapine treatment, whereas the DPP group received olanzapine and MCT for 8 weeks. The results revealed that ReHo in the right precuneus, left superior medial prefrontal cortex (MPFC), right parahippocampal gyrus and left rectus was significantly increased in the DPP group after 8 weeks of treatment. Patients in the DT group showed significantly increased ReHo in the left ventral MPFC/anterior cingulate cortex (ACC), left superior MPFC/middle frontal gyrus (MFG), left precuneus, right rectus and left MFG, and significantly decreased ReHo in the bilateral cerebellum VIII and left inferior occipital gyrus (IOG) after treatment. Support vector regression analyses showed that high ReHo levels at baseline in the right precuneus and left superior MPFC could predict symptomatic improvement of Positive and Negative Syndrome Scale (PANSS) after 8 weeks of DPP treatment. Moreover, high ReHo levels at baseline and alterations of ReHo in the left ventral MPFC/ACC could predict symptomatic improvement of PANSS after 8 weeks of DT treatment. This study suggests that MCT is associated with the modulation of ReHo in schizophrenia. ReHo in the right precuneus and left superior MPFC may predict individual therapeutic response for MCT in patients with schizophrenia.

Voxel-Wise Brain-Wide Functional Connectivity Abnormalities in Patients with Primary Blepharospasm at Rest.

Background: Primary blepharospasm (BSP) is one of the most common focal dystonia and its pathophysiological mechanism remains unclear. An unbiased method was used in patients with BSP at rest to observe voxel-wise brain-wide functional connectivity (FC) changes. Method: A total of 48 subjects, including 24 untreated patients with BSP and 24 healthy controls, were recruited to undergo functional magnetic resonance imaging (fMRI). The method of global-brain FC (GFC) was adopted to analyze the resting-state fMRI data. We designed the support vector machine (SVM) method to determine whether GFC abnormalities could be utilized to distinguish the patients from the controls. Results: Relative to healthy controls, patients with BSP showed significantly decreased GFC in the bilateral superior medial prefrontal cortex/anterior cingulate cortex (MPFC/ACC) and increased GFC in the right postcentral gyrus/precentral gyrus/paracentral lobule, right superior frontal gyrus (SFG), and left paracentral lobule/supplement motor area (SMA), which were included in the default mode network (DMN) and sensorimotor network. SVM analysis showed that increased GFC values in the right postcentral gyrus/precentral gyrus/paracentral lobule could discriminate patients from controls with optimal accuracy, specificity, and sensitivity of 83.33%, 83.33%, and 83.33%, respectively. Conclusion: This study suggested that abnormal GFC in the brain areas associated with sensorimotor network and DMN might underlie the pathophysiology of BSP, which provided a new perspective to understand BSP. GFC in the right postcentral gyrus/precentral gyrus/paracentral lobule might be utilized as a latent biomarker to differentiate patients with BSP from controls.

Increased Homotopic Connectivity in the Prefrontal Cortex Modulated by Olanzapine Predicts Therapeutic Efficacy in Patients with Schizophrenia.

Background: Previous studies have revealed the abnormalities in homotopic connectivity in schizophrenia. However, the relationship of these deficits to antipsychotic treatment in schizophrenia remains unclear. This study explored the effects of antipsychotic therapy on brain homotopic connectivity and whether the homotopic connectivity of these regions might predict individual treatment response in schizophrenic patients. Methods: A total of 21 schizophrenic patients and 20 healthy controls were scanned by the resting-state functional magnetic resonance imaging. The patients received olanzapine treatment and were scanned at two time points. Voxel-mirrored homotopic connectivity (VMHC) and pattern classification techniques were applied to analyze the imaging data. Results: Schizophrenic patients presented significantly decreased VMHC in the temporal and inferior frontal gyri, medial prefrontal cortex (MPFC), and motor and low-level sensory processing regions (including the fusiform gyrus and cerebellum lobule VI) relative to healthy controls. The VMHC in the superior/middle MPFC was significantly increased in the patients after eight weeks of treatment. Support vector regression (SVR) analyses revealed that VMHC in the superior/middle MPFC at baseline can predict the symptomatic improvement of the positive and negative syndrome scale after eight weeks of treatment. Conclusions: This study demonstrated that olanzapine treatment may normalize decreased homotopic connectivity in the superior/middle MPFC in schizophrenic patients. The VMHC in the superior/middle MPFC may predict individual response for antipsychotic therapy. The findings of this study conduce to the comprehension of the therapy effects of antipsychotic medications on homotopic connectivity in schizophrenia.

Decreased Nucleus Accumbens Connectivity at Rest in Medication-Free Patients with Obsessive-Compulsive Disorder.

Background: Patients with obsessive-compulsive disorder (OCD) experience deficiencies in reward processing. The investigation of the reward circuit and its essential connectivity may further clarify the pathogenesis of OCD. Methods: The current research was designed to analyze the nucleus accumbens (NAc) functional connectivity at rest in medicine-free patients with OCD. Forty medication-free patients and 38 gender-, education-, and age-matched healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. Seed-based functional connectivity (FC) was used to analyze the data. LIBSVM (library for support vector machines) was designed to identify whether altered FC could be applied to differentiate OCD. Results: Patients with OCD showed remarkably decreased FC values between the left NAc and the bilateral orbitofrontal cortex (OFC) and bilateral medial prefrontal cortex (MPFC) and between the right NAc and the left OFC at rest in the reward circuit. Moreover, decreased left NAc-bilateral MPFC connectivity can be deemed as a potential biomarker to differentiate OCD from HCs with a sensitivity of 80.00% and a specificity of 76.32%. Conclusion: The current results emphasize the importance of the reward circuit in the pathogenesis of OCD.

Altered Functional Connectivity Strength at Rest in Medication-Free Obsessive-Compulsive Disorder.

Background: Previous studies explored the whole-brain functional connectome using the degree approach in patients with obsessive-compulsive disorder (OCD). However, whether the altered degree values can be used to discriminate OCD from healthy controls (HCs) remains unclear. Methods: A total of 40 medication-free patients with OCD and 38 HCs underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Data were analyzed with the degree approach and a support vector machine (SVM) classifier. Results: Patients with OCD showed increased degree values in the left thalamus and left cerebellum Crus I and decreased degree values in the left dorsolateral prefrontal cortex, right precuneus, and left postcentral gyrus. SVM classification analysis indicated that the increased degree value in the left thalamus is a marker of OCD, with an acceptable accuracy of 88.46%, sensitivity of 87.50%, and specificity of 89.47%. Conclusion: Altered degree values within and outside the cortical-striatal-thalamic-cortical (CSTC) circuit may cocontribute to the pathophysiology of OCD. Increased degree values of the left thalamus can be used as a future marker for OCD understanding-classification.

Increased cerebellar-default-mode network connectivity at rest in obsessive-compulsive disorder.

Abnormalities of the cerebellum and default-mode network (DMN) in patients with obsessive-compulsive disorder (OCD) have been widely reported. However, alterations of reciprocal functional connections between the cerebellum and DMN at rest in OCD remain unclear. Forty patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scan. Seed-based functional connectivity (FC) and support vector machine (SVM) were applied to analyze the imaging data. Compared with HCs, patients with OCD exhibited increased FCs between the left Crus I-left superior medial prefrontal cortex (MPFC) and between the right Crus I-left superior MPFC, left middle MPFC, and left middle temporal gyrus (MTG). A significantly negative correlation was observed between the right Crus I-left MTG connectivity and the Yale-Brown Obsessive-Compulsive Scale compulsion subscale scores in the OCD group (r = - 0.476, p = 0.002, Bonferroni corrected). SVM classification analysis indicated that a combination of the left Crus I-left superior MPFC connectivity and the right Crus I-left middle MPFC connectivity can be used to discriminate patients with OCD from HCs with a sensitivity of 85.00%, specificity of 68.42%, and accuracy of 76.92%. Our study highlights the contribution of the cerebellar-DMN connectivity in OCD pathophysiology and provides new findings to OCD research.

Region-specific insular volumetric decreases in drug-naive, first-episode schizophrenia and their unaffected siblings.

Decreased insular volume may be one of the anatomical alterations caused by schizophrenia. The possibility of region-specific insular volumetric reduction as an endophenotype and/or a possible treatment predictor is a critical issue with great implications for the diagnosis and prognosis of the disease. The sample of the current study comprised 44 drug-naive and first-episode patients, 42 unaffected siblings, and 44 healthy controls. A computational anatomy toolbox (CAT12) was applied to analyze the structural images with a fine-grained, cross-validated brainnetome atlas. Correlation analysis and support vector regression (SVR) were used to determine the relationship between insular deficits and symptomatic severity among patients. The gray matter volume (GMV) values in the left hypergranular insula (G) exhibited the following pattern: patients < siblings < controls. GMV values in the right ventral agranular insula (vIa) and baseline Positive and Negative Syndrome Scale negative symptoms subscale scores among patients showed a positive correlation (r = 0.384, p = .010). Further SVR analysis exhibited a significantly positive correlation between GMV values in the right vIa and negative symptomatic improvement among patients (r = 0.537, p < .001). Results suggested the presence of region-specific insular volumetric decreases in first-episode schizophrenia. Thus, volumetric decrease in left G might be a potential endophenotype for schizophrenia, and GMV values in right vIa might be used to predict negative symptomatic improvement in schizophrenia.

Association between abnormal default mode network homogeneity and sleep disturbances in major depressive disorder.

Background: Sleep disturbance is a common comorbidity of major depressive disorder (MDD). However, network homogeneity (NH) changes of the default mode network (DMN) in MDD with sleep disturbances are unclear. Aims: The purpose of this study was to probe the abnormal NH in the DMN in MDD with sleep disturbances and to reveal the differences between MDD with or without sleep disturbances. Methods: Twenty-four patients with MDD and sleep disturbances (Pa_s), 33 patients with MDD without sleep disturbances (Pa_ns) and 32 healthy controls (HCs) were recruited in this study. Resting-state functional imaging data were analysed using NH. Results: Compared with Pa_ns and HCs, Pa_s showed decreased NH in the left superior medial prefrontal cortex and increased NH in the right precuneus. There was a negative correlation between NH in the left superior medial prefrontal cortex and sleep disturbances (r=-0.42, p=0.001) as well as a positive correlation between NH in the right precuneus and sleep disturbances (r=0.41, p=0.002) in patients with MDD. Conclusions: MDD with sleep disturbances is associated with abnormal NH in the DMN, which could differentiate pa_s from pa_ns. The DMN may play a crucial role in the neurobiological mechanisms of MDD with sleep disturbances.

Potential correlations between abnormal homogeneity of default mode network and personality or lipid level in major depressive disorder.

BACKGROUND: Default mode network (DMN) is one of the most recognized resting-state networks in major depressive disorder (MDD). However, the homogeneity of this network in MDD remains incompletely explored. Therefore, this study aims to determine whether there is abnormal network homogeneity (NH) of the DMN in MDD patients. At the same time, correlations between clinical variables and brain functional connectivity are examined. METHODS: We enrolled 42 patients diagnosed with MDD and 42 HCs. A variety of clinical variables were collected, and data analysis was conducted using the NH and independent component analysis methods. RESULTS: The study shows that MDD patients have higher NH values in the left superior medial prefrontal cortex (MPFC) and left posterior cingulate cortex (PCC) compared to HCs. Additionally, there is a positive correlation between NH values of the left superior MPFC and Eysenck Personality Questionnaire values. NH values of the left PCC are positively linked to CHOL levels, LDL levels, and utilization scores. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: Our findings indicate the presence of abnormal DMN homogeneity in MDD, underscoring the significance of DMN in the pathophysiology of MDD. Simultaneously, the study provides preliminary evidence for the correlation between clinical variables and brain functional connectivity.

Potential correlations between asymmetric disruption of functional connectivity and metabolism in major depressive disorder.

OBJECTIVE: Previous research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear. METHOD: We conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels. RESULTS: The third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: MDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels.

Reduced functional connectivity of the right dorsolateral prefrontal cortex at rest in obsessive-compulsive disorder.

BACKGROUND: Neuroimaging studies have revealed the role of the right dorsolateral prefrontal cortex (DLPFC) in the neurobiological mechanism of obsessive-compulsive disorder (OCD). However, only a few studies have examined the functional connectivity (FC) pattern of the right DLPFC at rest in OCD. OBJECTIVE: The aim of this research is to examine the FC patterns of the right DLPFC at rest in OCD. METHODS: Twenty-eight medication-free patients with OCD and 20 healthy controls underwent resting-state functional magnetic resonance imaging. Seed-based FC and support vector machine (SVM) were used to analyze the imaging data. RESULTS: The patients with OCD showed reduced FC values in the right middle temporal gyrus (MTG), right superior temporal gyrus, right ventral anterior cingulate cortex (vACC), and left Crus II. No brain regions showed a remarkable difference in FC values in patients with OCD after 8 weeks of medication treatment. The reduced right DLPFC-right MTG and right DLPFC-right vACC connectivities were correlated with the clinical symptoms of OCD. SVM results showed that reduced right DLPFC-right MTG connectivity at rest could predict the therapeutic response to OCD medication. CONCLUSIONS: The findings highlight the important role of the right DLPFC in the pathophysiological mechanism of OCD.

Fractional amplitude of low-frequency fluctuations in sensory-motor networks and limbic system as a potential predictor of treatment response in patients with schizophrenia.

BACKGROUND: Previous investigations have revealed substantial differences in neuroimaging characteristics between healthy controls (HCs) and individuals diagnosed with schizophrenia (SCZ). However, we are not entirely sure how brain activity links to symptoms in schizophrenia, and there is a need for reliable brain imaging markers for treatment prediction. METHODS: In this longitudinal study, we examined 56 individuals diagnosed with 56 SCZ and 51 HCs. The SCZ patients underwent a three-month course of antipsychotic treatment. We employed resting-state functional magnetic resonance imaging (fMRI) along with fractional Amplitude of Low Frequency Fluctuations (fALFF) and support vector regression (SVR) methods for data acquisition and subsequent analysis. RESULTS: In this study, we initially noted lower fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, coupled with higher fALFF values in the left hippocampus and right putamen in SCZ patients compared to the HCs at baseline. However, when comparing fALFF values in brain regions with abnormal baseline fALFF values for SCZ patients who completed the follow-up, no significant differences in fALFF values were observed after 3 months of treatment compared to baseline data. The fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, and the left postcentral gyrus were useful in predicting treatment effects. CONCLUSION: Our findings suggest that reduced fALFF values in the sensory-motor networks and increased fALFF values in the limbic system may constitute distinctive neurobiological features in SCZ patients. These findings may serve as potential neuroimaging markers for the prognosis of SCZ patients.

Shared and differential fractional amplitude of low-frequency fluctuation patterns at rest in major depressive disorders with or without sleep disturbance.

Objective: Sleep disturbances (SD) are commonly found in patients with major depressive disorder (MDD). This study aims to explore the influence of SD symptoms on clinical characteristics in patients with MDD and to investigate the shared and distinct fractional amplitude of low-frequency fluctuation (fALFF) patterns in these patients with or without SD symptoms. Methods: Twenty-four MDD patients with SD symptoms (Pa_s), 33 MDD patients without SD symptoms (Pa_ns) and 32 healthy controls (HCs) were included in this study. The fALFF and correlation analyses were applied to analyze the features of imaging and clinical data. Results: Pa_s showed more severe anxiety and depression than Pa_ns. Compared with Pa_ns, Pa_s exhibited increased fALFF value in the left precuneus. Patients shared abnormal fALFF in the frontal-occipital brain regions. There was a positive correlation between fALFF values of the left precuneus and sleep disturbance scores (r = 0.607, p = 0.0000056734) in all patients in addition to a negative correlation between fALFF values of the left MOG/cuneus and HAMD-17 total scores (r = -0.595, p = 0.002141) in Pa_s. The receiver operating characteristic (ROC) results of the fALFF could be used to discriminate Pa_s from Pa_ns with a specificity of 72.73% and a sensitivity of 70.83%. Conclusion: Pa_s displayed more serious anxiety and depression symptoms. Patients shared abnormal fALFF in the frontal-occipital brain regions, which may be a common characteristic for MDD. And increased fALFF value in the left precuneus might be a specific neuroimaging feature of MDD patients with SD symptoms.

Abnormal long- and short-range functional connectivity in patients with first-episode drug-naïve melancholic and non-melancholic major depressive disorder.

BACKGROUND: We attempted to explore the common and distinct long- and short-range functional connectivity (FC) patterns of melancholic and non-melancholic major depressive disorder (MDD) and their associations with clinical characteristics. METHODS: Fifty-nine patients with first-episode drug-naïve MDD, including 31 patients with melancholic features and 28 patients with non-melancholic features, underwent resting-state functional magnetic resonance imaging (fMRI) scanning to examine long- and short-range FC. Thirty-two healthy volunteers were recruited as controls. The support vector machines (SVM) was applied to distinguish the melancholic patients from the non-melancholic patients by using the FC of abnormal brain regions. RESULTS: Compared to healthy volunteers, patients with MDD showed increased long-range positive FC (lpFC) in the right insula/inferior frontal gyrus and left insula. Relative to non-melancholic patients, melancholic patients displayed decreased lpFC in the right lingual gyrus, decreased short-range positive FC (spFC) in the right middle temporal gyrus and right superior parietal lobule, increased lpFC in the left inferior parietal lobule, and increased spFC in the left middle occipital gyrus/inferior occipital gyrus, left cerebellum VII/IX, and bilateral cerebellum CrusII. Increased lpFC in the left inferior parietal lobule in melancholic patients was correlated with the TEPS abstract anticipatory scores. SVM results showed that FCs of five combinations within different brain regions could distinguish melancholic patients from non-melancholic patients. CONCLUSIONS: FC abnormalities in the default mode network and parietal-occipital brain regions may underlie the neurobiology of melancholic MDD. An increased lpFC in the left inferior parietal lobule correlated with anhedonia may be a distinctive neurobiological feature of melancholic MDD.

Deviant spontaneous neural activity as a potential early-response predictor for therapeutic interventions in patients with schizophrenia.

Objective: Previous studies have established significant differences in the neuroimaging characteristics between healthy controls (HCs) and patients with schizophrenia (SCZ). However, the relationship between homotopic connectivity and clinical features in patients with SCZ is not yet fully understood. Furthermore, there are currently no established neuroimaging biomarkers available for the diagnosis of SCZ or for predicting early treatment response. The aim of this study is to investigate the association between regional homogeneity and specific clinical features in SCZ patients. Methods: We conducted a longitudinal investigation involving 56 patients with SCZ and 51 HCs. The SCZ patients underwent a 3-month antipsychotic treatment. Resting-state functional magnetic resonance imaging (fMRI), regional homogeneity (ReHo), support vector machine (SVM), and support vector regression (SVR) were used for data acquisition and analysis. Results: In comparison to HCs, individuals with SCZ demonstrated reduced ReHo values in the right postcentral/precentral gyrus, left postcentral/inferior parietal gyrus, left middle/inferior occipital gyrus, and right middle temporal/inferior occipital gyrus, and increased ReHo values in the right putamen. It is noteworthy that there was decreased ReHo values in the right inferior parietal gyrus after treatment compared to baseline data. Conclusion: The observed decrease in ReHo values in the sensorimotor network and increase in ReHo values in the right putamen may represent distinctive neurobiological characteristics of patients with SCZ, as well as a potential neuroimaging biomarker for distinguishing between patients with SCZ and HCs. Furthermore, ReHo values in the sensorimotor network and right putamen may serve as predictive indicators for early treatment response in patients with SCZ.

Uncovering the Neural Correlates of Anhedonia Subtypes in Major Depressive Disorder: Implications for Intervention Strategies.

Major depressive disorder (MDD) represents a serious public health concern, negatively affecting individuals' quality of life and making a substantial contribution to the global burden of disease. Anhedonia is a core symptom of MDD and is associated with poor treatment outcomes. Variability in anhedonia components within MDD has been observed, suggesting heterogeneity in psychopathology across subgroups. However, little is known about anhedonia subgroups in MDD and their underlying neural correlates across subgroups. To address this question, we employed a hierarchical cluster analysis based on Temporal Experience of Pleasure Scale subscales in 60 first-episode, drug-naive MDD patients and 32 healthy controls. Then we conducted a connectome-wide association study and whole-brain voxel-wise functional analyses for identified subgroups. There were three main findings: (1) three subgroups with different anhedonia profiles were identified using a data mining approach; (2) several parts of the reward network (especially pallidum and dorsal striatum) were associated with anticipatory and consummatory pleasure; (3) different patterns of within- and between-network connectivity contributed to the disparities of anhedonia profiles across three MDD subgroups. Here, we show that anhedonia in MDD is not uniform and can be categorized into distinct subgroups, and our research contributes to the understanding of neural underpinnings, offering potential treatment directions. This work emphasizes the need for tailored approaches in the complex landscape of MDD. The identification of homogeneous, stable, and neurobiologically valid MDD subtypes could significantly enhance our comprehension and management of this multifaceted condition.

Disrupted interhemispheric coordination of sensory-motor networks and insula in major depressive disorder.

Objective: Prior researches have identified distinct differences in neuroimaging characteristics between healthy controls (HCs) and patients with major depressive disorder (MDD). However, the correlations between homotopic connectivity and clinical characteristics in patients with MDD have yet to be fully understood. The present study aimed to investigate common and unique patterns of homotopic connectivity and their relationships with clinical characteristics in patients with MDD. Methods: We recruited 42 patients diagnosed with MDD and 42 HCs. We collected a range of clinical variables, as well as exploratory eye movement (EEM), event-related potentials (ERPs) and resting-state functional magnetic resonance imaging (rs-fMRI) data. The data were analyzed using correlation analysis, support vector machine (SVM), and voxel-mirrored homotopic connectivity (VMHC). Results: Compared with HCs, patients with MDD showed decreased VMHC in the insula, and increased VMHC in the cerebellum 8/vermis 8/vermis 9 and superior/middle occipital gyrus. SVM analysis using VMHC values in the cerebellum 8/vermis 8/vermis 9 and insula, or VMHC values in the superior/middle occipital gyrus and insula as inputs can distinguish HCs and patients with MDD with high accuracy, sensitivity, and specificity. Conclusion: The study demonstrated that decreased VMHC in the insula and increased VMHC values in the sensory-motor networks may be a distinctive neurobiological feature for patients with MDD, which could potentially serve as imaging markers to discriminate HCs and patients with MDD.

Multiple-Network Alterations in Major Depressive Disorder With Gastrointestinal Symptoms at Rest Revealed by Global Functional Connectivity Analysis.

Objective: Gastrointestinal (GI) symptoms are prominent in major depressive disorder (MDD) and bring patients lots of complaints and troubles. We aimed to explore whether there were some distinctive brain image alterations in MDD with GI symptoms, which could be used to distinguish MDD with GI symptoms from those without GI symptoms and healthy controls (HCs). Methods: A total of 35 outpatients with GI symptoms, 17 outpatients without GI symptoms, and 28 HCs were recruited. All the participants were scanned by a resting-state functional magnetic resonance imaging. Imaging data were analyzed with the global functional connectivity (GFC) and support vector machine methods. Results: MDD with GI symptoms showed decreased GFC in the left superior medial prefrontal cortex (MPFC) compared with MDD without GI symptoms. Compared with HCs, MDD with GI symptoms showed decreased GFC in the bilateral middle temporal pole (MTP) and left posterior cingulate cortex/precuneus (PCC/Pcu), and increased GFC in the right insula and bilateral thalamus. SVM analysis showed that an accuracy was 78.85% in differentiating MDD with GI symptoms from MDD without GI symptoms by using the GFC of the left superior MPFC. A combination of GFC of the left PCC/Pcu and bilateral MTP exhibited the highest accuracy (87.30%) in differentiating patients with MDD with GI symptoms from HCs. Conclusion: MDD with GI symptoms showed abnormal GFC in multiple networks, including the default mode network and cortico-limbic mood-regulating circuit. Using abnormal GFC might work well to discriminate MDD with GI symptoms from MDD without GI symptoms and HCs.