The mediating role of family functioning between childhood trauma and depression severity in major depressive disorder and bipolar disorder.

BACKGROUND: Childhood trauma (CT) and family functioning exert significant influences on the course and long-term outcome of major depressive disorder (MDD) and bipolar disorder (BD) patients. Hence, we examined the intricate relationship between CT, family function, and the severity of depressive episodes in MDD and BD patients. METHODS: 562 patients with depressive episodes (336 MDD and 226 BD) and 204 healthy controls (HCs) were included in this retrospective study. The 17-item Hamilton Depression Rating Scale (HAMD-17), Childhood Trauma Questionnaire (CTQ), and Family Adaptability and Cohesion Evaluation Scale (FACES II-CV) were assessed. Pearson correlation analysis and mediation analysis were performed. RESULTS: CT had both a direct and indirect impact on depression severity in MDD and BD groups. In MDD, family adaptability mediated the impact of all CT subtypes on depression severity (Effect = 0.113, [0.030, 0.208]). In BD, family cohesion played a mediating role between emotional neglect (EN) and HAMD scores (Effect = 0.169, [0.008, 0.344]). Notable differences were observed in onset age, illness duration, episode frequency, family history, and CT subtypes between MDD and BD (P < 0.05). LIMITATIONS: This study has several limitations including recall bias, lack of objective family functioning measures, small sample size, and cross-sectional design. CONCLUSIONS: Family functioning mediated the impact of CT on depressive symptoms severity in MDD and BD patients. MDD patients with a history of CT exhibited reduced family adaptability, while BD patients with a history of EN had weaker familial emotional bonds. Our findings highlighted the importance of family-focused preventive interventions in mitigating the long-term effects of CT.

Electrophysiological predictors of early response to antidepressants in major depressive disorder.

BACKGROUND: Psychomotor retardation (PMR) is a core feature of major depressive disorder (MDD), which is characterized by abnormalities in motor control and cognitive processes. PMR in MDD can predict a poor antidepressant response, suggesting that PMR may serve as a marker of the antidepressant response. However, the neuropathological relationship between treatment outcomes and PMR remains uncertain. Thus, this study examined electrophysiological biomarkers associated with poor antidepressant response in MDD. METHODS: A total of 142 subjects were enrolled in this study, including 49 healthy controls (HCs) and 93 MDD patients. All participants performed a simple right-hand visuomotor task during magnetoencephalography (MEG) scanning. Patients who exhibited at least a 50 % reduction in disorder severity at the endpoint (>2 weeks) were considered to be responders. Motor-related beta desynchronization (MRBD) and inter- and intra-hemispheric functional connectivity were measured in the bilateral motor network. RESULTS: An increased MRBD and decreased inter- and intra-hemispheric functional connectivity in the motor network during movement were observed in non-responders, relative to responders and HCs. This dysregulation predicted the potential antidepressant response. CONCLUSION: Abnormal local activity and functional connectivity in the motor network indicate poor psychomotor function, which might cause insensitivity to antidepressant treatment. This could be regarded as a potential neural mechanism for the prediction of a patient's treatment response.

Individual suicide risk factors with resting-state brain functional connectivity patterns in bipolar disorder patients based on latent Dirichlet allocation model.

BACKGROUND: The widespread problem of suicide and its severe burden in bipolar disorder (BD) necessitate the development of objective risk markers, aiming to enhance individual suicide risk prediction in BD. METHODS: This study recruited 123 BD patients (61 patients with prior suicide attempted history (PSAs), 62 without (NSAs)) and 68 healthy controls (HEs). The Latent Dirichlet Allocation (LDA) model was used to decompose the resting state functional connectivity (RSFC) into multiple hyper/hypo-RSFC patterns. Thereafter, according to the quantitative results of individual heterogeneity over latent factor dimensions, the correlations were analyzed to test prediction ability. RESULTS: Model constructed without introducing suicide-related labels yielded three latent factors with dissociable hyper/hypo-RSFC patterns. In the subsequent analysis, significant differences in the factor distributions of PSAs and NSAs showed biases on the default-mode network (DMN) hyper-RSFC factor (factor 3) and the salience network (SN) and central executive network (CEN) hyper-RSFC factor (factor 1), indicating predictive value. Correlation analysis of the individuals' expressions with their Nurses' Global Assessment of Suicide Risk (NGASR) revealed factor 3 positively correlated (r = 0.4180, p < 0.0001) and factor 1 negatively correlated (r = - 0.2492, p = 0.0055) with suicide risk. Therefore, it could be speculated that patterns more associated with suicide reflected hyper-connectivity in DMN and hypo-connectivity in SN, CEN. CONCLUSIONS: This study provided individual suicide-associated risk factors that could reflect the abnormal RSFC patterns, and explored the suicide related brain mechanisms, which is expected to provide supports for clinical decision-making and timely screening and intervention for individuals at high risks of suicide.

Aberrant social reward dynamics in individuals with melancholic major depressive disorder: An ERP study.

BACKGROUND: Compared to monetary rewards, depressive symptoms are specifically associated with abnormal social reward processing. In addition, individuals with melancholic depression may exhibit more significant reward-related impairments. However, there is still limited understanding of the specific alterations in social reward processing in individuals with melancholic depression. METHODS: Forty patients with melancholic major depressive disorder (MDD), forty patients with non-melancholic MDD, and fifty healthy controls participated in the social incentive delay (SID) tasks with event-related potential (ERP) recording. We measured one anticipatory ERP(cue-N2) and two consummatory ERPs (FRN, fb-P3). Furthermore, we examined correlation between FRN and consummatory anhedonia. RESULTS: Melancholic MDD patients showed less anticipation of social rewards (cue-N2). Concurrently, melancholic individuals demonstrated diminished reception of social rewards, as evidenced by reduced amplitudes of FRN. Notably, the group x condition interaction effect on FRN was significant (F (2, 127) = 4.15, p = 0.018, η2ρ = 0.061). Melancholic MDD patients had similar neural responses to both gain and neutral feedback (blunted reward positivity), whereas non-melancholic MDD patients (t (39) = 3.09, p = 0.004) and healthy participants (t (49) = 5.25, p < 0.001) had smaller FRN amplitudes when receiving gain feedback relative to neutral feedback. In addition, there was a significant correlation between FRN and consummatory anhedonia in MDD patients. CONCLUSIONS: Our findings indicated that individuals with melancholic MDD exhibit attenuated neural responses to both anticipated and consumed social rewards. This suggests that aberrant processing of social rewards could serve as a potential biomarker for melancholic MDD.

The Clinical Characteristics and Antimicrobial Resistance of Staphylococcus aureus Isolated from Patients with Staphylococcal Scalded Skin Syndrome (SSSS) in Southwestern China.

Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This study aimed to investigate the clinical characteristics of SSSS patients in our hospital, the relative proportion of methicillin-resistant Staphylococcus aureus (MRSA) in skin and soft tissue secretions, and the drug sensitivity of S. aureus to better assist dermatologists in the diagnosis and treatment of SSSS. We reviewed the demographic characteristics, clinical manifestations, treatment regimens, therapeutic efficacy, laboratory test results, drug sensitivity, and outcome data of 79 SSSS patients from January 2012 to December 2021. Statistical analysis was performed using t tests and chi-square tests. Among the 79 SSSS patients, MRSA was detected in 35 (44.3%) isolates: 34 community-acquired (CA)-MRSA (97.1%) and 1 hospital-acquired (HA)-MRSA. The SSSS incidence increased annually from 2012 to 2014 and then decreased gradually after peaking in 2015. All the isolates were sensitive to vancomycin, tigecycline, linezolid, moxifloxacin, levofloxacin, and ciprofloxacin; were completely resistant to penicillin; and had low sensitivity to clindamycin and erythromycin. Interestingly, the sensitivity of MRSA to tetracycline increased annually after 2015. The resistance rates to common drugs previously used to treat SSSS increased. These findings may accelerate diagnosis and improve empirical antibiotic use, suggesting that clinicians should prescribe drugs according to antimicrobial susceptibility.

Pushing Forward the DNA Walkers in Connection with Tumor-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) are microparticles released from cells in both physiological and pathological conditions and could be used to monitor the progression of various pathological states, including neoplastic diseases. In various EVs, tumor-derived extracellular vesicles (TEVs) are secreted by different tumor cells and are abundant in many molecular components, such as proteins, nucleic acids, lipids, and carbohydrates. TEVs play a crucial role in forming and advancing various cancer processes. Therefore, TEVs are regarded as promising biomarkers for the early detection of cancer in liquid biopsy. However, the currently developed TEV detection methods still face several key scientific problems that need to be solved, such as low sensitivity, poor specificity, and poor accuracy. To overcome these limitations, DNA walkers have emerged as one of the most popular nanodevices that exhibit better signal amplification capability and enable highly sensitive and specific detection of the analytes. Due to their unique properties of high directionality, flexibility, and efficiency, DNA walkers hold great potential for detecting TEVs. This paper provides an introduction to EVs and DNA walker, additionally, it summarizes recent advances in DNA walker-based detection of TEVs (2018-2024). The review highlights the close relationship between TEVs and DNA walkers, aims to offer valuable insights into TEV detection and to inspire the development of reliable, efficient, simple, and innovative methods for detecting TEVs based on DNA walker in the future.

Flavonoidal alkaloids: Emerging targets for drug discovery from Nature's bounty.

This paper explores the potential of flavonoid alkaloids, a unique class of compounds that contain both flavonoid and alkaloid structures, as emerging targets for drug discovery. These compounds exhibit diverse biological activities, such as anti-inflammatory, anti-cancer, and anti-diabetic effects, which are attributed to the combination of different flavonoid scaffolds and alkaloid groups. Flavonoid alkaloids have attracted researchers' attention due to their diverse structures and important bio-activities. Therefore, this review summarizes recent advances in the extraction, purification, structural characterization, synthesis pathways and biological activities of flavonoid alkaloids from natural sources. Finally, the potential prospects and challenges associated with this class of compounds in pharmacological research are discussed along with details of a mechanistic investigation and future clinical applications in this research field.

Structure-function coupling and hierarchy-specific antidepressant response in major depressive disorder.

BACKGROUND: Extensive research has explored altered structural and functional networks in major depressive disorder (MDD). However, studies examining the relationships between structure and function yielded heterogeneous and inconclusive results. Recent work has suggested that the structure-function relationship is not uniform throughout the brain but varies across different levels of functional hierarchy. This study aims to investigate changes in structure-function couplings (SFC) and their relevance to antidepressant response in MDD from a functional hierarchical perspective. METHODS: We compared regional SFC between individuals with MDD (n = 258) and healthy controls (HC, n = 99) using resting-state functional magnetic resonance imaging and diffusion tensor imaging. We also compared antidepressant non-responders (n = 55) and responders (n = 68, defined by a reduction in depressive severity of >50%). To evaluate variations in altered and response-associated SFC across the functional hierarchy, we ranked significantly different regions by their principal gradient values and assessed patterns of increase or decrease along the gradient axis. The principal gradient value, calculated from 219 healthy individuals in the Human Connectome Project, represents a region's position along the principal gradient axis. RESULTS: Compared to HC, MDD patients exhibited increased SFC in unimodal regions (lower principal gradient) and decreased SFC in transmodal regions (higher principal gradient) (p < 0.001). Responders primarily had higher SFC in unimodal regions and lower SFC in attentional networks (median principal gradient) (p < 0.001). CONCLUSIONS: Our findings reveal opposing SFC alterations in low-level unimodal and high-level transmodal networks, underscoring spatial variability in MDD pathology. Moreover, hierarchy-specific antidepressant effects provide valuable insights into predicting treatment outcomes.

Sex differences in anhedonia in bipolar depression: a resting-state fMRI study.

Previous studies about anhedonia symptoms in bipolar depression (BD) ignored the unique role of gender on brain function. This study aims to explore the regional brain neuroimaging features of BD with anhedonia and the sex differences in these patients. The resting-fMRI by applying fractional amplitude of low-frequency fluctuation (fALFF) method was estimated in 263 patients with BD (174 high anhedonia [HA], 89 low anhedonia [LA]) and 213 healthy controls. The effects of two different factors in patients with BD were analyzed using a 3 (group: HA, LA, HC) × 2 (sex: male, female) ANOVA. The fALFF values were higher in the HA group than in the LA group in the right medial cingulate gyrus and supplementary motor area. For the sex-by-group interaction, the fALFF values of the right hippocampus, left medial occipital gyrus, right insula, and bilateral medial cingulate gyrus were significantly higher in HA males than in LA males but not females. These results suggested that the pattern of high activation could be a marker of anhedonia symptoms in BD males, and the sex differences should be considered in future studies of BD with anhedonia symptoms.

Distinct MRI-based functional and structural connectivity for antidepressant response prediction in major depressive disorder.

OBJECTIVE: Emerging studies have identified treatment-related connectome predictors in major depressive disorder (MDD). However, quantifying treatment-responsive patterns in structural connectivity (SC) and functional connectivity (FC) simultaneously remains underexplored. We aimed to evaluate whether spatial distributions of FC and SC associated treatment responses are shared or unique. METHODS: Diffusion tensor imaging and resting-state functional magnetic resonance imaging were collected from 210 patients with MDD at baseline. We separately developed connectome-based prediction models (CPM) to predict reduction of depressive severity after 6-week monotherapy based on structural, functional, and combined connectomes, then validated them on the external dataset. We identified the predictive SC and FC from CPM with high occurrence frequencies during the cross-validation. RESULTS: Structural connectomes (r = 0.2857, p < 0.0001), functional connectomes (r = 0.2057, p = 0.0025), and their combined CPM (r = 0.4, p < 0.0001) can significantly predict a reduction of depressive severity. We didn't find shared connectivity between predictive FC and SC. Specifically, the most predictive FC stemmed from the default mode network, while predictive SC was mainly characterized by within-network SC of fronto-limbic networks. CONCLUSIONS: These distinct patterns suggest that SC and FC capture unique connectivity concerning the antidepressant response. SIGNIFICANCE: Our findings provide comprehensive insights into the neurophysiology of antidepressants response.

Impulsivity and neural correlates of response inhibition in bipolar disorder and their unaffected relatives: A MEG study.

BACKGROUND: Response inhibition is a core cognitive impairment in bipolar disorder (BD), leading to increased impulsivity in BD. However, the relationship between the neural mechanisms underlying impaired response inhibition and impulsivity in BD is not yet clear. Individuals who are genetically predisposed to BD give a way of identifying potential endophenotypes. METHODS: A total of 97 participants, including 39 patients with BD, 22 unaffected relatives (UR) of patients with BD, and 36 healthy controls performed a Go/No-Go task during magnetoencephalography. We carried out time-frequency and connectivity analysis on MEG data. RESULTS: Decreased beta power, prolonged latency and increased peak frequency in rIFG, decreased beta power in pre-SMA and reduced rIFG-to-pre-SMA connectivity were found in BD relative to healthy controls. In the UR group, we found a decrease in the beta power of pre-SMA and prolonged latency of rIFG. Furthermore, increased motor impulsiveness in BD was related to abnormal alterations in beta oscillatory activity of rIFG and functional connectivity between rIFG and pre-SMA. CONCLUSIONS: Hypoactivity activity in rIFG and impaired dominant role of rIFG in the prefrontal control network may underlie the neuropathology of response inhibition dysfunction, resulting increased motor impulsivity in BD. Our findings point to measuring rIFG dysfunction as a potential means of identifying individuals at genetic high risk for transition to BD disease expression.

Based on white matter microstructure to early identify bipolar disorder from patients with depressive episode.

OBJECTIVE: Because of similar clinical manifestations, bipolar disorder (BD) patients are often misdiagnosed as major depressive disorder (MDD). This study aimed to compare the difference between depressed patients later converting to BD and unipolar depression (UD) according to diffusion tensor imaging (DTI). METHOD: Patients with MDD (562 participants) in depressive episode states and healthy controls (HCs) (145 participants) were recruited over 10 years. Demographic and magnetic resonance imaging (MRI) data were collected at the time of recruitment. All patients with MDD were followed up for 5 years and classified into the transfer to BD (tBD) group (83 participants) and UD group (160 participants) according to the follow-up results. DTI and functional magnetic resonance imaging at baseline were compared. RESULTS: Common abnormalities were found in both tBD and UD groups, including left superior cerebellar peduncle (SCP.L), right anterior limb of the internal capsule (ALIC.R), right superior fronto-occipital fasciculus (SFOF.R), and right inferior fronto-occipital fasciculus (IFOF.R). The tBD showed more extensive abnormalities than the UD in the body of corpus callosum, fornix, left superior corona radiata, left posterior corona radiata, left superior longitudinal fasciculus, and left superior fronto-occipital fasciculus. CONCLUSION: The study demonstrated the common and distinct abnormalities of tBD and UD when compared to HC. The tBD group showed more extensive disruptions of white matter integrity, which could be a potential biomarker for the early identification of BD.

Response inhibition related neural oscillatory patterns show reliable early identification of bipolar from unipolar depression in a Go/No-Go task.

BACKGROUND: Response inhibition is a key neurocognitive factor contributing to impulsivity in mood disorders. Here, we explored the common and differential alterations of neural circuits associated with response inhibition in bipolar disorder (BD) and unipolar disorder (UD) and whether the oscillatory signatures can be used as early biomarkers in BD. METHODS: 39 patients with BD, 36 patients with UD, 29 patients initially diagnosed with UD who later underwent diagnostic conversion to BD, and 36 healthy controls performed a Go/No-Go task during MEG scanning. We carried out time-frequency and connectivity analysis on MEG data. Further, we performed machine learning using oscillatory features as input to identify bipolar from unipolar depression at the early clinical stage. RESULTS: Compared to healthy controls, patients had reduced rIFG-to-pre-SMA connectivity and delayed activity of rIFG. Among patients, lower beta power and higher peak frequency were observed in BD patients than in UD patients. These changes enabled accurate classification between BD and UD with an accuracy of approximately 80 %. CONCLUSIONS: The inefficiency of the prefrontal control network is a shared mechanism in mood disorders, while the abnormal activity of rIFG is more specific to BD. Neuronal responses during response inhibition could serve as a diagnostic biomarker for BD in early stage.

Abnormal stability of spontaneous neuronal activity as a predictor of diagnosis conversion from major depressive disorder to bipolar disorder.

OBJECTIVE: Bipolar disorder (BD) is often misdiagnosed as major depressive disorder (MDD) in the early stage, which may lead to inappropriate treatment. This study aimed to characterize the alterations of spontaneous neuronal activity in patients with depressive episodes whose diagnosis transferred from MDD to BD. METHODS: 532 patients with MDD and 132 healthy controls (HCs) were recruited over 10 years. During the follow-up period, 75 participants with MDD transferred to BD (tBD), and 157 participants remained with the diagnosis of unipolar depression (UD). After excluding participants with poor image quality and excessive head movement, 68 participants with the diagnosis of tBD, 150 participants with the diagnosis of UD, and 130 HCs were finally included in the analysis. The dynamic amplitude of low-frequency fluctuations (dALFF) of spontaneous neuronal activity was evaluated in tBD, UD and HC using functional magnetic resonance imaging at study inclusion. Receiver operating characteristic (ROC) analysis was performed to evaluate sensitivity and specificity of the conversion prediction from MDD to BD based on dALFF. RESULTS: Compared to HC, tBD exhibited elevated dALFF at left premotor cortex (PMC_L), right lateral temporal cortex (LTC_R) and right early auditory cortex (EAC_R), and UD showed reduced dALFF at PMC_L, left paracentral lobule (PCL_L), bilateral medial prefrontal cortex (mPFC), right orbital frontal cortex (OFC_R), right dorsolateral prefrontal cortex (DLPFC_R), right posterior cingulate cortex (PCC_R) and elevated dALFF at LTC_R. Furthermore, tBD exhibited elevated dALFF at PMC_L, PCL_L, bilateral mPFC, bilateral OFC, DLPFC_R, PCC_R and LTC_R than UD. In addition, ROC analysis based on dALFF in differential areas obtained an area under the curve (AUC) of 72.7%. CONCLUSIONS: The study demonstrated the temporal dynamic abnormalities of tBD and UD in the critical regions of the somatomotor network (SMN), default mode network (DMN), and central executive network (CEN). The differential abnormal patterns of temporal dynamics between the two diseases have the potential to predict the diagnosis transition from MDD to BD.

The altered temporal properties of dynamic functional connectivity associated with suicide attempt in bipolar disorders.

OBJECTIVE: The suicide risk in bipolar disorder (BD) is the highest among psychiatric disorders, and the neurobiological mechanism of suicide in BD remains unclear. The study aimed to investigate the underlying relevance between the implicated abnormalities of dynamic functional connectivity (FC) and suicide attempt (SA) in BD. METHODS: We used the sliding window method to analyze the dynamic FC patterns from resting-state functional MRI data in 81 healthy controls (HC) and 114 BD patients (50 with SA and 64 with none SA). Then, the temporal properties of dynamic FC and the relationship between altered measures and clinical variables were explored. RESULTS: We found that one of the five captured brain functional states was more associated with SA. The SA patients showed significantly increased fractional window and dwell time in the suicide-related state, along with increased number of state transitions compared with none SA (NSA). In addition, the connections within subcortical network-subcortical network (SubC-SubC), default mode network-subcortical network (DMN-SubC), and attention network-subcortical network (AN-SubC) were significantly changed in SA patients relative to NSA and HC in the suicide-related state. Crucially, the above-altered measures were significantly correlated with suicide risk. CONCLUSIONS: Our findings suggested that the impaired dynamic FC within SubC-SubC, DMN-SubC, and AN-SubC were the important underlying mechanism in understanding SA for BD patients. It highlights the temporal properties of whole-brain dynamic FC could serve as the valuable biomarker for suicide risk assessment in BD.

Capturing the Individual Deviations From Normative Models of Brain Structure for Depression Diagnosis and Treatment.

BACKGROUND: The high heterogeneity of depression prevents us from obtaining reproducible and definite anatomical maps of brain structural changes associated with the disorder, which limits the individualized diagnosis and treatment of patients. In this study, we investigated the clinical issues related to depression according to individual deviations from normative ranges of gray matter volume. METHODS: We enrolled 1092 participants, including 187 patients with depression and 905 healthy control participants. Structural magnetic resonance imaging data of healthy control participants from the Human Connectome Project (n = 510) and REST-meta-MDD Project (n = 229) were used to establish a normative model across the life span in adults 18 to 65 years old for each brain region. Deviations from the normative range for 187 patients and 166 healthy control participants recruited from two local hospitals were captured as normative probability maps, which were used to identify the disease risk and treatment-related latent factors. RESULTS: In contrast to case-control results, our normative modeling approach revealed highly individualized patterns of anatomic abnormalities in depressed patients (less than 11% extreme deviation overlapping for any regions). Based on our classification framework, models trained with individual normative probability maps (area under the receiver operating characteristic curve range, 0.7146-0.7836) showed better performance than models trained with original gray matter volume values (area under the receiver operating characteristic curve range, 0.6800-0.7036), which was verified in an independent external test set. Furthermore, different latent brain structural factors in relation to antidepressant treatment were revealed by a Bayesian model based on normative probability maps, suggesting distinct treatment response and inclination. CONCLUSIONS: Capturing personalized deviations from a normative range could help in understanding the heterogeneous neurobiology of depression and thus guide clinical diagnosis and treatment of depression.

Brain-heart interaction disruption in major depressive disorder: disturbed rhythm modulation of the cardiac cycle on brain transient theta bursts.

Brain neurons support arousal and cognitive activity in the form of spectral transient bursts and cooperate with the peripheral nervous system to adapt to the surrounding environment. However, the temporal dynamics of brain-heart interactions have not been confirmed, and the mechanism of brain-heart interactions in major depressive disorder (MDD) remains unclear. This study aimed to provide direct evidence for brain-heart synchronization in temporal dynamics and clarify the mechanism of brain-heart interaction disruption in MDD. Eight-minute resting-state (closed eyes) electroencephalograph and electrocardiogram signals were acquired simultaneously. The Jaccard index (JI) was used to measure the temporal synchronization between cortical theta transient bursts and cardiac cycle activity (diastole and systole) in 90 MDD patients and 44 healthy controls (HCs) at rest. The deviation JI was used to reflect the equilibrium of brain activity between diastole and systole. The results showed that the diastole JI was higher than the systole JI in both the HC and MDD groups; compared to HCs, the deviation JI attenuated at F4, F6, FC2, and FC4 in the MDD patients. The eccentric deviation JI was negatively correlated with the despair factor scores of the HAMD, and after 4 weeks of antidepressant treatment, the eccentric deviation JI was positively correlated with the despair factor scores of the HAMD. It was concluded that brain-heart synchronization existed in the theta band in healthy individuals and that disturbed rhythm modulation of the cardiac cycle on brain transient theta bursts at right frontoparietal sites led to brain-heart interaction disruption in MDD.

Abnormal fractional amplitude of low-frequency fluctuations and regional homogeneity in major depressive disorder with non-suicidal self-injury.

OBJECTIVE: We conducted this resting-state functional magnetic resonance imaging (rsfMRI) study to characterize changes in regional homogeneity (ReHo) or fractional amplitude of low-frequency fluctuations (fALFF) in young adult patients with major depressive disorder (MDD), with or without non-suicidal self-injury (NSSI). METHODS: We recruited 54 MDD patients with NSSI (MDD/NSSI), 68 MDD patients without NSSI, which is referred to as simple MDD (sMDD), and 66 matched healthy controls (HCs). A combination of fALFF and ReHo analyses was conducted. The effects of NSSI on the brain and their relationship to clinical variables were examined in this study. RESULTS: MDD/NSSI patients have decreased fALFF in the right superior frontal gyrus (SFG) and the right inferior parietal lobe (IPL), decreased ReHo in the right SFG and the right middle temporal gyrus (MTG) and the left middle occipital gyrus (MOG). fALFF and ReHo values of the right SFG are positively correlated. The ReHo values of the right SFG and the number of recent self-injuries are positively correlated; the fALFF values of the right SFG are negatively correlated with NSSI severity. CONCLUSIONS: There is a difference in brain activity between MDD/NSSI and sMDD, which may serve as an important physiological marker to determine the risk of self-injury and suicide. SIGNIFICANCE: Abnormal brain activity in patients with NSSI may provide new perspectives and significant implications on the severity of MDD patients and the prevention of self-injury and suicide.

Links among genetic variants and hierarchical brain structural and functional networks for antidepressant treatment: A multivariate study.

BACKGROUND: Antidepressant treatment effects are strongly heritable and have substantial effects on brain function and structure, but the underlying mechanisms are still poorly understood. In this research, we aimed to evaluate the factors of single nucleotide polymorphisms (SNPs) and hierarchical brain structural and functional networks that were associated with antidepressant treatment. Moreover, we further explored the correlations and mediation pattern among "brain structure-brain function-gene" in major depressive disorder (MDD). METHODS: We analysed 405 SNPs and rich club/feeder/local connections of hierarchical structural and functional networks with three-way parallel independent component analysis in 179 MDD patients. The group-discriminative independent components of the three modalities between responders and non-responders of antidepressant treatment were identified. Pearson correlations and mediation analysis were further utilized to investigate the associations among SNPs and connections of the structural and functional networks. RESULTS: Notably, correlations with antidepressant treatment outcomes were found in structural, functional and SNP modalities simultaneously. The features of group-discriminative independent components included the shared feeder connections of hub regions with the inferior frontal orbital gyrus and amygdala in structural and functional modalities and genes enriched in circadian rhythmic processes and dopaminergic synapse pathways. The structural feeder network displayed close correlations with SNPs and the functional feeder network. Furthermore, the structural feeder network could mediate the association between SNPs and the functional feeder network, implying that genetic variants might influence brain function by affecting brain structure in MDD. CONCLUSIONS: These findings provide potential biomarkers for antidepressant therapy and provide a better grasp of the associations among SNPs and hierarchical structural and functional networks in MDD.