The amygdala volume moderates the relationship between childhood maltreatment and callous-unemotional traits in adolescents with conduct disorder.

CU traits, characterized by shallow affect, lack of fear, and absence of remorse, have been moderately associated with childhood maltreatment in a recent meta-analysis. However, the potential impact of brain structures remains undetermined. This paper examines the relationship between callous-unemotional (CU) traits, childhood maltreatment, and amygdala volumes. In this study, we used a region-of-interest (ROI) analysis to explore the interaction between the volumes of the amygdala, childhood maltreatment, and the manifestation of CU traits in adolescents diagnosed with conduct disorder (CD, N = 67), along with a comparison group of healthy-control youths (HCs, N = 89). The ROI analysis revealed no significant group differences in the bilateral amygdalar volumes. Significant positive correlation was discovered between all forms of child maltreatment (except for physical neglect) and CU traits across subjects. But the interaction of physical abuse and amygdala volumes was only significant within CD patients. Notably, a sensitivity analysis suggested that gender significantly influences these findings. These results contribute critical insights into the etiology of CU traits, emphasizing the need for customized clinical assessment tools and intervention strategies.

Predictive modeling of antidepressant efficacy based on cognitive neuropsychological theory.

BACKGROUND: We aimed to develop a clinical predictive model based on the cognitive neuropsychological (CNP) theory and machine-learning to examine SSRI efficacy in the treatment of MDD. METHODS: Baseline assessments including clinical symptoms (HAMD, HAMA, BDI, and TEPS scores), negative biases (NEO-PI-R-N and NCPBQ scores), sociodemographic characteristics (social support and SES), and a 5-min eye-opening resting-state EEG were completed by 69 participants with first-episode major depressive disorder (MDD) and 36 healthy controls. The clinical symptoms and negative bias were again assessed after an 8-week treatment of depression with selective serotonin reuptake inhibitors (SSRIs). A multi-modality machine-learning model was developed to predict the effectiveness of SSRI antidepressants. RESULTS: At baseline, we observed significant differences between MDD patients and healthy controls in terms of social support, clinical symptoms, and negative bias characteristics (p < 0.001). A negative association was found (p < 0.05) between neuroticism and alpha asymmetry in both the central and central-parietal areas, as well as between negative cognitive processing bias and alpha asymmetry in the parietal region. Compared to responders, non-responders exhibited less negative cognitive processing bias and greater alpha asymmetry in both central and central-parietal regions. Importantly, we developed a multi-modality machine-learning model with 83 % specificity using the above salient features. CONCLUSIONS: Research results support the CNP theory of depression treatment. To some extent, the multimodal clinical model constructed based on the CNP theory effectively predicted the efficacy of this treatment in this population. LIMITATIONS: Small sample and only focus on the mechanisms of delayed-onset SSRI treatment.

Sex-specific resting state brain network dynamics in patients with major depressive disorder.

Sex-specific neurobiological changes have been implicated in Major Depressive Disorder (MDD). Dysfunctions of the default mode network (DMN), salience network (SN) and frontoparietal network (FPN) are critical neural characteristics of MDD, however, the potential moderating role of sex on resting-state network dynamics in MDD has not been sufficiently evaluated. Thus, resting-state functional magnetic resonance imaging (fMRI) data were collected from 138 unmedicated patients with first-episode MDD (55 males) and 243 healthy controls (HCs; 106 males). Recurring functional network co-activation patterns (CAPs) were extracted, and time spent in each CAP (the total amount of volumes associated to a CAP), persistence (the average number of consecutive volumes linked to a CAP), and transitions across CAPs involving the SN, DMN and FPN were quantified. Relative to HCs, MDD patients exhibited greater persistence in a CAP involving activation of the DMN and deactivation of the FPN (DMN + FPN-). In addition, relative to the sex-matched HCs, the male MDD group spent more time in two CAPs involving the SN and DMN (i.e., DMN + SN- and DMN-SN + ) and transitioned more frequently from the DMN + FPN- CAP to the DMN + SN- CAP relative to the male HC group. Conversely, the female MDD group showed less persistence in the DMN + SN- CAP relative to the female HC group. Our findings highlight that the imbalance between SN and DMN could be a neurobiological marker supporting sex differences in MDD. Moreover, the dominance of the DMN accompanied by the deactivation of the FPN could be a sex-independent neurobiological correlate related to depression.

Potential neuropsychological mechanism involved in the transition from suicide ideation to action - a resting-state fMRI study implicating the insula.

BACKGROUND: Understanding the neural mechanism underlying the transition from suicidal ideation to action is crucial but remains unclear. To explore this mechanism, we combined resting-state functional connectivity (rsFC) and computational modeling to investigate differences between those who attempted suicide(SA) and those who hold only high levels of suicidal ideation(HSI). METHODS: A total of 120 MDD patients were categorized into SA group (n=47) and HSI group (n=73). All participants completed a resting-state functional MRI scan, with three subregions of the insula and the dorsal anterior cingulate cortex (dACC) being chosen as the region of interest (ROI) in seed-to-voxel analyses. Additionally, 86 participants completed the balloon analogue risk task (BART), and a five-parameter Bayesian modeling of BART was estimated. RESULTS: In the SA group, the FC between the ventral anterior insula (vAI) and the superior/middle frontal gyrus (vAI-SFG, vAI-MFG), as well as the FC between posterior insula (pI) and MFG (pI-MFG), were lower than those in HSI group. The correlation analysis showed a negative correlation between the FC of vAI-SFG and psychological pain avoidance in SA group, whereas a positive correlation in HSI group. Furthermore, the FC of vAI-MFG displayed a negative correlation with loss aversion in SA group, while a positive correlation was found with psychological pain avoidance in HSI group. CONCLUSION: In current study, two distinct neural mechanisms were identified in the insula which involving in the progression from suicidal ideation to action. Dysfunction in vAI FCs may gradually stabilize as individuals experience heightened psychological pain, and a shift from positive to negative correlation patterns of vAI-MFC may indicate a transition from state to trait impairment. Additionally, the dysfunction in PI FC may lead to a lowered threshold for suicide by blunting the perception of physical harm.

Trait- and state-like co-activation pattern dynamics in current and remitted major depressive disorder.

BACKGROUND: Distinguishing between trait- and state-like neural alternations in major depressive disorder (MDD) may advance our understanding of this recurring disorder. We aimed to investigate dynamic functional connectivity alternations in unmedicated individuals with current or past MDD using co-activation pattern analyses. METHODS: Resting-state functional magnetic resonance imaging data were acquired from individuals with first-episode current MDD (cMDD, n = 50), remitted MDD (rMDD, n = 44), and healthy controls (HCs, n = 64). Using a data-driven consensus clustering technique, four whole-brain states of spatial co-activation were identified and associated metrics (dominance, entries, transition frequency) were analyzed with respect to clinical characteristics. RESULTS: Relative to rMDD and HC, cMDD showed increased dominance and entries of state 1 (primarily involving default mode network (DMN)), and decreased dominance of state 4 (mostly involving frontal-parietal network (FPN)). Among cMDD, state 1 entries correlated positively with trait rumination. Conversely, relative to cMDD and HC, individuals with rMDD were characterized by increased state 4 entries. Relative to HC, both MDD groups showed increased state 4-to-1 (FPN to DMN) transition frequency but reduction in state 3 (spanning visual attention, somatosensory, limbic networks), with the former metric specifically related to trait rumination. LIMITATIONS: Further confirmation with longitudinal studies are required. CONCLUSIONS: Regardless of symptoms, MDD was characterized by increased FPN-to-DMN transitions and reduced dominance of a hybrid network. State-related effect emerged in regions critically implicated in repetitive introspection and cognitive control. Asymptomatic individuals with past MDD were uniquely linked to increased FPN entries. Our findings identify trait-like brain network dynamics that might increase vulnerability to future MDD.

Characteristics of white matter structural connectivity in healthy adults with childhood maltreatment.

Background: Childhood maltreatment (CM) is a common psychological stressor associated with multiple mental disorders. While CM is associated with vulnerability to depression and anxiety, little is known about the specific mechanism underlying this relationship.Objective: This study aimed to investigate the white matter (WM) of healthy adults with CM and their relationships with depression and anxiety to provide biological evidence for the development of mental disorders in subjects with childhood trauma.Methods: The CM group included 40 healthy adults with CM. The non-CM group included 40 healthy adults without CM. Diffusion tensor imaging (DTI) data were collected, and tract-based spatial statistics (TBSS) were applied to the whole brain to assess WM differences between the two groups; post-hoc fibre tractography was used to characterise the developmental differences; and mediation analysis was used to assess the relationships among the Child Trauma Questionnaire (CTQ) results, DTI indices, and depression and anxiety scores.Results: Relative to the non-CM group, the CM group revealed significantly lower fractional anisotropy (FA) in the right posterior corona radiata (PCR-R), right anterior corona radiata (ACR-R), left super corona radiata (SCR-L), anterior thalamic radiation (ATR), and right posterior limb of the internal capsule (PLIC-R). Additionally, shorter fibre bundles passed through the PCR-R, ACR-R, and ATR in the CM group compared with the non-CM group. Besides, the length of the ACR-R mediated the relationship between CM and trait anxiety.Conclusions: The alteration of white matter microstructure associated with childhood trauma in healthy adults may reflect biomarkers of childhood trauma. Besides, an alteration of WM microstructure in healthy adults with CM mediates the association between CM and trait anxiety, which may represent the vulnerability to developing mental disorders after childhood trauma experiences.

In this paper, we found specific alterations associated with CM in healthy adults, which may mediate the relationship between childhood trauma and trait anxiety in later life.

Structural abnormalities in adolescents with conduct disorder and high versus low callous unemotional traits.

There may be distinct conduct disorder (CD) etiologies and neural morphologies in adolescents with high callous unemotional (CU) traits versus low CU traits. Here, we employed surface-based morphometry methods to investigate morphological differences in adolescents diagnosed with CD [42 with high CU traits (CD-HCU) and 40 with low CU traits (CD-LCU)] and healthy controls (HCs, N = 115) in China. Whole-brain analyses revealed significantly increased cortical surface area (SA) in the left inferior temporal cortex and the right precuneus, but decreased SA in the left superior temporal cortex in the CD-LCU group, compared with the HC group. There were no significant cortical SA differences between the CD-HCU and the HC groups. Compared to the CD-HCU group, the CD-LCU group had a greater cortical thickness (CT) in the left rostral middle frontal cortex. Region-of-interest analyses revealed significant group differences in the right hippocampus, with CD-HCU group having lower right hippocampal volumes than HCs. We did not detect significant group differences in the amygdalar volume, however, the right amygdalar volume was found to be a significant moderator of the correlation between CU traits and the proactive aggression in CD patients. The present results suggested that the manifestations of CD differ between those with high CU traits versus low CU traits, and underscore the importance of sample characteristics in understanding the neural substrates of CD.

Persistent Ventral Anterior Cingulate Cortex and Resolved Amygdala Hyper-responses to Negative Outcomes After Depression Remission: A Combined Cross-sectional and Longitudinal Study.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mood disorder affecting more than 300 million people worldwide. Biased processing of negative information and neural hyper-responses to negative events are hallmarks of depression. This study combined cross-sectional and longitudinal experiments to explore both persistent and resolved neural hyper-responses to negative outcomes from risky decision making in patients with current MDD (cMDD) and remitted MDD (rMDD). METHODS: A total of 264 subjects participated in the cross-sectional study, including 117 patients with medication-naïve, first-episode current depression; 45 patients with rMDD with only 1 episode of depression; and 102 healthy control subjects. Participants completed a modified balloon analog risk task during functional magnetic resonance imaging. In the longitudinal arm of the study, 42 patients with cMDD were followed and 26 patients with rMDD were studied again after 8 weeks of antidepressant treatment. RESULTS: Patients with cMDD showed hyper-responses to loss outcomes in multiple limbic regions including the amygdala and ventral anterior cingulate cortex (vACC). Amygdala but not vACC hyperactivity correlated with depression scores in patients with cMDD. Furthermore, amygdala hyperactivity resolved while vACC hyperactivity persisted in patients with rMDD in both cross-sectional and longitudinal studies. CONCLUSIONS: These findings provide consistent evidence supporting differential patterns of amygdala and vACC hyper-responses to negative outcomes during depression remission. Amygdala hyperactivity may be a symptomatic and state-dependent marker of depressive neural responses, while vACC hyperactivity may reflect a persistent and state-independent effect of depression on brain function. These findings offer new insights into the neural underpinnings of depression remission and prevention of depression recurrence.

Decision-making biases in suicide attempters with major depressive disorder: A computational modeling study using the balloon analog risk task (BART).

BACKGROUND: In the last decade, suicidality has been increasingly theorized as a distinct phenomenon from major depressive disorder (MDD), with unique psychological and neural mechanisms, rather than being mostly a severe symptom of MDD. Although decision-making biases have been widely reported in suicide attempters with MDD, little is known regarding what components of these biases can be distinguished from depressiveness itself. METHODS: Ninety-three patients with current MDD (40 with suicide attempts [SA group] and 53 without suicide attempts [NS group]) and 65 healthy controls (HCs) completed psychometric assessments and the balloon analog risk task (BART). To analyze and compare decision-making components among the three groups, we applied a five-parameter Bayesian computational modeling. RESULTS: Psychological assessments showed that the SA group had greater suicidal ideation and psychological pain avoidance than the NS group. Computational modeling showed that both MDD groups had higher risk preference and lower ability to learn and adapt from within-task observations than HCs, without differences between the SA and NS patient groups. The SA group also had higher loss aversion than the NS and HC groups, which had similar loss aversion. CONCLUSIONS: Our BART and computational modeling findings suggest that psychological pain avoidance and loss aversion may be important suicide risk factor that are distinguishable from depression illness itself.

Trait-like white matter abnormalities in current and remitted depression.

Microstructural alterations to white matter (WM) have been implicated in the onset and recurrence of major depressive disorder (MDD). The present study aimed to identify trait-like WM abnormality in current and remitted depression, as well as changes to WM that could be specifically related to the state of clinical remission. Diffusion tensor imaging data were collected from 60 patients with medication-naive first episode current depression (cMDD), 41 patients with medication-naive remitted depression (rMDD), and 62 demographically-matched healthy control participants (HCs). Tract-based spatial statistics (TBSS) applied to the whole brain were used to detect microstructural differences of WM among the three groups. TBSS analyses showed that, compared with HCs, both the cMDD and rMDD groups exhibited significantly reduced FA values in the genus and body of the corpus callosum, and superior and anterior corona radiata, with no significant differences between the cMDD and rMDD groups. FA values in the corpus callosum were negatively correlated with the duration of illness in the rMDD group. Reduced WM integrity in the corpus callosum and corona radiata might reflect the trait markers of MDD, and could constitute a neuroanatomical marker of MDD.

Brain Anatomy in Boys with Conduct Disorder: Differences Among Aggression Subtypes.

Aggression is a core feature of conduct disorder (CD), but the motivation, execution of aggression may vary. A deeper understanding of the neural substrates of aggressive behaviours is critical for effective clinical intervention. Seventy-six Boys with CD (50 with impulsive aggression (I-CD) and 26 with premeditated aggression (P-CD)) and 69 healthy controls (HCs) underwent a structural MRI scan and behavioural assessments. Whole-brain analyses revealed that, compared to HCs, the I-CD group showed significant cortical thinning in the right frontal cortex, while the P-CD group demonstrated significant folding deficits in the bilateral superior parietal cortex. Both types of aggression negatively correlated with the left amygdala volume, albeit in different ways. The present results demonstrated that the complex nature of aggression relies on differentiated anatomical substrates, highlighting the importance of exploring differential circuit-targeted interventions for CD patients.

State-independent and -dependent behavioral and neuroelectrophysiological characteristics during dynamic decision-making in patients with current and remitted depression.

BACKGROUND: It is unclear whether the altered decision-making (DM) observed in patients with major depressive disorder (MDD) is neurophysiological and whether it improves with remission of depressive symptoms. The aim of this study was to identify developmental patterns of DM behavior, related cognitive characteristics, and electrophysiological abnormalities in patients with MDD across clinical stages. METHODS: A sample of 48 first-episode MDD patients (FD group), 41 remitted MDD patients (RD group), and 43 healthy controls (HCs) completed psychometric assessments and performed the balloon analogue risk task (BART) while event-related potentials (ERPs) were recorded. RESULTS: The RD group had lower depressiveness, self-blame, rumination, and catastrophizing tendencies, and higher mental resilience scores than the FD group, but retained significant differences from HCs. MDD patients showed a more conservative DM strategy than HCs, with no significant difference between the FD and RD groups. Compared to the FD group, the RD group had a smaller FRN for negative feedback and a trend toward a smaller P3 for positive feedback. Compared with HCs, the RD group had a smaller P3 during the positive feedback phase. FRN amplitude correlated positively with depression level and negatively with mental resilience. LIMITATIONS: Because a comparative cross-section design was employed, longitudinal studies are needed to make causal inferences. CONCLUSION: MDD patients presented a stable risk-avoidance bias in actively depressed and remission periods, consistent with a state-independent impairment pattern. Significantly reduced FRN amplitudes during remission indicated a state-dependent impairment pattern, and FRN amplitudes correlated with depression level. An abnormal feedback P3 component may be a state-independent characteristic that may become more pronounced with MDD progression.

Psychometric Properties and Measurement Invariance of the Childhood Trauma Questionnaire (Short Form) Across Genders, Time Points and Presence of Major Depressive Disorder Among Chinese Adolescents.

Purpose: The Childhood Trauma Questionnaire-Short Form (CTQ-SF) is a widely used self-report tool designed to assess juveniles' experiences of abuse and neglect. The current study examined the psychometric properties, particularly measurement invariance of the CTQ-SF in Chinese non-clinical adolescents and adolescents with major depressive disorder (MDD). Methods: Participants included 1,507 high school students (non-clinical sample) from Hunan Province and 281 adolescent patients with major depressive disorder (MDD sample) from The Second Xiangya Hospital. We examined the reliability and validity of CTQ-SF, confirm the five-factor model of the CTQ-SF. Multiple-group confirmatory factor analysis (CFA) was used to examine the measurement invariance across genders, presence of depression, and over time. Results: The CTQ-SF had good internal consistency in a non-clinical sample (Cronbach's α = 0.85) and MDD sample (Cronbach's α = 0.86). Good test-retest reliability (ICC = 0.72) and Adequate validity were also observed. Good fit of the five-factor CTQ-SF model was confirmed in both samples. Multiple-group CFA confirmed that the CTQ-SF had the scalar invariance across genders and the presence of MDD, as well as over time. Conclusion: The CTQ-SF is an effective and reliable tool for assessing child maltreatment in Chinese adolescents (non-clinical sample and MDD sample). The results suggest that the horizontal and longitudinal invariance of CTQ-SF are strongly established, which means CTQ-SF can be meaningfully used to compare outcomes among Chinese adolescents (non-clinical sample and MDD sample). The experience of child maltreatment, especially neglect (emotional and physical), was found to be common in Chinese adolescents.

Sex-specific neural responses to acute psychosocial stress in depression.

Major Depressive Disorder (MDD) is characterized by increased stress sensitivity. Emerging findings in healthy adults suggest that stress responses within limbic/striatal-prefrontal regions are moderated by sex and unfold over time. Thus, we hypothesized that stress response abnormalities in MDD might be affected by sex and stress exposure time. The Montreal Imaging Stress Task was administered to 124 unmedicated patients with first-episode MDD (76 females) and 243 healthy controls (HC; 137 females) during functional magnetic resonance imaging (fMRI). Based on prior studies, amygdala, hippocampus, medial orbitofrontal cortex (mOFC), nucleus accumbens (NAc) and dorsolateral prefrontal cortex (dlPFC) were selected as a priori regions of interest. In a complementary approach, we probed the effects of stress on the frontoparietal network (FPN) and a network including the amygdala, NAc and anterior cingulate cortex (ACC). Across groups, males exhibited higher dlPFC activity and right FPN amplitude than females. Relative to female HCs, the female MDD group had less deactivation in limbic/striatal regions (amygdala, NAc, hippocampus, Amygdala-NAc-ACC network). Furthermore, unlike female HCs, the female MDD group failed to show a significant increase of deactivation over stress exposure time in the amygdala, mOFC and NAc. Our findings confirm the importance of considering sex differences when investigating neural stress responses. Case-control differences in neural stress responses observed in females (but not males) provide insights into sex differences in the etiology and pathophysiology of depression. The failure to deactivate limbic/NAc regions in depressed females point to dysfunction of adaptive stress responses over stress exposure time.

Distinct stress-related medial prefrontal cortex activation in women with depression with and without childhood maltreatment.

BACKGROUND: Emerging evidence has highlighted the moderating effect of childhood maltreatment (CM) in shaping neurobiological abnormalities in major depressive disorder (MDD). However, whether neural mechanisms underlying stress sensitivity in MDD are affected by the history of CM is unclear. METHODS: Two hundred and thirteen medication-free female participants were recruited for a functional magnetic resonance imaging study assessing the effects of psychosocial stress on neural responses. The Montreal Imaging Stress Task was administrated to 44 female MDD patients with CM (MDD/CM), 32 female MDD patients without CM (MDD/noCM), 43 female healthy controls (HCs) with CM (HC/CM), and 94 female HCs without CM (HC/noCM). A CM (CM, noCM) × diagnosis (MDD, HC) whole-brain voxel-wise analysis was run to assess putative group differences in neural stress responses. RESULTS: A significant CM × Diagnosis interaction emerged in the medial prefrontal cortex (mPFC). Bonferroni-corrected simple effects analysis clarified that (1) the MDD/CM group had less mPFC deactivation than the HC/CM group, (2) the MDD/noCM group exhibited greater mPFC deactivation than the HC/noCM group, and (3) the MDD/CM group exhibited less mPFC deactivation relative to the MDD/noCM group. In addition, the mPFC-seed psychophysiological interaction analysis revealed that individuals in the CM groups had significantly greater stress-related mPFC-left superior frontal gyrus and mPFC-right posterior cerebellum connectivity relative to the noCM groups. CONCLUSIONS: Findings highlight distinct neural abnormalities in MDD depending on prior CM history, particularly potentiated stress-related mPFC recruitment among MDD individuals reporting CM. Moreover, CM history was generally associated with the disruption in functional connectivity centered on the mPFC.

Neuroanatomical changes associated with conduct disorder in boys: influence of childhood maltreatment.

Childhood maltreatment (CM) poses a serious risk to the physical, emotional and psychological well-being of children, and can advance the development of maladaptive behaviors, including conduct disorder (CD). CD involves repetitive, persistent violations of others' basic rights and societal norms. Little is known about whether and how CM influences the neural mechanisms underlying CD, and CD-characteristic neuroanatomical changes have not yet been defined in a structural magnetic resonance imaging (sMRI) study. Here, we used voxel-based morphometry (VBM) and surface-based morphometry (SBM) to investigate the influence of the CD diagnosis and CM on the brain in 96 boys diagnosed with CD (62 with CM) and 86 typically developing (TD) boys (46 with CM). The participants were 12-17 years of age. Compared to the CM- CD group, the CM+ CD group had structural gray matter (GM) alterations in the fronto-limbic regions, including the left amygdala, right posterior cingulate cortex (PCC), right putamen, right dorsolateral prefrontal cortex (dlPFC) and right anterior cingulate cortex (ACC). We also found boys with CD exhibited increased GM volume in bilateral dorsomedial prefrontal cortex (dmPFC), as well as decreased GM volume and decreased gyrification in the left superior temporal gyrus (STG) relative to TD boys. Regional GM volume correlated with aggression and conduct problem severity in the CD group, suggesting that the GM changes may contribute to increased aggression and conduct problems in boys with CD who have suffered CM. In conclusion, these results demonstrate previously unreported CM-associated distinct brain structural changes among CD-diagnosed boys.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Highlighting psychological pain avoidance and decision-making bias as key predictors of suicide attempt in major depressive disorder-A novel investigative approach using machine learning.

OBJECTIVE: Predicting suicide is notoriously difficult and complex, but a serious public health issue. An innovative approach utilizing machine learning (ML) that incorporates features of psychological mechanisms and decision-making characteristics related to suicidality could create an improved model for identifying suicide risk in patients with major depressive disorder (MDD). METHOD: Forty-four patients with MDD and past suicide attempts (MDD_SA, N = 44); 48 patients with MDD but without past suicide attempts (MDD_NS, N = 48-42 of whom with suicide ideation [MDD_SI, N = 42]), and healthy controls (HCs, N = 51) completed seven psychometric assessments including the Three-dimensional Psychological Pain Scale (TDPPS), and one behavioral assessment, the Balloon Analogue Risk Task (BART). Descriptive statistics, group comparisons, logistic regressions, and ML were used to explore and compare the groups and generate predictors of suicidal acts. RESULTS: MDD_SA and MDD_NS differed in TDPPS total score, pain arousal and avoidance subscale scores, suicidal ideation scores, and relevant decision-making indicators in BART. Logistic regression tests linked suicide attempts to psychological pain avoidance and a risk decision-making indicator. The resultant key ML model distinguished MDD_SA/MDD_NS with 88.2% accuracy. The model could also distinguish MDD_SA/MDD_SI with 81.25% accuracy. The ML model using hopelessness could classify MDD_SI/HC with 94.4% accuracy. CONCLUSION: ML analyses showed that motivation to avoid intolerable psychological pain, coupled with impaired decision-making bias toward under-valuing life's worth are highly predictive of suicide attempts. Analyses also demonstrated that suicidal ideation and attempts differed in potential mechanisms, as suicidal ideation was more related to hopelessness. ML algorithms show useful promises as a predictive instrument.

The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder.

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.

The Relationship Between Cognitive Dysfunction Through THINC-Integrated Tool (THINC-it) and Psychosocial Function in Chinese Patients With Major Depressive Disorder.

Background: Herein, we validate the psychometric properties of the Chinese version of the THINC-integrated tool (THINC-it) as a screening tool for cognitive deficits in patients with major depressive disorder. The primary aim of this study is to determine whether cognitive deficits as detected by the THINC-it tool in adults with major depressive disorder (MDD) are associated with workplace productivity and/or psychosocial function. Methods: Subjects aged 18-65 (n = 91) with MDD were evaluated and compared to age-, sex- and education- matched healthy controls (n = 95). Symptoms of cognitive dysfunction, workplace productivity, and psychosocial function were measured using the THINC-it tool, Hamilton Depression Scale (HAMD), Sheehan Disability Scale (SDS), The Work Productivity and Activity Impairment questionnaire- Specific Health Problem (WPAI-SHP). Results: There were significant differences in THINC-it scores (p < 0.01), the average of HAMD total score (p < 0.01) and all aspects of SDS (p < 0.01) between two groups. There were significant differences in the four aspects of WPAI between the two groups in the employed status (p <0.01). THINC-it subjective cognition and SDS total score, SDS work/school, SDS social, SDS family showed significantly correlation (r ranging from 0.255 to 0.386, p <0.01). SDS and THINC-it Objective cognition, THINC-it comprehensive cognition were no correlation between two groups. HAMD total score and SDS total score, SDS social, SDS family showed significantly correlation (r ranging.