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.

Effects of BDNF Val66Met polymorphisms on brain structures and behaviors in adolescents with conduct disorder.

Accumulating evidence suggests that neural abnormalities in conduct disorder (CD) may be subject to genetic influences, but few imaging studies have taken genetic variants into consideration. The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) has emerged as a high-interest genetic variant due to its importance in cortical maturation, and several studies have implicated its involvement in neurodevelopmental disorders. Thus, it is unclear how this polymorphism may influence brain anatomy and aberrant behaviors in CD. A total of 65 male adolescents with CD and 69 gender-, IQ- and socioeconomic status-matched healthy controls (HCs) (age range 13-17 years) were enrolled in this study. Analyses of variance (ANOVAs) were used to assess the main effects of CD diagnosis, BDNF genotype, and diagnosis-genotype interactions on brain anatomy and behaviors. We detected a significant main effect of BDNF genotype on temporal gyrification and antisocial behaviors, but not on CD symptoms. Diagnosis-genotype interactive effects were found for cortical thickness of the superior temporal and adjacent areas. These results suggest that the BDNF Val66Met polymorphism may exert its influence both on neural alterations and delinquent behaviors in CD patients. This initial evidence highlights the importance of elucidating potentially different pathways between BDNF genotype and cortical alterations or delinquent behaviors in CD patients.

MAOA genotype influences neural response during an inhibitory task in adolescents with conduct disorder.

Conduct disorder (CD), a common psychiatric disorder in children and adolescents, is characterized by encroaching upon other rights and violations of age-appropriate social expectations repeatedly and persistently. Individuals with CD often have high aggressiveness and low inhibitory capacity. The monoamine oxidase A (MAOA) gene has long been associated with aggression. Effects of MAOA genotype on inhibitory control have been examined in general population. Several studies had revealed reduced activation in prefrontal areas, especially the anterior cingulate cortex (ACC), in low-expression MAOA (MAOA-L) allele carriers compared to high-expression MAOA (MAOA-H) allele carriers. However, little is known about its genetic risk influences on inhibitory processes in clinical samples. In this study, functional magnetic resonance imaging (fMRI) was administered to a sample of adolescent boys with CD during the performance of a GoStop task, 29 of whom carrying MAOA-L allele and 24 carrying MAOA-H allele. Relative to MAOA-H carriers, MAOA-L carriers in CD showed more pronounced deactivation in the precuneus, supplementary motor area (SMA) and dorsal anterior cingulate cortex (dACC). Deactivation within the default mode network (DMN) and inhibitory-related areas in MAOA-L carriers may be related to compensation for low sensitivity to inhibition and/or an atypical allocation of cognitive resources. The results suggested a possible neural mechanism through which MAOA affects inhibitory processes in a clinical sample.

Serotonin transporter gene polymorphism (5-HTTLPR) L allele interacts with stress to increase anxiety symptoms in Chinese adolescents: a multiwave longitudinal study.

BACKGROUND: Previous studies of the interaction between a functional polymorphism in the serotonin transporter gene-linked promoter region (5-HTTLPR) and stress in anxiety-related phenotypes have produced inconsistent results. The aim of the current study was to examine the effect of the 5-HTTLPR × stress interaction on anxiety symptoms in Chinese adolescents. METHODS: A total of 651 healthy adolescents [323 females and 328 males; age 14-17 (mean = 16.27, standard deviation = 0.77)] participated in this study. At the initial assessment, participants completed self-report measures assessing anxiety symptoms, depressive symptoms and stressful life events. Additionally, anxiety symptoms and stressful life events were assessed once every 3 months for the subsequent 9 months. A hierarchical linear model (HLM) was used to investigate the 5-HTTLPR × stress interaction. RESULTS: The HLM indicated no main effect of 5-HTTLPR on anxiety symptoms. Significant 5-HTTLPR × stress interaction effect in predicting anxiety symptoms was found. Specifically, individuals with the 5-HTTLPR L allele exhibited more anxiety symptoms related to stressful life events. CONCLUSIONS: The association between stress and anxiety symptoms is moderated by 5-HTTLPR. The 5-HTTLPR L allele increases individuals' vulnerability to anxiety under stress situations.

Interaction between a serotonin transporter gene promoter region polymorphism and stress predicts depressive symptoms in Chinese adolescents: a multi-wave longitudinal study.

BACKGROUND: The serotonin transporter (5-HTT) gene may play an important role in the onset and development of mental disorders. Past studies have tested whether a functional polymorphism in the 5-HTT gene linked promoter region (5-HTTLPR) moderated the association between stress and depressive symptoms, but the results of these studies were inconsistent. Thus, the aim of the current study was to examine the interaction between 5-HTTLPR and stress that predict depressive symptoms in Chinese adolescents. METHODS: A total of 252 healthy adolescents (131 females and 121 males, aged from 14 to 18, mean = 16.00, standard deviation = 0.60) participated in this study. During the initial assessment, all participants completed the Center for Epidemiological Studies Depression Scale (CES-D) and Adolescent Life Events Questionnaire (ALEQ) and were genotyped for the 5-HTTLPR polymorphism. Participants subsequently completed CES-D and ALEQ once every three months during the subsequent 24 months. A multilevel model was used to investigate the 5-HTTLPR × stress interaction in predicting depressive symptoms. RESULTS: The results indicated no main effect of 5-HTTLPR and a significant 5-HTTLPR × stress interaction in females only. Females with at least one 5-HTTLPR S allele exhibited more depressive symptoms under stressful situations. No significant 5-HTTLPR × stress interaction was found in males. CONCLUSIONS: In Chinese adolescents, there are gender differences on the interaction between 5-HTTLPR and stress that predict depressive symptoms. The association between stress and depressive symptoms is moderated by 5-HTTLPR in Chinese female adolescents.

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.

Influence of psychosocial stress on activation in human brain regions: moderation by the 5-HTTLPR genetic locus.

Variants of the serotonin transporter linked polymorphic region (5-HTTLPR) of the serotonin transporter gene SLC6A4 have been related with the onset of depression, anxiety, and other mental disorders. Homozygotes for the short 5-HTTLPR variant, referred to as the SS genotype, have greater cortisol responses to experimentally induced psychosocial stress. In the current study, we used functional magnetic resonance imaging (fMRI) to compare regional brain activations across 5-HTTLPR genotypes in subjects performing the Montreal Imaging Stress Task (MIST). Subjects with an SS genotype had significant greater increases in cortisol concentrations after the task than subjects with at least one long 5-HTTLPR allele. Additionally, relative to L carriers, the SS group had greater activation in the dorsomedial prefrontal cortex(dmPFC), dorsal anterior cingulate cortex, anterior insula.

The MAOA Gene Influences the Neural Response to Psychosocial Stress in the Human Brain.

The stress response is regulated by many mechanisms. Monoamine oxidase A (MAOA) has been related to many mental illnesses. However, few studies have explored the relationship between MAOA and acute laboratory-induced psychosocial stress with functional magnetic resonance imaging (fMRI). In the current study, the Montreal Imaging Stress Task (MIST) and fMRI were used to investigate how MAOA influences the stress response. Increased cortisol concentrations were observed after the task; functional connectivity between the bilateral anterior hippocampus and other brain regions was reduced during stress. MAOA-H allele carriers showed greater deactivation of the right anterior hippocampus and greater cortisol response after stress than did MAOH-L allele carriers. Hippocampal deactivation may lead to disinhibition of the hypothalamic-pituitary-adrenal (HPA) axis and the initiation of stress hormone release under stress. Our results suggest that the MAOA gene regulates the stress response by influencing the right anterior hippocampus.

Gray Matter Changes in the Orbitofrontal-Paralimbic Cortex in Male Youths With Non-comorbid Conduct Disorder.

Conduct disorder is one of the most common developmental psychiatric disorders which is characterized by persistent aggressive and antisocial behaviors during childhood or adolescence. Previous neuroimaging studies have investigated the neural correlates underlying CD and demonstrated several constructive findings. However, Individuals with CD are at high risk for comorbidities, which might give rise to the inconsistencies of existed findings. It remains unclear which neuroanatomical abnormalities are specifically related to CD without comorbidities. Using structural magnetic resonance imaging (sMRI) data of 69 CD and 69 typically developing (TD) male youths (aged 14-17 years), the present study aims at investigating gray matter volume alterations of non-comorbid CD (i.e., not comorbid with attention deficit hyperactivity disorder, substance abuse disorder, anxiety or depression). We also examined how regional gray matter volumes were related to callous-unemotional (CU) traits and conduct problems in the CD group. The whole-brain analysis revealed decreased gray matter volumes in the right pre-postcentral cortex, supramarginal gyrus and right putamen in CD youths compared with TD youths. The region-of-interest analyses showed increased gray matter volumes in the superior temporal gyrus (STG) and right orbitofrontal cortex (OFC) in CD youths. Correlation analysis found that gray matter volume in the left amygdala was negatively correlated with CU traits in CD participants. These results demonstrated that gray matter volume in the orbitofrontal-paralimbic cortex, including OFC, STG and amygdala, might characterize the male youths with non-comorbid CD and might contribute to different severe forms and trajectories of CD.

Neuroticism modulates neural activities of posterior cingulate cortex and thalamus during psychosocial stress processing.

OBJECTIVE: Individuals with higher neuroticism are vulnerable to stress and are prone to develop depression, however, the neural mechanisms underlying it have not been clarified clearly. METHOD: The Montreal Imaging Stress Task (MIST) was administered to 148 healthy adults during functional magnetic resonance imaging (fMRI). Whole-brain voxel-wise regression analyses were used to detect associations of neuroticism with neural activity involved in perceiving and processing psychosocial stress. In addition, two-sample t-tests were conducted between the high-neurotic and low-neurotic group in order to supplement the results found in regression analyses. RESULTS: Higher neuroticism scores were associated with higher activities in the posterior cingulate cortex (PCC)/precuneus and thalamus (p < 0.05, false discovery rate correction). Moreover, two sample t-tests also revealed that the high-neurotic group had higher neural stress responses in precuneus and bilateral thalamus in comparison to the low-neurotic group (p < 0.05, false discovery rate correction). LIMITATIONS: Our study mainly recruited young adults, which may limit the generalizability of our findings. CONCLUSIONS: Our findings highlight the crucial role of PCC/precuneus and thalamus in the association between neuroticism and stress and may provide insight into the cognitive model of depression.

Topologically state-independent and dependent functional connectivity patterns in current and remitted depression.

OBJECTIVE: Identification of state-independent and -dependent neural biomarkers may provide insight into the pathophysiology and effective treatment of major depressive disorder (MDD), therefore we aimed to investigate the state-independent and -dependent topological alterations of MDD. METHOD: Brain resting-state functional magnetic resonance imaging (fMRI) data were acquired from 59 patients with unmedicated first episode current MDD (cMDD), 48 patients with remitted MDD (rMDD) and 60 demographically matched healthy controls (HCs). Using graph theory, we systematically studied the topological organization of their whole-brain functional networks at the global and nodal level. RESULTS: At a global level, both patient groups showed decreased normalized clustering coefficient in relative to HCs. On a nodal level, both patient groups showed decreased nodal centrality, predominantly in cortex-mood-regulation brain regions including the dorsolateral prefrontal cortex, posterior parietal cortex and posterior cingulate cortex. By comparison to cMDD patients, rMDD group had a higher nodal centrality in right parahippocampal gyrus. LIMITATIONS: The present study, an exploratory analysis, may require further confirmation with task-based and experimental studies. CONCLUSIONS: Deficits in the topological organization of the whole brain and cortex-mood-regulation brain regions in both rMDD and cMDD represent state-independent biomarkers.

Childhood Maltreatment Experience Influences Neural Response to Psychosocial Stress in Adults: An fMRI Study.

BACKGROUND: Childhood maltreatment is a strong risk factor for the development of depression in later life. However, the neurobiological mechanisms underlying this vulnerability are not well understood. As depression has been associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and increased responsiveness to psychosocial stressors, we speculated that childhood maltreatment may lead to lasting alteration of the stress response system, thereby increasing the risk of depression. This study investigated the effects of childhood maltreatment on the stress response in healthy subjects while controlling for psychiatric condition. METHODS: Forty-eight healthy young adults (24 females) with childhood maltreatment experience and 48 healthy controls (33 females) without such experience were administered the Montreal Imaging Stress Task during functional magnetic resonance imaging. Childhood maltreatment experience was assessed using the 28-item Childhood Trauma Questionnaire (CTQ). Between-group differences in subjective stress levels, whole brain activations and cortisol levels were assessed. RESULTS: Relative to healthy control subjects, individuals exposed to childhood maltreatment exhibited higher subjective stress and cortisol levels. Neurofunctionally, participants with histories of childhood maltreatment displayed significantly increased activation in the dorsolateral prefrontal cortex (dlPFC), insula and precuneus, and decreased activation in ventromedial prefrontal cortex (vmPFC) relative to healthy controls during the psychosocial stress task. Activations in dlPFC and insula correlated with CTQ scores in the childhood maltreatment group. CONCLUSION: The results of this study show that childhood maltreatment induces lasting changes in brain function and HPA-axis responsiveness to stress. The observed abnormal activation in the dlPFC, insula and vmPFC and enhanced cortisol response are similar to those seen in individuals with depression. This dysfunction might serve as a diathesis that embeds latent vulnerability to psychiatric disorders, and this mechanism provides evidence supporting the stress sensitization model.

State-independent alterations of intrinsic brain network in current and remitted depression.

BACKGROUND: It has been proposed that state-independent, or trait, neurobiological alterations across illness phases may contribute to the high recurrence of major depressive disorder (MDD). Although intrinsic brain network abnormalities have been implicated consistently in MDD neuropathology, MDD state-independent and -dependent resting-state network alterations have not been clearly studied. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were collected from 57 medication-naive first-episode current MDD patients, 35 remitted MDD patients, and 66 healthy controls (HCs). Independent component analysis (ICA) was used to extract subnetworks of the default mode network (DMN), central executive network (CEN), and salience network (SN). RESULTS: Relative to HCs, the current MDD and remitted MDD groups had decreased intra-intrinsic functional connectivity (iFC) in the dorsal lateral prefrontal cortex (dlPFC) of the left CEN, increased inter-FC between the SN and right CEN (rCEN), and decreased inter-FC between the anterior DMN (aDMN) and rCEN. The altered intra-iFC in the left CEN were correlated negatively with the depressive level in the remitted MDD. CONCLUSIONS: Hypoactivity of the dlPFC in the left CEN, increased inter-FC between the SN and rCEN, and decreased inter-FC between the aDMN and rCEN may reflect state-independent biomarkers of MDD.

State-Related Alterations of Spontaneous Neural Activity in Current and Remitted Depression Revealed by Resting-State fMRI.

Purpose: Although efforts have been made to identify neurobiological characteristic of major depressive disorder (MDD) in recent years, trait- and state-related biological characteristics of MDD still remains unclear. Using functional magnetic resonance imaging (fMRI), the aim of this study was to explore whether altered spontaneous neural activities in MDD are trait- or state- related. Materials and Methods: Resting-state fMRI data were analyzed for 72 current MDD (cMDD) patients (first-episode, medication-naïve), 49 remitted MDD (rMDD) patients, and 78 age- and sex- matched healthy control (HC) subjects. The values of amplitude of low-frequency fluctuation (ALFF) were compared between groups. Results: Compared with the cMDD group, the rMDD group had increased ALFF values in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe. Besides, compared with the HC group, the cMDD group had decreased ALFF values in the left middle occipital gyrus. Further analysis explored that the mean ALFF values in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe were correlated positively with BDI scores in rMDD patients. Conclusion: Abnormal activity in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe may be state-specific in current (first-episode, medication-naïve) and remitted (medication-naïve) depression patients. Furthermore, the state-related compensatory effect was found in these brain areas.

Atypical Frontotemporal Connectivity of Cognitive Empathy in Male Adolescents With Conduct Disorder.

Background: It has been suggested that adolescents with conduct disorder (CD) may have a deficit in the affective and cognitive domains empathy, but studies exploring networks within the key brain regions of affective and cognitive empathy in adolescents with CD are lacking. Methods: Functional connectivity (FC) analyses among key brain regions of the affective and cognitive empathy with resting-state functional magnetic resonance imaging (fMRI) were conducted in 30 adolescent boys with CD and 33 demographically matched healthy controls (HCs). Results: Atypical FC within the key brain regions of affective empathy was not observed in CD adolescents. However, we found that CD adolescents showed decreased frontotemporal connectivity within the key brain regions of cognitive empathy in relation to HCs, that is, the FCs between right temporoparietal junction and ventromedial prefrontal cortex as well as dorsomedial prefrontal cortex. Conclusion: These findings may provide insight into neural mechanism underlying a cognitive empathy deficiency of CD adolescents from the perspective of FC.

MAOA genotype modulates default mode network deactivation during inhibitory control.

It has been demonstrated, in a long line of research, that the low-activity genotype of the monoamine oxidase A (MAOA) gene is associated with aggression. Previous work has linked impaired response inhibition to aggression, but little is known about how this relates to the purported MAOA-aggression relationship in adolescents. Here, we examined how MAOA genotype influences neural correlates of inhibitory control in 74 healthy male adolescents using a GoStop and a Go/Nogo task while differentiating between action cancelation and action restraint. Carriers of the low-expressing MAOA alleles (MAOA-L) did not show altered brain activation in the prefrontal-subcortical inhibition network relative to carriers of the high-expressing alleles across inhibition conditions. However, they exhibited a more pronounced deactivation during response inhibition in the posterior cingulate cortex (PCC) and precuneus, areas belonging to the default mode network (DMN). Larger DMN suppression in MAOA-L carriers might represent a compensation mechanism for impaired cognitive control.

Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder.

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic-basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.

Prevalence and Correlates of Direct Self-Injurious Behavior among Chinese Adolescents: Findings from a Multicenter and Multistage Survey.

Direct self-injurious behavior (DSIB) has become an important focus due to its perniciousness and perplexity. Little is known about its prevalence and correlative factors in Chinese adolescents, including how data may differ according to gender. A multicenter, multistage stratified cluster random sampling was used to examine the previous 12-month prevalence of DSIB, as well as the possible correlates of demographics, risky behaviors, suicidality, and psychosocial factors associated with DSIB in a school-based sample of 11,880 students (49.5 % boys and 50.5 % girls). Approximately 30 % of the adolescents in the sample reported at least one incident of DSIB in the past 12-month period. After controlling for demographic variables, analyses of the independent relationships of DSIB with risky behaviors, suicidality, and psychosocial factors were conducted for each gender. Smoking, binge drinking, running away from home, suicide ideation, suicide plans, positive affect, and physical symptoms were identified as common factors associated with DSIB for both genders in the final model. In addition, truancy, fighting, physical inactivity, motor impulsiveness, and depressed affect were found to be related to DSIB in boys, whereas suicide attempts and somatic complaints were found to be related to DSIB in girls. Separation anxiety and social anxiety associated negatively with DSIB in boys and girls, respectively. DSIB was not found to independently relate to attention impulsiveness, non-planned impulsiveness, self-esteem, or harm avoidance in either genders. DSIB was prevalent in Chinese adolescents. Programs intended to promote physical and mental health in adolescents should take into account gender differences in DSIB-associated factors, including risky behaviors, suicidality, and psychosocial factors.

Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents.

Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR "SS" genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions.

Whole-brain resting-state functional connectivity identified major depressive disorder: A multivariate pattern analysis in two independent samples.

BACKGROUND: there has been a recent increase in the use of connectome-based multivariate pattern analysis (MVPA) of resting-state functional magnetic resonance imaging (fMRI) data aimed at distinguishing patients with major depressive disorder (MDD) from healthy controls (HCs). However, the validity of this method needs to be confirmed in independent samples. METHOD: we used resting-state fMRI to explore whole-brain functional connectivity (FC) patterns characteristic of MDD and to confirm the effectiveness of MVPA in distinguishing MDD versus HC groups in two independent samples. The first sample set included 29 MDD patients and 33 HCs and second sample set included 46 MDD patients and 57 HCs. RESULTS: for the first sample, we obtained a correct classification rate of 91.9% with a sensitivity of 89.6% and specificity of 93.9%. For the second sample, we observed a correct classification rate of 86.4% with a sensitivity of 84.8% and specificity of 87.7%. With both samples, we found that the majority of consensus FCs used for MDD identification were located in the salience network, default mode network, the cerebellum, visual cortical areas, and the affective network. LIMITATION: we did not analyze potential structural differences between the groups. CONCLUSION: results suggest that whole-brain FC patterns can be used to differentiate depressed patients from HCs and provide evidence for the potential use of connectome-based MVPA as a complementary tool in the clinical diagnosis of MDD.