Melancholic Major Depressive Disorder Research Articles

Neural substrates of predicting anhedonia symptoms in major depressive disorder via connectome-based modeling.

Anhedonia is a critical diagnostic symptom of major depressive disorder (MDD), being associated with poor prognosis. Understanding the neural mechanisms underlying anhedonia is of great significance for individuals with MDD, and it encourages the search for objective indicators that can reliably identify anhedonia. A predictive model used connectome-based predictive modeling (CPM) for anhedonia symptoms was developed by utilizing pre-treatment functional connectivity (FC) data from 59 patients with MDD. Node-based FC analysis was employed to compare differences in FC patterns between melancholic and non-melancholic MDD patients. The support vector machines (SVM) method was then applied for classifying these two subtypes of MDD patients. CPM could successfully predict anhedonia symptoms in MDD patients (positive network: r = 0.4719, p < 0.0020, mean squared error = 23.5125, 5000 iterations). Compared to non-melancholic MDD patients, melancholic MDD patients showed decreased FC between the left cingulate gyrus and the right parahippocampus gyrus (p_bonferroni = 0.0303). This distinct FC pattern effectively discriminated between melancholic and non-melancholic MDD patients, achieving a sensitivity of 93.54%, specificity of 67.86%, and an overall accuracy of 81.36% using the SVM method. This study successfully established a network model for predicting anhedonia symptoms in MDD based on FC, as well as a classification model to differentiate between melancholic and non-melancholic MDD patients. These findings provide guidance for clinical treatment.

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

BackgroundCompared 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. MethodsForty 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. ResultsMelancholic 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. ConclusionsOur 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.

Aberrant high-beta band functional connectivity during reward processing in melancholic major depressive disorder: An MEG study

ObjectiveTo identify the spatial–temporal pattern variation of whole-brain functional connectivity (FC) during reward processing in melancholic major depressive disorder (MDD) patients, and to determine the clinical correlates of connectomic differences. Methods61 MDD patients and 32 healthy controls were enrolled into the study. During magnetoencephalography (MEG) scanning, all participants completed the facial emotion recognition task. The MDD patients were further divided into two groups: melancholic (n = 31) and non-melancholic (n = 30), based on the Mini International Neuropsychiatric Interview (M.I.N.I.) assessment. Melancholic symptoms were examined by using the 6-item melancholia subscale from the Hamilton Depression Rating Scale (HAM-D6). The whole-brain orthogonalized power envelope connections in the high-beta band (20–35 Hz) were constructed in each period after the happy emotional stimuli (0–200 ms, 100–300 ms, 200–400 ms, 300–500 ms, and 400–600 ms). Then, the network-based statistic (NBS) was used to determine the specific abnormal connection patterns in melancholic MDD patients. ResultsThe NBS identified a sub-network difference at the mid-late period (300–500 ms) in response to happy faces among the three groups (corrected P = 0.035). Then, the post hoc and correlation analyses found five FCs were decreased in melancholic MDD patients and were related to HAM-D6 score, including FCs of left fusiform gyrus-right orbital inferior frontal gyrus (r = −0.52, P < 0.001), left fusiform gyrus-left amygdala (r = −0.26, P = 0.049), left posterior cingulate gyrus-right precuneus (r = −0.32, P = 0.025), left precuneus-right precuneus (r = −0.27, P = 0.049), and left precuneus-left inferior occipital gyrus (r = −0.32, P = 0.025). ConclusionIn response to happy faces, melancholic MDD patients demonstrated a disrupted functional connective pattern (20–35 Hz, 300–500 ms), which involved brain regions in visual information processing and the limbic system. The aberrant functional connective pattern in reward processing might be a biomarker of melancholic MDD.

Melancholic features and treatment outcome to selective serotonin reuptake inhibitors in major depressive disorder: A re-analysis of the STAR*D trial

BackgroundMelancholia has been positioned as a qualitatively different form of Major Depressive Disorder (MDD). Some studies have suggested that melancholic MDD patients may show lower remission when receiving treatment with Selective Serotonin Reuptake Inhibitors, but this has not yet been explored in large, representative samples of MDD. MethodsWe used data from the STAR*D, a multisite randomized controlled trial (n = 4041). We defined melancholia status through the BA Melancholia Empirical Index, constructed using items from the Inventory of Depressive Symptomatology (IDSC). The main outcome of interest was symptomatic remission defined as a Quick Inventory of Depressive Symptoms (Clinician version) (QIDS-C) below or equal to 5. Inverse probability weighting was used to control for confounding. Results3827 patients were eligible for this study. Melancholic patients were more likely to be unemployed, never married, to self-report an African American race, and to have a higher depressive severity. The adjusted 4-month probability of remission was 26.9 % (22.0, 45.5) for melancholic and 53.8 % (53.2, 58.5), for nonmelancholic patients. Compared with nonmelancholic, the difference in 4-month probability of remission was −26.9 % (−37.0, −15.6). Results were consistent across sensitivity analyses. LimitationsItems from IDSC were used as a surrogate measure of the BA Melancholia Index, and extrapolation of the results to agents other than citalopram and to psychotic MDD patients requires caution. ConclusionsMelancholic MDD patients showed lower probabilities of remission at 4-months receiving treatment with citalopram. The results of this study show how validly subtyping episodes could contribute to the personalized treatment of depression.

Affective Temperaments in Differentiation Between Melancholic and Nonmelancholic Depression: A Case-Control Study.

The association between major depressive disorder (MDD) and personality traits has been extensively studied. However, differences in personality traits between patients with melancholic MDD (MEL) and nonmelancholic MDD (NMEL) remain unclear. In this study, we aimed to determine whether neuroticism, which has been associated with MDD, and the five affective temperament subtypes assessed by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A) can be used to distinguish MEL and NMEL. A total of 106 patients with MDD (MEL, n = 52; NMEL, n = 54) and 212 age- and sex-matched healthy controls answered the Eysenck Personality Questionnaire-revised and the short version of TEMPS-A. In hierarchical logistic regression analysis, only depressive temperament scores were identified as a statistically significant feature distinguishing NMEL from MEL. Depressive temperament scores assessed by the short version of TEMPS-A were found to be significantly higher in NMEL patients than in MEL patients.

Neural association between cognitive function and anhedonia in adolescents with melancholic major depressive disorder: A fNIRS study

BackgroundCognitive dysfunction is common among adolescent patients with major depressive disorder (MDD). However, the pattern and magnitude of cognition impairment in patients during melancholic episodes remains unclear. The purpose of this study was to compare the neurocognitive performance and the underlying cerebral blood flow activation of adolescent patients with melancholic and non-melancholic features. MethodsFifty-seven and 44 adolescent patients with MDD with or without melancholic feature (MDD-MEL/nMEL) and 58 healthy controls (HCs) were recruited. We used the repeatable battery for the assessment of neuropsychological status (RBANS) measuring neurocognitive function, and used functional near infrared spectroscopy (fNIRS) monitoring cerebral hemodynamic changes, described by β value. The non-parametric test and post-hoc analysis were conducted in RBANS scores and β values among three groups. Spearman correlation and mediating analysis was performed for RBANS scores, β values, and clinical symptoms in the MDD-MEL group. ResultsThere were no significant difference in RBANS scores between MDD-MEL and MDD-nMEL group. Compared with patients in MDD-nMEL, patients in MDD-MEL have lower β values in eight channels (ch10, ch16, ch20, ch25, ch27, ch37, ch41, ch45). The cognitive function is significantly correlated with anhedonia, and the β values play a partial mediating role between anhedonia and cognitive function. LimitationIt's a cross-sectional study and monitoring longitudinal effects are needed to further elucidate the mechanism. ConclusionThe cognitive function in adolescents with MDD-MEL may not significantly differ from those with MDD-nMEL. However, the anhedonia may influenced the cognitive function by altering the function of medial frontal cortex.

Objective polysomnography-based sleep features and major depressive disorder subtypes in the general population

Insomnia and its opposite hypersomnia are part of the diagnostic criteria for major depressive disorder (MDD). However, no study has investigated whether the postulated sleep alterations in clinical subtypes of MDD are reflected in polysomnography (PSG)-derived objective sleep measures. The objective of this study was to establish associations between the melancholic, atypical and unspecified subtypes of MDD and objective PSG-based sleep features. This cross-sectional analysis included 1820 community-dwelling individuals who underwent PSG and a semi-structured psychiatric interview to elicit diagnostic criteria for MDD and its subtypes. Adjusted robust linear regression was used to assess associations between MDD subtypes and PSG-derived objective sleep measures. Current melancholic MDD was significantly associated with decreased absolute delta power and sleep efficiency and with increased wake after sleep onset. Remitted unspecified MDD was significantly associated with increased rapid eye movements density. No other significant associations were identified. Our findings reflect that some PSG-based sleep features differed in MDD subtypes compared with no MDD. The largest number of significant differences were observed for current melancholic MDD, whereas only rapid eye movements density could represent a risk factor for MDD as it was the only sleep measure that was also associated with MDD in remitted participants.

Stability of the Subtypes of Major Depressive Disorder in Older Adults and the Influence of Mild Cognitive Impairment on the Stability

ObjectivesTo assess 1) the longitudinal stability of the atypical, melancholic, combined atypical-melancholic and the unspecified subtypes of major depressive disorder (MDD) according to the diagnostic and statistical manual of mental disorders (DSM –IV) specifiers in older adults, and 2) the effect of mild cognitive impairment (MCI) on the stability of these subtypes. DesignProspective cohort study with a 5.1 year-follow-up. SettingPopulation-based cohort from Lausanne, Switzerland. ParticipantsA total of 1,888 participants (mean age: 61.7 years, women: 69.2%) with at least two psychiatric evaluations, one after the age of 65 years. MeasurementsSemistructured diagnostic interview to assess lifetime and 12-month DSM-IV Axis-1 disorders at each investigation and neuro-cognitive tests to identify MCI in participants aged 65 years and over. Associations between lifetime MDD status before and 12-month depression status after the follow-up were assessed using multinomial logistic regression. The effect of MCI on these associations was assessed by testing interactions between MDD subtypes and MCI status. Results1) Associations between depression status before and after the follow-up were observed for atypical (adjusted OR [95% CI] = 7.99 [3.13; 20.44]), combined (5.73 [1.50; 21.90]) and unspecified (2.14 [1.15; 3.98]), but not melancholic MDD (3.36 [0.89; 12.69]). However, there was a certain degree of overlap across the subtypes, particularly between melancholic MDD and the other subtypes. 2) No significant interactions were found between MCI and lifetime MDD subtypes regarding depression status after follow-up. ConclusionThe strong stability of the atypical subtype in particular highlights the need for identifying this subtype in clinical and research settings, given its well-documented links to inflammatory and metabolic markers.

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

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

Comparison of plasma catecholamine metabolites in melancholic and non-melancholic depression

Major depressive disorder (MDD) manifests either with or without melancholic features. Differences in catecholamine dynamics between these two types of MDD are yet to be clarified definitively. We compared and investigated serum catecholamine metabolite levels in patients presenting with MDD for the first time who had never received treatment. We enrolled 78 patients (male/female: 35/43; melancholic/non-melancholic: 30/48) at the Neuropsychiatry Branch of the University Hospital of University of Occupational and Environmental Health, Kitakyushu, Japan. The patients were screened for axis I psychiatric disorders using the Japanese version of the Mini-International Neuropsychiatric Interview, and blood sampling was performed on the first day of hospital visit. Major depressive episodes were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders IV, Text Revision , and severity of depression was evaluated using the 17-item Hamilton Depression Rating Scale. We observed no significant differences in serum 3-methoxy-4-hydroxyphenylglycol or homovanillic acid levels between healthy controls and untreated patients with either melancholic or non-melancholic MDD. These findings offer evidence suggesting that MDD cannot be simply classified into melancholic and non-melancholic subtypes, but is rather a highly heterogenous disorder with symptoms that extend seamlessly from the grief reactions experienced by healthy individuals. • Serum MHPG levels nor serum HVA levels did not differ among the the three group. • Catechoalminergic activity might not differ among the three group. • MDD is not a disease that can simply be classified into mechancholic and non-melancholic subtypes; rather it is highly heterogenous.

The aberrant dynamic amplitude of low-frequency fluctuations in melancholic major depressive disorder with insomnia.

BackgroundInsomnia is considered one of the manifestations of sleep disorders, and its intensity is linked to the treatment effect or suicidal thoughts. Major depressive disorder (MDD) is classified into various subtypes due to heterogeneous symptoms. Melancholic MDD has been considered one of the most common subtypes with special sleep features. However, the brain functional mechanisms in melancholic MDD with insomnia remain unclear.Materials and methodsMelancholic MDD and healthy controls (HCs, n = 46) were recruited for the study. Patients were divided into patients with melancholic MDD with low insomnia (mMDD-LI, n = 23) and patients with melancholic MDD with high insomnia (mMDD-HI, n = 30), according to the sleep disturbance subscale of the 17-item Hamilton Depression Rating Scale. The dynamic amplitude of low-frequency fluctuation was employed to investigate the alterations of brain activity among the three groups. Then, the correlations between abnormal dALFF values of brain regions and the severity of symptoms were investigated.ResultsLower dALFF values were found in the mMDD-HI group in the right middle temporal gyrus (MTG)/superior temporal gyrus (STG) than in the mMDD-LI (p = 0.014) and HC groups (p < 0.001). Melancholic MDD groups showed decreased dALFF values than HC in the right middle occipital gyri (MOG)/superior occipital gyri (SOG), the right cuneus, the bilateral lingual gyrus, and the bilateral calcarine (p < 0.05). Lower dALFF values than HC in the left MOG/SOG and the left cuneus in melancholic MDD groups were found, but no significant difference was found between the mMDD-LI group and HC group (p = 0.079). Positive correlations between the dALFF values in the right MTG/STG and HAMD-SD scores (the sleep disturbance subscale of the HAMD-17) in the mMDD-HI group (r = 0.41, p = 0.042) were found. In the pooled melancholic MDD, the dALFF values in the right MOG/SOG and the right cuneus (r = 0.338, p = 0.019), the left MOG/SOG and the left cuneus (r = 0.299, p = 0.039), and the bilateral lingual gyrus and the bilateral calcarine (r = 0.288, p = 0.047) were positively correlated with adjusted HAMD scores.ConclusionThe occipital cortex may be related to depressive symptoms in melancholic MDD. Importantly, the right MTG/STG may play a critical role in patients with melancholic MDD with more severe insomnia.

Overlapping and segregated changes of functional hubs in melancholic depression and non-melancholic depression

BackgroundPrevious research found associations between neuropsychiatric disorders and patterns of highly connected “hub” nodes, which are crucial in coordinating brain functions. Melancholic depression is considered a relatively distinct and homogenous subtype of major depressive disorder (MDD), which responds better to pharmacological treatments than placebos or psychotherapies. Accordingly, melancholic depression probably has distinct neuropathological underpinnings. This study aims to examine the overlapping and segregated changes of functional hubs in melancholic and non-melancholic MDD. MethodsThirty-one melancholic patients, 28 non-melancholic patients, and 32 healthy controls were included. Resting-state functional imaging data were analyzed using global functional connectivity. ResultsBoth melancholic and non-melancholic patients had increased GFC in the bilateral insula and decreased GFC in the PCC/precuneus compared to HCs. The distinction was that melancholic patients showed increased GFC in the bilateral thalamus, right inferior parietal lobule (IPL), and left cerebellum Crus I and decreased GFC in the left temporal lobe, whereas non-melancholic patients showed increased GFC in the left superior parietal lobe. Additionally, compared with non-melancholic patients, melancholic individuals displayed significant increases of GFC in the left IPL and cerebellum. ConclusionIncreased GFC of the insula and decreased GFC of the PCC and precuneus are the common abnormalities of melancholic and non-melancholic MDD. Hyperconnectivity of the IPL and cerebellum might be distinctive neuropathological features of melancholic MDD.

White Matter Network Disruption Is Associated With Melancholic Features in Major Depressive Disorder.

BackgroundThe efficacy and prognosis of major depressive disorder (MDD) are limited by its heterogeneity. MDD with melancholic features is an important subtype of MDD. The present study aimed to reveal the white matter (WM) network changes in melancholic depression.Materials and MethodsTwenty-three first-onset, untreated melancholic MDD, 59 non-melancholic MDD patients and 63 health controls underwent diffusion tensor imaging (DTI) scans. WM network analysis based on graph theory and support vector machine (SVM) were used for image data analysis.ResultsCompared with HC, small-worldness was reduced and abnormal node attributes were in the right orbital inferior frontal gyrus, left orbital superior frontal gyrus, right caudate nucleus, right orbital superior frontal gyrus, right orbital middle frontal gyrus, left rectus gyrus, and left median cingulate and paracingulate gyrus of MDD patients. Compared with non-melancholic MDD, small-worldness was reduced and abnormal node attributes were in right orbital inferior frontal gyrus, left orbital superior frontal gyrus and right caudate nucleus of melancholic MDD. For correlation analysis, the 7th item score of the HRSD-17 (work and interest) was positively associated with increased node betweenness centrality (aBC) values in right orbital inferior frontal gyrus, while negatively associated with the decreased aBC in left orbital superior frontal gyrus. SVM analysis results showed that abnormal aBC in right orbital inferior frontal gyrus and left orbital superior frontal gyrus showed the highest accuracy of 81.0% (69/83), the sensitivity of 66.3%, and specificity of 85.2% for discriminating MDD patients with or without melancholic features.ConclusionThere is a significant difference in WM network changes between MDD patients with and without melancholic features.

Abnormal dynamic functional connectivity of hippocampal subregions associated with working memory impairment in melancholic depression.

Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions - including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD. Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships. Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD. These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

Short-term and long-term effects of major depressive disorder subtypes on obesity markers and impact of sex on these associations

BackgroundOnly a few studies with conflicting results have examined the effects of sex on the prospective association between depression and subsequent obesity. Objective(1) To simultaneously assess the associations of the subtypes (atypical, melancholic, unspecified) of major depressive disorder (MDD) measured at baseline and subtypes of major depressive episodes (MDE) that emerged during a 5.5-year follow-up with changes in obesity markers (body mass index, waist circumference, fat mass) during this follow-up, and (2) to test the effect of sex on these associations. MethodsData from CoLaus|PsyCoLaus, a population-based cohort study including 2702 participants (50.1% women, mean age 49.6 years). Criteria for mental disorders were elicited using semi-structured interviews. ResultsHistory of atypical MDD at baseline was associated with a steeper increase in BMI and waist circumference, whereas atypical MDE during follow-up was associated with a steeper increase in the three studied obesity markers. Melancholic MDD at baseline was associated with a steeper increase in BMI. Several significant interactions with sex were found indicating higher increase in fat mass in men than in women following melancholic MDD reported at baseline, higher decrease in BMI and fat mass in women than in men related to melancholic MDE emerging during follow-up and higher increase in waist circumference in men than in women following unspecified MDD reported at baseline. LimitationsUrban sample which may not be representative for the whole population. ConclusionsOur results further advocate for the specific need of a thorough monitoring of obesity markers in patients with atypical MDD and suggest less favorable obesity marker changes mainly related to melancholic MDE in men.

Biological Mechanisms of Atypical and Melancholic Major Depressive Disorder

This review summarizes recent findings in molecular biology and neuroimaging and their applicability to the classification and identification of depression. We discuss whether there is reliable evidence that could become a basis for biomarkers or subtyping that may enhance our understanding of the biological foundations of depression and may be useful for clinical practice with respect to diagnosis and prognosis as well as the selection of treatments. The purpose of this investigation is to present molecular mechanisms that contribute to different origins of depressions that could prove useful in the daily psychiatric clinic-based practices. The authors have analyzed and summarized electronic publications available in PubMed, Science Direct, Google Scholar, and Scopus. The introduction of molecular diagnostic methods into medical practice is a promising method to improve the accuracy of the diagnosis of depression in clinical settings. The literature analysis revealed structural changes in some areas of the brain, its neuroplasticity, as well as changes at the molecular, epigenetic, and genetic levels. However, there are no current reliable biomarkers for differential diagnosis of the types and subtypes of depression. Major depressive disorder is a biologically and genetically heterogeneous disorder. Given its complexity, subtyping is worthwhile to identify biological bases of conditions. The literature review provides ample findings that reveal possible underlying biological mechanisms associated with atypical and melancholic depression. Additional focused research should be continued with respect to the molecular and genetic biology of different types of depression. There already are promising findings, but additional research to define biologically based depressive subtypes is needed and worthwhile.

Abnormal Default-Mode Network Homogeneity in Melancholic and Nonmelancholic Major Depressive Disorder at Rest.

Background Melancholic depression has been assumed as a severe type of major depressive disorder (MDD). We aimed to explore if there were some distinctive alterations in melancholic MDD and whether the alterations could be used to discriminate the melancholic MDD and nonmelancholic MDD. Methods Thirty-one outpatients with melancholic MDD, thirty-three outpatients with nonmelancholic MDD, and thirty-two age- and gender-matched healthy controls were recruited. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with the network homogeneity (NH) and support vector machine (SVM) methods. Results Both patient groups exhibited increased NH in the right PCC/precuneus and right angular gyrus and decreased NH in the right middle temporal gyrus compared with healthy controls. Compared with nonmelancholic patients and healthy controls, melancholic patients exhibited significantly increased NH in the bilateral superior medial frontal gyrus and decreased NH in the left inferior temporal gyrus. But merely for melancholic patients, the NH of the right middle temporal gyrus was negatively correlated with TEPS total and contextual anticipatory scores. SVM analysis showed that a combination of NH values in the left superior medial frontal gyrus and left inferior temporal gyrus could distinguish melancholic patients from nonmelancholic patients with accuracy, sensitivity, and specificity of 79.66% (47/59), 70.97% (22/31), and 89.29%(25/28), respectively. Conclusion Our findings showed distinctive network homogeneity alterations in melancholic MDD which may be potential imaging markers to distinguish melancholic MDD and nonmelancholic MDD.

Shared and distinct homotopic connectivity changes in melancholic and non-melancholic depression

ObjectivePrevious studies have revealed different neuroimaging features between melancholic and non-melancholic major depressive disorder (MDD). However, homotopic connectivity of melancholic and non-melancholic MDD remains unknown. The present study aimed to explore common and distinct homotopic connectivity patterns of melancholic and non-melancholic MDD and their associations with clinical characteristics. MethodsSixty-four patients with MDD and thirty-two healthy controls were scanned by resting-state functional magnetic resonance imaging (fMRI). Voxel-mirrored homotopic connectivity (VMHC) and pattern classification were applied to analyze the imaging data. ResultsRelative to healthy controls, melancholic patients displayed decreased VMHC in the fusiform gyrus, posterior cingulate cortex (PCC), superior occipital gyrus (SOG), postcentral gyrus and precentral/postcentral gyrus, and non-melancholic patients displayed decreased VMHC in the PCC. Compared with non-melancholic patients, melancholic patients displayed reduced VMHC in the precentral gyrus and precentral/postcentral gyrus. Support vector machine (SVM) results exhibited VMHC in the precentral gyrus could distinguish melancholic patients from non-melancholic patients with more than 0.6 for specificity, sensitivity and accuracy. ConclusionThe study demonstrated common and distinct homotopic connectivity patterns in melancholic and non-melancholic patients. Decreased VMHC in the PCC may be a state-related change for depression, and reduced VMHC in the precentral gyrus and postcentral gyrus may be a distinctive neurobiological feature for melancholic MDD. VMHC in precentral gyrus might be served as potential imaging markers to discriminate melancholic patients from non-melancholic MDD.

Melancholic features in major depression – a European multicenter study

There is still a debate, if melancholic symptoms can be seen rather as a more severe subtype of major depressive disorder (MDD) or as a separate diagnostic entity. The present European multicenter study comprising altogether 1410 MDD in- and outpatients sought to investigate the influence of the presence of melancholic features in MDD patients. Analyses of covariance, chi-squared tests, and binary logistic regression analyses were accomplished to determine differences in socio-demographic and clinical variables between MDD patients with and without melancholia. We found a prevalence rate of 60.71% for melancholic features in MDD. Compared to non-melancholic MDD patients, they were characterized by a significantly higher likelihood for higher weight, unemployment, psychotic features, suicide risk, inpatient treatment, severe depressive symptoms, receiving add-on medication strategies in general, and adjunctive treatment with antidepressants, antipsychotics, benzodiazepine (BZD)/BZD-like drugs, low-potency antipsychotics, and pregabalin in particular. With regard to the antidepressant pharmacotherapy, we found a less frequent prescription of selective serotonin reuptake inhibitors (SSRIs) in melancholic MDD. No significant between-group differences were found for treatment response, non-response, and resistance. In summary, we explored primarily variables to be associated with melancholia which can be regarded as parameters for the presence of severe/difficult-to treat MDD conditions. Even if there is no evidence to realize any specific treatment strategy in melancholic MDD patients, their prescribed medication strategies were different from those for patients without melancholia.

Disrupted Regional Homogeneity in Melancholic and Non-melancholic Major Depressive Disorder at Rest.

Background: Melancholic depression has been viewed as one severe subtype of major depressive disorder (MDD). However, it is unclear whether melancholic depression has distinct changes in brain imaging. We aimed to explore specific or distinctive alterations in melancholic MDD and whether the alterations could be used to separate melancholic MDD from non-melancholic MDD or healthy controls.Materials and Methods: Thirty-one outpatients with melancholic MDD and thirty-three outpatients with non-melancholic MDD and thirty-two age- and gender-matched healthy controls were recruited. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with the regional homogeneity (ReHo) and support vector machine (SVM) methods.Results: Melancholic MDD patients exhibited lower ReHo in the right superior occipital gyrus/middle occipital gyrus than non-melancholic MDD patients and healthy controls. Merely for non-melancholic MDD patients, decreased ReHo in the right middle frontal gyrus was negatively correlated with the total HRSD-17 scores. SVM analysis results showed that a combination of abnormal ReHo in the right fusiform gyrus/cerebellum Crus I and the right superior occipital gyrus/middle occipital gyrus exhibited the highest accuracy of 83.05% (49/59), with a sensitivity of 90.32% (28/31), and a specificity of 75.00% (21/28) for discriminating patients with melancholic MDD from patients with non-melancholic MDD. And a combination of abnormal ReHo in the right fusiform gyrus/cerebellum VI and left postcentral gyrus/precentral gyrus exhibited the highest accuracy of 98.41% (62/63), with a sensitivity of 96.77% (30/31), and a specificity of 100.00%(32/32) for separating patients with melancholic MDD from healthy controls.Conclusion: Our findings showed the distinctive ReHo pattern in patients with melancholic MDD and found brain area that may be associated with the pathophysiology of non-melancholic MDD. Potential imaging markers for discriminating melancholic MDD from non-melancholic MDD or healthy controls were reported.