Non-melancholic Depression Research Articles

Disrupted functional connectivity of bilateral nucleus accumbens in major depressive disorder with and without melancholic features.

Our study aims to explore the differences in functional connectivity in the nucleus accumbens (NAc) between patients with melancholic depression and non-melancholic depression (NMD) and their relation to melancholic depression's pathogenesis. We recruited 60 melancholic depression, 58 NMD, and 80 healthy controls, all matched for gender, age, and education. Functional connectivity analysis focused on bilateral NAc as the region of interest, comparing it with the whole brain and correlating significant differences with clinical scores. Melancholic depression patients showed reduced functional connectivity between the left NAc and anterior brain regions, and between the right NAc and temporal and frontal areas, compared to healthy controls. In contrast, NMD patients displayed reduced functional connectivity only between the left NAc and the posterior cingulate cortex. Melancholic depression patients also exhibited increased functional connectivity between the right NAc and the middle frontal gyrus, unlike NMD patients. The findings suggest that melancholic depression patients exhibit unique NAc functional connectivity patterns, particularly with the default mode network and prefrontal areas, suggesting atypical reward-circuitry interactions. The right NAc's connection to the prefrontal gyrus may distinguish melancholic depression from NMD.

Markers of positive affect and brain state synchrony discriminate melancholic from non-melancholic depression using naturalistic stimuli.

Melancholia has been proposed as a qualitatively distinct depressive subtype associated with a characteristic symptom profile (psychomotor retardation, profound anhedonia) and a better response to biological therapies. Existing work has suggested that individuals with melancholia are blunted in their display of positive emotions and differ in their neural response to emotionally evocative stimuli. Here, we unify these brain and behavioural findings amongst a carefully phenotyped group of seventy depressed participants, drawn from an established Australian database (the Australian Genetics of Depression Study) and further enriched for melancholia (high ratings of psychomotor retardation and anhedonia). Melancholic (n = 30) or non-melancholic status (n = 40) was defined using a semi-structured interview (the Sydney Melancholia Prototype Index). Complex facial expressions were captured whilst participants watched a movie clip of a comedian and classified using a machine learning algorithm. Subsequently, the dynamics of sequential changes in brain activity were modelled during the viewing of an emotionally evocative movie in the MRI scanner. We found a quantitative reduction in positive facial expressivity amongst participants with melancholia, combined with differences in the synchronous expression of brain states during positive epochs of the movie. In non-melancholic depression, the display of positive affect was inversely related to the activity of cerebellar regions implicated in the processing of affect. However, this relationship was reduced in those with a melancholic phenotype. Our multimodal findings show differences in evaluative and motoric domains between melancholic and non-melancholic depression through engagement in ecologically valid tasks that evoke positive emotion. These findings provide new markers to stratify depression and an opportunity to support the development of targeted interventions.

Reduced gray matter volume of the hippocampal tail in melancholic depression: evidence from an MRI study

BackgroundMelancholic depression (MD) is one of the most prevalent and severe subtypes of major depressive disorder (MDD). Previous studies have revealed inconsistent results regarding alterations in grey matter volume (GMV) of the hippocampus and amygdala of MD patients, possibly due to overlooking the complexity of their internal structure. The hippocampus and amygdala consist of multiple and functionally distinct subregions, and these subregions may play different roles in MD. This study aims to investigate the volumetric alterations of each subregion of the hippocampus and amygdala in patients with MD and non-melancholic depression (NMD).MethodsA total of 146 drug-naïve, first-episode MDD patients (72 with MD and 74 with NMD) and 81 gender-, age-, and education-matched healthy controls (HCs) were included in the study. All participants underwent magnetic resonance imaging (MRI) scans. The subregional segmentation of hippocampus and amygdala was performed using the FreeSurfer 6.0 software. The multivariate analysis of covariance (MANCOVA) was used to detect GMV differences of the hippocampal and amygdala subregions between three groups. Partial correlation analysis was conducted to explore the relationship between hippocampus or amygdala subfields and clinical characteristics in the MD group. Age, gender, years of education and intracranial volume (ICV) were included as covariates in both MANCOVA and partial correlation analyses.ResultsPatients with MD exhibited a significantly lower GMV of the right hippocampal tail compared to HCs, which was uncorrelated with clinical characteristics of MD. No significant differences were observed among the three groups in overall and subregional GMV of amygdala.ConclusionsOur findings suggest that specific hippocampal subregions in MD patients are more susceptible to volumetric alterations than the entire hippocampus. The reduced right hippocampal tail may underlie the unique neuropathology of MD. Future longitudinal studies are required to better investigate the associations between reduced right hippocampal tail and the onset and progression of MD.

Does theta burst stimulation have differential benefit for those with melancholic or non-melancholic depression?

BackgroundTo determine if theta burst stimulation (TBS) is of preferential benefit to those with melancholic or non-melancholic depression as an adjunctive treatment for treatment resistant depression (TRD). MethodsFifty-two patients receiving TBS at a private psychiatric hospital participated in a naturalistic study. Four diagnostic strategies were used to assign melancholic versus non-melancholic depression subtype status. Depression symptoms were assessed at baseline, mid-treatment, and end of treatment using the Montgomery-Ǻsberg Depression Rating Scale – Self-Assessment (MADRS-S). Forty-one participants also completed the MADR-S at a six-week follow-up assessment. ResultsWe quantified poor correlations between the four study measures of melancholia; a finding suggesting that valid measurement of melancholia is likely to remain problematic. TBS led to significant reductions in depression symptoms from baseline to end of treatment, with this effect maintained at follow up. Response rates for the whole sample were 61.5 % at end of treatment and 53.7 % at follow-up, while remission rates were 34.6 % at end of treatment and 31.7 % at follow-up. Improvement rates as well as responder and remission rates were comparable for the melancholic and non-melancholic groups, irrespective of the diagnostic strategy used. LimitationsThe study was naturalistic (i.e., there being no control group, and concomitant medication changes were allowed), depression severity was assessed only by use of self-report measures, and the sample size was relatively small. ConclusionTBS appears to be non-specific, in that we failed to quantify any statistically significant differential benefit for those with melancholic compared to those with non-melancholic depression.

Structural Neuroimaging and Molecular Signatures of Drug‐Naive Depression With Melancholic Features

Objectives: Melancholic depression (MD) is a common subtype of major depressive disorder (MDD). It is difficult to treat because its neurobiological basis is poorly understood. Therefore, to investigate whether MD patients have any structural changes in gray matter (GM) and the molecular foundation of these changes, we combined voxel‐based morphometry (VBM) analysis with neurotransmitter system‐derived mapping from public data.Methods: 137 drug‐naive MDD patients and 75 healthy controls (HCs) were recruited for structural magnetic resonance imaging. The imaging results were analyzed using VBM analysis. MDD patients were then divided into MD and nonmelancholic depression (NMD) subgroups according to their scores on the Montgomery–Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale. Next, we analyzed the spatial correlation between the changes in the gray matter volume (GMV) maps and the neurotransmitter receptor/transporter protein density maps provided by the JuSpace toolbox.Results: Compared to HCs, patients with MD had significant GMV reduction in the bilateral hippocampus, bilateral thalamus, right amygdala, and right posterior cingulate cortex (PCC)/precuneus. Compared to patients with NMD, MD patients had significant GMV reduction in the bilateral PCC/precuneus and lateral occipital cortex. Moreover, compared to HCs, changes in GMV introduced by MD were spatially associated with the serotonin transporter, cannabinoid receptor, and μ‐opioid receptor. Compared to NMD patients, changes in GMV introduced by MD were spatially associated with the vesicular acetylcholine transporter.Conclusion: The present study discovered abnormal GMV alterations in patients with subtypes of depression. We also found a series of neurotransmitter receptors that may be associated with the alterations. The findings of the current study may provide a more comprehensive understanding of the molecular mechanisms underlying the structural abnormalities in subtypes of depression and potentially offer new insights into developing new therapeutic strategies.

Impact of dysfunctional parenting, affective temperaments, and stressful life events on the development of melancholic and non-melancholic depression: A path analysis study.

The influence of psychosocial factors on differentiating between melancholic depression (MEL) and non-melancholic depression (NMEL) remains unclear. In this study, we aimed to investigate the interrelationship between dysfunctional parenting, personality traits, stressful life events, and the diagnosis of MEL and NMEL among patients with major depressive disorder (MDD). Ninety-eight patients with MDD completed the following self-administered questionnaires: the Parental Bonding Instrument (PBI) for dysfunctional parenting, the short version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A) for affective temperaments, and the Life Experiences Survey (LES) for stressful life events. The data were analyzed using single and multiple regression analyses and path analysis. Dysfunctional parenting did not have a significant direct effect on MEL. However, paternal care had a significant indirect effect on MEL through depressive temperament. The total indirect effect of paternal care on MEL was significant (indirect path coefficient = 0.161, p <0.05). In other words, low levels of paternal care were associated with the development of NMEL via increased depressive temperament. None of the paths from paternal care to MEL via negative change scores of the LES were significant. This study used cross-sectional data, so the possibility that current depressive status may affect the assessment of LES and TEMPS-A cannot be ruled out. We found that low levels of paternal care did not directly affect the development of NMEL, but affected the development of NMEL through the mediation of depressive temperament rather than stressful life events.

Peripheral inflammatory markers in melancholic versus non-melancholic depression

BackgroundPeripheral inflammation has been associated with major depression, however there is a paucity of studies examining whether inflammatory profiles differ across depressive subtypes. The current study sought to compare peripheral inflammatory markers in patients with melancholic versus non-melancholic depression and with healthy controls. MethodEighty outpatients with a current major depressive episode (MDE) were assigned as having a melancholic or a non-melancholic depressive subtype based on clinician diagnosis and the Sydney Melancholic Prototypic Index (SMPI). Participants provided peripheral venous blood from which plasma levels of cytokines and other inflammatory markers (C-reactive protein (CRP), neutrophil/lymphocyte ratio, plasma cytokines) were compared across the two patient groups and also to a group of 81 age-matched healthy controls. ResultsPatients with melancholic and non-melancholic depression demonstrated increased CRP and decreased interferon-gamma (IFN-γ) levels compared to controls. Using clinician diagnosis of subtype, interleukin-12 (IL-12) and interleukin-10 (IL-10) levels were elevated in melancholic patients versus non-melancholic and control groups, with no differences found for the other measured markers of inflammation. ConclusionStudy findings demonstrate shared inflammatory changes across certain inflammatory markers (CRP and IFN-γ) and increases in IL-12 and IL-10 levels specific to melancholic depression. While generally supportive of previous work, our peripheral inflammation findings in melancholic depression are relatively novel and suggest this subgroup may benefit from anti-inflammatory therapies. Further studies are required to replicate these findings.

Is melancholia a distinct syndrome? Recurrence, chronicity, and severity give evidence in the 50 year follow-up of the Lundby Study.

Whether melancholia is a distinct syndrome has long been debated. One aspect of a valid syndrome is whether it allows for determination of a prognosis. The aim of this study is to investigate the course of melancholic depression versus non-melancholic depression with a focus on: (i) time to and probability of recovery from the first depressive episode, (ii) time to and risk of the first recurrence, (iii) rate of recurrence, (iv) time with depression or antidepressant medication, and (v) suicide risk. The Lundby Study is a longitudinal community study on mental health that followed a geographically defined population (N = 3,563) for up to 50 years, 1947-1997. Subjects with first onset depression were assessed as melancholic (N = 46) or non-melancholic (N = 381) using the DSM-IV melancholic specifier. These diagnoses were made in retrospect using all available information from semi-structured interviews by psychiatrists, key informants, registers, and patient records. We found no significant difference between melancholic- and non-melancholic depression in time to and probability of recovery from the first depressive episode. The time to first recurrence was shorter in melancholic than in non-melancholic depression and the risk of first recurrence for the melancholic group was 2.77 (95% confidence interval [CI] 1.83-4.20) times the risk in the non-melancholic group. The median rate of recurrence was higher in the melancholic group, at 0.19 recurrences per year at risk (interquartile range [IQR] 0.08-0.47), compared to the non-melancholic group, at 0.10 recurrences per year at risk (IQR 0.05-0.21) (p < 0.03). The median percentage of time being depressed or on antidepressant medication was higher in the melancholic group, 17% (IQR 3-20%), compared to the non-melancholic group, 8% (IQR 7-33%) (p < 0.001). The risk of suicide was higher in the melancholic group, hazard ratio 4.13 (95% CI 1.49-11.48, p < 0.01). To conclude, melancholic depression had a more recurrent, chronic, and severe course with a higher suicide risk than did non-melancholic depression in the Lundby population. Although our use of retrospective diagnosis might limit interpretation of results, the findings indicate that melancholia may be useful in determining prognosis and may be a valid psychopathological syndrome.

Burnout and depression: Points of convergence and divergence

BackgroundDebate is ongoing as to whether burnout can be differentiated from depression. This study evaluated whether burnout and depression could be distinguished using a new burnout measure and other variables. MethodsScores on the Sydney Burnout Measure (SBM) were compared between participants with self-diagnosed burnout (BO-all group; n = 622) and clinically-diagnosed depression (DEP-all group; n = 90). The latter group was split into melancholic (DEP-mel; n = 56) and non-melancholic (DEP-nonmel; n = 34) depression subgroups for subsequent analyses. Differences in reporting of depressive symptoms and causal attributions were also evaluated. ResultsWhile total SBM scores showed poor differentiation, the BO-all group had lower social withdrawal and higher empathy loss subscale scores than the depression groups. Odds ratios were significant for several of the depressive symptoms and causal attribution items when comparing the BO-all group to the DEP-all and DEP-mel groups, while only a few items were significant when comparing the BO-all and DEP-nonmel groups. LimitationsParticipants in the depression group were assigned by clinician-based depression diagnoses, rather than by a standardised diagnostic interview, and the group had a relatively small sample size. Participants in the burnout group were self-diagnosed and not assessed for comorbid psychiatric diagnoses. ConclusionsThere were some nuanced symptoms differences between burnout and depression, but many of the SBM symptoms were not specific to burnout. Results also suggested that burnout overlaps more with non-melancholic than melancholic depression, and that differentiation of burnout and depression may rely more on weighting causal factors over symptoms.

Changes of cortical thickness in the first episode, drug-naive depression patients with and without melancholic features

Melancholic depression (MD) is a more severe type of major depressive disorder (MDD) with a core feature of anhedonia. However, its pathophysiology remains unclear. The current study aims to investigate whether there is a significant difference in cortical thickness (CT) that can be used to differentiate MD patients from non-melancholic depression (NMD) patients. We recruited 137 first-episode drug-naive MDD patients and 75 healthy controls (HCs) for structural magnetic resonance imaging, analyzed using the Surface-based morphometry approach. Meanwhile, the MDD patients were divided into the MD and NMD subgroups according to their scores on the Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale. No significant CT differences among the three groups were found. We also did not find significant CT changes between the NMD and the HCs groups or between the MD and NMD groups. However, the CT of the left postcentral gyrus and right precuneus among MD patients were larger than HCs. Moreover, the CT of the left postcentral gyrus and right precuneus were not correlated with the severity of the disease and illness duration. The findings suggest that the CT alterations of the left postcentral gyrus and the right precuneus are distinct pathological mechanisms for MD.

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.

Atrophy of bilateral nucleus accumbens in melancholic depression.

Evidence from previous literature suggests that the nucleus accumbens (NAc), hippocampus, and amygdala play critical roles in the reward circuit. Meanwhile, it was also suggested that abnormalities in the reward circuit might be closely associated with the symptom of anhedonia of depression. However, few studies have investigated the structural alterations of the NAc, hippocampus, and amygdala in depression with anhedonia as the main clinical manifestation. Thus, the current study aimed to explore the structural changes of the subcortical regions among melancholic depression (MD) patients, especially in the NAc, hippocampus, and amygdala, to provide a theoretical basis for understanding the pathological mechanisms of MD. Seventy-two MD patients, 74 nonmelancholic depression (NMD) patients, and 81 healthy controls (HCs) matched for sex, age, and years of education were included in the study. All participants underwent T1-weighted MRI scans. Subcortical structure segmentation was performed using the FreeSurfer software. MD and NMD patients had reduced left hippocampal volume compared with HCs. Meanwhile, only MD patients had reduced bilateral NAc volumes. Moreover, correlation analyses showed correlations between left NAc volume and late insomnia and lassitude in MD patients. The reduced hippocampal volume may be related to the pathogenesis of major depressive disorder (MDD), and the reduced volume of the NAc may be the unique neural mechanism of MD. The findings of the current study suggest that future studies should investigate the different pathogenic mechanisms of different subtypes of MDD further to contribute to the development of individualized diagnostic and treatment protocols.

Apathy in melancholic depression and abnormal neural activity within the reward-related circuit

Major depressive disorder is a heterogeneous syndrome, of which the most common subtype is melancholic depression (MEL). Previous studies have indicated that anhedonia is frequently a cardinal feature in MEL. As a common syndrome of motivational deficit, anhedonia is closely associated with dysfunction in reward-related networks. However, little is currently known about apathy, another syndrome of motivational deficits, and the underlying neural mechanisms in MEL and non-melancholic depression (NMEL). Herein, the Apathy Evaluation Scale (AES) was used to compare apathy between MEL and NMEL. On the basis of resting-state functional magnetic resonance imaging, functional connectivity strength (FCS) and seed-based functional connectivity (FC) were calculated within reward-related networks and compared among 43 patients with MEL, 30 patients with NMEL, and 35 healthy controls. Patients with MEL had higher AES scores than those with NMEL (t = −2.20, P = 0.03). Relative to NMEL, MEL was associated with greater FCS (t = 4.27, P < 0.001) in the left ventral striatum (VS), and greater FC of the VS with the ventral medial prefrontal cortex (t = 5.03, P < 0.001) and dorsolateral prefrontal cortex (t = 3.18, P = 0.005). Taken together the results indicate that reward-related networks may play diverse pathophysiological roles in MEL and NMEL, thus providing potential directions for future interventions in the treatment of various depression subtypes.

Clinical Characteristics of Melancholic and Nonmelancholic Depressions.

This study aimed to compare clinical-demographic features of melancholic and nonmelancholic depressions. We included 141 depressed inpatients classified as melancholic and nonmelancholic by the Sydney Melancholia Prototype Index (SMPI) and Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. Results were controlled for confounders, including severity measures. Melancholic patients by both diagnostic systems were more severely depressed and presented more psychotic symptoms, neurological soft signs, and psychomotor disturbances. Melancholic patients classified by the SMPI were also older at illness onset and had fewer suicide attempts. After controlling for confounders, although all differences remained significant for SMPI diagnosis, the DSM-5 diagnosis of melancholia was only associated with further impaired motor sequencing. The results obtained with the SMPI support the hypothesis that melancholia has clinical features qualitatively different from those of nonmelancholic depressions. Contrarily, the DSM-5 specifier seems to reflect the severity of depressive episodes rather than core clinical features of melancholia.

Revisiting the concept of bipolar depression: comparison of diagnostic validators between melancholic and non-melancholic episodes.

The current definition of bipolar disorder derives with minimal changes from one that emerged through expert consensus in the late 1970s, and the topic of its validity tended to be neglected in the literature. The aim of this exploratory study was to compare patients with bipolar disorder with a history of melancholic and non-melancholic depressive episodes in a series of external diagnostic validators. One hundred eight subjects were categorized as melancholic or non-melancholic in relation to their history of depressive episodes through the clinician-rated Sydney Melancholia Prototype Index (SMPI). The external validators used were clinical-demographic variables, family history of bipolar disorder, neurocognitive performance and functional outcome. There were 43.5% of the patients with a history of melancholia and 56.5% of non-melancholic depression. Non-melancholic depressions were overrepresented in females, while melancholic depressions had a female:male ratio closer to unity. Patients with melancholia had more history of BD in first-degree relatives and better functional outcome than those with non-melancholic depression. There were no differences between groups regarding neurocognitive performance. Results tended to be unchanged when controlled for confounders. Our preliminary results highlight the inherent heterogeneity in the current concept of bipolar depression, and suggest the need for further clinical research to elucidate its validity.

A comparison of the antianhedonic effects of repeated ketamine infusions in melancholic and non-melancholic depression.

Melancholic depression may respond differently to certain treatments. The aim of this study was to compare the antianhedonic effects of six intravenous injections of 0.5 mg/kg ketamine in patients with melancholic and non-melancholic depression, which remain largely unknown. Individuals experiencing melancholic (n = 30) and non-melancholic (n = 105) depression were recruited and assessed for anhedonic symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS). The presence of melancholic depression was measured with the depression scale items at baseline based on DSM-5 criteria. A total of 30 (22.2%) patients with depression fulfilled the DSM-5 criteria for melancholic depression. Patients with melancholic depression had a non-significant lower antianhedonic response (43.3 vs. 50.5%, t = 0.5, p > 0.05) and remission (20.0 vs. 21.0%, t = 0.01, p > 0.05) to repeated-dose ketamine infusions than those with non-melancholic depression. The melancholic group had significantly lower MADRS anhedonia subscale scores than the non-melancholic group at day 26 (p < 0.05). After six ketamine infusions, the improvement of anhedonic symptoms was found in both patients with melancholic and non-melancholic depression, and the efficacy was similar in both groups.

Neurocognitive function of patients with melancholic and non-melancholic major depressive episodes: An exploratory study.

The aim of this exploratory study was to compare the neurocognitive performance of patients undergoing melancholic and non-melancholic major depressive episodes. Considering potential limitations of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) specifier, we employed an additional tool that has proven useful in identifying melancholia (the Sydney Melancholia Prototype Index). One hundred forty-one depressed inpatients were classified as melancholic or non-melancholic according to the Sydney Melancholia Prototype Index and the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria and compared on a neurocognitive battery selected to assess attention and processing speed, verbal memory, working memory and executive functions. Results were controlled for several potential confounders. Patients diagnosed as melancholic by the two diagnostic systems displayed lower scores in executive measures, semantic verbal fluency and phonological verbal fluency. On attention and processing speed, patients with melancholia underperformed those with non-melancholic depression only when diagnosed by the Sydney Melancholia Prototype Index. After controlling for confounders, associations between melancholic status and executive dysfunction remained significant for the Sydney Melancholia Prototype Index but not for the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) diagnosis. In this study, melancholia diagnosed by the Sydney Melancholia Prototype Index (but not by the Diagnostic and Statistical Manual of Mental Disorders [5th ed.] criteria) was characterized by a greater compromise of tests assessing executive functions than non-melancholic depressions, even after controlling for depressive severity. These preliminary results might contribute to generating hypotheses about differences in the cognitive profile and pathophysiological substrate between melancholic and non-melancholic depressions. Likewise, the pattern of findings supports the hypothesis that the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) melancholia specifier might identify more severe forms of depressive episodes rather than a qualitatively different subtype.

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 utility of the Sydney Melancholia Prototype Index (SMPI) for predicting response to electroconvulsive therapy in depression: A CARE Network study

An enhanced understanding of clinical predictors of positive ECT outcome could assist with the decision to prescribe ECT for select patients. Reliable predictors of ECT response such as psychotic symptoms and age have been identified, however, studies of melancholia and ECT response have been inconsistent. The Sydney Melancholia Prototype Index (SMPI) is a clinical measure designed to differentiate melancholic and non-melancholic depression. This study aimed to investigate whether melancholic depression (as measured by the clinician rated version of the SMPI) predicted a better response to ECT than non-melancholic depression. The study included data collated from four participating sites in the Clinical Alliance for ECT and Related treatments (CARE) network. The primary outcome was response (>50% improvement) on the Montgomery Asberg Depression Rating Scale (MADRS) and the secondary outcome was raw change in MADRS score. Of the 329 depressed patients included in the study, 81% had melancholic features and 76% met criteria for clinical response. SMPI defined melancholia was associated with older age, higher pre-treatment mood scores and presence of psychosis. Melancholia as defined by the SMPI, however, did not significantly predict either clinical response or overall mood improvement with ECT in multivariate analyses. Instead, older age, greater pre-treatment depression severity and the use of bifrontal compared to right unilateral ultrabrief ECT were significant predictors of mood improvement. Path analysis showed that higher pre-treatment mood score and older age were independently associated with mood improvement with ECT.

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.