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Gordon Parker - One of the best experts on this subject based on the ideXlab platform.
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Melancholia defined with the precision of a machine
Journal of Affective Disorders, 2020Co-Authors: Gordon Parker, Michael J SpoelmaAbstract:ABSTRACT Background : The status of Melancholia as a categorical or dimensional condition remains unclear, and no measure of Melancholia has achieved definitive status. This study aimed to use a machine learning approach to assess whether a pre-established cut-off score on the Sydney Melancholia Prototype Index (SMPI) provided clear differentiation of melancholic/non-melancholic depression, and to identify the items making the most distinct contribution. Methods : We analysed amalgamated data sets of 1513 clinically depressed patients assessed via the clinician-rated version of the SMPI (SMPI-CR). We also evaluated the self-report version of the SMPI (SMPI-SR) in a combined clinical/community sample of 2025 depressed patients and senior high school students. Rule ensembles were derived in which the outcome measure was the presence/absence of Melancholia (defined as scoring at or above a SMPI cut-off score that had been established in previous studies) and the predictive variables were the individual SMPI items. Results : The pre-established SMPI cut-off score was confirmed as differentiating melancholic/non-melancholic with near perfect accuracy for the SMPI-CR, and with very high accuracy for the SMPI-SR. The relative importance of all SMPI items was quantified. Limitations : It is difficult to validate SMPI-assigned diagnoses due to the lack of any similar measures. Conclusions : The SMPI-CR was confirmed to be a highly precise instrument for differentiating melancholic and non-melancholic depression. Its use will advance clinical decision making and studies evaluating causes, mechanisms and treatments for the two depressive sub-types, as well as assist clarification as to whether Melancholia is categorically or dimensionally distinct from non-melancholic depression.
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Melancholia: An Attempt at Definition Based on a Review of Empirical Data.
The Journal of nervous and mental disease, 2019Co-Authors: Diego J. Martino, Alejandro G. Szmulewicz, Marina P. Valerio, Gordon ParkerAbstract:We sought to identify clinical features that best discriminate Melancholia from nonmelancholic depressive conditions. An extensive review of studies using latent factor models that identified a melancholic depression dimension/factor was undertaken. Clinical variables extracted from these studies were analyzed in terms of their contribution to a diagnosis of Melancholia and their consistency across studies. Psychomotor retardation and mood nonreactivity were the most relevant clinical features for the identification of melancholic depressions. Other clinical features commonly described as weighted to Melancholia, such as anhedonia, psychomotor agitation, late insomnia, or appetite/weight loss, seemed less useful in distinguishing these subtypes of depression. Study results are considered in relation to the potential limitations of current operational definitions of Melancholia, and how symptom sets could be modified.
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The properties and utility of the CORE measure of Melancholia.
Journal of affective disorders, 2016Co-Authors: Gordon Parker, Stacey MccrawAbstract:Abstract Background The CORE measure was designed to assess a central feature of Melancholia - signs of psychomotor disturbance (PMD) - and so provide an alternate non-symptom based measure of Melancholia or of its probability. This review evaluates development and application studies undertaken over the last 25 years to consider how well it has met its original objectives. Methods All studies published using the CORE measure as either the only or an adjunctive measure of Melancholia were obtained and are considered in this review. Results Findings suggest high reliability in quantifying CORE scores can be achieved and that it has construct validity as a measure of PMD. A number of application studies assessing socio-demographic factors, cognitive and motor impairment, dexamethasone suppression and thyrotropin-releasing hormone, response to psychotherapy and to electroconvulsive therapy support its validity as a measure of Melancholia, while functional brain imaging studies suggest that the measure identifies regions of decreased connectivity. Limitations Use of the CORE benefits from rater training and for subjects to be assessed at or near nadir of their depressive episode. There have been insufficient studies evaluating genetic factors, and the treatment response of CORE-defined melancholic patients to antidepressant drugs of differing classes. Conclusions The CORE, either as a proxy or direct measure of Melancholia, provides a strategy for assigning depressed subjects a diagnosis or melancholic or non-melancholic depression or for estimating the probability of Melancholia.
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the utility of facial analysis algorithms in detecting Melancholia
2016Co-Authors: Matthew P Hyett, Abhinav Dhall, Gordon ParkerAbstract:Facial expressions reliably reflect an individual’s internal emotional state and form an important part of effective social interaction and communication. In clinical psychiatry, facial affect is routinely assessed, and any identified deviations from normal affective range and reactivity may signal the presence of a potential psychiatric disorder. An example is melancholic depression or ‘Melancholia’ where facial immobility and non-reactivity are viewed as sensitive diagnostic indicators of the illness. However, affect in depressive disorders such as Melancholia, and indeed psychiatric conditions more broadly, is largely assessed by clinicians, without biological or computational quantification. While such clinical assessment provides useful qualitative descriptors of illness features, the inherent subjectivity of this approach raises concerns regarding diagnostic reliability, and may hinder communication between clinicians. Methodological advances and algorithm development in the field of affective computing have the potential to overcome such limitations through objective characterization of facial features. Among these methods are implicit face analysis techniques, which are based on local spatio-temporal descriptors such as the space-time interest points and Bag-of-Words framework, and explicit face analysis techniques based on deformable model fitting methods such as Constrained Local Models and Active Appearance Models. In this chapter we overview these approaches and discuss their application toward detection and diagnosis of depressive disorders, in particular their capacity to delineate Melancholia from the residual non-melancholic conditions.
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anhedonia in melancholic and non melancholic depressive disorders
Journal of Affective Disorders, 2015Co-Authors: Amelia Paterson, Gordon Parker, Kathryn Fletcher, Maurizio Fava, Dan V Iosifescu, Diego A PizzagalliAbstract:Abstract Background Anhedonia represents a core symptom of major depression and may be a potential marker for Melancholia. However, current understanding of this construct in depressive sub-types is limited. Method Participants were recruited from the Black Dog Institute (Sydney) and Massachusetts General Hospital (Boston). Diagnostic groups were derived on the basis of agreement between clinician and DSM-IV diagnosis from structured interviews. Currently depressed unipolar melancholic, non-melancholic and healthy control participants were administered a probabilistic reward task (PRT) to assess a behavioural correlate of anhedonia-blunted reward-based learning. Self-reported measures of anhedonia, approach and avoidance motivation were completed by the Sydney sample. Results Relative to healthy controls and non-melancholic participants, melancholic depressed participants had reduced response bias, highlighting blunted reward learning. Moreover, although non-melancholic participants were characterized by a delayed response bias, melancholic depressed participants failed to develop a bias throughout blocks. Response bias showed no associations with self-report measures of hedonic tone in depressed participants. Positive associations were observed between response bias, approach and avoidance motivation in non-melancholic participants only. Limitations Possible medication, fatigue and anxiety effects were not controlled; small sample sizes; inclusion criteria may have excluded those with severe Melancholia and led to underestimation of group differences. Conclusions Melancholia is characterised by a reduced ability to modulate behaviour as a function of reward, and the motivational salience of rewarding stimuli may differ across depressive sub-types. Results support the view that Melancholia is a distinct sub-type. Further exploration of reward system functioning in depressive sub-types is warranted.
Michael Maes - One of the best experts on this subject based on the ideXlab platform.
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increased serum immunoglobulin responses to gut commensal gram negative bacteria in unipolar major depression and bipolar disorder type 1 especially when Melancholia is present
Neurotoxicity Research, 2020Co-Authors: Denitsa Simeonova, Michael Maes, Marta Kubera, Drozdstoy Stoyanov, Jean Claude Leunis, Andre F Carvalho, Marianna MurdjevaAbstract:Major depressive disorder (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis while the latter may occur in bipolar disorder (BD). There are differences between MDD and BD type 1 (BP1) and 2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria as well as IgG responses to oxidized LDL (oxLDL) in 29 BP1, 37 BP2, 44 MDD, and 30 healthy individuals. Increased IgM/IgA responses to Pseudomonas aeruginosa significantly discriminated patients with affective disorders (MDD plus BD) from controls. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with Melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses to C. koseri. IgG to oxLDL was significantly associated with increased bacterial translocation. In conclusion, MDD, BP1, and BP2 are accompanied by an immune response due to the increased load of LPS while these aberrations in the gut-brain axis are most pronounced in BP1 and Melancholia. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular, and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.
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associations of serum cytokine receptor levels with Melancholia staging of illness depressive and manic phases and severity of depression in bipolar disorder
Molecular Neurobiology, 2017Co-Authors: Marcin Siwek, Magdalena Sowakucma, Krzysztof Styczen, Paulina Misztak, Rafal J Nowak, Bernadeta Szewczyk, Dominika Dudek, Janusz K Rybakowski, Gabriel Nowak, Michael MaesAbstract:To examine cytokine receptor biomarkers in bipolar disorder (BD), we recruited 133 well-phenotyped BD patients and 50 normal controls and measured serum levels of soluble interleukin 1 receptor antagonist (sIL-1RA), soluble interleukin-2 receptor (sIL-2R), sIL-6R, and tumor necrosis factor receptor 60 and 80 kDa (sTNFR60/80). sIL-1RA and sTNFR80 are significantly higher in BD than in controls and sTNFR80 and higher in melancholic than in non-melancholic patients and controls. Kapczinski's stages 3 + 4 are characterized by lowered sIL-2R and increased sTNFR80 levels. Acute phase depression is characterized by increased sTNFR80 levels as compared with controls, manic, and euthymic patients. Both sTNFR60 and sTNFR80 levels are significantly and positively related with severity of depression but not mania. Logistic regression analysis showed that the significant predictors for BD are increased sIL-1RA levels, nicotine dependence and a family history of depression and alcoholism. The risk factors for stages 3 + 4 are lowered sIL-2R levels and nicotine dependence. Melancholia is predicted by higher sTNFR80 levels and female sex. Severity of depression is predicted by female sex, nicotine dependence, and increased sTNFR60 and sTNFR80 levels. Cell-mediated immunity is activated during a current episode of depression but not (hypo)mania or the euthymic state. There are no associations between the biomarkers and age at onset, duration of illness, severity of mania, bipolar (BP)2 or BP1 subtypes, rapid cycling, atypical depression, psychotic or suicidal symptoms, and a family history of psychiatric disease. The results show that increased sIL-1RA may be a trait marker of BD, increased sTNFR80 a state marker of the depressive phase, especially Melancholia, while lower sIL-2R but higher sTNFR80 may be staging biomarkers.
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activation of cell mediated immunity in depression association with inflammation Melancholia clinical staging and the fatigue and somatic symptom cluster of depression
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2012Co-Authors: Michael Maes, Ivana Mihaylova, Marta Kubera, Karl RingelAbstract:Abstract Background Depression is characterized by activation of cell-mediated immunity (CMI), including increased neopterin levels, and increased pro-inflammatory cytokines (PICs), such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). These PICs may induce depressive, melancholic and chronic fatigue (CF) symptoms. Methods We examined serum neopterin and plasma PIC levels in depressive subgroups in relation to the depressive subtypes and the melancholic and CF symptoms of depression. Participants were 85 patients with depression and in 26 normal controls. Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of CF with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Results Serum neopterin was significantly higher in depressed patients and in particular in those with Melancholia. There were positive correlations between serum neopterin, the plasma PICs and the number of previous depressive episodes. Neopterin and TNFα were associated with Melancholia, while both PICs were associated with CF. Melancholia-group membership was predicted by the HDRS and neopterin, and CF group membership by age, the FF score and serum TNFα. Discussion Depression and Melancholia are accompanied by CMI activation, suggesting that neopterin plays a role in their pathophysiology, e.g. through activation of oxidative and nitrosative stress and apoptosis pathways. The intertwined CMI and inflammatory responses are potentially associated with the onset of depression and with the melancholic and CF symptoms of depression. Exposure to previous depressive episodes may magnify the size of CMI and PIC responses, possibly increasing the likelihood of new depressive episodes. CMI activation and inflammation may contribute to the staging or recurrence of depression.
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functional or psychosomatic symptoms e g a flu like malaise aches and pain and fatigue are major features of major and in particular of melancholic depression
Neuro endocrinology letters, 2009Co-Authors: Michael MaesAbstract:BACKGROUND: Major depression is characterized by multifarious symptoms and symptoms clusters, such as the melancholic and anxiety symptom clusters. There is a strong comorbidity and a biological similarity between major depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). OBJECTIVE: The aim of the present study was to examine "psychosomatic" symptoms reminiscent of ME/CFS in major depression. METHODS: Toward this end, we examined the 12-item Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale and the Hamilton Depression Rating Scale (HDRS) in 103 major depressed patients by means of multivariate pattern recognition methods. results: Our findings support the existence of two factors, i.e. a fatigue and somatic (FS and a depression factor, i.e. sadness, irritability, sleep disorders, autonomic symptoms, and a subjective experience of infection. Cluster analysis performed on the 12 FF items found two different clusters, which were separated by highly significant differences in the F&S items, the most significant being a subjective experience of infection, aches and pain, muscular tension, fatigue, concentration difficulties and failing memory. Multivariate analyses showed that the differences between both clusters were quantitatively, and not qualitatively, and reflected the severity of the F&S dimension. There was a strong association between the F&S symptoms and Melancholia and chronic depression. Treatment resistant depression was characterized by higher scores on the depression factor score. There was a strong correlation between the HDRS score and the FF items, fatigue, a subjective experience of infection, and sadness. Our findings show that F&S symptoms are a major feature of depression and largely predict severity of illness, and chronic and melancholic depression. CONCLUSIONS: It is concluded that the diagnostic criteria of depression and Melancholia and rating scales to measure severity of illness should be modified to include the F&S symptom profile.
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relationships between interleukin 6 activity acute phase proteins and function of the hypothalamic pituitary adrenal axis in severe depression
Psychiatry Research-neuroimaging, 1993Co-Authors: Michael Maes, Herbert Y Meltzer, Joseph R Calabrese, Simon Scharpe, Eugene Bosmans, E Suy, Paul CosynsAbstract:Recent studies from this laboratory have provided some evidence that major depression, in particular Melancholia, may be accompanied by an immune response. The present study was designed to investigate whether severe depression is characterized by increased interleukin-6 (Il-6) activity and whether Il-6 production is related to altered levels of acute phase reactants and to abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis. Measurements were made in 8 healthy control subjects and 24 depressed inpatients of Il-6 production in culture supernatants of mitogen-stimulated peripheral leukocytes and plasma levels of haptoglobin (Hp), transferrin (Tf), and postdexamethasone cortisol. Il-6 activity was significantly higher in melancholic subjects than in healthy control subjects and in patients with minor depression or nonmelancholic major depression. Il-6 production was significantly correlated with Hp (positively) and Tf (negatively) plasma levels. There were significant and positive correlations between Il-6 activity and postdexamethasone cortisol values. The findings may suggest that increased Il-6 activity in severe depression is related to hypotransferrinemia, hyperhaptoglobinemia, and hyperactivity of the HPA axis.
R J Davidson - One of the best experts on this subject based on the ideXlab platform.
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Functional but not structural subgenual prefrontal cortex abnormalities in Melancholia
Molecular Psychiatry, 2004Co-Authors: D A Pizzagalli, T R Oakes, M K Chung, C L Larson, H C Abercrombie, S M Schaefer, R M Benca, R J DavidsonAbstract:Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of Melancholia—a subtype of depression characterized by anhedonia—but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in Melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5–6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in Melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.
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Functional but not structural subgenual prefrontal cortex abnormalities in Melancholia
Molecular Psychiatry, 2004Co-Authors: D A Pizzagalli, T R Oakes, M K Chung, C L Larson, H C Abercrombie, S M Schaefer, R M Benca, A S Fox, R J DavidsonAbstract:Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of Melancholia—a subtype of depression characterized by anhedonia—but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in Melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5–6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in Melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.
Dusan Hadzipavlovic - One of the best experts on this subject based on the ideXlab platform.
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the superiority of antidepressant medication to cognitive behavior therapy in melancholic depressed patients a 12 week single blind randomized study
Acta Psychiatrica Scandinavica, 2013Co-Authors: Gordon Parker, Bianca Blanch, Amelia Paterson, Dusan Hadzipavlovic, Elizabeth Sheppard, Vijaya Manicavasagar, Howe SynnottAbstract:Objective To pursue the previously long-standing but formally untested clinical view that Melancholia is preferentially responsive to antidepressant medication in comparison with psychotherapy [specifically Cognitive Behavior Therapy (CBT)]. Second, to determine whether a broader action antidepressant medication sequencing regimen is superior to a Selective Serotonin Reuptake Inhibitor (SSRI) alone. Method We sought to recruit a large sample of participants with melancholic depression for a 12-week trial but inclusion criteria compromised recruitment and testing the second hypothesis. The first hypothesis was evaluated by comparing 18 participants receiving antidepressant medication to 11 receiving CBT. Primary study measures were the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Endogenous Subscale (HES), rated blindly, while several secondary measures also evaluated outcome. Results Participants receiving medication had a superior 12-week outcome to those receiving CBT, with significant differences present on primary measures as early as 4 weeks. At trial conclusion, the percentage improvement in HAM-D scores was 61.1% vs. 34.4%, respectively [Number Needed to Treat (NNT) = 3.7] and with those in receipt of medication returning non-significantly higher HAM-D responder (66.6% vs. 36.4%, NNT = 2.8) and remission (66.7% vs. 45.4%, NNT = 4.7) rates. Conclusion As the sample size was small and participants evidenced only moderate levels of depression severity, the study risked being underpowered and idiosyncratic. Despite the small sample, the superiority of antidepressant medication to CBT in those with a melancholic depression was distinctive in this pilot study.
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measuring Melancholia the utility of a prototypic symptom approach
Psychological Medicine, 2009Co-Authors: Gordon Parker, Dusan Hadzipavlovic, Matthew P Hyett, Kathryn Fletcher, Melissa Barrett, Howe SynnottAbstract:Background Melancholia has long resisted classification, with many of its suggested markers lacking specificity. The imprecision of depressive symptoms, in addition to self-report biases, has limited the capacity of existing measures to delineate melancholic depression as a distinct subtype. Our aim was to develop a self-report measure differentiating melancholic and non-melancholic depression, weighting differentiation by prototypic symptoms and determining its comparative classification success with a severity-based strategy. Method Consecutively recruited depressed out-patients (n=228) rated 32 symptoms by prototypic or 'characteristic' relevance (using the Q-sort strategy) and severity [using the Severity-based Depression Rating System (SDRS) strategy]. Clinician diagnosis of melancholic/non-melancholic depression was the criterion measure, but two other formal measures of Melancholia (Newcastle and DSM-IV criteria) were also tested. Results The prevalence of 'Melancholia' ranged from 20.9% to 54.2% across the subtyping measures. The Q-sort measure had the highest overall correct classification rate in differentiating melancholic and non-melancholic depression (81.6%), with such decisions supported by validation analyses. Conclusions In differentiating a melancholic subtype or syndrome, prototypic symptoms should be considered as a potential alternative to severity-based ratings.
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the differential impact of age on the phenomenology of Melancholia
Psychological Medicine, 2001Co-Authors: Gordon Parker, Dusan Hadzipavlovic, Kay Roy, Kay Wilhelm, Philip B. MitchellAbstract:Background. We pursue an observation that age may influence the clinical features of Melancholia and, in particular, psychomotor disturbance. Methods. Two large clinical databases were amalgamated allowing the clinical features of 124 depressed subjects meeting DSM-III-R and clinical criteria for Melancholia to be contrasted with 218 subjects diagnosed as having a non-melancholic depression by both criteria sets. Psychomotor disturbance was assessed by the CORE measure and by seven classical endogeneity symptoms of Melancholia which, when summed, created a ENDOG score. Results. There was no impact of age on ENDOG scores in either the melancholics or non-melancholics. In the melancholics, increasing age was associated with increasing CORE scores and with agitation scale scores in particular. In a set of discriminant function analyses seeking to identify the comparative utility of a set of predictors of melancholic ( versus non-melancholic) groups, age was significant, and while CORE and ENDOG scores were individual predictors, their combined entry established that the CORE score alone made the ENDOG score redundant, and that the addition of age then made little impact. Conclusions. Melancholia appears to have a later age of onset than non-melancholic depression, while its phenotypic expression appears to change with age, with psychomotor disturbance being more distinct in older subjects. Such an effect may have a number of clinical implications, including possible differential effects of varying antidepressant treatments.
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cognitive function in depression a distinct pattern of frontal impairment in Melancholia
Psychological Medicine, 1999Co-Authors: Mariepaule Austin, Gordon Parker, Kay Wilhelm, Philip B. Mitchell, Ian B Hickie, Henry Brodaty, J Chan, Kerrie Eyers, M Milic, Dusan HadzipavlovicAbstract:Background. Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes. Methods. Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate. Results. The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of Melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired. Conclusions. Using narrower definitions of Melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.
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defining Melancholia properties of a refined sign based measure
British Journal of Psychiatry, 1994Co-Authors: Gordon Parker, Dusan Hadzipavlovic, Kay Wilhelm, Philip B. Mitchell, Ian B Hickie, Henry Brodaty, Philip Boyce, Kerrie EyersAbstract:We hypothesised that psychomotor disturbance is specific to the melancholic subtype of depression and capable of defining Melancholia more precisely than symptom-based criteria sets. We studied 413 depressed patients, and examined the utility of a refined, operationally driven set of clinician-rated signs, principally against a set of historically accepted symptoms of endogeneity. We specified items defining psychomotor disturbance generally as well as those weighted either to agitation or to retardation. We demonstrated the system's capacity to differentiate 'melancholic' and 'non-melancholic' depression (and the comparable success of DSM-III-R and Newcastle criteria systems) by reference to several patient, illness and treatment response variables, to an independent measure of psychomotor disturbance (reaction time) and to a biological marker (the dexamethasone suppression test).
Howe Synnott - One of the best experts on this subject based on the ideXlab platform.
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the superiority of antidepressant medication to cognitive behavior therapy in melancholic depressed patients a 12 week single blind randomized study
Acta Psychiatrica Scandinavica, 2013Co-Authors: Gordon Parker, Bianca Blanch, Amelia Paterson, Dusan Hadzipavlovic, Elizabeth Sheppard, Vijaya Manicavasagar, Howe SynnottAbstract:Objective To pursue the previously long-standing but formally untested clinical view that Melancholia is preferentially responsive to antidepressant medication in comparison with psychotherapy [specifically Cognitive Behavior Therapy (CBT)]. Second, to determine whether a broader action antidepressant medication sequencing regimen is superior to a Selective Serotonin Reuptake Inhibitor (SSRI) alone. Method We sought to recruit a large sample of participants with melancholic depression for a 12-week trial but inclusion criteria compromised recruitment and testing the second hypothesis. The first hypothesis was evaluated by comparing 18 participants receiving antidepressant medication to 11 receiving CBT. Primary study measures were the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Endogenous Subscale (HES), rated blindly, while several secondary measures also evaluated outcome. Results Participants receiving medication had a superior 12-week outcome to those receiving CBT, with significant differences present on primary measures as early as 4 weeks. At trial conclusion, the percentage improvement in HAM-D scores was 61.1% vs. 34.4%, respectively [Number Needed to Treat (NNT) = 3.7] and with those in receipt of medication returning non-significantly higher HAM-D responder (66.6% vs. 36.4%, NNT = 2.8) and remission (66.7% vs. 45.4%, NNT = 4.7) rates. Conclusion As the sample size was small and participants evidenced only moderate levels of depression severity, the study risked being underpowered and idiosyncratic. Despite the small sample, the superiority of antidepressant medication to CBT in those with a melancholic depression was distinctive in this pilot study.
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inching toward bethlehem mapping Melancholia
Journal of Affective Disorders, 2010Co-Authors: Howe Synnott, Gordon Parker, Kathryn Fletcher, Melissa Barrett, Michael Breakspear, Annemarie ReesAbstract:Abstract Background: As Melancholia has resisted symptom-based definition, this report considers possible explanations and options for moving forward. Clinician-assigned melancholic and non-melancholic groups were initially compared to refine a candidate set of differentiating symptoms alone for examination against a set of non-clinical validators. Analyses then examined the capacity of both the refined symptom and validator sets to discriminate the assigned melancholic and non-melancholic subjects. Methods: Subjects completed measures assessing symptoms and correlates (putative validators) of diagnostic sub-type, and were assessed independently by two psychiatrists. Results: Analyses identified 14 severity-based symptoms as discriminating clinically-diagnosed groups — with melancholic subjects differing significantly from non-melancholic subjects across a number of validators. Such symptom-based discrimination was superior to DSM-IV and Newcastle Index assignment in a study sub-set. While the refined symptom set had an overall accurate classificatory rate of 68%, use of the combined sets of refined symptoms and validators improved classification to 80%. Conclusions: Melancholia definition is improved by the use of correlates in addition to depressive symptoms, suggesting that Melancholia may be mapped more precisely by use of multiple co-ordinates or data sources.
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measuring Melancholia the utility of a prototypic symptom approach
Psychological Medicine, 2009Co-Authors: Gordon Parker, Dusan Hadzipavlovic, Matthew P Hyett, Kathryn Fletcher, Melissa Barrett, Howe SynnottAbstract:Background Melancholia has long resisted classification, with many of its suggested markers lacking specificity. The imprecision of depressive symptoms, in addition to self-report biases, has limited the capacity of existing measures to delineate melancholic depression as a distinct subtype. Our aim was to develop a self-report measure differentiating melancholic and non-melancholic depression, weighting differentiation by prototypic symptoms and determining its comparative classification success with a severity-based strategy. Method Consecutively recruited depressed out-patients (n=228) rated 32 symptoms by prototypic or 'characteristic' relevance (using the Q-sort strategy) and severity [using the Severity-based Depression Rating System (SDRS) strategy]. Clinician diagnosis of melancholic/non-melancholic depression was the criterion measure, but two other formal measures of Melancholia (Newcastle and DSM-IV criteria) were also tested. Results The prevalence of 'Melancholia' ranged from 20.9% to 54.2% across the subtyping measures. The Q-sort measure had the highest overall correct classification rate in differentiating melancholic and non-melancholic depression (81.6%), with such decisions supported by validation analyses. Conclusions In differentiating a melancholic subtype or syndrome, prototypic symptoms should be considered as a potential alternative to severity-based ratings.