Philip Mitchell | The University of New South Wales (original) (raw)

Papers by Philip Mitchell

Research paper thumbnail of A clinical approach to treatment resistance in depressed patients: What to do when the usual treatments don’t work well enough?

World Journal of Biological Psychiatry, Dec 8, 2020

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Research paper thumbnail of Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some “sham” forms active?

Biological Psychiatry, Feb 1, 2000

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Research paper thumbnail of Stimulus Intensity in Transcranial Magnetic Stimulation (TMS) Studies

Journal of Ect, Dec 1, 2001

... Mitchell, Philip BMD, FRANZCP, FRACPsych.; Sachdev, Perminder S. Ph.D., MD, FRANZCP. Article ... more ... Mitchell, Philip BMD, FRANZCP, FRACPsych.; Sachdev, Perminder S. Ph.D., MD, FRANZCP. Article Outline. Collapse Box Author Information. School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney and Department of Psychiatry, Prince of Wales ...

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Research paper thumbnail of Acute rCBF changes in depressed patients receiving repetitive transcranial magnetic stimulation (rTMS)

Nuclear Medicine Communications, Apr 1, 1999

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Research paper thumbnail of Junior clinical academic psychiatrists in Australia: The University of New South Wales initiative

Australasian Psychiatry, Dec 20, 2018

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Research paper thumbnail of Cover Image, Volume 186B, Number 8, December 2021

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

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Research paper thumbnail of Efficacy and Safety of Repeated Subcutaneous Ketamine Injections for Treatment Resistant Depression - The KADS Study: A Randomised, Double-Blind, Comparator-Controlled Trial

Social Science Research Network, 2022

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Research paper thumbnail of Polygenic Scores and Onset of Major Mood or Psychotic Disorders Among Offspring of Affected Parents

American Journal of Psychiatry

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Research paper thumbnail of Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder

Translational Psychiatry

Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors ... more Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Unrelated HR participants of European ancestry (n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS;n = 41) compared against the bottom two quintiles (Low-BD-PRS;n = 41). The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-...

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Research paper thumbnail of Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Translational Psychiatry

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs wide... more Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+...

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Research paper thumbnail of Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

JAMA Psychiatry, 2021

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Research paper thumbnail of Age-dependent genetic variants associated with longitudinal changes in brain structure across the lifespan

SummaryHuman brain structure changes throughout our lives. Altered brain growth or rates of decli... more SummaryHuman brain structure changes throughout our lives. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental, and neurodegenerative diseases. Here, we identified common genetic variants that affect rates of brain growth or atrophy, in the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal MRI data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genesGPR139, DACH1andAPOEare associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene-set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain deve...

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Research paper thumbnail of Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, ... more BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset.MethodsWe performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronologi...

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Research paper thumbnail of T45TRANSDIAGNOSTIC Family History of Mental Illness, Polygenic Risk and Developmental Psychopathology Leading to Severe Mental Illness

European Neuropsychopharmacology, 2019

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Research paper thumbnail of SU77BRAIN Cortical Trajectories, Polygenic Risk and Environmental Interactions in a Prospective Longitudinal Study of Young People At-Risk of Bipolar Disorder

European Neuropsychopharmacology, 2019

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Research paper thumbnail of Are there subtypes of bipolar depression?

Acta Psychiatrica Scandinavica, 2016

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Research paper thumbnail of Non Invasive Brain Stimulation Therapy Restores Neuroplasticity in Depression

Brain Stimulation, 2015

s / Brain Stimulation 8 (2015) 343e359 349 learning paradigms, C57Bl6/J mice receive daily iTBS i... more s / Brain Stimulation 8 (2015) 343e359 349 learning paradigms, C57Bl6/J mice receive daily iTBS immediately prior to undergoing a skilled pellet-reaching task for 10 days. In a separate group; Thy1-GFPM mice undergo cranial window insertion overlying the right motor cortex to enable visualisation of excitatory cortical neurons in the upper layers of the motor cortex. Images of synaptic structures are collected at regular intervals before and after iTBS and analysed for alterations in connectivity resulting from stimulation. Preliminary analysis suggests daily iTBS significantly increases accuracy but not speed of pellet reaching, relative to sham stimulation (handling control). Preliminary analysis of the imaging data suggests a single session of iTBS does not alter dendritic spine density. These results will help characterise the biological mechanisms underlying rTMS, which will undoubtedly pave the way forward in the therapeutic applications of non-invasive brain stimulation in health and disease.

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Research paper thumbnail of Sub-typing depression, II. Clinical distinction of psychotic depression and non-psychotic melancholia

Psychological Medicine, 1995

SYNOPSISWe have attempted to clarify clinical differentiating features of psychotic depression. F... more SYNOPSISWe have attempted to clarify clinical differentiating features of psychotic depression. Forty-six depressed subjects meeting DSM-III-R criteria for major depression with psychotic features were compared with (i) DSM-defined melancholic, (ii) Newcastle-defined endogenous, and (iii) a residual DSM-defined major depressive episode group. Additionally, a ‘bottom up’ latent class analysis (LCA) suggested a larger sample of 82 ‘psychotic depressive’ subjects, and multivariate analyses contrasted these subjects with both LCA-identified melancholic and all residual depressed subjects. Analyses suggested that, in addition to two features with absolute specificity (delusions and hallucinations), both the DSM-defined and LCA-defined ‘psychotic depressive’ subjects were significantly more likely to demonstrate marked psychomotor disturbance, to report two morbid cognitions (feeling sinful and guilty; feeling deserving of punishment), as well as be more likely to report constipation, ter...

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Research paper thumbnail of Sub-typing depression, I. Is psychomotor disturbance necessary and sufficient to the definition of melancholia?

Psychological Medicine, 1995

SYNOPSISMelancholia is most commonly distinguished from non-melancholic depression by the presenc... more SYNOPSISMelancholia is most commonly distinguished from non-melancholic depression by the presence of psychomotor disturbance (PMD) and a set of ‘endogeneity’ symptoms. We examine the capacity of an operationalized clinician-rated measure of PMD (the CORE system) to predict diagnostic assignment to ‘melancholic/endogenous’ classes by the DSM-III-R and Newcastle systems. Examining a pre-established CORE cut-off score (≥ 8) against independent diagnostic assignment, PMD was present in 51% of those assigned as melancholic by DSM-III-R, and 85% of those assigned as endogenous by the Newcastle system, quantifying the extent to which it is ‘necessary’ to the two definitions of ‘melancholia’. Additionally, multivariate analyses established that the addition of a refined set of historically suggested endogeneity symptoms added only slightly to overall discrimination of melancholic and non-melancholic depressives. While only few endogeneity symptoms independent of psychomotor disturbance wer...

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Research paper thumbnail of Sub-typing depression, III. Development of a clinical algorithm for melancholia and comparison with other diagnostic measures

Psychological Medicine, 1995

SYNOPSISWe describe the development of a clinical algorithm to differentiate melancholic from non... more SYNOPSISWe describe the development of a clinical algorithm to differentiate melancholic from non-melancholic depression, using refined sets of ‘endogeneity’ symptoms together with clinician-rated CORE scores assessing psychomotor disturbance. Assignment by the empirically developed algorithm is contrasted with assignment by DSM-III-R and with several other melancholia subtyping indices. Both the numbers of ‘melancholies’ assigned by the several systems and their capacity to distinguish ‘melancholics’ on clinical, demographic and a biological index test (the DST) varied across the systems with the algorithm being as ‘successful’ as several systems that include inter-episode and treatment response variables. Analyses provide information on the criteria set developed for DSM-IV definition of ‘melancholia’.

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Research paper thumbnail of A clinical approach to treatment resistance in depressed patients: What to do when the usual treatments don’t work well enough?

World Journal of Biological Psychiatry, Dec 8, 2020

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Research paper thumbnail of Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some “sham” forms active?

Biological Psychiatry, Feb 1, 2000

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Research paper thumbnail of Stimulus Intensity in Transcranial Magnetic Stimulation (TMS) Studies

Journal of Ect, Dec 1, 2001

... Mitchell, Philip BMD, FRANZCP, FRACPsych.; Sachdev, Perminder S. Ph.D., MD, FRANZCP. Article ... more ... Mitchell, Philip BMD, FRANZCP, FRACPsych.; Sachdev, Perminder S. Ph.D., MD, FRANZCP. Article Outline. Collapse Box Author Information. School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney and Department of Psychiatry, Prince of Wales ...

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Research paper thumbnail of Acute rCBF changes in depressed patients receiving repetitive transcranial magnetic stimulation (rTMS)

Nuclear Medicine Communications, Apr 1, 1999

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Research paper thumbnail of Junior clinical academic psychiatrists in Australia: The University of New South Wales initiative

Australasian Psychiatry, Dec 20, 2018

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Research paper thumbnail of Cover Image, Volume 186B, Number 8, December 2021

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Efficacy and Safety of Repeated Subcutaneous Ketamine Injections for Treatment Resistant Depression - The KADS Study: A Randomised, Double-Blind, Comparator-Controlled Trial

Social Science Research Network, 2022

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Polygenic Scores and Onset of Major Mood or Psychotic Disorders Among Offspring of Affected Parents

American Journal of Psychiatry

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder

Translational Psychiatry

Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors ... more Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Unrelated HR participants of European ancestry (n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS;n = 41) compared against the bottom two quintiles (Low-BD-PRS;n = 41). The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-...

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Research paper thumbnail of Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Translational Psychiatry

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs wide... more Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+...

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Research paper thumbnail of Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

JAMA Psychiatry, 2021

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Age-dependent genetic variants associated with longitudinal changes in brain structure across the lifespan

SummaryHuman brain structure changes throughout our lives. Altered brain growth or rates of decli... more SummaryHuman brain structure changes throughout our lives. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental, and neurodegenerative diseases. Here, we identified common genetic variants that affect rates of brain growth or atrophy, in the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal MRI data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genesGPR139, DACH1andAPOEare associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene-set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain deve...

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Research paper thumbnail of Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, ... more BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset.MethodsWe performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronologi...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of T45TRANSDIAGNOSTIC Family History of Mental Illness, Polygenic Risk and Developmental Psychopathology Leading to Severe Mental Illness

European Neuropsychopharmacology, 2019

Bookmarks Related papers MentionsView impact

Research paper thumbnail of SU77BRAIN Cortical Trajectories, Polygenic Risk and Environmental Interactions in a Prospective Longitudinal Study of Young People At-Risk of Bipolar Disorder

European Neuropsychopharmacology, 2019

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Are there subtypes of bipolar depression?

Acta Psychiatrica Scandinavica, 2016

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Non Invasive Brain Stimulation Therapy Restores Neuroplasticity in Depression

Brain Stimulation, 2015

s / Brain Stimulation 8 (2015) 343e359 349 learning paradigms, C57Bl6/J mice receive daily iTBS i... more s / Brain Stimulation 8 (2015) 343e359 349 learning paradigms, C57Bl6/J mice receive daily iTBS immediately prior to undergoing a skilled pellet-reaching task for 10 days. In a separate group; Thy1-GFPM mice undergo cranial window insertion overlying the right motor cortex to enable visualisation of excitatory cortical neurons in the upper layers of the motor cortex. Images of synaptic structures are collected at regular intervals before and after iTBS and analysed for alterations in connectivity resulting from stimulation. Preliminary analysis suggests daily iTBS significantly increases accuracy but not speed of pellet reaching, relative to sham stimulation (handling control). Preliminary analysis of the imaging data suggests a single session of iTBS does not alter dendritic spine density. These results will help characterise the biological mechanisms underlying rTMS, which will undoubtedly pave the way forward in the therapeutic applications of non-invasive brain stimulation in health and disease.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Sub-typing depression, II. Clinical distinction of psychotic depression and non-psychotic melancholia

Psychological Medicine, 1995

SYNOPSISWe have attempted to clarify clinical differentiating features of psychotic depression. F... more SYNOPSISWe have attempted to clarify clinical differentiating features of psychotic depression. Forty-six depressed subjects meeting DSM-III-R criteria for major depression with psychotic features were compared with (i) DSM-defined melancholic, (ii) Newcastle-defined endogenous, and (iii) a residual DSM-defined major depressive episode group. Additionally, a ‘bottom up’ latent class analysis (LCA) suggested a larger sample of 82 ‘psychotic depressive’ subjects, and multivariate analyses contrasted these subjects with both LCA-identified melancholic and all residual depressed subjects. Analyses suggested that, in addition to two features with absolute specificity (delusions and hallucinations), both the DSM-defined and LCA-defined ‘psychotic depressive’ subjects were significantly more likely to demonstrate marked psychomotor disturbance, to report two morbid cognitions (feeling sinful and guilty; feeling deserving of punishment), as well as be more likely to report constipation, ter...

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Sub-typing depression, I. Is psychomotor disturbance necessary and sufficient to the definition of melancholia?

Psychological Medicine, 1995

SYNOPSISMelancholia is most commonly distinguished from non-melancholic depression by the presenc... more SYNOPSISMelancholia is most commonly distinguished from non-melancholic depression by the presence of psychomotor disturbance (PMD) and a set of ‘endogeneity’ symptoms. We examine the capacity of an operationalized clinician-rated measure of PMD (the CORE system) to predict diagnostic assignment to ‘melancholic/endogenous’ classes by the DSM-III-R and Newcastle systems. Examining a pre-established CORE cut-off score (≥ 8) against independent diagnostic assignment, PMD was present in 51% of those assigned as melancholic by DSM-III-R, and 85% of those assigned as endogenous by the Newcastle system, quantifying the extent to which it is ‘necessary’ to the two definitions of ‘melancholia’. Additionally, multivariate analyses established that the addition of a refined set of historically suggested endogeneity symptoms added only slightly to overall discrimination of melancholic and non-melancholic depressives. While only few endogeneity symptoms independent of psychomotor disturbance wer...

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Research paper thumbnail of Sub-typing depression, III. Development of a clinical algorithm for melancholia and comparison with other diagnostic measures

Psychological Medicine, 1995

SYNOPSISWe describe the development of a clinical algorithm to differentiate melancholic from non... more SYNOPSISWe describe the development of a clinical algorithm to differentiate melancholic from non-melancholic depression, using refined sets of ‘endogeneity’ symptoms together with clinician-rated CORE scores assessing psychomotor disturbance. Assignment by the empirically developed algorithm is contrasted with assignment by DSM-III-R and with several other melancholia subtyping indices. Both the numbers of ‘melancholies’ assigned by the several systems and their capacity to distinguish ‘melancholics’ on clinical, demographic and a biological index test (the DST) varied across the systems with the algorithm being as ‘successful’ as several systems that include inter-episode and treatment response variables. Analyses provide information on the criteria set developed for DSM-IV definition of ‘melancholia’.

Bookmarks Related papers MentionsView impact