Journal of Affective Disorders 144 (2013) 199–207

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Journal of Affective Disorders
journal homepage: www.elsevier.com/locate/jad

Research report

Discriminating melancholic and non-melancholic depression by
prototypic clinical features
Gordon Parker a,b,n, Stacey McCraw a,b, Bianca Blanch a,b, Dusan Hadzi-Pavlovic a,b,
Howe Synnott b, Anne-Marie Rees a,babSchool of Psychiatry, University of New South Wales, Sydney, NSW, Australia
Black Dog Institute, Sydney, Australiaa r t i c l e i n f oabstract

Article history:
Received 5 January 2012
Received in revised form
27 June 2012
Accepted 27 June 2012
Available online 4 August 2012

Background: Melancholia is positioned as either a more severe expression of clinical depression or as aseparate entity. Support for the latter view emerges from differential causal factors and treatment
responsiveness but has not been convincingly demonstrated in terms of differential clinical features.
We pursue its prototypic clinical pattern to determine if this advances its delineation.
Methods: We developed a 24-item measure (now termed the Sydney Melancholia Prototype Index or
SMPI) comprising 12 melancholic and 12 non-melancholic prototypic features (both symptoms andillness correlates). In this evaluative study, 278 patients referred for tertiary level assessment at a
specialized mood disorders clinic completed the self-report SMPI as well as a depression severity
measure and a comprehensive assessment schedule before clinical interview, while assessing clinicians
completed a clinician version of the SMPI items following their interview. The independent variable(diagnostic gold standard) was the clinician’s judgment of a melancholic versus non-melancholic
depressive episode. Discriminative performance was evaluated by Receiver Operating Characteristics(ROC) analysis of four strategies for operationalising the SMPI self-report and SMPI clinician measures,and with the former strategies compared to ROC analysis of the depression severity measure. The
external validity of the optimally discriminating scores on each measure was tested against a range ofclinical variables.
Result: Comparison of the two self-report measures established that the SMPI provided greater discrimination than the depression severity measure, while comparison of the self-report and clinician-rated SMPI
measures established the latter as more discriminating of clinically diagnosed melancholic or nonmelancholic depression. ROC analyses favoured self-report SMPI distinction of melancholic from nonmelancholic depression being most optimally calculated by a ‘difference’ score of at least four or moremelancholic than non-melancholic items being afﬁrmed (sensitivity of 0.69, speciﬁcity of 0.77). For theclinician-rated SMPI measure, ROC analyses conﬁrmed the same optimal difference score of four or more as
highly discriminating of melancholic and non-melancholic depression (sensitivity of 0.84, speciﬁcity of 0.92).
As the difference score had positive predictive values of 0.90 and 0.70 (for the respective clinician-rated andself-report SMPI forms) and respective negative predictive values of 0.88 and 0.70, we conclude that theclinician-rated version had superior discrimination than the self-report version. External validating data
quantiﬁed the self-rated and clinician-rated Index-assigned non-melancholic patients having a higher
prevalence of anxiety disorders, a higher number of current and lifetime stressors, as well as elevated scoreson several personality styles that are viewed as predisposing to and shaping such non-melancholic disorders.
Limitations: Assigned melancholic and non-melancholic diagnoses were determined by clinician judgement,
risking a circularity bias across diagnostic assignment and clinical weighting of melancholic and nonmelancholic features. The robustness of the Index requires testing in primary and secondary levels of caresettings.
Conclusions: The clinician-rated SMPI differentiated melancholic and non-melancholic depressed subjects at ahigher level of conﬁdence than the self-report SMPI, and with a highly acceptable level of discrimination. The
measure is recommended for further testing of its intrinsic and applied properties.
& 2012 Elsevier B.V. All rights reserved.

Keywords:
Depression
Melancholia
Depression measurement
Discriminant index
Sydney Melancholia Prototype Index.

nCorresponding author at: Black Dog Institute, Prince of Wales Hospital, Randwick 2031, Sydney, Australia. Tel.: þ 61 2 9382 4372; fax: þ61 2 9382 4343.
E-mail address: g.parker@unsw.edu.au (G. Parker).

0165-0327/$ - see front matter & 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jad.2012.06.042

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G. Parker et al. / Journal of Affective Disorders 144 (2013) 199–207

1. Introduction
There has been a longstanding view positioning melancholia as a
distinct ‘type’ of depression that appears more quintessentiallybiological, and which has been variably termed ‘endogenous’, ‘endogenomorphic’, ‘autonomous’, ‘vital’, ‘Type A’ as well as ‘melancholic’
depression (Jackson, 1986; Parker et al., 2010; Parker and HadziPavlovic, 1996a; Taylor and Fink, 2006). The arguments in favour ofits distinct status have included (Parker et al., 1996,, 2010) a somewhat distinctive pattern of symptoms and signs, a greater relevanceof genetic and other biological – as against psychosocial – determinants, concomitant evidence of biological dysfunction particularly
involving the hypothalamic–pituitary–adrenal axis, a differentiallystronger response to physical treatments such as antidepressantdrugs and electroconvulsive therapy than to psychotherapy, and alow placebo response rate.
The longstanding binary view positioned such a depressive ‘type’
as distinct from a second ‘type’ – variably termed ‘neurotic’ or‘reactive’ depression in terms of clinical symptoms and preferential
causes. Despite some consistency in the clinical (‘endogeneity’)
symptoms long listed as having some speciﬁcity to melancholia,
the advent and application of differing multivariate analytic
approaches in the 1950’s – whether factor, cluster and (later) latentclass analysis (Parker and Hadzi-Pavlovic, 1996a) – failed to deliver
support for a clear-cut symptom-deﬁned binary solution.
Reasons for failing to so differentiate melancholia would
include it actually not being a distinctive depressive type andsimply being a more severe expression of depression—essentiallythe unitary or dimensional view. Alternatively, it could be thatmelancholia is a differing ‘type’ but lacking a pristine clinicalboundary so disallowing clear clinical delineation and/or that its
putative clinical symptoms and signs are limited in terms of their
speciﬁcity and capacity to deﬁne melancholia. For example, and as
we have quantiﬁed (Parker et al., 1996), none of the historicallyweighted endogeneity symptoms show absolute speciﬁcity and, atbest, show modest differential prevalences. Even if a symptom
demonstrates discriminatory potential, identifying how it is best
operationalised and measured is rarely straightforward. If not
absolute, deciding whether to impose a cut-off for its ‘presence’along dimensions of severity, persistence or some other parameteris problematic. Further, age, gender and duration of episode may
impact on symptom ratings, while response biases (e.g., excessive
subjective weighting versus denial and minimisation) inﬂuence
self-reporting—just as assessment by external observers can beinﬂuenced by rating biases.
Finally, if melancholic depression is a ‘circuit disorder’ involving disruption of neurocircuits, then the actual site or dynamics
of the disruption may account for certain symptoms (e.g., abulia,
psychomotor agitation) being distinctive in some individuals andminimal or even absent in others. Thus, even if melancholia is adiscrete condition, its symptom markers are limited by multiple
factors that must confound any analytic study seeking to delineate it simply on the basis of symptoms with any precision.
Historical approaches to deﬁning and classifying melancholia
over recent decades have involved relatively few strategies. First,
and most commonly, limiting deﬁnition to a prescribed numberof symptoms (as occurs in DSM-IV). Second, melding clinicalsymptoms with non-symptom correlates of melancholia. The
latter approach has only a few examples. One was the Newcastle
Index (Carney et al., 1965) which weighted items such as‘adequate personality’, ‘no adequate psychogenesis’ and previous
episodes in addition to symptoms. Another was the DSM-III-R
classiﬁcation of melancholia which included items such as
absence of any pre-morbid personality disturbance, previous
episodes with good recovery and previous good response tosomatic therapies in addition to symptoms.

Narrower strategies have been evaluated. First, weighting andmeasuring signs of psychomotor disturbance (PMD), with theview that such observable signs are surface markers of underlying
neuropathological processes in melancholia, a model reﬂecting
PMD’s longstanding position as a central marker of melancholia(Berrios, 1988). Following on Widlöcher’s (1983) development ofa reﬁned measure, we developed the observer-rated CORE measure (Parker and Hadzi-Pavlovic, 1996b) of PMD—with thatmeasure so named to capture its reference to ‘core’ signs ofmelancholia. Limitations to rating signs validly include the realitythat not all patients present at the nadir or depths of theirdepressive episode and that the motor signs of PMD are seemingly less overt or severe in younger melancholic patients.
In the last few years, we have favoured diagnostic measurement
melding clinical features and non-symptom correlates, and offer
several reasons. First, the approach concedes limitations (justdetailed) to relying on any symptom set alone. Second, it reﬂects anumber of the longstanding prototypic ascriptions to the concept ofmelancholia—with even its synonym ‘endogenous depression’ proceeding beyond symptoms. Third, it is consistent with the approachto deﬁning many medical conditions (e.g., Parkinson’s disease) andwhere diagnosis is based on a range of antecedent and course ofillness factors in addition to symptoms. Fourth, we have alreadydemonstrated (Parker et al., 2010) that adding course of illness andcontext variables to reﬁned symptoms actually improves delineationof melancholic and non-melancholic depression made by symptom
deﬁnition alone—and in that report made an analogy to navigational
strategies that rely on multiple reference points to improve precision. Further, it acknowledges the likely reality that melancholia is‘fuzzy’, and suggests that deﬁnition might better be weighted toprototypic delineation rather than to seeking absolute deﬁnition.
We therefore developed (Parker et al., 2012) the SERDEX
measure (SElf-Report of Depressive EXperiences) which lists 12
items weighted to melancholic depression in a left-hand column
and 12 items weighted to the non-melancholic depressive conditions in a right-hand column. Individuals are invited to tick any
item from either column that they regard as ‘characteristic’ interms of their depressive experience, whether (dependent on theclinical or study objective) experienced currently or over time.
The listed items assess symptoms historically favoured as mostdifferentiating of melancholic and non-melancholic depression,
but also assess premorbid interpersonal functioning, distal andproximal stressors, the context and impact of proximal stressors
on inducing and maintaining the depression, and trait emotional
dysregulation levels. Each item was selected and often progressively reﬁned in its deﬁnition by considering its utility in previous
studies undertaken by our research group over the last twenty
years (e.g., Parker and Hadzi-Pavlovic, 1996a; Parker et al., 2010)
and with all having been tested empirically to quantify theirdifferentiating potential. For example, while early morning
wakening is commonly listed as a symptom of ‘endogenous’ or‘melancholic’ depression, we have never quantiﬁed it as having
distinctive differentiation across melancholic and non-melancholic depression and it was therefore not included. After ticking
relevant items, respondents are then requested to judge whether
their ‘proﬁle’ or clinical prototype is best captured by Description
A (left-hand column descriptors), Description B (right-handcolumn), is somewhat closer to A than to B, is somewhat closer
to B than to A, or is an equal mix or A and B descriptors—with thissecond ‘prototypic’ measurement component seeking to determine overall ‘pattern’ correspondence to melancholic or nonmelancholic depression. For the present study we developed anequivalent clinician-rated version of the measure.
We reported the properties of the initial self-report measure inan earlier paper (Parker et al., 2012) with that development study
involving a sample of 141 unipolar depressed patients assessed at

G. Parker et al. / Journal of Affective Disorders 144 (2013) 199–207

our tertiary referral Black Dog Institute, and demonstrated that
non-symptom variables were superior to symptoms in differentiating melancholic and non-melancholic depression. In thispaper, we analyse diagnostic differentiation and validation datafrom a larger sample and, in addition, examine the utility of aclinician-rated version of the measure.

2. Methods
As for the previous pilot study (Parker et al., 2012), the current
sample was recruited entirely from the Depression Clinic at theBlack Dog Institute, a tertiary service providing diagnostic andmanagement advice to referring general practitioners and psychiatrists. While weighted to those with more severe and/or
treatment-resistant mood disorders, not all patients wereassessed at the nadir of their episode (including some being inpartial remission) as a consequence of Clinic waiting time. The
Human Research Ethics Committee for the University of New
South Wales approved the study protocol. All participants were
provided with a description of the study prior to clinical assessment and written informed consent was then obtained.
For the current analyses, we report on a larger sample of 278
patients. All were required to score symptom items in terms of
their current episode (‘‘when at your worst’’) and whether thesymptom was a characteristic feature of their episode or not, withall questionnaires being completed prior to clinical assessment.
Sample recruitment occurred from May 2009 to December 2010.
While we did not formally record the non-participation rate, weestimate it as low (in the order of ten per cent) and generally due
to poor English skills or an incapacitating mood state compromising some patients’ capacities to complete questionnaires.
For all patients, the Clinic’s six clinicians were required tomake a judgement as to whether they diagnosed the patient as
having a current melancholic or non-melancholic depressive
episode, and to rate their level of conﬁdence (1–5) in the
diagnostic allocation to melancholic or non-melancholic status,but, in this study we did not exclude any patients on the basis of
the conﬁdence score. Such clinician judgements were derived
from their clinical interview – which focuses on depressive
symptom patterns, examines family history, developmental factors, personality proﬁle and previous response to any drug andnon-drug treatments – and sometimes involves an interview ofcorroborative witnesses (e.g., family members, referring healthpractitioners). Intake clinicians also completed a clinician-rated
version of the SERDEX measure for the current depressive episodeand again required afﬁrming any symptom that was characteristic
when the patient was at their worst.
While we had varying numbers of recruited patients complete
differing assessment components, this report (and analyses) wererestricted to 278 patients for whom we had complete data sets inrelation to our principal measures (i.e., SERDEX items, depression
severity and Mood Assessment Program). Of the sample of 278(51.4% female, mean age 41.2 years), 43.5% were clinicallydiagnosed with a melancholic depression and were non-signiﬁcantly older than the non-melancholic subjects (42.6 vs 40.2,
t ¼1.5, p ¼0.14). Of the 278 subjects, the rating clinicians failed tocomplete the ﬁve-point prototype scale at the bottom of the index
for 11 subjects, so that analyses of that variable involved 267 of
the 278 subjects.

201

depression rated on 0–3 scales, allowing respective rating optionsof ‘not at all’, ‘somewhat’, ‘very’ and ‘extremely’ characteristic.
The 32 symptoms captured ones historically weighted to bothmelancholic and non-melancholic depression. Comparative analyses of those two key study measures would allow the utility ofeach approach (i.e., symptoms only versus symptoms plus illness
correlates) to be compared. Sample members also completed the
Mood Assessment Program or MAP (Parker et al., 2008), a
computerised measure providing current and historical data on
depression and anxiety, current global functioning, lifetime anxiety disorders, the Temperament and Personality or T&P personality proﬁle (Parker et al., 2006) and stressor severity measures(both lifetime and preceding 12 months), as well as recording
background and lifetime treatment data – with such variables
being analysed in the validation component of this study. Statedepression severity was measured by both the DMI-10 (Depression in the Medially Ill) measure (Parker et al., 2002) – which
provides a 0–30 severity score – and The Quick Inventory ofDepressive Symptomatology (QIDS-SR16; Rush et al., 2003) –which provides a 0–27 severity score.

3. Results
3.1. Item discrimination across the SERDEX measures
Table 1 reports prevalence rates for all 24 items in theclinically diagnosed melancholic and non-melancholic subgroups. If items are truly more prevalent in melancholia, wewould anticipate that all 12 descriptor A items would return
signiﬁcantly higher prevalence rates in the melancholic than the
non-melancholic sub-set—as conﬁrmed (examining chi squaredata) for 6 of the items in the self-report measure and all 12 in theclinician-rated measure. Conversely, we would expect that all 12
descriptor B items would return higher prevalence rates in the
non-melancholic than melancholic sub-set—conﬁrmed for 8 selfreport and 10 clinician-rated items. Third, if items had highspeciﬁcity we would expect distinctive differentiation in prevalence of items across the melancholic and non-melancholic
subjects. Inspection of Table 1 data fails to identify any item
selectively afﬁrmed by one diagnostic sub-set only, and that item
differentiation across melancholic and non-melancholic sub-sets
was slight to moderate only, but—and of importance - far more
distinctive for the clinician-rated than for the self-report measure.
Table 1 reports prevalence data for each item and with any
over-representation of putative melancholic items being afﬁrmedby the subjects and by the assessing clinician in the melancholic
subjects (and of putative non-melancholic items in the nonmelancholic subjects) quantiﬁed by odds ratios. Across the selfreport and clinician-rated SERDEX forms the most discriminating
Descriptor A (melancholia) items were anergia, episodes being
more severe than expected from circumstances, episodes ‘coming
out of the blue’ and anticipatory anhedonia. For the non-melancholic Descriptor B set, the most discriminating items across both
rating approaches were whether or not the episode severity was‘explainable’, anticipatory anhedonia was absent, there was an
explanatory cause, mood reactivity, and concentration impairment reﬂecting worry or distracting thoughts. In essence, themost discriminating items were consistently identiﬁed acrossself-report and clinician-rated assessment and such items wereequally likely to be symptom or non-symptom variables.

2.1. Materials
3.2. Analyses of prototypic assignments
In addition to completing the SERDEX form, all subjects
completed a self-report Severity of Depressive Symptoms (SDS)
form (Parker et al., 2010) comprising 32 clinical symptoms ofTable 2 records how the clinically diagnosed melancholic andnon-melancholic members scored the single ﬁve-point self-report

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G. Parker et al. / Journal of Affective Disorders 144 (2013) 199–207

Table 1
Items endorsed by sample member for self-report and clinician rated SERDEX measures for clinically diagnosed melancholic (Mel) and non-melancholic (Non-Mel)
patients.
Description A

Self-report measure (n¼278) Clinician measure (n¼278)

1. Low energy and extremely hard to get out of bed and get going
2. Depressed mood completely prevents getting any real pleasure in life, and normally pleasing or
humorous things won’t lift mood
3. Mood and energy levels are worse in the mornings
4. Completely lose interest in things, including hobbies and activities that would usually be enjoyedwhen not depressed
5. Cannot look forward to anything in life
6. In walking and talking, distinctly physically slowed, at times almost feeling ‘paralysed’ or as if
walking through sand7. Concentration is distinctly affected
8. Tend to lose weight when depressed (and before any antidepressant or other drugs are commenced)
9. The severity of depressive episodes appears far worse than would be expected given thecircumstances that may precede them or appear to cause them
10. Early years were no more difﬁcult – when compared to most people – in terms of having any major
difﬁculties with parents or bullying
11. When not depressed relationships and work performance are generally good
12. Depressions can sometimes come ‘out of the blue’ without any particularly clear reason
Description B

Mel
(%)

Nonmel
(%)

w2

Mel
(%)

Nonmel
(%)

w2

82.6
81.0

61.8
70.7

14.4nnn 2.9nnn 89.3
3.9n
1.8n
82.6

43.3
32.5

62.1nnn 10.9nnn
69.3nnn 9.9nnn

67.8
81.0

49.7
71.3

9.2n
3.4

62.8
87.6

24.2
39.5

42.1nnn 5.3nnn
66.2nnn 10.8nnn

78.5
46.3

56.1
31.8

15.3nnn 2.9nnn 79.3
6.0n
1.8n
54.5

33.1
10.8

58.6nnn
62.4nnn

84.3
28.9
66.1

75.8
25.5
42.7

3.0
1.7
87.6
0.4
1.2
43.8
15.1nnn 2.6nnn 73.6

61.1
15.3
15.3

24.1nnn 4.5nnn
27.7nnn 4.3nnn
96.2nnn 14.4nnn

53.7

36.3

8.4n

52.9

27.4

18.8nnn

3.0nnn

77.7
74.4

68.8
51.6

2.7
1.6
72.7
15.0nnn 2.7nnn 70.2

38.2
24.8

32.7nnn
57.0nnn

4.3nnn7.1nnn

OR

2.1n
1.7

2.0n

Self-report measure

1.Even when depression is severe, can generally look forward to something really nice coming up
2. Become distinctly more irritable and/or angry when depressed
3. Even when depression is severe, can generally be cheered up when people are really supportive
4. Mood lifts (even if temporarily) and can get some temporary relief when something nice happens
5. If concentration is affected during a depressive episode, it is usually because of worrying too muchand having lots of distracting thoughts
6. Often get (non-medication related) food cravings and/or increased appetite when depressed
7. Views self as generally more inclined than most people to become emotional about things(regardless of whether depressed or not)8. Every time depression develops, some cause that explains the depression is apparent
9. The severity of depressions can be explained by the type of stressful events that precede them andtheir impact with personality style
10. Even when not depressed, tends to have some difﬁculties in dealing with my partner, family andother relationships
11. Even when not depressed, tend to worry more than most people, particularly when under stress
12. In childhood and adolescence, experienced more stressful events and major difﬁculties withparents and others than most people experience2

OR

7.8nnn9.9nnnClinician measure
OR

Mel
(%)

Nonw2
mel (%)

12.1nn
0.2
0.0
6.8n
6.7n

3.9nn
1.1
1.0
1.9n
1.9n

5.8
49.6
9.1
20.7
19.0

40.1
56.7
48.4
64.3
59.2

42.8nnn 10.9nnn
1.4
1.3
49.1nnn 9.4nnn
52.6nnn 6.9nnn
45.5nnn 6.2nnn

37.6
53.5

0.9
5.9n

1.3
1.8n

24.8
22.3

31.8
45.2

1.7
15.7nnn

25.6
20.7

43.3
45.9

9.3n
2.2n
19.1nnn 3.3nnn

9.9
6.6

53.5
57.3

57.2nnn 10.5nnn
77.0nnn 19.0nnn

28.1

39.5

3.9n

17.4

43.3

21.2nnn

3.6nnn

52.1
28.1

58.0
52.2

1.0
1.3
25.6
16.4nnn 2.8nnn 28.1

59.9
49.7

32.4nnn
13.2nnn

4.3nnn
2.5nn

Mel
(%)

Nonw
mel (%)

6.6
61.2
23.1
39.7
57.9

21.7
63.7
23.6
55.4
72.6

32.2
38.8

1.7n

OR

1.4
2.9nnnItems are slightly modiﬁed from actual self-report and clinician-rated forms.
np o 0.05.
p o0.01.
po 0.001.

nn

nnn

Table 2Overall descriptor pattern endorsed by clinically diagnosed melancholic and non-melancholic patients according to the single-item self-rated (n ¼278) and clinician-rated(n¼ 267) prototypic measure.
SERDEX ratings by clinicallydiagnosed melancholic and nonmelancholic patients
Melancholic patients
Self-rated SERDEXClinician-rated SERDEX
Non-melancholic patients
Self-rated SERDEXClinician-rated SERDEX

1 Description A best
matches my experienceof depression

2 Description A issomewhat closer to myexperience than B

3 My depression has
equal features of
Descriptions A and B

4 Description B issomewhat closer to myexperience than A

5 Description B best
matches my experienceof depression

42 (34.7%)
55 (47.8%)

49 (40.5%)
48 (41.7%)

19 (15.7%)8 (7.0%)11 (9.1%)
3 (2.6%)0 (0.0%)1 (0.9%)17 (10.8%)
3 (2.0%)32 (20.4%)
10 (6.6%)

63 (40.1%)
37 (24.3%)

30 (19.1%)
64 (42.1%)

15 (9.6%)
38 (25.0%)

Examining for differential distribution for those clinically judged as either having a melancholic or non-melancholic depression, the clinician-rated SERDEX generated a chisquare of 179.2 (p o0.001) and the self-rated SERDEX a chi square of 57.9 (p o0.001).

prototypic measure or were so rated by the clinician in regard totheir overall clinical proﬁle as matching Description A (prototypic
melancholia), Description B (prototypic non-melancholic depression) or a mix. Data for the self-report version quantiﬁed that

75.2% of the clinically-diagnosed melancholic patients favoured
Description A (‘best’ or ‘closer’) and only 9.1% favoured Description B as ‘best’ or ‘closer’. For the clinician-rated measure,discrimination was even more distinctive (i.e., 89.5% vs. 3.5%,

G. Parker et al. / Journal of Affective Disorders 144 (2013) 199–207

respectively). Turning to the clinically-diagnosed non-melancholic patients, there was far less speciﬁcity on the self-reportmeasure (28.7% favoured Description B as ‘best’ or ‘closer’ and31.2% favoured Description A) but with superior rates (of 67.1%
versus 8.6%, respectively) for the clinician-rated prototype measure. Thus, on the self-report measure, Description A was
weighted by the melancholic patients and showed distinct skewing, while the non-melancholic patients showed a spread acrossthe ﬁve options and with their pattern more approximating to anormal distribution rather than being loculated to Description B.
By contrast, the clinician-rated measure was skewed to theputative diagnostic category.
We examined agreement between self-report and clinicianrated forms, and quantiﬁed weighted kappas of 0.21 for themelancholic and 0.09 for the non-melancholic subjects, establishing a lack of agreement between self-report and clinician-rated
assignment to one of the ﬁve prototypic categories, and suggesting limitations to one or both measures.
3.3. Examining the comparative capacity of the derived self-report
SERDEX and the SDS symptom severity measures to differentiate
clinically deﬁned melancholic and non-melancholic depression
We undertook a series of ROC analyses examining the capacity ofa (i) ‘total melancholia’ score (i.e., number of the 12 Description A
items afﬁrmed), (ii) ‘total non-melancholia’ score (i.e., number of the
12 Description B items afﬁrmed), (iii) total ‘difference’ score(i.e., subtracting the total number of afﬁrmed Description B fromafﬁrmed Description A items) and the (iv) ‘prototype’ assignment
chosen by the patient (i.e., A, A4B, A¼ B, B4A and B options). As
graphed and quantiﬁed in Fig. 1, the least discriminating measures
were the ‘total melancholia’ score (AUC¼ 0.72, CI¼0.66–0.78,
po0.001) and ‘total non-melancholia’ score (AUC¼0.69, CI¼0.63–
0.75, po0.001) and with both comparable in their discrimination(CI¼ 0.04–0.12, p¼0.41). The prototype score was only slightly

203

more discriminating (AUC¼0.74, CI¼0.69–0.80; po0.001) thanthese two strategies. A total ‘difference’ score of 4 or more melancholic than non-melancholic items was, however, the most discriminating in terms of its AUC (0.76), being formally superior to thetotal non-melancholic score (CI¼  0.11–0.03, po0.001) and nonsigniﬁcantly superior to both the total melancholia score(CI¼  0.08–0.00, po0.06) and the prototype score (CI¼  0.01–
0.05, po0.25). The total ‘difference’ score of 4 or more was therefore
judged as the optimal discriminating strategy, and quantiﬁed ashaving a sensitivity of 0.69, speciﬁcity of 0.77, positive predictive
value of 0.70 and negative predictive value of 0.77.
We then undertook a similar analysis of total SDS severity
scores, identiﬁed a total score of 54 or more as having the greatest
discrimination of clinically diagnosed melancholic and non-melancholic patients (AUC¼0.68, CI ¼0.62–0.75, p o0.001) and thus
far less discriminating than all four applications of the SERDEX
measure. That SDS cut-off score had a sensitivity of 0.61, speciﬁcity of 0.65, positive predictive value of 0.57 and negative
predictive value of 0.69. Fig. 1 plots the ROC curves for the four
self-report SERDEX applications and for the total SDS score,demonstrating the superiority all four SERDEX approaches to
the SDS measure and, as noted in the previous paragraph, thatof the four SERDEX applications, the greatest differentiation wasevident in the SERDEX ‘difference’ score of 4 or more.
3.4. Examining the comparative capacity of derived clinician-rated
SERDEX measures to differentiate clinically deﬁned melancholic andnon-melancholic depression
The series of ROC curve analyses performed for the self-rated
SERDEX were repeated for the clinician-rated SERDEX measure(see Fig. 2). The total number of melancholic items (AUC ¼0.93,
CI ¼0.90–0.96, p o0.001) and the difference score (AUC ¼0.93,
CI ¼0.90–0.96, po0.001) were formally comparable in theirdiscrimination (CI ¼0.02–0.02, p ¼0.70). The least discriminating

Fig. 1. ROC curve analysis for the sum of melancholic (A) items, non-melancholic (B) items, the difference (A)–(B) score, prototype score and SDS total score for the selfrated SERDEX measure.

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G. Parker et al. / Journal of Affective Disorders 144 (2013) 199–207

Fig. 2. ROC curve analysis for the sum of melancholic (A) items, non-melancholic (B) items, the difference (A)–(B) score, prototype score and SDS total score for theclinician-rated SERDEX measure.

measure was the total number of non-melancholic items afﬁrmed(AUC¼0.87). While the formally most discriminating measure
was the prototype score (AUC¼0.94), it was comparable in its
discrimination to the total number of melancholic items(AUC¼0.93, CI ¼0.03–0.01, p o0.38) and a difference score(AUC¼0.93, CI ¼0.03–0.01), p o0.44). As the ‘difference’ score
was quantiﬁed here by ROC analysis as 4 or more for putativemelancholia – and thus had the same cut-off as quantiﬁed for the
self-report measure – and had high discrimination (comparable totwo other highly discriminating strategies), we viewed it as the
optimal identiﬁed strategy, and therefore tested that strategy in
our shortly reported validity analyses. The ‘difference score’ of
4 or more was quantiﬁed as having a sensitivity of 0.84, speciﬁcityof 0.92, positive predictive value of 0.90 and negative predictive
value of 0.88.
3.5. Examining the validity of the derived SERDEX ‘difference’measures
Ascriptions for melancholia (see Parker and Hadzi-Pavlovic,
1996a) as against non-melancholic depression include an older
age and older age at onset, greater likelihood of a family history,
decreased likelihood of disordered personality and life event
stressors to onset, and greater responsivity to antidepressantdrugs and ECT. We therefore examined (see Table 3) the extent
to which our data set allowed examination of any such validating
variables for those assigned as melancholic or non-melancholic by
SERDEX ‘difference’ scores (i.e., a difference score of 4 or more
being indicative of melancholia).
In relation to the self-report SERDEX measure, those who scored
4 or more (i.e., putative melancholia) did not differ by age, family
history variables, a measure of developmental difﬁculties(i.e., difﬁculties with parents) or by rates of co-morbid drug or
alcohol problems. They did score higher on two state depression
measures (signiﬁcantly for the DMI-10), reported a signiﬁcantly

longer current depressive episode, returned a higher global functioning score (indicating greater impairment), and reported fewer
current and lifetime stressors. They were less likely to have one ormore lifetime anxiety disorders, showing lower rates of social
anxiety and obsessive compulsive disorder (OCD) in particular. On
the MAP-incorporated Temperament and Personality measure(Parker and Manicavasagar, 2005) assessing personality styles
viewed as predisposing to depression, they did not differ in returning lower scores on any personality style scale (actually scoringhigher on ‘personal reserve’), while they also failed to differ on thetwo scales assessing disordered personality functioning (i.e., low
cooperativeness and effectiveness). They were, however, more likely
to report having received electroconvulsant therapy (ECT).
In relation to the clinician-rated SERDEX measure, those whoscored 4 or more (i.e., putative ‘melancholia’) had a longer
duration for their current depressive episode but did not differ
on state depression measures or on the global functioning score.
They were signiﬁcantly more likely to have received ECT. They
were less likely to report a history of difﬁculty with parents,
reported fewer current and lifetime stressors and were less likely
to have a lifetime diagnosis of one or more anxiety disorders, withthe strongest differences observed speciﬁcally with respect tosocial phobia, generalised anxiety disorder and OCD. On the 10
Temperament and Personality scales, so assigned melancholicpatients were signiﬁcantly more likely to return lower scoreson ﬁve of eight scales (i.e., irritability, anxious worrying, selfcriticism, interpersonal sensitivity and self-focused) and also rate
signiﬁcantly higher on effectiveness and cooperativeness, suggesting lower levels of personality dysfunction.

4. Discussion
Melancholia is variably positioned as a more ‘severe’ form ofdepression or as a separate ‘type.’ If the former position is valid

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G. Parker et al. / Journal of Affective Disorders 144 (2013) 199–207

Table 3Comparisons of those assigned by a cut-off score of 4 or more to melancholic (and non-melancholic) depression by the self-rated and clinician-rated SERDEX measure(difference score of 4 or more for melancholia) against validator variables.
MAP variable

Self-rated SERDEX n¼ 278

Clinician-rated SERDEX n¼278

Mel (n¼ 121)

Non-mel (n¼ 157)Sig.

Mel (n¼114)

Non-mel (n ¼164)

Sig.

Sex-female (%)
Age at assessment
Age at depression onset
Current depression (days)
DMI-10 total score
QIDS total score
Global functioning total score
Family history of depression (%)
Family history of bipolar (%)
Family history of alcoholism (%)
Difﬁculty with parents (%)
Drug problem (%)
Alcohol problem (%)

55.0
41.9
21.8
76.7
22.1
16.0
15.4
66.9
17.9
37.5
38.3
8.3
15.0

48.7
40.0
20.5
43.5
19.0
14.9
12.7
72.7
16.7
36.7
48.7
13.9
19.6

0.30
0.23
0.37
o 0.001
o 0.001
0.33
o 0.001
0.28
0.77
0.90
0.084
0.15
0.32

49.1
42.1
22.3
72.4
21.0
15.2
14.5
67.5
13.2
34.2
36.8
7.9
13.2

53.0
40.4
20.5
55.2
20.1
15.6
13.6
71.8
20.1
39.0
49.4
14.0
20.7

0.52
0.29
0.24
o .001
0.35
0.33
0.19
0.44
0.13
0.41
0.038
0.12
0.10

Lifetime Anxiety Disorders (%)
Social phobia
GAD
Panic
Agoraphobia
OCD
PTSD
1 or more lifetime anxiety disorders
Total no. current stressors
Total no. lifetime stressors
Tricyclics—ever used (%)
ECT—ever received (%)

20.8
27.5
26.7
15.8
15.0
14.7
51.7
2.2
4.3
20.8
8.3

36.7
33.5
22.2
18.4
26.6
17.1
64.6
3.2
5.4
21.5
0.6

0.004
0.28
0.38
0.58
0.020
0.60
0.030
o 0.001
o 0.001
0.89
0.001

17.5
23.7
22.8
12.3
14.0
11.7
46.5
1.9
4.2
25.4
7.9

38.4
36.0
25.0
20.7
26.8
19.1
67.7
3.4
5.5
18.3
1.2

o 0.001
o 0.029
0.67
0.067
0.011
0.11
o 0.001
o 0.001
o 0.001
0.15
0.005

Personality Styles
Social avoidance
Irritability
Perfectionism
Anxious worrying
Personal reserve
Self-criticism
Interpersonal sensitivity
Self-focused
Cooperativeness
Effectiveness

12.2
11.0
16.8
14.3
11.0
16.1
8.6
4.1
23.0
14.9

11.2
10.4
18.0
14.6
9.3
15.5
9.1
3.7
23.2
15.9

0.11
0.45
0.07
0.70
o 0.05
0.31
0.43
0.39
0.67
0.18

11.4
9.5
17.5
12.8
9.2
14.9
7.2
3.3
24.4
16.6

11.9
11.6
17.3
15.6
10.7
16.4
10.1
4.3
22.3
14.4

0.46
o 0.050.70
o 0.001
0.06
o 0.05o 0.001
o 0.005
o 0.001
o 0.005

then it might be simply quantiﬁed on appropriate measures ofseverity and differentiated from non-melancholic clinical depression. If it is a distinct ‘type’, its formal clinical deﬁnition isimportant if there are aetiological and/or treatment implications.
Assuming the latter model, then why has it proved resistant toclear deﬁnition? Two principal reasons for its ineffability havebeen offered and must be respected in developing measurement
approaches. First, that it is more a ‘system’ (rather than focal)
disorder involving disruptions in functional neurocircuits, particularly involving frontal-subcortical pathways and varying neurotransmitter contributions. The site(s) of such disruptions and thecontribution of differing neurotransmitters might all contribute todifferential symptoms across differing patients—as occurs for
Parkinson’s disease, and with the similarities and overlaps
between melancholia and Parkinson’s disease being considered
in depth by Austin and Mitchell (1995). Second, and as detailed in
the Introduction, its symptoms and their measurement are
difﬁcult to operationalise clearly, making reliance on symptom
measurement alone problematic. Such a problem is not unique tomelancholia. Parkinson’s disease also lacks a gold standard
laboratory diagnostic test, but this does not argue against neurologists seeking to deﬁne the condition and differentiate it fromother salient conditions—assessing both clinical symptoms andillness correlates. Thus, the rationale for our development andevaluation of the previously named SERDEX measure—pursuingdelineation of melancholia using multiple symptom and course ofillness ‘signals’, while respecting their intrinsic fuzziness and that,at best, only prototypic (rather than pristine) deﬁnition might beachievable.
We chose candidate descriptors that reﬂected historical ascriptions and which we had reﬁned from previous studies over thelast two decades. One of the higher-order ascriptions to melancholia is that it is more ‘biological’ in its origins with certain overrepresented rather than speciﬁc symptoms (e.g., anergia, anhedonia), while the residual non-melancholic disorders (oncetermed ‘reactive’ and ‘neurotic’ depression) are more generally
positioned as reﬂecting the impact of stress with or without acontribution of a predisposing personality style. Such a model
framed our development and validation strategies.
In this journal we previously reported (Parker et al., 2012) the
utility of the SERDEX measure in a relatively small sample of 141
patients and as a self-report strategy only, but there demonstrated that context and course of illness variables were moredifferentiating than symptom variables. In this report the sample
was doubled and we examined the properties of both self-reportand clinician-rated versions. A key study limitation was theaccuracy of assigning a diagnosis of melancholic versus nonmelancholic depression—in that it weighted clinical judgment(and therefore had attendant limitations). A second limitation
was the circularity of our logic. Our clinicians weighted certain
symptoms and illness correlates in making a diagnosis of melancholia and which alone might have ensured their over-representation in those assigned a diagnosis of ‘melancholia’ andunder-representation in the residual non-melancholic class. Such

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G. Parker et al. / Journal of Affective Disorders 144 (2013) 199–207

limitations can only be conceded in the absence of independent
raters and a benchmark diagnostic standard.
For both the self-report and clinician-rated SERDEX items forms,
all 24 items had higher prevalences in their putative diagnostic (i.e.,
clinically deﬁned melancholic or non-melancholic) group, but withnot all differences formally signiﬁcant. Chi square and odds ratio
analyses identiﬁed greater speciﬁcity and more signiﬁcant differences in the clinician-rated than the self-report SERDEX item set, aﬁnding that could reﬂect the circularity issue noted in the previous
paragraph or clinicians being more valid raters. Agreement between
self-report and clinician ratings was weak, indicating that one
strategy was likely to be superior to the other. The ‘spread’ ofself-report SERDEX responses by non-melancholic patients acrossthe ﬁve A–B prototypic patterns was also noteworthy and may
reﬂect diagnostic imprecision or a rater bias. In relation to the last,
we suspect that some patients may have interpreted the form as
indicating that the Descriptor A set captured a more ‘serious’depression and so preferentially rated items that would afﬁrm theseverity of their perceived condition to the clinician for assessment.
If a valid interpretation, it adds to arguments favouring theclinician-rated version above the self-report version. Conversely,the ‘success’ of the clinician-rated measure may also reﬂect a rater
bias, as noted in the previous paragraph.
Irrespective of the rater strategy, we demonstrated that the mostdiscriminating items were equally likely to be symptoms or courseof illness variables, and thus arguing against reliance on symptoms
only. Similarly, the ﬁve-point prototype measure (asking whether
the depressive picture corresponded more closely to the Item A or
Item B set) showed greater differentiation across the clinician-rated
rather than the self-rated version. In relation to the former,
speciﬁcity was impressive in relation to the clinically diagnosed
melancholic patients (with nearly 90% rated as matching or being
closer to Description A and only 3% to Description B). Speciﬁcity
across both self-report and clinician-rated approaches was lessimpressive for those receiving a clinical diagnosis of a non-melancholic depression, with matching or closeness to Description B being
achieved by 67% of those non-melancholic patients assigned byclinician ratings and 29% of those using the self-report measure.
A key set of ROC analyses quantiﬁed whether the self-rated
SERDEX measure approach (i.e., symptoms plus illness correlates)
was superior to self-rating of symptoms only (as assessed by ourcomprehensive 32-item SDS measure). All four self-report SERDEX applications were superior to use of the SDS (symptoms
only) approach, and this again underlies what is perhaps the mostimportant study ﬁnding.
We formally quantiﬁed that an item ‘difference’ score (i.e.,
subtracting the afﬁrmed number of Descriptor B items from the
afﬁrmed number of Descriptor A items) was the mostdiscriminating—having a sensitivity of 0.69 and speciﬁcity of
0.77. A set of ROC analyses indicated that, for the clinician-rated
SERDEX approaches, both the ‘prototype’ and ‘difference’ scores
effected the greatest discrimination (i.e., respective sensitivities of0.90 and 0.84, and speciﬁcities of 0.90 and 0.92). While suchanalyses generate optimised cut-off scores (respecting nuances ofthe sample under analysis) and would be unlikely to be quantiﬁed
at such high levels in replication studies, the key conclusion hereis again in indicating that the clinician-rated version of the
SERDEX measure appeared distinctly superior to the self-rated
version. As the ‘difference’ score was the most discriminating inanalyses of the self-report SERDEX and close to being the mostdiscriminating in the clinician-rated SERDEX, we favour its use.
Finally, we sought to examine the validity of the SERDEX
measures by directly comparing the extent to which optimal‘difference’ scores identiﬁed ‘melancholic’ and ‘non-melancholic’groups whose constituents met the ascriptions accorded to thosedepressive sub-types. While validation was limited (in that we

did not demonstrate anticipated distinct differences in family
history, age and depression severity), once again the clinicianrated SERDEX version generated greater empirical support than
did the self-rated version. So assigned non-melancholic patients
had distinctly higher rates of anxiety, current and lifetimestressors, early parental difﬁculties, at-risk personality styles
and disordered personality functioning, consistent with the attribution that non-melancholic depression is commonly underpinned by stress and personality causal factors.
It is important to note that assessment of symptoms by themeasure focuses on their presence during a previous or current(as here) episode and not on assessing their severity. This is ofadvantage if melancholic and non-melancholic depressive conditions are to be distinguished by their differential clinical pattern
and not by severity per se. Our studies have been undertaken inclinical samples only to this stage, and it would be important for
future replication studies to be undertaken in community samples. While the clinician-rated version of the measure was superior in this study, there would be wisdom in examining both theself-report and clinician-rated versions in any such community
studies although we would argue for any assessment of the latterversion involving raters with clinical skills.
As the SERDEX acronym incorporates its original emphasis ona self-report measure and the data distinctly favour the clinicianrated measure, the measure requires renaming. Respecting somehistory and its correspondence to the model employed in the
Newcastle Index (Carney et al., 1965) we have elected to re-nameit the Sydney Melancholia Prototype Index (SMPI), with comparable self-report and clinician-rated versions. We suggest that themeasure is worthy of further evaluation in deﬁnitional, causal andtreatment studies. Its salience may best lie in that its underlying
model approximates to a clinician’s approach to formulating a
depressive ‘pattern’ in evaluating symptoms, illness correlates
and potential risk factors. As noted by McHugh and Slavney(2012), psychiatry might beneﬁt from addressing psychiatricdisorders ‘‘in the same way that internists address physicaldisorders, explaining the clinical manifestations as products ofnature to be comprehended not simply by their outward show
but by the causal processes and generative mechanisms known to
provoke them’’.

Role of funding sourceThis study was supported by an NHMRC program grant (510135). The NHMRC
did not participate in the study design, nor in the data collection and analysis
process, or in any phase of the manuscript preparation.

Conflict of interest
Nothing to declare.

Acknowledgments
This study was funded by an NHMRC Program Grant (510135) and an
Infrastructure Grant from the NSW Department of Health.

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