depression subtyping in ptsd patients

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Annals of Clinical Psychiatry, Vol. 9, No. 4, 1997 Depression Subtyping in PTSD Patients Joseph I. Constans, Ph.D., 1,2,3 Karen Lenhoff, PhJD.,1 and Michele McCarthy, Ph-D. 1 A Structured Clinical Interview for the DSM-IV (SCID) and psychological testing were ad- ministered to 260 combat veterans in order to investigate the relationship between symptoms of post-traumatic stress disorder (PTSD) and melancholic features of depression. Sixty-seven percent of PTSD patients experiencing comorbid major depression acknowledged symptoms indicative of a melancholic-depression subtype. Correlational and regression analyses show that the presence of melancholic features is related to severity of emotional-numbing expe- rienced by the PTSD patients. These results suggest PTSD patients are likely to experience depressive episodes phenomenologicallysimilar to melancholic-depression. It is likely that acknowledgment of melancholic symptoms is due to (a) the inclusion of guilt as a melancholic feature, and (b) the similarities between emotional numbing symptoms and other melancholic features. INTRODUCTION Post-traumatic stress disorder (PTSD) is diag- nosed based on a cluster of symptoms occurring fol- lowing the experience of a trauma, including reexperiencing of the traumatic event, avoidance of trauma-related cues, emotional numbing, and arousal symptoms. Major depressive episodes, while not con- sidered a necessary component of pathological reac- tions to trauma, commonly cooccur with PTSD. Data from the National Comorbidity Survey found lifetime comorbidity between PTSD and all depressive disor- ders to be higher than 50% (1). For individuals with combat-related PTSD, lifetime prevalence of major depressive disorder (MDD) may be as high as 70% (2). Major depression that cooccurs with PTSD, however, appears to differ both biologically and psy- chologically from non-trauma-related depression. In- dividuals with MDD typically show nonsuppression New Orleans Veterans Affairs Medical Center, New Orleans, Louisiana. Department of Psychiatry, Louisiana State University Medical Center, New Orleans, Louisiana. ^o whom correspondence should be addressed at Psychology Service (116B), VAMC, 1601 Perdido St., New Orleans, Louisi- ana 70146. of cortisol following administration of dexametha- sone. In contrast, patients with PTSD and comorbid MDD typically have either failed to show nonsup- pression (3,4) or have shown hypersuppression (5) after dexamethasone challenge. In terms of response to antidepressant medications, major depression is significantly more treatment-resistant in patients with PTSD than in those patients without PTSD (6-8). Fi- nally, differences also have been found between PTSD/MDD and MDD-only patients in psychologi- cal constructs believed related to the etiology of de- pression. Veterans diagnosed with PTSD/MDD were found to have a greater tendency toward an intro- jective, self-critical, and guilt-laden depression than non-PTSD veterans who were experiencing a MDD (9). The goal of this paper is to extend this line of research by assessing the phenomenological features of depression occurring in PTSD patients and inves- tigate the relationship between depressive features and PTSD symptoms. It is predicted that PTSD pa- tients experiencing comorbid depression are more likely to report a number of DSM-IV melancholic symptoms of depression (10) including a distinctive quality of their mood state (depressive mood states qualitatively different from feelings of sadness), ex- cessive guilt, and anhedonia (11,12). It is further hy- 235 1040-1237/97/1200-0235S12.50/1 © 1997 American Academy of Clinical Psychiatrists KEY WORDS: PTSD; melancholia; major depression.

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Page 1: Depression Subtyping in PTSD Patients

Annals of Clinical Psychiatry, Vol. 9, No. 4, 1997

Depression Subtyping in PTSD Patients

Joseph I. Constans, Ph.D.,1,2,3 Karen Lenhoff, PhJD.,1 and Michele McCarthy, Ph-D.1

A Structured Clinical Interview for the DSM-IV (SCID) and psychological testing were ad-ministered to 260 combat veterans in order to investigate the relationship between symptomsof post-traumatic stress disorder (PTSD) and melancholic features of depression. Sixty-sevenpercent of PTSD patients experiencing comorbid major depression acknowledged symptomsindicative of a melancholic-depression subtype. Correlational and regression analyses showthat the presence of melancholic features is related to severity of emotional-numbing expe-rienced by the PTSD patients. These results suggest PTSD patients are likely to experiencedepressive episodes phenomenologically similar to melancholic-depression. It is likely thatacknowledgment of melancholic symptoms is due to (a) the inclusion of guilt as a melancholicfeature, and (b) the similarities between emotional numbing symptoms and other melancholicfeatures.

INTRODUCTION

Post-traumatic stress disorder (PTSD) is diag-nosed based on a cluster of symptoms occurring fol-lowing the experience of a trauma, includingreexperiencing of the traumatic event, avoidance oftrauma-related cues, emotional numbing, and arousalsymptoms. Major depressive episodes, while not con-sidered a necessary component of pathological reac-tions to trauma, commonly cooccur with PTSD. Datafrom the National Comorbidity Survey found lifetimecomorbidity between PTSD and all depressive disor-ders to be higher than 50% (1). For individuals withcombat-related PTSD, lifetime prevalence of majordepressive disorder (MDD) may be as high as 70%(2).

Major depression that cooccurs with PTSD,however, appears to differ both biologically and psy-chologically from non-trauma-related depression. In-dividuals with MDD typically show nonsuppression

New Orleans Veterans Affairs Medical Center, New Orleans,Louisiana.

Department of Psychiatry, Louisiana State University MedicalCenter, New Orleans, Louisiana.

^o whom correspondence should be addressed at PsychologyService (116B), VAMC, 1601 Perdido St., New Orleans, Louisi-ana 70146.

of cortisol following administration of dexametha-sone. In contrast, patients with PTSD and comorbidMDD typically have either failed to show nonsup-pression (3,4) or have shown hypersuppression (5)after dexamethasone challenge. In terms of responseto antidepressant medications, major depression issignificantly more treatment-resistant in patients withPTSD than in those patients without PTSD (6-8). Fi-nally, differences also have been found betweenPTSD/MDD and MDD-only patients in psychologi-cal constructs believed related to the etiology of de-pression. Veterans diagnosed with PTSD/MDD werefound to have a greater tendency toward an intro-jective, self-critical, and guilt-laden depression thannon-PTSD veterans who were experiencing a MDD(9).

The goal of this paper is to extend this line ofresearch by assessing the phenomenological featuresof depression occurring in PTSD patients and inves-tigate the relationship between depressive featuresand PTSD symptoms. It is predicted that PTSD pa-tients experiencing comorbid depression are morelikely to report a number of DSM-IV melancholicsymptoms of depression (10) including a distinctivequality of their mood state (depressive mood statesqualitatively different from feelings of sadness), ex-cessive guilt, and anhedonia (11,12). It is further hy-

2351040-1237/97/1200-0235S12.50/1 © 1997 American Academy of Clinical Psychiatrists

KEY WORDS: PTSD; melancholia; major depression.

Page 2: Depression Subtyping in PTSD Patients

236 Constans, Lenhoff, and McCarthy

pothesized that reasons for the high rates of melan-cholic depression in PTSD patients are due to thesimilarity between symptoms of emotional numbingand symptoms of a melancholic depression.

METHOD

Participants in this study included 260 veteranswho were evaluated at a Department of Veterans Af-fairs medical center for a possible service-connectedpsychiatric disability. Evaluation procedures includeda completion of the Structured Clinical Interview forthe DSM-IV (13) administered by a masters-level cli-nician who had been thoroughly trained in the useof this instrument. The SCID includes serial assess-ment of melancholic, catatonic, and atypical depres-sive features for all individuals meeting criteria for acurrent depressive episode. In the SCID administra-tion, catatonic criteria are administered to those notexperiencing melancholic features, and atypical cri-teria are administered to subjects not meeting crite-ria for either melancholia or catatonia. This interviewprovided for a structured, rule-governed assessmentof DSM-IV depression-specifier features.

The structured interview was followed by a clini-cal interview conducted by a doctoral-level psycholo-gist who also reviewed the patient's responses to theSCID. Finally, all subjects completed the followingmeasures of PTSD, depression, and general anxiety:Beck Depression Inventory (14), Combat ExposureScale (15), State-Trait Anxiety Inventory (16), Min-nesota Multiphasic Personality Inventory II (17), andthe Mississippi Scale for Combat-Related PTSD (18).

RESULTS

Descriptive Information

Of the original sample of 260 combat veterans,43 received a primary diagnosis of either schizophre-nia, schizoaffective disorder, schizophreniform disor-der, delusional disorder, or bipolar I disorder, andthese individuals were excluded from subsequentanalyses. Of the remaining 217 subjects, 183 (84%)qualified for a diagnosis of PTSD based upon war-related trauma. Ninety-four of 183 PTSD subjects(51%) also qualified for a diagnosis of current MDD.Of the 35 veterans without PTSD, 15 (43%) met cri-teria for current MDD.

Frequency of Depression Subtypes

Of particular interest to this study is the fre-quency of melancholic, catatonic, and atypical fea-tures in those individuals with MDD. This frequencyinformation is presented in Table 1 for subjects withand without PTSD. Sixty-seven percent of thePTSD/MDD veterans qualified for a diagnosis ofmelancholic depression compared with 20% in theMDD/no-PTSD group. A chi-square analysis wasused to test for differences in the prevalence of mel-ancholic depression subtype in PTSD and non-PTSDpatients. For this and subsequent analyses, subjectsqualifying for atypical or uncategorized depressionwere considered to have nonmelancholic depression.The main reason for combining these groups was theemphasis in this study on melancholic versus nonmel-ancholic depression occurring in PTSD. Results ofthis analysis show an overrepresentation of melan-cholic depression in PTSD subjects when comparedwith the non-PTSD, depressed subjects, x2(l, N =105) = 6.66, p < .01.

Severity of Psychopathology in Depressed, PTSDVeterans

The remaining analyses were conducted onlywith PTSD-diagnosed veterans. This sample was sub-divided into three groups: MDD patients with mel-ancholic features (n = 63), MDD patients withoutmelancholic features (n = 31), and patients withoutcurrent MDD (n = 86). A one-way analysis of vari-ance and pairwise least significant difference com-parisons were conducted to test for possible groupdifferences on measures of depression, anxiety,PTSD, and level of exposure to combat stressors. Asshown in Table 2, there were no differences amongthe three groups in terms of level of combat expo-sure. Although PTSD veterans with depression re-ported higher levels of PTSD symptoms, depression,and generalized anxiety, no differences emerged be-

Table 1. Depression Subtypes in Patients with and withoutPTSD

MDD subtype

Melancholic subtypeAtypical subtypeCatatonic subtypeNeither subtype

PTSD/MDD(n =94)

63 (67%)5 (5%)0

26 (28%)

Non-PTSD/MDD(n = 15)

3 (20%)2 (13%)0

10 (67%)

Page 3: Depression Subtyping in PTSD Patients

Depression Subtypes 237

tween those depressed patients with and withoutmelancholic depression. Also, the two groups withMDD did not differ on either age of first depressiveepisode, F(1, 65) = 1.18, p > .28, or number of pre-vious depressive episodes, F(1, 28) < 1.

Comorbid Disorders

The three diagnostic groups (PTSD/melancholicdepression, PTSD/nonmelancholic depression, andPTSD/no current MDD) were compared on the pres-ence of other SCID-diagnosed disorders (see Table3). Inspection of the relative frequency of other dis-orders suggests comparable rates of comorbidity.

Predictors of Melancholia in PTSD/MDD

In order to determine the melancholic symp-toms that best differentiated melancholic from non-melancholic depression, the melancholic featurecriteria were compared for all PTSD/MDD patientswith and without melancholic depressions. Thisanalysis was possible, as all but three subjects meet-ing criteria for MDD were queried with the entireset of items for melancholic features. As is shown inTable 4, items tapping guilt, distinctiveness of moodstate, and early awakening showed greatest dis-criminability between the two groups.

A correlation matrix was formed between thePTSD symptom clusters and specific melancholic

items. PTSD symptom clusters were created by av-eraging SCID responses within each of the followingfour PTSD-symptom groups: reexperiencing symp-toms (five items: intrusive thoughts, nightmares,flashbacks, psychological distress, physiological reac-tivity), avoidance symptoms (two items: avoidance ofinternal and external stimuli), emotional-numbingsymptoms (five items: dissociative amnesia, change insignificant activities, feeling cut off, numbing, andforeshortened future), and arousal symptoms (fiveitems: insomnia, irritability, concentration problems,hypervigilance, and exaggerated startle). The analysisincluded all PTSD subjects who were queried withthe entire set of melancholic-specifier items (n = 91).As presented in Table 5, all melancholic items werepositively correlated with the emotional-numbingcluster. No significant relationships existed betweenany other PTSD symptom cluster and the melan-cholic items. The strongest correlation in the matrixwas between the melancholic-specifier guilt item andthe emotional-numbing cluster.

A regression equation was formed to test the hy-pothesis that melancholic features may be related toseverity of emotional numbing present in PTSD pa-tients. Use of this strategy allowed us to determinethe unique variance of each symptom cluster. Re-sponses to all SCID melancholic items were summedto form the dependent variable in the equation. Allfour PTSD symptom-cluster variables as definedabove were entered simultaneously into the regres-sion equation predicting severity of melancholicsymptoms. The regression equation proved signifi-cant, R2 = .30,F(4, 86) = 9.26, p < .0001. Inspectionof the beta weights for this equation shows that onlyemotional-numbing symptoms predicted severity ofmelancholic symptoms (see Table 6).

CONCLUSIONS

Sixty-seven percent of the veterans experiencingPTSD with current MDD met criteria for melan-cholic depression based on their responses to a SCIDinterview. In contrast, we found that only 20% of thenon-PTSD veterans experiencing current MDD metcriteria for melancholia. The frequency of this mel-ancholic subtype in the PTSD subjects is beyond thatexpected in an outpatient sample. In other investiga-tions studying prevalence of a melancholic depres-sion subtype, it has been estimated that less than20% of depressed outpatients meet criteria for mel-ancholic depression (19). Our finding does not ap-

Table 2. Mean Scores on Psychological Measures for PTSDVeterans with Melancholic Depression, with Nonmelancholic

Depression, and without Depression"

BDIMississippiMMPI2-PKSTAI (state)STAI (trait)CES

PTSD/melancholic

(n = 63)

36 (9.5)*137 (31.2)*

96 (9.5)*64 (12.5)*62 (10.1)*29 (9.5)*

PTSD/non-melancholic

(n = 31)

35 (13.2)*126 (23.4)^93 (11.3)*65 (10.2)*59 (10.5)*31 (8.4)*

PTSD/noMDD (n = 86)

24 (10.9)c

118 (18.9)'83 (16.3)c

56 (10.2)c

54 (10.4)c

27 (10.1)*

"Values in parentheses are standard deviations. BDI, BeckDepression Inventory; Mississippi, Mississippi Scale for Combat-Related PTSD; MMPI2-PK, Minnesota Multiphasic PersonalityInventory II-PK subscale (t score); STAI (state), State-TraitAnxiety Inventory (State version); STAI (trait), State-TraitAnxiety Inventory (Trait version); CES, Combat Exposure Scale.Superscript b denotes significantly different from c at .05 level.Superscript be denotes neither statistically different from b nor c.

Page 4: Depression Subtyping in PTSD Patients

Constans, Lenhoff, and McCarthy

Table 3. Presence of Comorbid Disorders for PTSD Veterans"

ETOH dependenceLifetimeCurrent

Other substance dependenceLifetimeCurrent

Panic with or without agoraphobiaLifetimeCurrent

Social phobiaLifetimeCurrent

OCDLifetimeCurrent

Any somatoform disoderCurrent

Melancholic MDD(n - 63)

35 (55.6)8 (12.7)

19 (30.2)7 (11.1)

6 (9.5)6 (9.5)

3 (4.8)2 (3.2)

4 (6.3)3 (4.8)

5 (7.9)

Nonmelancholic No(n = 31)

20 (64.5)8 (25.8)

10 (32.3)4 (12.9)

4 (12.9)3 (9.7)

5 (16.1)4 (12.9)

5 (16.1)4 (12.9)

1 (3.2)

current MDD(n = 86)

48 (55.8)13 (15.1)

19 (22.1)4 (4.7)

5 (5.8)2 (2.3)

4 (4.7)4 (4.7)

4 (4.7)5 (5.8)

4 (4.7)

"Values in parentheses are percent of patients meeting diagnostic criteria.

238

Table 4. Melancholic Symptoms Acknowledged by PTSD Patients with andwithout Melancholic Depression

Loss of pleasureLack of reactivityDistinctiveness of moodMorning depressionEarly awakeningPsychomotor retardationAnorexiaGuilt

Melancholicdepression

63/63 (100%)42/63 (67%)56/63 (89%)32/63 (51%)49/63 (78%)45/63 (71%)20/63 (32%)47/63 (75%)

Nonmelacholicdepression

26/31 (84%)9/31 (29%)

12/28 (39%)4/28 (14%)6/28 (21%)

13/28 (46%)1/28 (4%)3/28 (11%)

Percentdifference

1638503757252864

Table 5. Correlation Coefficients between Melancholic Items and PTSD Symptom Clusters (n=91)

Loss of pleasureLack of reactivityDistinctiveness of moodMorning depressionEarly awakeningPsychomotor retardationAnorexiaGuilt

Reexperiencing

-.11.02.04.11

-.06.07

-.01.12

PTSD symptom clusters

Avoidant

.07

.09-.06-.02-.04.11.06.03

Numbing

.36**

.38**

.23*

.21*

.24*

.38**

.26*

.48**

Arousal

.07

.16

.09

.06

.16

.03

.11-.06

*Significant at the .05 level.* 'Significant at the .01 level.

Page 5: Depression Subtyping in PTSD Patients

Depression Subtypes 239

pear to be a function of mere over-acknowledgmentof symptoms, as the melancholic and nonmeiancholicsubgroups did not differ from one another on meas-ures of depression, PTSD, and anxiety. Similarly,PTSD/melancholics did not show a significantlygreater number of other comorbid disorders whencompared to either PTSD/no depression orPTSD/nonmelancholic groups. Therefore, whilesome potential confounds such as group differencesin substance abuse cannot be ruled out by a struc-tured interview alone, we did not find evidence tosupport any such differences.

Why then did so many PTSD/MDD subjectsqualify for a melancholic feature specifier? Our studyoffers two possible explanations. First, the analysis ofthe specific melancholic criteria shows that the guiltitem best differentiated melancholies from nonmel-ancholics. Only three of the PTSD/MDD subjects(11%) qualifying for nonmeiancholic depression re-ported excessive guilt compared with 75% of thePTSD/melancholic subjects. This finding suggeststhat those PTSD subjects experiencing guilt reactionsto trauma may comprise a large portion of subjectswith melancholic features. In addition to the simplepresence of guilt as a symptom of melancholic de-pression, those PTSD subjects experiencing guilt re-actions are more likely to experience a distinctivequality to their depressed mood state and severe an-hedonia, thereby further increasing probability ofmeeting criteria for a melancholic specifier (20).

The second potential explanation for the over-representation of melancholic depression in PTSDpatients is based on analyses of the relationship be-tween PTSD symptoms and depressive subtypes.These analyses indicate higher emotional-numbingsymptoms are associated with a greater severity ofmelancholic symptoms. No other PTSD symptomcluster is related to the presence of melancholia. Itis possible that strong emotional-numbing symptomsmay lead the subjects to acknowledge a distinctive-ness of mood state and lack of reactivity. In fact, phe-

nomenological descriptions of emotional numbingare quite similar to conceptualizations of anhedoniaand mood distinctiveness, two melancholic criteria.

It is important to note that these subjects meet-ing criteria for a melancholic depression subtypelikely are not experiencing a "true" endogenous de-pression. Melancholies are more likely to respond toantidepressant medications and show higher rates ofnonsuppression of cortisol in DST (21). As pre-viously noted, the exact opposite pattern is typicallyfound in subjects with MDD and PTSD. Depressionin PTSD appears to be particularly resistant to treat-ment with antidepressants and PTSD/MDD subjectsmay show hypersuppression in response to a DST.Furthermore, we found that the acknowledgment ofsymptoms believed to best represent the construct ofmelancholia (i.e., psychomotor retardation, unreac-tive mood, pervasive anhedonia) showed the smallestdifferences between melancholic and nonmeiancholicdepressed veterans in our sample (21).

Instead, our pattern of results is consistent withprevious suggestions that a subset of PTSD patientsmay experience a depression subtype of PTSD(5,12,22). Our data suggest a large percentage ofPTSD patients experiencing depression may be dis-tinguished by their high frequency and severity ofemotional-numbing symptoms. The affective experi-ence of emotional numbing in turn may result in ac-knowledgment of symptoms that characterize anendogenous depression.

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Table 6. Summary of Regression Analysis for VariablesPredicting Severity of Melancholic Symptoms

Variable

Reexperiencing symptomsAvoidance symptomsEmotional-numbing symptomsArousal symptoms

B

-.05-.101.31.08

SEB

.25

.45

.22

.22

Beta

-.02-.02.54*.04

*p < .00001.

Page 6: Depression Subtyping in PTSD Patients

240 Constans, Lenhoff, and McCarthy

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