gender differences in chronic major and double depression

Journal of Affective Disorders 60 (2000) 1–11www.elsevier.com/ locate / jad

Research report

Gender differences in chronic major and double depression

a , b c d e*S.G. Kornstein , A.F. Schatzberg , M.E. Thase , K.A. Yonkers , J.P. McCullough ,f g f e h iG.I. Keitner , A.J. Gelenberg , C.E. Ryan , A.L. Hess , W. Harrison , S.M. Davis ,

fM.B. KelleraMedical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA

bStanford University School of Medicine, Stanford, CA, USAcUniversity of Pittsburgh and Western Psychiatric Institute, Pittsburgh, PA, USA

dUniversity of Texas Southwestern Medical Center, Dallas, TX, USAeVirginia Commonwealth University, Richmond, VA, USA

fBrown University, Providence, RI, USAgUniversity of Arizona, Tucson, AZ, USA

hPfizer, Inc. and College of Physicians and Surgeons, Columbia University School of Medicine, New York, NY, USAiQuintiles, Inc., Research Triangle Park, NC, USA

Received 8 April 1998; accepted 8 September 1999

Abstract

Background: While the sex difference in prevalence rates of unipolar depression is well established, few studies haveexamined gender differences in clinical features of depression. Even less is known about gender differences in chronic formsof depression. Methods: 235 male and 400 female outpatients with DSM-III-R chronic major depression or doubledepression (i.e., major depression superimposed on dysthymia) were administered an extensive battery of clinician-rated andself-report measures. Results: Women were less likely to be married and had a younger age at onset and greater familyhistory of affective disorder compared to men. Symptom profile was similar in men and women, with the exception of moresleep changes, psychomotor retardation and anxiety /somatization in women. Women reported greater severity of illness andwere more likely to have received previous treatment for depression with medications and/or psychotherapy. Greaterfunctional impairment was noted by women in the area of marital adjustment, while men showed more work impairment.Limitations: Since our population consisted of patients enrolling in a clinical trial, study exclusion criteria may have affectedgender-related differences found. Conclusions: Chronicity of depression appears to affect women more seriously than men,as manifested by an earlier age of onset, greater family history of affective disorders, greater symptom reporting, poorersocial adjustment and poorer quality of life. These findings represent the largest study to date of gender differences in apopulation with chronic depressive conditions. 2000 Elsevier Science B.V. All rights reserved.

Keywords: Chronic depression; Gender differences; Age of onset; Symptoms; Family history; Functional impairment

*Corresponding author. Department of Psychiatry, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980710,Richmond, VA 23298-0710, USA. Tel.: 1 1-804-8289-452; fax: 1 1-804-8285-058.

0165-0327/00/$ – see front matter 2000 Elsevier Science B.V. All rights reserved.PI I : S0165-0327( 99 )00158-5

2 S.G. Kornstein et al. / Journal of Affective Disorders 60 (2000) 1 –11

1. Introduction Young et al. (1990) found no differences inclinician-rated endogenous symptoms of depression,

The most consistent finding in epidemiologic global severity, or functional impairment; however,studies of nonbipolar depression is the sex difference like Frank et al., they noted more appetite increasein prevalence rates, with both major depression and and weight gain in women. Using a community-dysthymia being about twice as common in women based sample, Angst and Dobler-Mikola (1984) alsoas in men (Weissman and Klerman, 1977; Weissman found that depressed women experienced more appe-et al., 1993; Kessler et al., 1993). Numerous theories tite or weight changes, as well as more sleephave been proposed to account for this difference disturbances and feelings of worthlessness or guilt(Blehar and Oren, 1995; Wolk and Weissman, 1995), than depressed men; women in their study alsoranging from biologically based theories concerning reported a greater number of depressive symptomssex differences in neuroendocrine function to psy- than men. Finally, a gender-based comparison of 249chosocial theories regarding differences in coping depressed patients in a primary care sample (Wil-styles (Nolen-Hoeksema, 1995), temperament liams et al., 1995) revealed higher scores in women(Perugi et al., 1990), and social status. on self-report measures of depression, anxiety and

Considerably less attention has been paid to somatic symptoms; in addition, women reportedgender differences in clinical manifestations of de- more appetite changes and feelings of failure andpression, such as symptom profile, course of illness remorse. In summary, the literature suggests thatand functional impairment. In addition to knowing depressed men and women generally present withthat women are more likely to experience depression, similar symptoms, severity of illness and functionalit would be interesting and useful to know if men impairment, however women tend to report moreand women present differently when they become distress and have more appetite and weight increase,depressed. Such differences, if they exist, may have anxiety and somatic symptoms.clinical implications for gender-specific assessment Studies that have examined course features ofand treatment planning, as well as theoretical impli- major depressive disorder have shown no sex differ-cations for achieving a more comprehensive under- ences in age of onset (Frank et al., 1988; Burke etstanding of the basis for gender differences in al., 1990; Kessler et al., 1993; Weissman et al., 1993;depression. Thase et al., 1994), duration of episode (Frank et al.,

A few studies have examined gender differences 1988; Thase et al., 1994; Eaton et al., 1997), orin severity of illness, symptoms and functional number of previous episodes (Frank et al., 1988;impairment in major depression. Frank et al. (1988) Thase et al., 1994). Some researchers have alsofound no differences in symptom severity or func- noted no gender differences in chronicity or recur-tional impairment in 230 men and women outpatients rence (Keller et al., 1986; Kessler et al., 1993; Thasewith recurrent major depression based on the Hamil- et al., 1994; Eaton et al., 1997; Simpson et al.,ton Rating Scale for Depression (17-item HAM-D; 1997); however, several longitudinal studies haveHamilton, 1960) and the Global Assessment Scale suggested that women are more likely than men to(GAS; Endicott et al., 1976). However, women had experience a chronic or recurrent course of depres-significantly higher scores on the self-report Beck sion (Aneshensel, 1985; Sargeant et al., 1990;Depression Inventory (BDI; Beck et al., 1961), as Keitner et al., 1991; Ernst and Angst, 1992; Winokurwell as on a clinician-rated measure of reverse et al., 1993).vegetative symptoms. Specific symptom differences Until now, studies of gender differences in depres-included more appetite and weight increase, hypo- sion have focused exclusively on patients withchondriasis, somatic anxiety and expressed anger and episodic depression. No study has examined suchhostility in women, and more weight loss in men. In differences in patients with chronic forms of depres-contrast, Thase et al. (1994) reported higher HAM-D sive illness. The chronic depressions have become an(17-item) scores in women but no differences in BDI important area of focus in recent years, as researchor GAS scores in 84 outpatients with major depres- has shown that 20–30% of patients with depressivesion. In a mixed inpatient–outpatient sample of 498 disorders will experience a chronic course of illnesspatients with moderate to severe major depression, (Keller et al., 1992). Moreover, chronic depressions

S.G. Kornstein et al. / Journal of Affective Disorders 60 (2000) 1 –11 3

tend to be underrecognized, undertreated, and associ- compulsive disorder, or schizotypal, antisocial, orated with significant morbidity, disability and cost severe borderline personality disorder were excluded(Keller et al., 1982; Hays et al., 1995). Three types from the study.of chronic depression were described in DSM-III-R Subjects were evaluated extensively at baseline(American Psychiatric Association, 1987): chronic with both clinician-rated and self-report instruments.major depression (i.e., major depression with a Clinician-rated instruments included the Structuredduration of $ two years without antecedent Interview for DSM-III-R-Patient Version (SCID-P;dysthymia), double depression (major depressive Spitzer et al., 1989a), Structured Interview for DSM-disorder superimposed on dysthymia), and pure III-R Personality Disorders (SCID-II; Spitzer et al.,dysthymia. 1989b), HAM-D, CGI, Cornell Dysthymia Rating

Given the clinical importance of chronic depres- Scale (CDRS; Mason et al., 1993), Montgomery–sive disorders, it is relevant to examine whether the Asberg Depression Rating Scale (MADRS; Mon-gender differences reviewed above are also found in tgomery and Asberg, 1979), and Global Assessmentpatients presenting with chronic forms of depression. of Functioning (GAF) scale (American PsychiatricThis study will explore gender differences in demo- Association, 1987). Self-report instruments includedgraphic variables, severity of illness, symptom pro- the Beck Depression Inventory (BDI), the Medicalfile, course features and functional impairment in a Outcomes Study Health Status Questionnaire (SF-36;large clinical cohort of men and women with DSM- Ware and Sherbourne, 1992), the Quality of LifeIII-R chronic major depression or double depression. Enjoyment and Satisfaction Questionnaire (Q-LES-We have previously published a preliminary analysis Q; Endicott et al., 1993), and the Social Adjustmentof gender differences in the subgroup of 294 subjects Scale-Self-Report (SAS-SR; Weissman and Bot-with chronic major depression (Kornstein et al., hwell, 1976).1995). We now report data from the total sample of Statistical analyses were conducted on demograph-635 subjects with chronic depression. ics, baseline characteristics and psychometric ratings

measured prior to the first dose of double-blind studymedication. Age was analyzed using an analysis of

2. Methods variance (ANOVA) model adjusting for treatmentgroup (sertraline or imipramine), depression type

Subjects in this study were 635 outpatients (235 (chronic or double), and pooled investigator site.men and 400 women) with DSM-III-R chronic major Categorical demographic characteristics were ana-depression or double depression recruited through lyzed for gender differences with a Mantel–Haenszeladvertisement or medical referral for participation in chi-square test stratifying on the same parameters.a large prospective multi-center study comparing Comparisons were conducted as follows: marriedsertraline and imipramine in the treatment of chronic versus not married, college graduate and higherdepression. Subjects were 21–65 years of age and versus some college or less, and unemployed versusmet DSM-III-R criteria for chronic major depression not unemployed. Treatment effects were included as(i.e., major depression lasting at least two years a check on randomization.without antecedent dysthymia) or double depression Because a significant sex difference was found for(major depressive disorder superimposed on age, gender comparisons for all baseline characteris-dysthymia). A 24-item Hamilton Depression Rating tics and psychometric ratings included an adjustmentScale (HAM-D) score of 18 or more and a Clinical for age, in addition to treatment group, depressionGlobal Impression (CGI) Improvement score of 3 or type, and pooled investigator site. Quantitative pa-more following one week of placebo washout were rameters, such as total scores and derived factoralso required for admission to the study. Individuals scores, were analyzed with analysis of covariance.with organic mental disorders, unstable medical Categorical parameters were analyzed with logisticconditions, anorexia nervosa or bulimia nervosa in regression. Due to small percentages for rare events,the past year, alcohol or substance abuse or depen- some categorical parameters were instead analyzeddence in the past six months, any primary diagnosis either with a Mantel–Haenszel chi-square testof anxiety disorder in the past six months, obsessive stratifying on treatment group, depression type,


Table 1pooled site and age category, or with Fisher’s exactDemographic variables in male and female subjects with chronictest. Analysis of previous treatments also included anmajor or double depression

adjustment for age of onset of major depression.Males FemalesSimilar methods were performed for pre- versus(n 5 235) (n 5 400)postmenopausal women. Note that sample sizes vary

aMean age (SD) in years 42.8 (9.7) 40.0 (10.1)**slightly between parameters due to sporadic missingdata.

RaceResults were noted as statistically significant if a White 213 (90.6%) 364 (91.0%)

P-value of 0.05 or less was obtained. Since this is Black 7 (3.0%) 18 (4.5%)the first comprehensive evaluation of gender differ- Hispanic 6 (2.6%) 11 (2.8%)

Asian 3 (1.3%) 1 (0.3%)ences in patients with chronic depression, the objec-Other 6 (2.6%) 6 (1.5%)tive of this paper was to test for gender differences in

an exploratory manner, rather than test a specific set Marital status *of a priori hypotheses. Therefore, the P-values Single 61 (26.1%) 101 (25.3%)reported here are best interpreted as descriptive Married 103 (44.0%) 138 (34.6%)

Divorced/separated 66 (28.2%) 131 (32.8%)statistics that identify differences between genders,Co-habitating 3 (1.3%) 16 (4.0%)rather than confirm hypotheses that such differencesWidowed 1 (0.4%) 13 (3.3%)

exist. Given the exploratory and descriptive nature ofthe paper, alpha levels were not adjusted to control Education *for multiple comparisons. Graduate /professional 46 (19.7%) 54 (13.6%)

College degree 55 (23.6%) 85 (21.4%)Some college 84 (36.0%) 168 (42.3%)High school 37 (15.9%) 76 (19.1%)

3. ResultsOccupational status *

3.1. Diagnostic subtypes Employed 151 (66.5%) 239 (61.1%)Housewife 0 62 (15.9%)Student 8 (3.5%) 20 (5.1%)Four hundred women and 235 men were enrolledRetired 9 (4.0%) 2 (0.5%)

in the study. Of the women, 199 (49.8%) were Unemployed 59 (26.0%) 68 (17.4%)diagnosed with chronic major depression and 201

a **P , 0.01, *P , 0.05.(50.2%) with double depression. The distribution ofdiagnostic subtypes in men was more skewed, with95 (40.4%) meeting criteria for chronic major de- significantly more likely to be married (44.0% vs.

2pression and 140 (59.6%) for double depression. 34.6%; P 5 0.030; x 5 4.72; df 5 1) and to have aBecause a recent comparative analysis (McCullough college or graduate /professional education (43.3%

2et al., in press) showed a lack of differences in these vs. 35.0%; P 5 0.023; x 5 5.19; df 5 1); however,two subtypes across a wide range of variables, they were also significantly more likely to be un-including symptoms and other clinical characteris- employed (i.e., not retired, student, housewife, or

2tics, family history and treatment response, we have employed) (26.0% vs. 17.4%; P 5 0.016; x 5 5.85;not divided the total sample by subtype for gender df 5 1). There were no statistically significant differ-analyses. ences in race. Because of the significant sex differ-

ence in age, all subsequent analyses included an3.2. Demographic variables adjustment for age.

As shown in Table 1, women in the study were 3.3. Severity of illnesssignificantly younger than men (40.0 vs. 42.8; P ,

0.001; f 5 11.37; df 5 1,623). There were also sig- Women had significantly higher BDI scores thannificant gender differences in marital status, educa- men (25.6 vs. 23.0; P , 0.001; f 5 15.82; df 5

tional level and occupational status. Men were 1,610). Clinician-rated measures of severity were


Table 2 significantly more psychomotor retardation (6.97 vs.Severity of illness in male and female subjects with chronic major 6.57; P 5 0.003; f 5 9.19; df 5 1,622) and anxiety /or double depression

somatization (6.05 vs. 5.85; P 5 0.041; f 5 4.21;Males Females df 5 1,622) than men.(n 5 235) (n 5 400) An additional comparison of symptom profiles in

HAM-D score mean (SD) 24.7 (5.2) 25.3 (5.0) pre- vs. postmenopausal women revealed few differ-aCGI mean (SD) 4.1 (0.6) 4.2 (0.5)* ences. Premenopausal women (n 5 301) were sig-

BDI mean (SD) 23.0 (8.5) 25.6 (8.9)**nificantly more likely to report loss of interest thanCornell Dysthymia mean (SD) 40.0 (9.6) 41.1 (9.4)postmenopausal women (n 5 74) (98.0% vs. 93.2%;MADRS mean (SD) 26.1 (7.7) 25.1 (7.0)P 5 0.045, Fisher’s exact test). There were no sig-a **P , 0.01, *P , 0.05.nificant differences in HAM-D factor scores.

generally similar for both genders, although the CGIseverity score was also significantly higher in women 3.5. Course of illness(P 5 0.011; f 5 6.55; df 5 1,622) (see Table 2).

As indicated in Table 4, women showed a sig-3.4. Symptom profile nificantly younger age of onset of major depression

than men (23.4 vs. 27.3; P 5 0.010; f 5 6.60; df 5

Statistical comparison of individual items from the 1,613). Similarly, a younger age of onset ofDSM-III-R criteria for major depression revealed dysthymia in women was found in the doublesimilar symptoms in men and women (see Table 3), depression subgroup (15.5 vs. 19.0; P 5 0.177; f 5

with the exception of a significantly greater fre- 1.83; df 5 1,315), however this difference was notquency of sleep changes in women (84.3% vs. statistically significant. There were no statistically

275.7%; P 5 0.010; x 5 6.57; df 5 1). HAM-D factor significant gender differences in duration of currentanalysis indicated that women also presented with major depressive episode, number of previous major

Table 3Symptom profile in male and female subjects with chronic major or double depression

Males Females(n 5 235) (n 5 400)

DSM-III-R criteria for major depressionDepressed mood 228 (97.0%) 390 (97.5%)Loss of interest /pleasure 226 (96.2%) 389 (97.3%)Weight /appetite changes 113 (48.1%) 222 (55.5%)

aSleep changes 178 (75.7%) 337 (84.3%)*Psychomotor changes 104 (44.3%) 195 (48.8%)Fatigue / loss of energy 223 (94.9%) 381 (95.3%)Worthlessness /guilt 188 (80.0%) 323 (80.8%)Difficulty concentrating 211 (89.8%) 343 (85.8%)Suicidal thoughts 104 (44.3%) 182 (45.5%)

Mean number of DSM-III-R symptoms (SD) 6.70 (1.26) 6.91 (1.21)

HAM-D factors [Mean (SD)]Psychomotor retardation 6.57 (1.71) 6.97 (1.75)**Anxiety /somatization 5.85 (2.06) 6.05 (1.95)*Weight (loss) 0.31 (0.66) 0.26 (0.61)Cognitive disturbance 3.17 (1.67) 3.03 (1.54)Diurnal variation 1.08 (0.77) 1.07 (0.80)Sleep (insomnia) 2.85 (1.80) 2.67 (1.79)a **P , 0.01, *P , 0.05.


Table 4Course of illness features, previous treatment and family history in chronic major or double depression


Age of onset of major depressionaMean (SD) in years 27.3 (12.5) 23.4 (11.6)*

Duration of current MDEMean (SD) in years 5.8 (8.0) 6.2 (8.3)

Nature of current MDESingle episode 89 (37.9%) 138 (34.6%)Recurrent episode 146 (62.1%) 261 (65.4%)

Number of previous MDEsMean (SD) 1.7 (2.1) 1.8 (2.1)

Age of onset of dysthymiaMean (SD) in years 19.0 (13.4) 15.5 (12.8)

Duration of dysthymiaMean (SD) in years 22.6 (14.3) 23.9 (12.7)

Previous treatmentHx of psychotropic use 122 (51.9%) 240 (60.2%)*Hx of psychotherapy 122 (52.1%) 250 (62.7%)*Hx of ECT 4 (1.7%) 2 (0.5%)Hx of psych hospitalization 26 (11.1%) 40 (10.0%)

Family history of affective disorderFirst-degree relative 113 (51.6%) 245 (65.7%)**Second-degree relative 47 (24.6%) 109 (32.7%)a **P , 0.01, *P , 0.05.

depressive episodes, or likelihood of the current 65.7% of women, compared to 51.6% of men (P 52episode being recurrent. 0.001; x 5 10.34; df 5 1) (see Table 4).

3.6. Previous treatment 3.8. Functional impairment

A significantly higher percentage of women had Women in the study showed slightly greaterreceived previous treatment for depression with functional impairment than men, as indicated bypsychotropic medications (60.2% vs. 51.9%; P 5 significantly lower GAF scores (P 5 0.005; f 5 7.87;

20.011; x 5 6.53; df 5 1) and/or psychotherapy df 5 1,604) (see Table 5).2(62.7% vs. 52.1%; P 5 0.048; x 5 3.90; df 5 1), Differences in functional impairment were also

even after adjusting for age of onset of major seen on the SAS-SR. Women showed significantlydepressive disorder (see Table 4). Despite these higher scores on the marital (P 5 0.002; f 5 9.38;differences, men and women had comparable his- df 5 1,277) subscale of the SAS, while men showedtories of psychiatric hospitalization and previous significantly greater work impairment (P 5 0.016;treatment with electroconvulsive therapy. f 5 5.85; df 5 1,394). (It should be noted that differ-

ences in marital or work impairment refer to differ-3.7. Family history ences between married men and women or working

men and women and are not affected by demo-Women were significantly more likely than men to graphic differences between sexes.)

report a family history of affective disorder. A first- On the SF-36, women showed significantly lowerdegree relative with affective disorder was noted by scores than men in the areas of physical functioning


Table 5Functional impairment in male and female subjects with chronic major or double depression


b aGAF mean (SD) 53.8 (5.7) 52.4 (8.2)**bQ-LES-Q mean (SD) 54.1 (10.0) 53.0 (9.9)

cSAS-SR mean (SD)Total score 2.57 (0.49) 2.61 (0.49)Work 2.26 (0.65) 2.12 (0.59)*Housework 2.69 (0.53) 2.86 (0.75)Social / leisure 3.06 (0.71) 2.98 (0.69)Extended family 2.12 (0.54) 2.18 (0.50)Marital 2.55 (0.69) 2.79 (0.71)**Parental 2.23 (0.68) 2.27 (0.71)Family unit 2.48 (0.86) 2.62 (0.85)

bSF-36 mean (SD)Physical functioning 82.2 (21.3) 78.7 (23.6)**Role limitation due to physical problem 63.1 (40.2) 64.0 (40.4)Bodily pain 65.7 (24.8) 61.9 (22.3)**General health 61.8 (20.9) 64.1 (21.0)Vitality 23.9 (16.1) 17.6 (14.7)**Social functioning 52.1 (26.2) 48.4 (26.1)Role limitation due to emotional problem 22.3 (32.3) 18.9 (27.6)Mental health 31.4 (14.1) 29.4 (14.2)a **P , 0.01, *P , 0.05.b Lower scores indicate greater impairment.c Higher scores indicate greater impairment.

(P 5 0.001; f 5 11.31; df 5 1,609), bodily pain (P 5 they fare worse than men across most measurement0.002; f 5 9.52; df 5 1,612), and vitality (P , 0.001; areas in our study.f 5 27.44; df 5 1,609). (Lower scores on the SF-36 Women in our sample had a mean age of onset ofindicate greater impairment). major depressive disorder of 23, whereas men had

their first depressive episode at age 27. That thewomen were less likely to be married or to haveobtained a college or graduate education may be

4. Discussion attributable to this difference in age of onset, andmay underscore the functional impairment seen with

This study provides the largest sample to date to chronic depression. The negative impact of early-examine gender differences in the presentation and onset chronic depression on educational attainment,course of the chronic unipolar disorders. In contrast particularly in women, has been explored in detail into studies of episodic depression, we found a another manuscript (Berndt et al., in press).younger age of illness onset, greater family history Women in our study were also more likely thanof affective disorder, greater symptom reporting, men to report a positive family history of affectivepoorer social adjustment and poorer quality of life in disorder. This finding may explain the difference inwomen compared with men. Not only are women age of onset, since early onset of illness has beenmore vulnerable to becoming depressed, based on shown to be associated with increased rates ofthe 2:1 prevalence ratio of depression in the general affective disorder among relatives (Weissman et al.,population (Kessler et al., 1993; Weissman et al., 1984; Klein et al., 1988). Previous studies by1993), but when they become chronically depressed, Merikangas et al. (1985) and Kupfer et al. (1989), in


which first-degree relatives of male and female Despite the difference in self-reported severity,probands with depression were interviewed, con- men and women in our study, in contrast to thecluded that sex of the proband had no effect on the findings of Ernst and Angst (1992), presented with apresence of depression in family members. However, similar number of depressive symptoms. Symptomneither of these studies enrolled chronically de- profiles were similar as well, with the exception ofpressed patients. Since our family history data were more sleep changes, psychomotor retardation andobtained by patient interview and not by direct anxiety / somatization in women. Greater sleep dis-interviews of family members, this result should be turbance in depressed women has been previouslyconsidered provisional. reported (Angst and Dobler-Mikola, 1984), as have

Functional impairment as it relates to chronic more anxiety and somatic symptoms (Frank et al.,depression also appears to differ by gender. On the 1988; Williams et al., 1995); an association betweenSAS-SR, women reported greater impairment in anxiety and retardation in depressed women has alsomarital adjustment than men, whereas men reported been noted (Katz et al., 1993). We did not findgreater work impairment. Whether these differences significantly greater appetite and weight changes inrepresent true impairment or whether they simply women compared with men, as has been found inreflect sociocultural expectations regarding gender several other studies (Angst and Dobler-Mikola,roles is difficult to ascertain. However, the socio- 1984; Frank et al., 1988; Young et al., 1990;demographic differences found regarding marital and Williams et al., 1995), perhaps because we did notoccupational status (i.e., women being less likely to specifically assess reverse vegetative symptoms inbe married and men being more likely to be un- this study.employed) lend support to the notion that marital and A greater frequency of somatic symptoms inwork impairment reflect true gender differences. It is women was also evident on the SF-36, a self-reportalso possible that marital maladjustment predated measure assessing general health and quality of life.and may have contributed to the development of Specifically, women indicated more severe impair-depression in some women. Crowther (1985) has ment than men in the areas of physical functioning,shown that depressed women perceive their mar- bodily pain and vitality. Williams et al. (1995) haveriages as significantly more maladjusted than de- previously noted that depressed women rate theirpressed men, and family members of depressed men health significantly more poorly than men. This morereport better family functioning than those of de- negative perception of their physical health is con-pressed women (Keitner et al., 1987). In the same sistent with the greater level of distress seen on othervein, work difficulties may have predated and con- self-report measures, and may reflect a greatertributed to depression in some men. ‘‘subjective’’ vulnerability to depression in women

Our finding of greater severity scores in women on that carries over to all areas of functioning.depression self-report measures is consistent with The major limitations of this study relate to theprevious studies of major depression (Frank et al., way in which the study group was ascertained.1988; Williams et al., 1995), and suggests an in- Specifically, the exclusion criteria used to enroll acreased level of distress in women at the time of study group suitable for a clinical trial directlypresentation, or, perhaps, a tendency of men to affected comorbidity rates, and thereby could haveminimize their symptoms. This higher level of influenced gender-related differences found in otherdistress may also explain why women in our study variables, e.g., age of onset, severity, or functionalsought prior treatment for depression (both medica- impairment. For example, the exclusion from thetions and psychotherapy) more frequently than men. study of patients with active or recent alcohol andKessler et al. (1981) has previously noted that substance abuse disorders may have affected ourwomen are more prone to seek professional help for findings with regard to age of onset; an associationtheir depression than men; furthermore, physicians between early age at onset of depression and comor-tend to diagnose and treat psychiatric problems in bid substance abuse has been described (Klein et al.,women to a greater extent than they do men (Wil- 1988), and therefore, we may have excluded someliams et al., 1995). men with early-onset depression. On the other hand,


one of the major strengths of the study is its large, have focused solely on differences in prevalence;carefully diagnosed, and trans-national sample. however, to be complete, they must also addressMoreover, the female:male ratio of 1.7:1 in our study differences in the clinical manifestations of theexactly matches that of the National Comorbidity illness. For example, the tendency of women to useStudy (Kessler et al., 1993), suggesting that our ruminative coping styles (Nolen-Hoeksema, 1995)sample is representative of depressives in the general might predict not only risk of depression, but alsopopulation. A related shortcoming is the lack of chronicity of illness. Another concern with existingcomparison groups, particularly a group with more theories is that they have tended to be either purelyacute or episodic major depression and, for per- biological (e.g., hormones), purely psychologicalsonality and psychosocial functioning measures, (e.g., ruminative coping styles) or purely sociologicalhealthy, nondepressed controls. (e.g., social roles); a more integrated theoretical

One might argue that some of the observed approach is clearly needed to fully account for thedifferences, while statistically significant, were not complexity of gender differences in depression.robust or clinically significant, or that a correctionfor multiple comparisons would have identifiedfewer significant differences. However, the consis- 5. Conclusiontency of such differences across multiple measureshelps to support our assumption that the findings are This exploratory study of male and female patientsindeed real and not isolated or random observations. with chronic major and double depression is the firstUltimately, clinical significance will be determined to examine gender differences in a chronic depres-by treatment outcomes and relapse and recurrence sive population. We have provided further evidencerates, which will be investigated in subsequent regarding gender similarities and differences in thereports. phenomenology of unipolar mood disorders, as well

Our findings have both clinical and theoretical as further understanding of differences betweenimplications. Given our findings of a younger age of episodic and chronic depressions. Our findings of aonset and greater family history of affective disorder younger age of onset, greater family history ofin women, as well as more negative psychosocial affective disorder, greater symptom reporting, poorerconsequences with regard to marital status and social adjustment and poorer quality of life ineducational attainment, young women should be women suggest that chronicity of depression mayscreened carefully for the presence of depressive affect women more seriously than men. Whether thedisorders, especially if there is a positive family differences found have implications for response tohistory of depression, and treated promptly. Success- antidepressant treatment, degree of improvement inful outcomes, in terms of both symptomatic and psychosocial functioning with treatment, or risk ofpsychosocial improvement, have been demonstrated relapse or recurrence will be addressed in futureeven among chronically depressed patients (Keller et reports.al., 1998; Miller et al., 1998) with proper recognitionand adequate treatment. In addition, gender differ-ences in symptom presentation (i.e., greater presence Acknowledgementsof sleep changes, psychomotor retardation, anxietyand somatic symptoms in women) should aid the This study was completed under contracts fromclinician in more careful assessment and diagnosis. Pfizer Pharmaceuticals to the following investigators:Furthermore, our findings with regard to self-re- M.B.K., M.D. (Program Director), G.I.K., M.D., Ivanported marital versus work impairment suggest dif- W. Miller, Ph.D., Brown University; James H. Koc-ferent areas of focus for psychotherapy in women sis, M.D., John C. Markowitz, M.D., Cornell Uni-and men. versity; Daniel N. Klein, Ph.D., Fritz Henn, M.D.,

Our findings may also provide valuable insights David Schlager, M.D., SUNY at Stony Brook;for the formulation of theories regarding gender J.P.M., Ph.D., S.G.K., M.D., Virginia Commonwealthdifferences in depression. Until now, such theories University; Robert M.A. Hirschfeld, M.D., James


recurrent depression: are there any that are significant? Am. J.Russell, M.D., University of Texas, Galveston;Psychiatry 145, 41–45.Michael E. Thase, M.D., Robert Howland, M.D.,

Hamilton, M., 1960. A rating scale for depression. J. Neurol.University of Pittsburgh; John S. Carman, M.D.,Neurosurg. Psychiatry 23, 56–62.

Psychiatry and Research, Atlanta; A. John Rush, Hays, R.D., Wells, K.B., Sherbourne, C.D., Rogers, W., 1995.M.D., George Trapp, M.D., University of Texas Functioning and well-being outcomes of patients with depres-

sion compared with chronic general medical illnesses. Arch.Southwestern; A.F. Schatzberg, M.D., Lorrin Koran,Gen. Psychiatry 52, 11–19.M.D., Stanford University; A.J.G., M.D., Pedro

Katz, M.M., Wetzler, S., Cloitre, M., Swann, A., Secunda, S.,Delgado, M.D., University of Arizona; John Feig-Mendels, J., Robins, E., 1993. Expressive characteristics of

hner, M.D., Feighner Research Institute, San Diego; anxiety in depressed men and women. J. Affect. Disord. 28,Jan A. Fawcett, M.D., John Zajecka, M.D., Rush 267–277.Institute for Mental Well-Being, Chicago. Keitner, G.I., Miller, I.W., Epstein, N.B., Bishop, D.S., Fruzzetti,

A.E., 1987. Family functioning and the course of majordepression. Comp. Psychiatry 28, 54–64.

Keitner, G.I., Ryan, C.E., Miller, I.W., Kohn, R., Epstein, N.B.,1991. 12-Month outcome of patients with major depression andReferencescomorbid psychiatric or medical illness (compound depres-sion). Am. J. Psychiatry 148, 345–350.

American Psychiatric Association, 1987. Diagnostic and Statistical Keller, M.B., Gelenberg, A.J., Hirschfeld, R.M.A., Rush, A.J.,Manual of Mental Disorders, 3rd ed., revised. American Thase, M.E., Kocsis, J.H., Markowitz, J., Fawcett, J., Koran,Psychiatric Association, Washington, DC. L.M., Klein, D.N., Russell, J.M., Kornstein, S.G., McCullough,

Aneshensel, C.S., 1985. The natural history of depressive symp- J.P., Davis, S., Harrison, W., 1998. The treatment of chronictoms. Res. Commun. Mental Health 5, 45–74. depression, part 2: a double-blind randomized trial of sertraline

Angst, J., Dobler-Mikola, A., 1984. Do the diagnostic criteria and imipramine. J. Clin. Psychiatry 59, 598–607.determine the sex ratio in depression? J. Affect. Disord. 7, Keller, M.B., Klerman, G.L., Lavori, P.W., Fawcett, J.A., Coryell,189–198. W., Endicott, J., 1982. Treatment received by depressed

Beck, A.T., Ward, C.H., Mendelson, M., Mock, J., Erbaugh, J., patients. JAMA 248, 1848–1855.1961. An inventory for measuring depression. Arch. Gen. Keller, M.B., Lavori, P.W., Meuller, T.I., Endicott, J., Coryell, W.,Psychiatry 4, 561–571. Hirschfeld, R.M.A., Shea, T., 1992. Time to recovery,

Berndt, E.R., Koran, L.M., Finkelstein, S.N., Gelenberg, A.J., chronicity and levels of psychopathology in major depression:Kornstein, S.G., Miller, I.M., Thase, M.E., Trapp, G., Keller, a 5-year prospective follow-up of 431 subjects. Arch. Gen.M.B. Lost human capital from early-onset chronic depression. Psychiatry 49, 809–816.Am. J. Psychiatry, in press. Keller, M.B., Lavori, P.W., Rice, J., Coryell, W., Hirschfeld,

Blehar, M.C., Oren, D.A., 1995. Women’s vulnerability to mood R.M.A., 1986. The persistent risk of chronicity in recurrentdisorders: integrating psychobiology and epidemiology. De- episodes of nonbipolar major depressive disorder: a prospectivepression 3, 3–12. follow-up. Am. J. Psychiatry 143, 24–28.

Burke, K.C., Burke, J.D., Regier, D.A., Rae, D.S., 1990. Age at Kessler, R.C., Brown, R.L., Broman, C.L., 1981. Sex differencesonset of selected mental disorders in five community popula- in psychiatric help-seeking: evidence from four large-scaletions. Arch. Gen. Psychiatry 47, 511–518. surveys. J. Health Soc. Behav. 22, 49–64.

Crowther, J.H., 1985. The relationship between depression and Kessler, R.C., McGonagle, K.A., Swartz, M., Blazer, D.G.,marital adjustment: a descriptive study. J. Nerv. Ment. Dis. Nelson, C.B., 1993. Sex and depression in the National173, 227–231. Comorbidity Survey I: lifetime prevalence, chronicity and

Eaton, W.W., Anthony, A.C., Gallo, J., Cai, G., Tien, A., recurrence. J. Affect. Disord. 29, 85–96.Romanoski, A., Lyketsos, C., Chen, L., 1997. Natural history Klein, D.N., Taylor, E.B., Dickstein, S., Harding, K., 1988.of diagnostic interview schedule DSM-IV major depression. Primary early-onset dysthymia: comparison with primary non-Arch. Gen. Psychiatry 54, 993–999. bipolar nonchronic major depression on demographic, clinical,

Endicott, J., Spitzer, R.L., Fleiss, J.L., Cohen, J., 1976. The Global familial, personality and socioenvironmental characteristics andAssessment Scale: a procedure for measuring overall severity short-term outcome. J. Abnorm. Psychol. 97, 387–398.of psychiatric disturbance. Arch. Gen. Psychiatry 33, 766–771. Kornstein, S.G., Schatzberg, A.F., Yonkers, K.A., Thase, M.E.,

Endicott, J., Nee, J., Harrison, W., Blumenthal, R., 1993. Quality Keitner, G.I., Ryan, C.E., Schlager, D., 1995. Gender differ-of Life Enjoyment and Satisfaction Questionnaire: a new ences in presentation of chronic major depression 31, 711–718.measure. Psychopharmacol. Bull. 29, 321–326. Kupfer, D.J., Frank, E., Carpenter, L.L., Neiswanger, N., 1989.

Ernst, C., Angst, J., 1992. The Zurich study, XII: sex differences Family history in recurrent depression. J. Affect. Disord. 17,in depression: evidence from longitudinal epidemiological data. 113–119.Eur. Arch. Psychiatry Clin. Neurosci. 241, 222–230. Mason, B.J., Kocsis, J.H., Leon, A.C., Thompson, S., Frances,

Frank, E., Carpenter, L.L., Kupfer, D.J., 1988. Sex differences in A.F., Morgan, R.O., Parides, M.K., 1993. Measurement of


severity and treatment response in dysthymia. Psychiatr. Ann. Structured Interview for DSM-III-R Personality Disorders23, 625–631. (SCID-II). New York State Psychiatric Institute, Biometrics

Merikangas, K.R., Weissman, M.M., Pauls, D.L., 1985. Genetic Research.factors in the sex ratio of major depression. Psychol. Med. 15, Thase, M.E., Reynolds, C.F., Frank, E., Simons, A.D., McGeary,63–69. J., Fasiczka, A.L., Garamoni, G.G., Jennings, J.R., Kupfer,

McCullough, J.P., Klein, D.N., Keller, M.B., Holzer, C.E., Davis, D.J., 1994. Do depressed men and women respond similarly toS.M., Kornstein, S.G., Howland, R.H., Thase, M.E., Harrison, cognitive behavior therapy? Am. J. Psychiatry 151, 500–505.W.H. Comparison of DSM-III-R chronic major depression and Ware, J.E., Sherbourne, C., 1992. The MOS 36-item Short-Formmajor depression superimposed on dysthymia (double depres- Health Survey (SF-36). Med. Care 30, 473–481.sion): a study of the validity and value of differential diagnosis. Weissman, M.M., Bland, R., Joyce, P.R., Newman, S., Wells, J.E.,J. Abnorm. Psychol. in press. Wittchen, H.U., 1993. Sex differences in rates of depression:

Miller, I.W., Keitner, G.I., Schatzberg, A.F., Klein, D.N., Thase, cross-national perspectives. J. Affect. Disord. 29, 77–84.M.E., Rush, A.J., Schlager, D.S., Kornstein, S.G., Davis, S.M., Weissman, M.M., Bothwell, S., 1976. Assessment of socialHarrison, W.M., Keller, M.B., 1998. The treatment of chronic adjustment by patient self-report. Arch. Gen. Psychiatry 33,depression, part 3: psychosocial functioning before and after 1111–1115.treatment with sertraline or imipramine. J. Clin. Psychiatry 59, Weissman, M.M., Klerman, G.L., 1977. Sex differences in the608–619. epidemiology of depression. Arch. Gen. Psychiatry 34, 98–

Montgomery, S.A., Asberg, M., 1979. New depression scale 111.designed to be sensitive to change. Br. J. Psychiatry 134, Weissman, M.M., Wickramaratne, P., Merikangas, K.R., Leckman,382–389. J.F., Prusoff, B.A., Caruso, K.A., Kidd, K.K., Gammon, G.D.,

Nolen-Hoeksema, S., 1995. Gender differences in coping with 1984. Onset of major depression in early adulthood: increaseddepression across the lifespan. Depression 3, 3–12. family loading and specificity. Arch. Gen. Psychiatry 43, 430–

Perugi, G., Musetti, L., Simonini, E., Piagentini, F., Cassano, 434.G.B., Akiskal, H.S., 1990. Gender-mediated clinical features of Williams, J.B., Spitzer, R.L., Linzer, M., Kroenke, K., Hahn, S.R.,depressive illness: the importance of temperamental differ- deGruy, F.V., Lazev, A., 1995. Gender differences in depressionences. Br. J. Psychiatry 157, 835–841. in primary care. Am. J. Obstet. Gynecol. 173, 654–659.

Sargeant, J.K., Bruce, M.L., Florio, L.P., Weissman, M.M., 1990. Winokur, G., Coryell, W., Keller, M., Endicott, J., Akiskal, H.,Factors associated with 1-year outcome of major depression in 1993. A prospective follow-up of patients with bipolar andthe community. Arch. Gen. Psychiatry 47, 519–526. primary unipolar affective disorder. Arch. Gen. Psychiatry 50,

Simpson, H.B., Nee, J.C., Endicott, J., 1997. First-episode major 457–465.depression: few sex differences in course. Arch. Gen. Psychi- Wolk, S.I., Weissman, M.M., 1995. Women and depression. In:atry 54, 633–639. Annual Review of Psychiatry, Vol. 14. American Psychiatric

Spitzer, R.L., Williams, J.B.W., Gibbon, M., First, M.B., 1989a. Association Press, Washington, DC, pp. 59–95.Structured Interview for DSM-III-R-Patient Version (SCID-P). Young, M.A., Scheftner, W.A., Fawcett, J., Klerman, G.L., 1990.New York State Psychiatric Institute, Biometrics Research. Gender differences in the clinical features of unipolar depres-

Spitzer, R.L., Williams, J.B.W., Gibbon, M., First, M.B., 1989b. sive disorder. J. Nerv. Ment. Dis. 178, 200–203.

gender differences in chronic major and double depression

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