Skip to main content
    • Aa
    • Aa

Predictors of first lifetime episodes of major depression in midlife women

  • J. T. Bromberger (a1), H. M. Kravitz (a2), K. Matthews (a3), A. Youk (a4), C. Brown (a5) and W. Feng (a4)...

Little is known about factors that predict first lifetime episodes of major depression in middle-aged women. It is not known whether health-related factors and life stress pose more or less of a risk to the onset of clinical depression than does the menopausal transition.


The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to assess diagnoses of lifetime, annual and current major depression in a community-based sample of premenopausal or early perimenopausal African American and White women. Menstrual cycle characteristics, psychosocial and health-related factors, and blood samples for assay of reproductive hormones were obtained annually. Two hundred and sixty-six women without a history of major depression at baseline constituted the cohort for the current analyses.


Over 7 years of follow-up, 42 (15.8%) women met criteria for a diagnosis of major depression. Frequent vasomotor symptoms (VMS; hot flashes and/or night sweats) (HR 2.14, p=0.03) were a significant predictor of major depression in univariate analyses. After simultaneous adjustment for multiple predictors in Cox proportional hazards analyses, frequent VMS were no longer significant; lifetime history of an anxiety disorder (HR 2.20, p=0.02) and role limitations due to physical health (HR 1.88, p=0.07) at baseline and a very stressful life event (HR 2.25, p=0.04) prior to depression onset predicted a first episode of major depression.


Both earlier (e.g. history of anxiety disorders) and more proximal factors (e.g. life stress) may be more important than VMS in contributing to a first episode of major depression during midlife.

Corresponding author
*Address for correspondence: J. T. Bromberger, Ph.D., Departments of Epidemiology and Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. (Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

HK Armenian , LA Pratt , J Gallo , WW Eaton (1998). Psychopathology as a predictor of disability: a population-based follow-up study in Baltimore, Maryland. American Journal of Epidemiology 148, 269275.

RV Bijl , R De Graaf , A Ravelli , F Smit , WA Vollebergh (2002). Gender and age-specific first incidence of DSM-III-R psychiatric disorders in the general population. Results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Social Psychiatry and Psychiatric Epidemiology 37, 372379.

JA Blumenthal , MA Babyak , KA Moore , WE Craighead , S Herman , P Khatri (1999). Effects of exercise training on older patients with major depression. Archives of Internal Medicine 159, 23492356.

JE Brazier , R Harper , NM Jones , A O'Cathain , KJ Thomas , T Usherwood , L Westlake (1992). Validating the SF-36 health survey questionnaire: new outcome measure for primary care. British Medical Journal 305, 160164.

N Breslau , L Schultz , E Peterson (1995). Sex differences in depression: a role for preexisting anxiety. Psychiatry Research 58, 112.

J Cohen (1960). A coefficient of agreement for nominal scales. Educational and Psychological Measurement 20, 3746.

LS Cohen , CN Soares , AF Vitonis , MW Otto , BL Harlow (2006). Risk for new onset of depression during the menopausal transition. The Harvard Study of Moods and Cycles. Archives of General Psychiatry 63, 385390.

SE Daley , C Hammen , U Rao (2000). Predictors of first onset and recurrence of major depression in young women during the 5 years following high school graduation. Journal of Abnormal Psychology 109, 525533.

R De Graaf , RV Bijl , A Ravelli , F Smit , WA Vollebergh (2002). Predictors of first incidence of DSM-III-R psychiatric disorders in the general population: findings from the Netherlands Mental Health Survey and Incidence Study. Acta Psychiatrica Scandinavica 106, 303313.

E Ernst , JI Rand , C Stevinson (1998). Complimentary therapies for depression: an overview. Archives of General Psychiatry 55, 10261032.

EW Freeman , MD Samuel , H Lin , DB Nelson (2006). Associations of hormones and menopausal status with depressed mood in women with no history of depression. Archives of General Psychiatry 63, 375382.

EW Freeman , MD Sammel , L Liu , CR Gracia , DB Nelson , L Hollander (2004). Hormones and menopausal status as predictors of depression in women in transition to menopause. Archives of General Psychiatry 61, 6270.

RH Friis , HU Wittchen , H Pfister , R Lieb (2002). Life events and changes in the course of depression in young adults. European Psychiatry 17, 241253.

JJ Gallo , DR Royall , JC Anthony (1993). Risk factors for the onset of depression in middle age and later life. Social Psychiatry and Psychiatric Epidemiology 28, 101108.

E Gold , A Colvin , N Avis , JT Bromberger , G Greendale , L Powell , B Sternfeld , K Matthews (2006). Longitudinal analysis of vasomotor symptoms and race/ethnicity across the menopausal transition: Study of Women's Health Across the Nation (SWAN). American Journal of Public Health 96, 12261235.

C Hammen (1991). Generation of stress in the course of unipolar depression. Journal of Abnormal Psychology 100, 555561.

C Hammen , PA Brennan (2002). Interpersonal dysfunction in depressed women: impairments independent of depressive symptoms. Journal of Affective Disorders 72, 145156.

KL Harkness , SM Monroe , AD Simons , M Thase (1999). The generation of life events in recurrent and non-recurrent depression. Psychological Medicine 29, 135144.

KS Kendler , CA Prescott (1999). A population-based twin study of lifetime major depression in men and women. Archives of General Psychiatry 56, 3944.

KS Kendler , LM Thornton , CO Gardner (2000). Stressful life events and previous episodes in the etiology of major depression in women: and evaluation of the ‘kindling’ hypothesis. American Journal of Psychiatry 157, 12431251.

RC Kessler (1997). The effects of stressful life events on depression. Annual Review of Psychology 48, 191214.

RC Kessler (2003). Epidemiology of women and depression. Journal of Affective Disorders 74, 513.

RC Kessler , P Berglund , O Demler , R Jin , D Koretz , KR Merikangas , AJ Rush , EE Walters , PS Wang (2003). The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). Journal of the American Medical Association 289, 30953105.

RC Kessler , KA McGonagle , S Zhao , CB Nelson , M Hughes , S Eshleman , HU Wittchen , KS Kendler (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Archives of General Psychiatry 51, 819.

KA Matthews , RR Wing , LH Kuller , EN Meilahn , P Plantinga (1994). Influence of the perimenopause on cardiovascular risk factors and symptoms of middle-aged healthy women. Archives of Internal Medicine 154, 23492355.

BS McEwen , SE Alves (1999). Estrogen actions in the central nervous system. Endocrine Reviews 20, 279307.

CA McHorney , JE Ware Jr., JF Lu , CD Sherbourne (1994). The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Medical Care 32, 4066.

SM Monroe , KL Harkness (2005). Life stress, the ‘kindling’ hypothesis, and the recurrence of depression: considerations from a life stress perspective. Psychological Review 112, 417445.

DL Musselman , E Betan , H Larsen , LS Phillips (2003). Relationship of depression to diabetes types 1 and 2: epidemiology, biology, and treatment. Biological Psychiatry 54, 317329.

JY Nazroo , AC Edwards , GW Brown (1997). Gender differences in the onset of depression following a shared life event: a study of couples. Psychological Medicine 27, 919.

J Ormel , GI Kempen , DJ Deeg , EI Brilman , E van Sonderen , J Relyveld (1998). Functioning, well-being, and health perception in late middle-aged and older people: comparing the effects of depressive symptoms and chronic medical conditions. Journal of the American Geriatrics Society 46, 3948.

MS Rose , ML Koshman , S Spreng , R Sheldon (1999). Statistical issues encountered in the comparison of health-related quality of life in diseased patients to published general population norms: problems and solutions. Journal of Clinical Epidemiology 52, 405412.

R Rugulies (2002). Depression as a predictor for coronary heart disease. A review and meta-analysis. American Journal of Preventive Medicine 23, 5161.

N Santoro (2005). The menopausal transition. American Journal of Medicine 118, 8S13S.

PJ Schmidt (2005). Depression, the perimenopause, and estrogen therapy. Annals of the New York Academy of Sciences 1052, 2740.

PJ Schmidt , JH Murphy , N Haq , MA Danaceau , L St Clair (2002). Basal plasma hormone levels in depressed perimenopausal women. Psychoneuroendocrinology 27, 907920.

PJ Schmidt , L Nieman , MA Danaceau , MB Tobin , CA Rocca , JH Murphy , DR Rubinow (2000). Estrogen replacement in perimenopause-related depression: a preliminary report. American Journal of Obstetrics and Gynecology 183, 414420.

CN Soares , H Joffe , M Steiner (2004). Menopause and mood. Clinical Obstetrics and Gynecology 47, 576591.

MF Sowers , S Crawford , B Sternfeld , D Morganstein , EB Gold , GA Greendale , D Evans , R Neer , K Matthews , S Sherman , A Lo , G Weiss , J Kelsey (2000). SWAN: a multi-center, multi-ethnic, community-based cohort study of women and the menopause. In Menopause: Biology and Pathobiology (ed. R. Lobo , J. Kelsey and R. Marcus ), pp. 175178. Academic Press: San Diego.

RL Spitzer , JB William , M Gibbon , MB First (1992). The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Archives of General Psychiatry 49, 624629.

JE Ware Jr., CD Sherbourne (1992). The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical Care 30, 473483.

JB Williams , M Gibbon , MB First , RL Spitzer , M Davies , J Borus , MJ Howes , J Kane , HG Pope Jr., B Rounsaville (1992). The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test–retest reliability. Archives of General Psychiatry 49, 630636.

HU Wittchen , K Beesdo , A Bittner , RD Goodwin (2003). Depressive episodes: evidence for a causal role of primary anxiety disorders? European Psychiatry 18, 384393.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 6
Total number of PDF views: 35 *
Loading metrics...

Abstract views

Total abstract views: 193 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st September 2017. This data will be updated every 24 hours.