Advertisement

Overweight and Obesity Affect Treatment Response in Major Depression

      Background

      Epidemiologic and clinical studies suggest comorbidity between major depressive disorder (MDD) and obesity. To elucidate the impact of weight on the course of depression beyond comorbidity, we investigated psychopathology, attention, neuroendocrinology, weight change, and treatment response in MDD patients, depending on their weight.

      Methods

      Four hundred eight inpatients with MDD participated in the Munich Antidepressant Response Signature Study, designed to discover biomarkers and genotypes that are predictive for clinical outcome. Psychopathology and anthropometric parameters were monitored weekly in 230 patients. In subsamples, combined dexamethasone–corticotropin-releasing hormone and attention tests were conducted at admission and discharge. One thousand twenty-nine diagnosed matched controls served for morphometric comparisons.

      Results

      Patients with MDD had a significantly higher body mass index (BMI) compared with healthy controls. Patients with high BMI (≥25) showed a significantly slower clinical response, less improvement in neuroendocrinology and attention, and less weight gain than did patients with normal BMI (18.5 ≤ BMI < 25) during antidepressant treatment.

      Conclusions

      Our findings suggest that overweight and obesity characterize a subgroup of MDD patients with unfavorable treatment outcome.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Press, Washington, DC1994
        • Aronne L.J.
        • Segal K.R.
        Weight gain in the treatment of mood disorders.
        J Clin Psychiatry. 2003; 64: 22-29
        • Baskin M.L.
        • Ard J.
        • Franklin F.
        • Allison D.B.
        Prevalence of obesity in the United States.
        Obes Rev. 2005; 6: 5-7
        • Besedovsky H.
        • del Rey A.
        • Sorkin E.
        • Dinarello C.A.
        Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones.
        Science. 1986; 233: 652
        • Binder E.B.
        • Salyakina D.
        • Lichtner P.
        • Wochnik G.M.
        • Ising M.
        • Pütz B.
        • et al.
        Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.
        Nat Genet. 2004; 36: 1319-1325
        • Bjorntorp P.
        • Rosmond P.
        Obesity and cortisol.
        Nutrition. 2000; 16: 924-936
        • Brickenkamp R.
        Test d2. Aufmerksamkeits-Belastungs-Test (8. Auflage). Hogrefe, Goettingen, Germany2002
      1. Centers for Disease Control and Prevention. BMI—categories. Available at: http://www.cdc.gov/nccdphp/dnpa/about_us/index.htm. Accessed 2006 May.

        • Cheung C.C.
        • Clifton D.K.
        • Steiner R.A.
        Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus.
        Endocrinology. 1997; 138: 4489-4492
        • Cohen R.
        • Lohr I.
        • Paul R.
        • Boland R.
        Impairments of attention and effort among patients with major affective disorders.
        J Neuropsychiatry Clin Neurosci. 2001; 13: 385-395
        • Elenkov I.J.
        • Iezzoni D.G.
        • Daly A.
        • Harris A.G.
        • Chrousos G.P.
        Cytokine dysregulation, inflammation and well-being.
        Neuroimmunomodulation. 2005; 12: 255-269
        • Elias M.F.
        • Elias P.K.
        • Sullivan L.M.
        • Wolf P.A.
        • D’Agostino R.B.
        Lower cognitive function in the presence of obesity and hypertension: The Framingham heart study.
        Int J Obes. 2003; 27: 260-268
        • Faith M.S.
        • Matz P.E.
        • Jorge M.A.
        Obesity-depression associations in the population.
        J Psychosom Res. 2002; 53: 935-942
        • Flier J.S.
        What’s in a name?.
        J Clin Endocrinol Metab. 1998; 83: 1407-1413
        • Gold P.W.
        • Chrousos G.P.
        Organization of the stress system and its dysregulation in melancholic and atypical depression: High vs low CRH/NE states.
        Mol Psychiatry. 2002; 7: 254-275
        • Hasler G.
        • Pine D.S.
        • Gamma A.
        • Milos G.
        • Ajdacic V.
        • Eich D.
        • et al.
        The associations between psychopathology and being overweight: A 20-year prospective study.
        Psychol Med. 2004; 34: 1047-1057
        • Heiman M.L.
        • Ahima R.S.
        • Craft L.S.
        • Schoner B.
        • Stephens T.W.
        • Flier J.S.
        Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress.
        Endocrinology. 1997; 138: 3859-3863
        • Holsboer F.
        The corticosteroid receptor hypothesis of depression.
        Neuropsychopharmacology. 2000; 23: 477-501
        • Kaestner F.
        • Hettich M.
        • Peters M.
        • Sibrowski W.
        • Hetzel G.
        • Ponath G.
        • et al.
        Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity.
        J Affect Disord. 2005; 87: 305-311
        • Kendler K.S.
        • Eaves L.J.
        • Walters E.E.
        • Neale M.C.
        • Heath A.C.
        • Kessler R.C.
        The identification and validation of distinct depressive syndromes in a population-based sample of female twins.
        Arch Gen Psychiatry. 1996; 53: 391-399
        • Kunzel H.E.
        • Binder E.B.
        • Nickel T.
        • Ising M.
        • Fuchs B.
        • Majer M.
        • et al.
        Pharmacological and nonpharmacological factors influencing hypothalamic-pituitary-adrenocortical axis reactivity in acutely depressed psychiatric in-patients, measured by the Dex-CRH test.
        Neuropsychopharmacology. 2003; 28: 2169-2178
        • Ljung T.
        • Ottosson M.
        • Ahlberg A.C.
        • Edén S.
        • Odén B.
        • Okret S.
        • et al.
        Central and peripheral glucocorticoid receptor function in abdominal obesity.
        J Endocrinol Invest. 2002; 25: 229-235
        • Majer M.
        • Ising M.
        • Kunzel H.
        • Binder E.B.
        • Holsboer F.
        • Modell S.
        • Zihl J.
        Impaired divided attention predicts delayed response and risk to relapse in subjects with depressive disorders.
        Psychol Med. 2004; 34: 1453-1463
        • McElroy S.L.
        • Kotwal R.
        • Malhotra S.
        • Nelson E.B.
        • Keck P.E.
        • Nemeroff C.B.
        Are mood disorders and obesity related?.
        J Clin Psychiatry. 2004; 65: 634-651
        • Miller G.E.
        • Freedland K.E.
        • Carney R.M.
        • Stetler C.A.
        • Banks W.A.
        Pathways linking depression, adiposity, and inflammatory markers in healthy young adults.
        Brain Behav Immun. 2003; 17: 276-285
        • Nierenberg A.A.
        • Alpert J.E.
        • Pava J.
        • Rosenbaum J.F.
        • Fava M.
        Course and treatment of atypical depression.
        J Clin Psychiatry. 1998; 59: 5-9
        • Onyike C.U.
        • Crum R.M.
        • Lee H.B.
        • Lyketsos C.G.
        • Eaton W.W.
        Is obesity associated with major depression?.
        Am J Epidemiol. 2003; 158: 1139-1147
        • Oswald W.D.
        • Roth E.
        Der Zahlen-Verbindungs-Test (2. Auflage). Hogrefe, Goettingen, Germany1987
        • Overall J.E.
        • Rhoades H.M.
        Use of the Hamilton Rating Scale for classification of depressive disorders.
        Compr Psychiatry. 1982; 23: 370-376
        • Papakostas G.I.
        • Petersen T.
        • Iosifescu D.V.
        • Burns A.M.
        • Nierenberg A.A.
        • Alpert J.E.
        • et al.
        Obesity among outpatients with major depressive disorder.
        Int J Neuropsychopharmacol. 2005; 8: 59-63
        • Pollmacher T.
        • Haack M.
        • Schuld A.
        • Reichenberg A.
        • Yirmiya R.
        Low levels of circulating inflammatory cytokines—Do they affect human brain functions?.
        Brain Behav Immun. 2002; 16: 525-532
        • Rajala M.W.
        • Scherer P.E.
        Minireview: The adipocyte—At the crossroads of energy homeostasis, inflammation, and atherosclerosis.
        Endocrinology. 2003; 144: 3765-3773
        • Salehi M.
        • Ferenczi A.
        • Zumoff B.
        Obesity and cortisol status.
        Horm Metab Res. 2005; 37: 193-197
        • Schiepers O.J.G.
        • Wichers M.C.
        • Maes M.
        Cytokines and major depression.
        Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29: 201-217
        • Shanley L.J.
        • Irving A.J.
        • Harvey J.
        Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity.
        J Neurosci. 2001; 21: RC186
        • Simon G.E.
        • Von Korff M.
        • Saunders K.
        • et al.
        Association between obesity and psychiatric disorders in the US adult population.
        Arch Gen Psychiatry. 2006; 63: 824-830
        • Stover E.
        • Fenton W.
        • Rosenfeld A.
        • Insel T.R.
        Depression and comorbid medical illness: The National Institute of Mental Health perspective.
        Biol Psychiatry. 2003; 54: 184-186
        • Stunkard A.J.
        • Faith M.S.
        • Allison K.C.
        Depression and obesity.
        Biol Psychiatry. 2003; 54: 330-337
        • Vicennati V.
        • Pasquali R.
        Abnormalities of the hypothalamic-pituitary-adrenal axis in nondepressed women with abdominal obesity and relations with insulin resistance: Evidence for a central and a peripheral alteration.
        J Clin Endocrinol Metab. 2000; 85: 4093-4098
        • Wisse B.E.
        The inflammatory syndrome: The role of adipose tissue cytokines in metabolic disorders linked to obesity.
        J Am Soc Nephrol. 2004; 15: 2792-2800
        • Wittchen H.U.
        • Höfler M.
        • Gander F.
        • Pfister H.
        • Storz S.
        • Üstün B.
        • et al.
        Screening for mental disorders: Performance of the Composite International Diagnostic–Screener (CID-S).
        Int J Methods Psychiatr Res. 1999; 8: 59-70
        • Zihl J.
        • Gron G.
        • Brunnauer A.
        Cognitive deficits in schizophrenia and affective disorders: Evidence for a final common pathway disorder.
        Acta Psychiatr Scand. 1998; 97: 351-357
        • Zimmerman P.
        • Fimm B.
        Testbatterie zur Aufmerksamkeitsprüfung (TAP). Psytest, Freiburg, Germany1993 ([Test battery for the examination of attention] (: Version 1.02b))
        • Zimmermann U.
        • Kraus T.
        • Himmerich H.
        • Schuld A.
        • Pollmacher T.
        Epidemiology, implications and mechanisms underlying drug-induced weight gain in psychiatric patients.
        J Psychiatr Res. 2003; 37: 193-220

      Linked Article

      • Errata
        Biological PsychiatryVol. 62Issue 4
        • Preview
          In the online version of “Overweight and Obesity Affect Treatment Response in Major Depression” by Kloiber et al. that originally became available as an article-in-press on January 22, 2007, there were some errors in Table 3. The “(d2)” was mistakenly typeset next to “Divided attention,” but should have been set next to “Selective attention” in the first column, first row. Also, in the third column, Standard deviations data were erroneously reported instead of Standard errors. The table has since been corrected, and the correct version of Table 3 now appears in the article online, as well as in this print issue of Biological Psychiatry (Biol Psychiatry 2007;62:321-326).
        • Full-Text
        • PDF