Abstract
Depression is a major cause of disability worldwide, but we know little about the underlying fundamental biology. Research is hindered by the difficulties of modelling a disorder of higher cognitive functions in animals. Depression can be understood as the interaction of genetic susceptibility and environmental factors; however, current classifications are purely descriptive. The complexity of this field is best approached by rigorous explorations of known candidate systems in conjunction with the use of genomic tools to discover new targets for antidepressants and to predict therapeutic outcomes.
Key Points
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A triad of symptoms characterizes depression: low or depressed mood, anhedonia, and low energy or fatigability. Other symptoms, such as sleep and psychomotor disturbances, pessimism, guilty feelings, low self-esteem, suicidal tendencies, and food-intake and body-weight dysregulation, are also often present. The prevalence of depression is consistently high worldwide and several lines of evidence indicate an important contribution of depression to medical morbidity
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A key problem in the diagnosis of depression is the fact that the classification systems that exist today are solely based on the subjective descriptions of symptoms but there is no biological feature that separates one subtype from another. Is each subtype of depression the result of different biological abnormalities or are they different manifestations of the same underlying disease process?
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A main obstacle for depression research is the fact that this condition affects higher cognitive human processes such as motivation and self-esteem, which cannot be easily modelled in animals. Although there are some animal models for depression, it is unclear whether they really model the same disorder that affects humans.
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It has been proposed that understanding the pathways and mechanisms that underlie antidepressant treatments can advance our understanding of depression. Currently accepted methods of treatment include electroconvulsive therapy, cognitive-behavioral and interpersonal psychotheraphy, and pharmacological treatments that affect biogenic-amine-dependent neurotransmission. Indeed, one of the cornerstones of research on depression has been the so-called monoamine hypothesis, which invokes imbalances in monoamine brain systems as a cause of depression.
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Other factors have also been implicated in the appearance of depression, but it is still a matter of debate whether they are causally involved in the pathology. They include alterations of the hypothalamus-pituitary-adrenal axis, circadian disturbances, infectious agents such as the Borna-disease virus, and neuroimmune mediators. In addition, a genetic component seems to be involved in the disease but the evidence in support of this idea is still incomplete.
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Pharmacogenetic and pharmacogenomic approaches might lead to newer, more effective solutions to the problem of depression. For example, pharmacogenetic strategies that lead to the identification of the best antidepressant drug on the basis of the genetic profile of each patient would be of great value. However, research on this area is fraught with complex issues that require careful consideration.
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References
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, Washington, DC, 1994).
Zis, A. P. & Goodwin, F. K. Major affective disorder as a recurrent illness: a critical review. Arch. Gen. Psychiatry 36, 835–839 (1979).
Sundstrom, I. M., Bixo, M., Bjorn, I. & Astrom, M. Prevalence of psychiatric disorders in gynecologic outpatients. Am. J. Obstet. Gynecol. 184, 8–13 (2001).
Lyness, J. M., Caine, E. D., King, D. A., Cox, C. & Yoediono, Z. Psychiatric disorders in older primary care patients. J. Gen. Intern. Med. 14, 249–254 (1999).
Lindeman, S. et al. The 12-month prevalence and risk factors for major depressive episode in Finland: representative sample of 5993 adults. Acta Psychiatr. Scand. 102, 178–184 (2000).
Dubini, A., Mannheimer, R. & Pancheri, P. Depression in the community: results of the first Italian survey. Int. Clin. Psychopharmacol. 16, 49–53 (2001).
Fichter, M. M. et al. Prevalence of mental illness in Germany and the United States. Comparison of the Upper Bavarian Study and the Epidemiologic Catchment Area Program. J. Nerv. Ment. Dis. 184, 598– 606 (1996).
Tomoda, A., Mori, K., Kimura, M., Takahashi, T. & Kitamura, T. One-year prevalence and incidence of depression among first-year university students in Japan: a preliminary study. Psychiatry Clin. Neurosci. 54, 583– 588 (2000).
Weissman, M. M. et al. Cross-national epidemiology of major depression and bipolar disorder. JAMA 276, 293– 299 (1996).A detailed assessment of lifetime and annual rate depression prevalence in ten countries: Canada, France, Germany, Italy, Korea, Lebanon, New Zealand, Puerto Rico, Taiwan and the United States.
Blazer, D. G., Kessler, R. C., McGonagle, K. A. & Swartz, M.S. The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. Am. J. Psychiatry 151, 979–986 (1994).
Greenberg, P. E., Stiglin, L. E., Finkelstein, S. N. & Berndt, E. R. The economic burden of depression in 1990. J. Clin. Psychiatry 54, 405–418 ( 1993).Estimates that the total cost of depression in the United States was $43.7 billion per year in 1990.
Murray, C. J. L. & Lopez, A. D. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk factors in 1990 and Projected to 2020 (Harvard Univ. Press, Cambridge, Massachusetts, 1996).
Murphy, S. L. Deaths: Final data for 1998. Natl Vital Stat Rep 48 , 1–105 (2000).
Olsson, G. I. & von Knorring, A. L. Adolescent depression: prevalence in Swedish high-school students. Acta Psychiatr. Scand. 99, 324–331 (1999).
Klerman, G. L. in The Harvard Guide to Modern Psychiatry (ed. Nicholi, J.) 253–281 (Belknap/Harvard Univ. Press, Cambridge, 1978).
Kerr, T. A., Schapira, K. & Roth, M. The relationship between premature death and affective disorders. Br. J. Psychiatry 115, 1277– 1282 (1969).
Harris, E. C. & Barraclough, B. Excess mortality of mental disorder . Br. J. Psychiatry 173, 11– 53 (1998).
Pratt, L. A. et al. Depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up. Circulation 94, 3123–3129 (1996).
Glassman, A. H. & Shapiro, P. A. Depression and the course of coronary artery disease. Am. J. Psychiatry 155, 4–11 (1998). References 18 and 19 report that a history of depression increases the risk of myocardial infarction and the risk of death after infarction.
Michelson, D. et al. Bone mineral density in women with depression. N. Engl. J. Med. 335, 1176–1181 (1996).
Agid, O. et al. Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia. Mol. Psychiatry 4, 163 –172 (1999).Shows that loss of a parent (mother more than father) before age nine is a significant predictor of depression later in life.
Nemeroff, C. B. The preeminent role of early untoward experience on vulnerability to major psychiatric disorders: the nature–nurture controversy revisited and soon to be resolved. Mol. Psychiatry 4, 106–108 (1999).
Lewis, A. J. Melancholia: a clinical survey of depressive states. Natl Vital Stat Rep 80, 277–378 ( 1934).A classic description of depression.
Garside, R. F., Kay, D. W., Wilson, I. C., Deaton, I. D. & Roth, M. Depressive syndromes and the classification of patients. Psychol. Med. 1, 333– 338 (1971).
Gurland, B. Aims, organization, and initial studies of the Cross-National Project. Int. J. Aging Hum. Dev. 7, 283–293 (1976).
Katz, M. M., Secunda, S. K., Hirschfeld, R. M. & Koslow, S. H. NIMH clinical research branch collaborative program on the psychobiology of depression. Arch. Gen. Psychiatry 36, 765 –771 (1979).
World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnosis Guidelines (World Health Organization, Geneva, Switzerland, 1992 ).
Akiskal, H. S. Dysthymia and cyclothymia in psychiatric practice a century after Kraepelin . J. Affect. Disord. 62, 17– 31 (2001).
Seligman, M. E. Learned helplessness as a model of depression. Comment and integration. J. Abnorm. Psychol. 87, 165–179 (1978).
Seligman, M. E., Maier, S. F. & Geer, J. H. Alleviation of learned helplessness in the dog. J. Abnorm. Psychol. 73, 256–262 (1968).
Seligman, M. E., Rosellini, R. A. & Kozak, M. J. Learned helplessness in the rat: time course, immunization, and reversibility. J. Comp. Physiol. Psychol. 88, 542–547 (1975).
Kalin, N. H. & Carnes, M. Biological correlates of attachment bond disruption in humans and nonhuman primates. Prog. Neuropsychopharmacol. Biol. Psychiatry 8, 459–469 (1984).
Plotsky, P. M. & Meaney, M. J. Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Brain Res. Mol. Brain Res. 18, 195– 200 (1993).
Blanchard, D. C. & Blanchard, R. J. Behavioral correlates of chronic dominance-subordination relationships of male rats in a seminatural situation. Neurosci. Biobehav. Rev. 14 , 455–462 (1990). References 29 – 34 examine animal syndromes that model aspects of the depression phenotype.
Weissman, M. M. et al. The efficacy of drugs and psychotherapy in the treatment of acute depressive episodes. Am. J. Psychiatry 136, 555–558 (1979).
Kovacs, M., Rush, A. J., Beck, A. T. & Hollon, S. D. Depressed outpatients treated with cognitive therapy or pharmacotherapy. A one-year follow-up. Arch. Gen. Psychiatry 38, 33–39 (1981).References 35 and 36 show that brief, structured psychotherapies are effective in the treatment of depression, and that they can be successfully combined with pharmacological treatments.
Nobel Foundation. Nobel Lectures — Physiology or Medicine, 1901–1970 (Elsevier, Amsterdam, 1970).
Bunney, W. E. & Davis, J. M. Noradrenaline in depressive reactions. A review. Arch. Gen. Psychiatry 13, 483– 494 (1965).
Schildkraut, J. J., Gordon, E. K. & Durell, J. Catecholamine metabolism in affective disorders. I. Normetanephrine and VMA excretion in depressed patients treated with imipramine . J. Psychiatr. Res. 3, 213– 228 (1965).
Coppen, A. The biochemistry of affective disorders. Br. J. Psychiatry 113, 1237–1264 (1967).
Delgado, P. L. et al. Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch. Gen. Psychiatry 47, 411 –418 (1990).
Miller, H. L. et al. Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Arch. Gen. Psychiatry 53, 117–128 ( 1996).
Charney, D. S. Monoamine dysfunction and the pathophysiology and treatment of depression . J. Clin. Psychiatry 59, 11– 14 (1998).References 41 – 43 show that noradrenaline- and serotonin-selective probes can potentially identify subsets of depressed patients who might respond differentially to selective noradrenaline or serotonin reuptake inhibitors.
Thase, M. E., Frank, E. & Kupfer, D. J. in Handbook of Depression: Treatment, Assessment, and Research (eds Beckham, E. E. & Leber, W. R.) 816–913 (Dorsey, Homewood, Illinois, 1985).
Veith, R. C. et al. Sympathetic nervous system activity in major depression. Basal and desipramine-induced alterations in plasma noradrenaline kinetics. Arch. Gen. Psychiatry 51, 411–422 (1994).
Wong, M. L. et al. Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone. Proc. Natl Acad. Sci. USA 97, 325–330 ( 2000).References 45 and 46 report increased activity of sympathetic systems in depression.
Siever, L. J. & Davis, K. L. Overview: toward a dysregulation hypothesis of depression. Am. J. Psychiatry 142, 1017–1031 (1985).
Johnstone, E. C. et al. Neurotic illness and its response to anxiolytic and antidepressant treatment. Psychol. Med. 10, 321– 328 (1980).
Sachar, E. J., Hellman, L., Fukushima, D. K. & Gallagher, T. F. Cortisol production in depressive illness: a clinical and biochemical clarification . Arch. Gen. Psychiatry 23, 289– 298 (1970).
Spiess, J., Rivier, J., Rivier, C. & Vale, W. Primary structure of corticotropin-releasing factor from ovine hypothalamus. Proc. Natl Acad. Sci. USA 78, 6517–6521 (1981).
Gold, P. W. et al. Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Am. J. Psychiatry 141 , 619–627 (1984).
Nemeroff, C. B. et al. Elevated concentrations of CSF corticotropin-releasing-factor-like immunoreactivity in depressed patients. Science 226 , 1342–1344 (1984).
Holsboer, F., Girken, A., Stalia, G. K. & Muller, O. A. Blunted corticotropin and normal cortisol response to human corticotropin-releasing factor in depression. N. Engl. J. Med. 311, 1127 (1984).
Gold, P. W. et al. Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease. Pathophysiologic and diagnostic implications . N. Engl. J. Med. 314, 1329– 1335 (1986).
Gold, P. W., Wong, M. L., Chrousos, G. P. & Licinio, J. Stress system abnormalities in melancholic and atypical depression: molecular, pathophysiological, and therapeutic implications. Mol. Psychiatry 1, 257–264 ( 1996).
Demitrack, M. A. et al. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J. Clin. Endocrinol. Metab. 73, 1224–1234 ( 1991).
Whybrow, P. C. & Prange, A. J. Jr., A hypothesis of thyroid-catecholamine-receptor interaction. Its relevance to affective illness. Arch. Gen. Psychiatry 38, 106–113 (1981).
Gold, P. W. & Chrousos, G. P. The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences . Proc. Assoc. Am. Physicians 111, 22– 34 (1999).
Whybrow, P. C., Coppen, A., Prange, A. J. Jr, Noguera, R. & Bailey, J. E. Thyroid function and the response to liothyronine in depression. Arch. Gen. Psychiatry 26, 242–245 ( 1972).
Joffe, R. T. Refractory depression: treatment strategies, with particular reference to the thyroid axis. J. Psychiatry Neurosci. 22, 327–331 (1997).
Kramer, M. S. et al. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281, 1640–1645 (1998).
Zobel, A. W. et al. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated . J. Psychiatr. Res. 34, 171– 181 (2000).
Kupfer, D. J., Shaw, D. H., Ulrich, R., Coble, P. A. & Spiker, D. G. Application of automated REM analysis in depression . Arch. Gen. Psychiatry 39, 569– 573 (1982).Documents decreased latency to rapid-eye-movement–sleep onset in depressed patients.
Gerner, R. H., Post, R. M., Gillin, J. C. & Bunney, W. E. Jr Biological and behavioral effects of one night's sleep deprivation in depressed patients and normals. J. Psychiatr. Res. 15, 21–40 (1979).
Lipkin, W. I., Travis, G. H., Carbone, K. M. & Wilson, M. C. Isolation and characterization of Borna disease agent cDNA clones. Proc. Natl. Acad. Sci. USA 87, 4184– 4188 (1990).
Rott, R. et al. Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 228, 755–756 (1985).
Bode, L., Zimmermann, W., Ferszt, R., Steinbach, F. & Ludwig, H. Borna disease virus genome transcribed and expressed in psychiatric patients. Nature Med. 1, 232–236 (1995).
Bode, L., Durrwald, R., Rantam, F. A., Ferszt, R. & Ludwig, H. First isolates of infectious human Borna disease virus from patients with mood disorders. Mol. Psychiatry 1, 200–212 ( 1996).
De La Torre, J. C. et al. Detection of borna disease virus antigen and RNA in human autopsy brain samples from neuropsychiatric patients. Virology 223, 272–282 ( 1996).
Kim, Y. K. et al. Failure to demonstrate Borna disease virus genome in peripheral blood mononuclear cells from psychiatric patients in Korea. J. Neurovirol. 5, 196–199 ( 1999).
Tsuji, K., Toyomasu, K., Imamura, Y., Maeda, H. & Toyoda, T. No association of borna disease virus with psychiatric disorders among patients in northern Kyushu, Japan. J. Med. Virol. 61, 336–340 (2000).References 65 – 71 report that Borna-disease virus (BDV) might infect a small, but significant portion of patients with depression; however, these findings have not been fully replicated. A causal relation between depression and BDV is at present unclear.
Solomon, G. F. Psychoneuroimmunology: interactions between central nervous system and immune system. J. Neurosci. Res. 18, 1– 9 (1987).
Sternberg, E. M. Emotions and disease: from balance of humors to balance of molecules. Nature Med. 3, 264–267 ( 1997).
Licinio, J., Wong, M. L. & Gold, P. W. Localization of interleukin-1 receptor antagonist mRNA in rat brain. Endocrinology 129, 562– 564 (1991).
Rothwell, N. J. & Hopkins, S. J. Cytokines and the nervous system II: Actions and mechanisms of action. Trends Neurosci. 18, 130–136 ( 1995).
Van Wagoner, N. J. & Benveniste, E. N. Interleukin-6 expression and regulation in astrocytes. J. Neuroimmunol. 100, 124–139 (1999).
Rothwell, N. J. & Luheshi, G. N. Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci. 23, 618–625 ( 2000).
Connor, T. J. & Leonard, B. E. Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sci. 62, 583–606 ( 1998).
Weiss, J. M., Sundar, S. K., Becker, K. J. & Cierpial, M. A. Behavioral and neural influences on cellular immune responses: effects of stress and interleukin-1. J. Clin. Psychiatry 50, S43–S53 (1989).
Buckingham, J. C., Loxley, H. D., Taylor, A. D. & Flower, R. J. Cytokines, glucocorticoids and neuroendocrine function. Pharmacol. Res. 30, 35–42 ( 1994).
Rivier, C. Effect of peripheral and central cytokines on the hypothalamic–pituitary–adrenal axis of the rat. Ann. NY Acad. Sci. 697, 97–105 (1993).
Ramamoorthy, S. et al. Regulation of the human serotonin transporter by interleukin-1β . Biochem. Biophys. Res. Commun. 216, 560 –567 (1995).
Maes, M. et al. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9, 853–858 ( 1997).
Wong, M. L., Bongiorno, P. B., Rettori, V., McCann, S. M. & Licinio, J. Interleukin (IL) 1β, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: pathophysiological implications . Proc. Natl Acad. Sci. USA 94, 227– 232 (1997).Shows that central and peripheral cytokine compartments are integrated but differentially regulated: central cytokines are counter-regulated to a smaller extent than peripherally secreted ones.
Licinio, J. & Wong, M. L. The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection. Mol. Psychiatry 4, 317–327 (1999).
Lander, E. S. & Schork, N. J. Genetic dissection of complex traits. Science 265, 2037– 2048 (1994).
Fava, M. & Kendler, K. S. Major depressive disorder. Neuron 28, 335–341 ( 2000).
Sullivan, P. F., Neale, M. C. & Kendler, K. S. Genetic epidemiology of major depression: review and meta-analysis. Am. J. Psychiatry 157, 1552–1562 (2000). Shows that depression is caused by both genetic and environmental factors.
Kendler, K. S., Neale, M. C., Kessler, R. C., Heath, A. C. & Eaves, L. J. The lifetime history of major depression in women. Reliability of diagnosis and heritability. Arch. Gen. Psychiatry 50, 863–870 ( 1993).Shows that major depression as assessed over one's lifetime might be a rather highly heritable disorder of moderate reliability rather than a moderately heritable disorder of high reliability.
Lesch, K. P. et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527–1531 (1996). Discovery of a polymorphism in the regulatory region of the serotonin transporter gene that reduces transcriptional efficiency and might be correlated with anxiety traits.
Smeraldi, E. et al. Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol. Psychiatry 3, 508–511 ( 1998).Proposes that genotyping the serotonin transporter regulatory region might be used as a tool to predict treatment response in depression.
Kim, D. K. et al. Serotonin transporter gene polymorphism and antidepressant response. Neuroreport 11, 215– 219 (2000).
Benedetti, F. et al. Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression. Am. J. Psychiatry 156, 1450–1452 (1999).
Wong, M. L., Khatri, P., Licinio, J., Esposito, A. & Gold, P. W. Identification of hypothalamic transcripts upregulated by antidepressants. Biochem. Biophys. Res. Commun. 229, 275–279 (1996).
Hyman, S. E. Mental illness. Genetically complex disorders of neural circuitry and neural communication. Neuron 28, 321– 323 (2000). PubMedReviews the complexity of depression genetics.
Selye, H. A syndrome produced by diverse nocuous agents. Nature 138, 32 (1936).In this one-page article, Selye launched the field of stress biology. He showed that the organism had common responses to various types of stressor, and described those responses as much as it was possible using the methods available to him in the 1930s.
Chrousos, G. P. & Gold, P. W. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis . JAMA 267, 1244–1252 (1992).
Brady, L. S., Whitfield, H. J. Jr, Fox, R. J., Gold, P. W. & Herkenham, M. Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications . J. Clin. Invest. 87, 831– 837 (1991).
Brady, L. S., Gold, P. W., Herkenham, M., Lynn, A. B. & Whitfield, H. J. Jr The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic implications . Brain Res. 572, 117–125 (1992).
Michelson, D. et al. Chronic imipramine is associated with diminished hypothalamic-pituitary-adrenal axis responsivity in healthy humans. J. Clin. Endocrinol. Metab. 82, 2601–2606 ( 1997).References 98 – 100 show that attenuation of hypothalamus–pituitary–adrenal axis activity is a direct pharmacological effect of antidepressants.
Habib, K. E. et al. Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates. Proc. Natl Acad. Sci. USA 97, 6079–6084 (2000).
Acknowledgements
We are grateful to Kevin Kelly. J.L. is supported by grants from the National Institutes of Health and by awards from the Dana and Stanley Foundations. M.-L.W. is supported by a grant from the National Institutes of Health and by a NARSAD award.
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Glossary
- DSM-IV
-
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders Fourth Edition.
- CYCLOTHYMIA
-
A mild form of bipolar disorder, characterized by recurring episodes of hypomania and depression.
- ANHEDONIA
-
Loss of interest or pleasure in almost all activities.
- MORBIDITY
-
The incidence or prevalence of a disease in a population.
- LEARNED HELPLESSNESS
-
A cessation of the attempts to reach a goal as a consequence of the idea that rewards are not contingent on the attempts. Learned helplessness is accompanied by motivational and emotional deficits that have been proposed to model certain aspects of depression.
- COGNITIVE–BEHAVIOURAL PSYCHOTHERAPY
-
Form of psychotherapy that aims to strengthen self-esteem and provide the patient with support and understanding. Cognitive–behavioural psychotherapy emphasizes the analysis of the problems at hand, and the definition of concrete goals and solutions so that the patient can recognize progress.
- INTERPERSONAL PSYCHOTHERAPY
-
Form of psychotherapy used for the treatment of depression, which explores the relationships between the patient and other people, particularly around the time when the depression began, and uses the difficulties in those relationships as a treatment focus.
- MONOAMINE OXIDASE
-
Enzyme located on the outer mitochondrial membrane, which catalyses the hydrolysis of biogenic amines such as catecholamines and serotonin.
- TRICYCLIC DRUGS
-
Molecules that inhibit biogenic amine reuptake, therefore prolonging the period during which these neurotransmitters are active at the synaptic cleft.
- INTERLEUKIN-1β
-
Signalling molecule involved in the inflammatory response that can act as an endogenous pyrogen.
- POLYMORPHISM
-
The simultaneous existence in the same population of two or more genotypes in frequencies that cannot be explained by recurrent mutations.
- DIFFERENTIAL DISPLAY
-
A method for the rapid, accurate and sensitive detection of altered gene expression between different cell populations. The method is based on the amplification of 3′-terminal portions of messenger RNAs and resolution of these fragments on a DNA sequencing gel, allowing for the direct comparison of most of the mRNAs between related cells.
- SERIAL ANALYSIS OF GENE EXPRESSION
-
A method for the analysis of gene expression that converts polyadenylated messenger RNA into complementary DNA by reverse transcription. Oligonucleotide 'tags' are then hybridized to the cDNA, ligated to form concatemers that are amplified by PCR, and finally cloned and sequenced. The number of tags present indicates the prevalence of the gene, therefore providing a quantitative profile of cellular gene expression.
- TOTAL GENE EXPRESSION ANALYSIS
-
A procedure that aims to elucidate entire gene expression patterns for a given tissue or cell. It requires a complex series of steps that involve multiplex PCR, complementary DNA cloning, in vitro transcription, cDNA construction, sequencing gel analysis and quantification.
- DNA MICROARRAY
-
Device used to interrogate complex nucleic acid samples by hybridization. Microarrays make it possible to count the number of different RNA or complementary DNA molecules that are present in the sample of interest as a preparative stage for their subsequent characterization.
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Wong, ML., Licinio, J. Research and treatment approaches to depression. Nat Rev Neurosci 2, 343–351 (2001). https://doi.org/10.1038/35072566
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DOI: https://doi.org/10.1038/35072566
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