Toward a Biology of Affective Disorders

Gershon, Elliot S.; Dünner, David L.; Goodwin, Frederick K.

doi:10.1001/archpsyc.1971.01750130003001

Cited by 108 publications

(11 citation statements)

References 99 publications

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“…The first studies into the genetics of depression began over 30 years ago. [4][5][6][7][8] Since then it has been repeatedly demonstrated that affective disorders run in families, with certain gene polymorphisms and environmental stressors postulated to increase susceptibility. Despite significant progress in our understanding of the probable causes of MDD, however, we are still some distance from identifying proven aetiological risks for depression and understanding the mechanisms behind their action.…”

Section: Introductionmentioning

confidence: 99%

Molecular studies of major depressive disorder: the epigenetic perspective

2007

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Major depressive disorder (MDD) is a common and highly heterogeneous psychiatric disorder encompassing a spectrum of symptoms involving deficits to a range of cognitive, psychomotor and emotional processes. As is the norm for aetiological studies into the majority of psychiatric phenotypes, particular focus has fallen on the interplay between genetic and environmental factors. There are, however, several epidemiological, clinical and molecular peculiarities associated with MDD that are hard to explain using traditional geneand environment-based approaches. Our goal in this study is to demonstrate the benefits of looking beyond conventional 'DNA þ environment' and 'DNA Â environment' aetiological paradigms. Epigenetic factors -inherited and acquired modifications of DNA and histones that regulate various genomic functions occurring without a change in nuclear DNA sequence -offer new insights about many of the non-Mendelian features of major depression, and provide a direct mechanistic route via which the environment can interact with the genome. The study of epigenetics, especially in complex diseases, is a relatively new field of research, and optimal laboratory techniques and analysis methods are still being developed. Incorporating epigenetic research into aetiological studies of MDD thus presents a number of methodological and interpretive challenges that need to be addressed. Despite these difficulties, the study of DNA methylation and histone modifications has the potential to transform our understanding about the molecular aetiology of complex diseases.

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Section: Introductionmentioning

confidence: 99%

Molecular studies of major depressive disorder: the epigenetic perspective

2007

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“…In addition to psychosocial stressors, biological, and genetic components contribute to depression. Genetic studies have demonstrated familial inheritance for both unipolar and bipolar depression [23,38,89]. Both of these disorders are primarily episodic and recurrent, with increasing frequency of major depressive episodes developing over time.…”

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confidence: 99%

The hypothalamic–pituitary–gonadal axis in mood disorders

Young¹,

Korszun²

2002

Endocrinology and Metabolism Clinics of North America

104

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This article has demonstrated that stress and HPA axis activation affect the reproductive axis. Despite similarities in the HPA axis picture between women with major depression and those with hypothalamic amenorrhea and exercise or nutritional amenorrhea, no abnormalities in LH secretion have been documented in major depression. Lower estradiol in the follicular phase in depressed women and lower testosterone in depressed men however, have been observed [81, 92]. Although PMS would appear to be the best candidate for a mood disorder associated with abnormalities in reproductive hormones, no abnormalities in LH, estradiol or progesterone have been documented in PMS either [62]. Similarly, blockade of progesterone appears to be ineffective as a treatment for PMS [79]. Complete elimination of monthly cycling with leuprolide improves mood, however. No published studies have examined women with major depression to determine whether leuprolide will exacerbate or improve depressive symptoms. Some studies suggest beneficial effects of estrogen on mood in postmenopausal women, but no placebo controlled studies have explored estrogen augmentation in the treatment of major depression in either post- or premenopausal women, although estrogen is beneficial in women with perimenopause-related mood disorders [78].

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“…These studies were for many years the major evidence for genetic factors in manic-depressive illness and in schizophrenia and still constitute an important support for the genetic hypothesis in these disorders, despite methodological criticisms that were later applied [2]. In these studies, the concordance of schizophrenia and manic-depressive illness for identical (monozygotic) twins was much higher than the concordance in fraternal (dizygotic) twins, suggesting that genetics rather than shared environment produced the concordance.…”

Section: Es Gershonmentioning

confidence: 99%