Sex differences in depression and anxiety disorders: Potential biological determinants

doi:10.1016/j.yhbeh.2006.06.031

Hormones and Behavior

Volume 50, Issue 4, November 2006, Pages 534-538

https://doi.org/10.1016/j.yhbeh.2006.06.031 Get rights and content

Abstract

The phenomenon of higher rates of affective disorders in women illustrates many of the difficulties as well as promises of translating preclinical models to human disorders. Abnormalities in the regulation of the hypothalamic–pituitary adrenal axis and the sympathoadrenomedullary system have been identified in depression and anxiety disorders, and these disorders are clearly precipitated and exacerbated by stress. Despite the striking sex difference in the prevalence of depression and anxiety disorders, attempts to identify corresponding sex differences in stress response reactivity in animal models have met with limited success. Processes which may contribute to increased rates of affective disorders in women are greater fluxes in reproductive hormones across the life span, and increased sensitivity to catecholamine augmentation of emotional memory consolidation.

Section snippets

Sex differences in stress responses

Abnormalities in the regulation of the hypothalamic–pituitary adrenal axis and the sympathoadrenomedullary system have been identified in depression and anxiety disorders, and these disorders are clearly precipitated and exacerbated by stress (Gold and Chrousos, 2002). Surprisingly, evidence from animal studies to date suggests that females are relatively resistant to the behavioral and neurobiological effects of acute and chronic stress. For example, although chronic stress over 21 days

Problems and promises of animal models

A major problem with animal models of affective disorders that involve behavioral measures reminiscent of depression in humans is that the core clinical features of the disorders are subjective experiences, rather than observable behaviors. Several of the classic animal models of depression, such as learned helplessness, separation, the forced swim test, and chronic restraint stress, could be argued to be equally good models of anxiety disorders, based on the behavioral features of the models.

Sex differences and hormonal modulation of affective disorders as a window into pathophysiology

Sex differences can be a window that provides new perspectives on biological mechanisms in affective illness. For example, the finding that increased risk of depression at puberty is limited to girls with a family history of depression, and only presents as they reach Tanner stage III of puberty (Angold et al., 1999), begs the question as to how depression-related genetic polymorphisms could contribute to systems that are differentially sensitive to estrogen or other reproductive hormones that

Effects of reproductive hormone fluxes

Compared to men, women are subject to greater fluxes in reproductive hormones across the life span. Changes in reproductive hormones in utero, during puberty, the estrus cycle, pregnancy, and menopause clearly alter brain structure and function, and are likely to play a role in the increased prevalence of affective disorders in women. HPA axis responsiveness increases (Altemus et al., 1997b, Kirschbaum et al., 1999) and glucocorticod feedback sensitivity (Altemus et al., 1997a) and brain GABA

Conclusion

Better understanding of the pathophysiology of affective disorders will point the way to better treatment and prevention of these disorders. Advancement toward this goal has been limited by the symptom-based diagnostic system in psychiatry. Psychiatry has been the last of the medical specialties to move to an biologically based diagnostic system, primarily due to the inaccessibility of the brain. However, in the near future, neurobiology is expected to play an increasing role in the definition

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Sex differences in depression and anxiety disorders: Potential biological determinants

Abstract

Section snippets

Sex differences in stress responses

Problems and promises of animal models

Sex differences and hormonal modulation of affective disorders as a window into pathophysiology

Effects of reproductive hormone fluxes

Conclusion

Brain Res.

Neuropsychopharmacology

Biol. Psychiatry

Am. J. Obstet. Gynecol.

Prog. Neuro-psychopharmacol. and Biol. Psychiat.

J. Affective Dis.

Brain Res.

Neuropsychopharmacology

Neuroscience

Physiol. Behav.

Psychoneuroendocrinology

Psychoneuroendocrinology

Neurosci. Lett.

Contraception

Am. J. Obstet. Gyn.

Physiol. Behav.

Neuropsychopharmacology

Suppression of hypothalamic–pituitary–adrenal axis responses to stress in lactating women

J. Clin. Endocrinol. Metab.

Increased vasopressin and ACTH responses to stress in the mid-luteal phase of the menstrual cycle

Pubertal changes in hormone levels and depression in girls

Psychol. Med.

Diagnostic and Statistical Manual of Mental Disorders

Spironolactone in the treatment of premenstrual tension: a double-blind study of spironolactone vs. bendroflumethiazide and placebo

Curr. Ther. Res. Clin. Exper.

The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function

Psychological Med.

Sex-related influences on the neurobiology of emotionally influenced memory

Ann. N. Y. Acad. Sci.

Antiandrogenic treatment of obsessive–compulsive neurosis

Acta Psychiatr. Scand.

A research agenda for DSM-V

Repeated restraint stress facilitates fear conditioning, independently of causing hippocampal CA3 dendritic atrophy

Behav. Neurosci.

Gonadal steroid modulation of oxytocin and vasopressin gene expression in the hypothalamus of the osmotically stimulated rat

Endocrinology

Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive compulsive disorder: differences by diagnosis and family history

Am. J. Med. Genetics

Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study

Arch. Gen. Psychiatry

Stress activation of cortex and hippocampus is modulated by sex and stage of estrus

Endocrinology

Differential response to antidepressants in women with premenstrual syndrome/premenstrual dysphoric disorder

Arch. Gen. Psychiatry

Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs. low CRH/NE states

Mol. Psych.

The infrequency of “pure culture” diagnoses among the anxiety disorders

J.Clin.Psychiatry