The neurobiology of depression
Eleni Palazidou *
East London Foundation Trust, Tower Hamlets Centre for Mental Health, Mile End Hospital, London E1 4DG, UK
Introduction or background: Depressive disorder is a long term, relapsing condition associated with high levels of disability and mortality. It has a neurobiological basis and is associated with functional and structural brain abnormalities. Downloaded from http://bmb.oxfordjournals.org/ by guest on May 10, 2013
Sources of data: The data discussed have been obtained mainly from metaanalyses, randomized controlled clinical trials and key review papers as well as animal studies. Areas of agreement: Genetic vulnerability and stress are key factors in its aetiopathogenesis. Dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis reduces hippocampal volumes and prefrontal cortex (PFC) activity in depressed patients and disrupts homeostasis within the neurocircuit of depression. Antidepressant drugs increase brain-derived neurotrophin, restoring neuronal growth and activity and modulate interactions between the neurocircuit anatomical structures. Areas of controversy: It remains to be conﬁrmed whether structural changes in the brain are purely abnormalities in neuroplasticity and are fully reversible, whether they predate depression and whether they increase in the long term. Growing points: Investigation of the molecular mechanisms mediating gene and environment interaction is a growing and potentially fruitful area of research in the neurobiology of depression. Further elucidation of the neuroanatomical and physiological connections between the limbic structures and PFC may help identify key areas to target in treatment. The role of the dysregulation of the HPA axis and identiﬁable stressors in the recent or remote past which are not always present in depression need further study. Areas timely for developing research: Prospective studies examining the interaction between changes in brain function and structure in relation to stress and identiﬁed relevant genes and how these may be inﬂuenced by antidepressant drug treatment and the long-term course of depression would help clarify their role in the pathophysiology of this disorder.
*Correspondence address. East London Foundation Trust, Tower Hamlets Centre for Mental Health, Mile End Hospital, 1st Floor Burdett House, Bancroft Rd, London E1 4DG, UK. E-mail: eleni. firstname.lastname@example.org
Keywords: depression/stress/neuroplasticity/genes/brain-derived neurotrophin/cytokines/antidepressants Accepted: January 10, 2012
British Medical Bulletin 2012; 101: 127–145 DOI:10.1093/bmb/lds004
& The Author 2012. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: email@example.com
The last 50 years have been witness to a diversity of theories, each one claiming to have the key to the aetiology of depression, based on the narrow perspective of its own discipline (genetic, social, psychological or biochemical). However, in the last decade or so, thanks to technological advances, major leaps have been made in our understanding of the workings of the brain, particularly, its significant capacity for plasticity in interacting with the environment ( physical and psychological). It has become increasingly clear that both psychosocial and biological factors are highly relevant and far from contradicting each other, they are inextricably linked in the genesis of this multifaceted condition. This paper aims to give a brief overview of the key research findings in the pathophysiology of depression and show how these can be integrated into a ‘psychobiological model’ of understanding the nature of this condition. The pathophysiology will be discussed in relation to the clinical presentation and course of the depressive illness and how it can inform the clinical management of this disorder and help...