Neurobiology of Depression by British Medical Bulletin
Published Online February 14, 2012
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.
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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
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
References: Downloaded from http://bmb.oxfordjournals.org/ by guest on May 10, 2013 British Medical Bulletin 2012;101 Downloaded from http://bmb.oxfordjournals.org/ by guest on May 10, 2013 144 Downloaded from http://bmb.oxfordjournals.org/ by guest on May 10, 2013 British Medical Bulletin 2012;101