Neurobiology of Depression: An Integrated View Of Key Findings

V. Maletic; M. Robinson; T. Oakes; S. Iyengar; S. G. Ball; J. Russell


Int J Clin Pract. 2007;61(12):2030-2040. 

In This Article


As the underlying neurobiological model of depression is increasingly understood, treatment providers are directed to recognise that the factors that may initiate a MDD episode and those that maintain the illness are likely to be very different. Genetic and stress vulnerabilities interplay to initiate a cascade of neurobiological alterations that disrupt a dynamic system. Progressive effects of recurrent and chronic MDD may then be potentiated by further structural and functional abnormalities.

Given these long-term consequences, an essential objective of treatment must be to restore normative functioning and prevent further neurobiological structural alterations. Increasing 5-HT and NE neurotransmission is likely to initiate true recovery with the restoration of neurotrophic support, glucocorticoid signalling and neuroendocrine regulation. The use of dual reuptake inhibitors enhances the probability of remission as it addresses the complex interplay of the emotional and physical symptoms of MDD. Painful physical symptoms are increasingly recognised as having a significant impact on functioning and recovery; thus, affirming the need for antidepressant treatments that can effectively reduce these symptoms as well.

From the neurobiological model, the treatment guidelines of early, comprehensive and progressive treatment require a change in perspective for both patients and providers. A residual symptom may be interpreted as a proxy of an active disease state, with ensuing structural alterations and systemic consequences. With remission and recovery as the goal, patients will need to be educated about the benefits of long-term treatment rather than episodic or incomplete intervention. A biopsychosocial treatment model that incorporates cognitive-behavioural or interpersonal therapy along with pharmacological interventions serves to address both the initiation and maintenance factors and can reduce the risk of relapse.[89] Once remission is attained, maintenance of effect may become the more appropriate term, rather than relapse prevention, to emphasise the necessity for an ongoing collaboration between patient and physician in order to maintain neurobiological homeostasis.

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