Book Chapter or Conference Paper Title

Gamma-Aminobutyric Acid Involvement in Depressive Illness Interactions with Corticotropin-Releasing Hormone and Serotonin

Document Type

Book Chapter

Book Title or Conference Proceedings Title

The Neurobiological Basis of Suicide


Brain and Mind Institute




Yogesh Dwivedi


Taylor & Francis, LLC


There is little doubt that genetic and experiential factors contribute to the neurochemical processes responsible for the development of major depressive disorder (MDD) (Caspi et al., 2003; Kendler et al., 2005; Millan, 2006). In this regard, MDD is a biochemically heterogeneous disorder, and any of several neurochemical and/or receptor alterations provoked by stressful experiences might contribute to the development of depressive symptoms. Moreover, the effectiveness of antidepressants in attenuating MDD symptoms might be tied to the particular neurochemical alterations elicited by stressors in any given individual, and multitargeting as a strategy for the treatment of depression has received increased attention (Millan, 2006, 2009).

Although considerable evidence had pointed to a role for serotonergic processes in subserving MDD (Pineyro and Blier, 1999), it is clear that attributing MDD uniquely to serotonin (5-HT) is not a sustainable perspective. Considerable evidence has indicated that the nature of the 5-HT changes associated with depression (e.g., in postmortem analyses of depressed individuals that died by suicide) are highly variable (Anisman, 2009; Stockmeier, 2003). Moreover, drug treatments that affect 5-HT processes are effective in only a portion of patients, not all symptoms resolve with treatment, and recurrence rates are exceedingly high (Millan, 2006). Although not dismissing a role for 5-HT in the evolution or maintenance of MDD, it has been maintained that other processes might contribute in this regard. These have included several growth factors and cytokines, such as brain-derived neurotrophic factor (BDNF) (Duman and Monteggia, 2006) and various interleukins (Anisman et al., 2008; Dantzer et al., 2008), corticotropin-releasing hormone (CRH), and other peptides, such as neuromedin B and somatostatin (Merali et al., 2004, 2006; Nemeroff, 1996; Reul and Holsboer, 2002). There has also been a rejuvenation of the view that γ-aminobutyric acid A (GABAA) functioning might contribute to depressive illness (Rupprecht et al., 2006; Sanacora and Saricicek, 2007; Sequeira and Turecki, 2006; Tunnicliff and Malatynska, 2003), possibly by moderating the interplay between CRH and 5-HT (Hayley et al., 2005).


This work was published before the author joined Aga Khan University.