Electroconvulsive therapy (ECT) represented for over 70 years, and still represents, one of the most effective treatments for both major depression (MD) and a few other severe psychiatric conditions (Zomberg and Pope, 1993, Pagnin et al., 2004 and Taylor, 2008) with an effectiveness rate greater than 60%, although it is not without side effects (MacQueen et al., 2007). The morbidity/mortality of ECT ranges between 2 and 4 per 100,000 sessions and 1 per 10,000 patients, similar to that of anaesthetic induction in minor surgery (Fink, 1979 and Philbert et al., 1995). In spite of this evidence, its mechanism of action is still elusive (Altar et al., 2004 and Frazer et al., 2005). Different parameters, such as cortisol, adrenocorticotropic hormone, corticotrophin-releasing factor, thyroid-releasing hormone, thyroid-stimulating hormone, prolactin, oxytocin, vasopressin, dehydroepiandrosterone sulfate and tumor necrosis factor α, have been proposed as possible substrates of the effect of ECT, but most of the data derived from animal and human research are generally inconsistent (Wahlund and von Rosen, 2003).
Over the past decades, different studies have suggested that Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin recognized to mediate the survival, differentiation and outgrowth of selected neurons during development and adulthood, as well as to modulate the synaptic functions and the neuronal plasticity in several brain areas, might be involved in the pathophysiology of mood disorders (Duman et al., 1997 and Duman, 2004). BDNF is also present in peripheral tissues, in particular it is mainly stored in human platelets and circulates in plasma at levels 100-fold lower than those of serum (Yamamoto and Gurney, 1990). It has been suggested that the difference between serum and plasma BDNF may correspond to the amount of BDNF stored in circulating platelets (Fujimura et al., 2002). Although the regulation of BDNF in plasma is still poorly understood and there are other potential cellular sources of plasma BDNF including vascular endothelial and smooth muscle cells, activated macrophages and lymphocytes, the amount of plasma BDNF has been considered to partly reflect BDNF secretion in the central nervous system (Lommatzsch et al., 2005); interestingly, it has been observed that central and peripheral BDNF changes are positively correlated in rodents (Karege et al., 2002). Recently, decreased plasma and serum BDNF levels have been observed in drug-free depressed patients, as compared with those detected in healthy subjects (Shimizu et al., 2003, Gonul et al., 2005, Aydemir et al., 2005, Piccinni et al., 2008a and Piccinni et al., 2008b).
Electroconvulsive seizures (ECS) have been shown to increase the levels of BDNF mRNA, proteins and the tyrosine kinase receptor B (TrkB) mRNA in the rat hippocampus, while chronic ECS administration blocked the down-regulation of BDNF mRNA in the same area in response to restraint-induced stress (Lindefors et al., 1995, Nibuya et al., 1995 and Angelucci et al., 2002). Preclinical observations in animals on the ECS-induced mossy fiber sprouting of hippocampal neurons (Duman and Vaidya, 1998, Vaidya et al., 1999 and Lamont et al., 2001) and neurogenesis (Parent et al., 1997 and Madsen et al., 2000) have anticipated more recent studies indicating a possible relationship between the neurotrophic effect of ECT and the increase of the brain levels of N-acetylaspartate ( Michael et al., 2003 and Lang et al., 2007), an index of neuron functionality ( Tsai et al., 1995 and Sager et al., 2001). A few studies in depressed patients have shown that ECT may increase the amount of serum and plasma BDNF ( Taylor, 2008). The first evidence of serum BDNF levels increase in treatment-resistant depressed patients receiving ECT was recently published ( Bocchio-Chiavetto et al., 2006) and subsequently confirmed only in responders ( Okamoto et al., 2008). A similar finding was reported also for BDNF plasma levels ( Marano et al., 2007). These results suggest that one of the putative mechanisms of ECT might be mediated by BDNF and related substances ( Taylor, 2008). Two of the abovementioned studies ( Marano et al., 2007 and Okamoto et al., 2008) included both unipolar and bipolar depressed patients with a 2:1 ratio ( Marano et al., 2007). Although the relationship between the polarity of a patient's illness and the ECT outcome is still controversial, most observations up-to present suggest that the unipolar/bipolar distinction may have no predictive value in determining ECT outcome ( Daly et al., 2001).
Many factors including sex, age, diagnosis, presence of psychosis, duration of index episode, medication treatment failure prior to ECT and medication during ECT course, have been proposed as predictors of response to ECT in patients suffering from depression (Bloch et al., 2005, Kho et al., 2005 and Pluijms et al., 2006), however no agreement exists on the predictive values of such variables (Dombrovski et al., 2005). The aim of the present study was, therefore, to assess plasma BDNF levels in depressed patients who failed to respond to medications and received ECT, as well as to explore the possible correlation between the biological parameter and the clinical changes along the ECT course.
