Background. The dorsolateral prefrontal cortex (DLPFC) is involved in the pathophysiology of major depression. In particular, metabolic (functional hypometabolism) and structural alterations have been described. In this study metabolic changes within the DLPFC of severely depressed patients before and after electroconvulsive therapy (ECT) were evaluated by proton STEAM spectroscopy (¹H-MRS).Method. Twelve severely depressed patients with a diagnosis of major depressive episode, unipolar with melancholic features (DSM-IV), were enrolled, and the left dorsolateral prefrontal cortex (DLPFC) was investigated before and after unilateral ECT by ¹H-MRS. Three of the four non-responding patients were remeasured a third time after a combined ECT/antidepressant pharmacotherapy. The results were compared with 12 age- and gender-matched controls.Results. In depressed patients reduced glutamate/glutamine (Glx) levels were measured pre-ECT; Glx concentrations correlated negatively with severity of depression. After successful treatment, Glx increased significantly and levels no longer differed from those of age-matched controls.Conclusions. Our results indicate that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in glutamate/glutamine metabolism, which can be reversed by successful ECT.

There is abundant evidence that the serotonin (5-HT) system is modulating mood and several behavioural traits and that disturbances in the regulation of this system can be associated with severe behavioural malfunctions, as aggressive implusive and suicidal behaviour.¹ Recently a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was identified² and the presence of one or two short alleles was associated with anxiety-related personality traits³ and several psychiatric disturbances, such as affective disorder⁴ or severe alcohol dependence.⁵ With respect to the importance of the 5-HT transporter in serotonergic transmission, we have genotyped the DNA of 58 Caucasian suicide victims (with unknown psychiatric diagnoses) and 110 healthy controls for the biallelic functional polymorphism in the 5-HTTLPR. We found a highly significant increased frequency of suicide victims being carriers of one or two short alleles (Fisher's Exact Test, two sided, P = 0.0003), which suggests that a genetically altered protein function within the serotonergic pathway might be involved in suicidality, independently from the clinical diagnosis.