Recent studies with intravenous infusion of the NMDA receptor antagonist ketamine showed robust and rapid antidepressant effects within hours after treatment. Ketamine is a racemic mixture consisting of two enantiomers, R- and S-ketamine. In contrast to ketamine, S-ketamine is reported to be less prone to psychomimetic side effects, such as derealisation and hallucinations. In this report we describe the effect of ketamine and S-ketamine infusion therapy, respectively, in two patients with treatment-resistant major depression. Severity of depression was rated using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). While one patient did not respond to either treatment, in the other patient intravenous administration of ketamine as well as S-ketamine showed an antidepressant effect as assessed by a decrease in HAMD-21 and BDI at days 1 and 3 after infusion which faded until day 6. Both patients experienced psychomimetic side effects during ketamine infusion which were absent during treatment with S-ketamine. We conclude that S-ketamine might exert similar antidepressant effects as ketamine in drug-resistant depression but may be better tolerated by the patients.

reduction in patients with ADHD compared with major depression and healthy volunteers.Objective: Results in adult attention deficit hyperactivity disorder (ADHD) on structural brain changes and the clinical relevance are contradictory. The aim of this study was to investigate whether in adult patients with ADHD hippocampal or amygdala volumes differs from that in healthy controls and patients with major depression (MD). Method: Twenty patients with ADHD, 20 matched patients with MD and 20 healthy controls were studied with high resolution magnetic resonance imaging. Results: Amygdala volumes in patients with ADHD were bilaterally smaller than in patients with MD and healthy controls. In ADHD, more hyperactivity and less inattention were associated with smaller right amygdala volumes, and more symptoms of depression with larger amygdala volumes. Conclusion: This study supports findings that the amygdala plays an important role in the systemic brain pathophysiology of ADHD. Whether patients with ADHD and larger amygdala volumes are more vulnerable to affective disorders needs further investigation. Significant outcomes• Amygdala volumes were smaller in adult patients with attention deficit hyperactivity disorder (ADHD) than in patients with major depression and healthy controls, supporting a role of the amygdala in emotional dysregulation in ADHD.• More hyperactivity and less inattention were related to smaller right amygdala volumes.• The presence of more depressive symptoms in ADHD patients was associated with larger amygdala volumes in line with findings that the amygdala increases in size with major depressive disorder.• Hippocampal volumes were not altered in adult patients with ADHD. Limitations• The cross-sectional design does not allow changes in amygdala volume to be assessed.• The relatively small sample size does not allow generalization of the results, which would first need to be replicated.• Associations between clinical data and structural volumes are limited to the ADHD group • Current medication may have confounded the results.

Bipolar disorders are lifelong lasting affective disorders, with an episodic course of the illness in most cases. The lifetime prevalence is around 2-5%, the illness usually appears in early adulthood and causes significant impairment in psychosocial functioning. This is a selective review focusing on recent developments and issues of interest in the psychopharmacological treatment of bipolar disorders. It is based primarily on the results of adequately powered, randomised, controlled trials (RCTs). These studies were systematically retrieved by means of a Medline search. The past 10 years have led to a broadening of the psychopharmacological treatment options for bipolar disorders. The proof of efficacy for the combination of fluoxetine/olanzapine as well as quetiapine in the acute treatment of bipolar I depression were important steps. While lithium remains the gold standard in the maintenance treatment of bipolar disorders, valproate, olanzapine, lamotrigine, aripiprazole, and quetiapine have been shown efficacious for this indication, with quetiapine possessing the broadest approval status of all drugs for the different treatment phases of this illness. Despite this progress there remains a huge demand regarding new compounds for nearly every area in the psychopharmacological treatment of bipolar disorders. In addition new methodological approaches regarding the proof of effectiveness in clinical practice are urgently needed.

Brain monoaminergic neurotransmission is involved in the pathophysiology of various psychiatric disorders including depression. Reliable indicators of central monoaminergic activity might be helpful to specifically identify and differentiate dysfunctions in individual patients in order to selectively adjust medication and predict clinical response. In patients with depression, predictors of treatment response to serotonergic versus non-serotonergic (e.g., noradrenergic) antidepressants could be of considerable clinical relevance by avoiding unfavorable factors such as a prolonged duration of the disorder, risk of suicidality and therapy-resistance. Consequently, these tools might help to decrease direct and indirect costs of treatment. The loudness dependence of the N1/P2 component of auditory evoked potentials (LD) has been proposed as a noninvasive neurophysiological indicator of central serotonergic function. This review focuses on recent studies providing evidence for the validity of LD as an indirect serotonergic marker and highlights data on the clinical application in terms of prediction of treatment response in patients with depression.

The in vivo assessment of brain serotonergic function might be of clinical relevance in neuropsychiatry. The loudness dependence of auditory evoked potentials (LD) has been proposed as an indirect indicator of cortical serotonergic activity, whereas single photon emission computed tomography (SPECT) and [123I]ADAM allow the selective assessment of brain serotonin transporters (SERT). The aim of this study was to investigate LD and SERT availability as independent variables of the brain serotonergic system in healthy volunteers. Fifteen (six male, nine female) subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analyzed using dipole source analysis. SPECT was performed four hours after injection of 137 +/- 11.4 MBq [123I]ADAM. As a measure of SERT availability specific ADAM brainstem binding was used. LD correlated significantly with SERT availability (Pearson's correlations: rho = -0.57, p < 0.05). The correlations remained significant after controlling for the effects of age or gender (partial correlations: rho = -0.60, p < 0.05) but were pronounced in the female group (rho = -0.83, p < 0.01). Associations between LD and SERT availability contribute to the understanding of the central serotonergic system and further validate the use of neurophysiological approaches as indirect measures of neurochemical brain activity.