Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol.

While an excess of glucocorticoids is associated with hippocampal pathology in mood disorders, lithium exerts robust neuroprotective and neurotrophic effects. Here, 21 stably remitted bipolar I patients who had been on chronic lithium maintenance therapy, on average, for more than a decade, and 19 carefully matched healthy controls were studied using 3 T (1)H-magnetic resonance spectroscopy of left and right hippocampus. Salivary cortisol samples were obtained to assess activity of the hypothalamus-pituitary-adrenal system. Absolute concentrations of N-acetylaspartate (NAA), choline-containing compounds and total creatine were similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate concentrations were significantly increased as an effect of patient status (patients>controls) and laterality (left hippocampus>right hippocampus). Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across groups and within the patient group, diurnal saliva cortisol levels showed a significant inverse relationship with both Glu and NAA. Taken together, these results add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.

Electroconvulsive monotherapy in confusion psychosis: a potential standard regimen?

We report on the successful use of continuation electroconvulsive therapy (ECT) as prophylactic treatment of relapse in a case of confusion psychosis. The 20-year-old patient exacerbated in an almost annual rhythm and had been characterized as pharmacologically treatment-resistant since he failed to respond to any psychopharmacological therapy including sufficient clozapine as well as mood-stabilizing and sedating pharmacological treatments. After the diagnosis of confusion psychosis, the patient received ECT as monotherapy and showed a marked reduction of symptoms. Continuation ECT was then conducted for 7 months after the patient was discharged from hospital. Two years later, our patient is still in remission while continuation ECT has been tapered; no prophylactic psychotropic medication was prescribed in the last 2 years. Implications of this case on the therapy of confusion psychosis as well as on the diagnostic classification of confusion psychosis within our current systems are discussed.

P300 is enhanced in responders to vagus nerve stimulation for treatment of major depressive disorder.

BACKGROUND: Vagus nerve stimulation (VNS) is a new therapy option for treatment of otherwise therapy-refractory major depressive disorder. However, the mechanism of central nervous action is poorly understood. Electroencephalographic (EEG) studies may be of interest since chronic peripheral current application to the vagus nerve may exert lasting neurophysiologically detectable effects on central electrical activity. In an exploratory study, we investigated the effects of VNS on auditory event-related potentials (ERP). METHODS: Thirteen depressive patients (mean Hamilton depression score (HAMD) at baseline=24.2) receiving VNS were investigated prior to implantation and 10 weeks after standard cycling VNS. Stimulation intensity was 0.94+/-0.46 mA, pulse width 0.250 mus, and frequency 20 Hz. 1 h prior to follow-up investigation, VNS was turned off. Auditory ERP were elicited using a standard auditory oddball paradigm and were recorded with 29-channel EEG. RESULTS: Post VNS, grand averages of the auditory ERP did not show significant differences as compared to baseline recording. However, differential effects were found when separating ERP of responders (N=5, mean HAMD post VNS=8.8) and non-responders (N=8, mean HAMD post VNS=22.4). In VNS responders only, P300 at midline electrodes Fz and Cz was significantly increased and correlated with HAMD scores. CONCLUSION: Auditory ERP seem to provide a useful tool for investigating VNS-induced changes concerning information processing in major depressive disorder. In our sample, enhancement of P300 distinguished VNS responders from non-responders 10 weeks after therapy onset. Our findings may be relevant for the understanding of both neurophysiological mechanism of action of VNS and pathophysiology of depression.