High levels of pro-inflammatory substances such as cytokines have been described in the blood and cerebrospinal fluid of schizophrenia patients. Animal models of schizophrenia show that under certain conditions an immune disturbance during early life, such as an infection-triggered immune activation, might trigger lifelong increased immune reactivity. A large epidemiological study clearly demonstrated that severe infections and autoimmune disorders are risk factors for schizophrenia. Genetic studies have shown a strong signal for schizophrenia on chromosome 6p22.1, in a region related to the human leucocyte antigen (HLA) system and other immune functions. Another line of evidence demonstrates that chronic (dis)stress is associated with immune activation. The vulnerability-stress-inflammation model of schizophrenia includes the contribution of stress on the basis of increased genetic vulnerability for the pathogenesis of schizophrenia, because stress may increase pro-inflammatory cytokines and even contribute to a lasting pro-inflammatory state. Immune alterations influence the dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission. The activated immune system in turn activates the enzyme indoleamine 2,3-dioxygenase (IDO) of the tryptophan/kynurenine metabolism which influences the serotonergic and glutamatergic neurotransmission via neuroactive metabolites such as kynurenic acid. The described loss of central nervous system volume and the activation of microglia, both of which have been clearly demonstrated in neuroimaging studies of schizophrenia patients, match the assumption of a (low level) inflammatory neurotoxic process. Further support for the inflammatory hypothesis comes from the therapeutic benefit of anti-inflammatory medication. Metaanalyses have shown an advantageous effect of cyclo-oxygenase-2 inhibitors in early stages of schizophrenia. Moreover, intrinsic anti-inflammatory, and immunomodulatory effects of antipsychotic drugs are known since a long time. Anti-inflammatory effects of antipsychotics, therapeutic effects of anti-inflammtory compounds, genetic, biochemical, and immunological findings point to a major role of inflammation in schizophrenia.

Obsessive-compulsive (OC) disorder is a disabling disorder resulting in tremendous individual and social burden. It has a large overlap with depression and anxiety disorders and shows treatment resistance in a relevant proportion of patients. Since a couple of years, different noninvasive brain stimulation methods have been investigated to improve OC symptoms. The application of transcranial direct current stimulation (tDCS) has shown inconsistent results which can probably be attributed to a lack in randomized controlled trials with adequate sample size. Anodal stimulation of pre-supplementary motor areas has shown promising results, and there is also sparse data on orbitofrontal and prefrontal stimulation. Here, we provide the first report on a patient with treatment-refractory OC disorder treated with sertraline and an enhanced prefrontal tDCS protocol (twice per day, 10 days) with a classic left-anodal/right cathodal montage, experiencing a 22% reduction of OC symptoms as well as reduction in depression (-10%) and anxiety symptoms (-21%). Due to multifactorial origin of OC disorder and the variety of brain circuits involved, there are probably multiple approaches for brain stimulation regarding site, polarity, and frequency to be assessed in future studies.

Treatment success should not only be assessed with the classic "tic-scales", but also with the GAF and GTS-QOL. Although improvement of tics seems to be positively correlated with improved functional outcome, symptomatic improvement may lead to unexpected major psychosocial changes - which both the patient and the clinicians in charge - should be prepared for.

Introduction: Current pathophysiological hypotheses of Gilles de la Tourette Syndrome (GTS) refer to temporally abnormal neuronal activation in cortico-striato-thalamo-cortical (CSTC) networks. Modifying cortical activity by non-invasive brain-stimulation appears to be a new treatment option in GTS.Background: Previous studies suggested therapeutic effects of cathodal transcranial direct current stimulation (tDCS) to pre-supplementary motor areas (SMA), however, treatment modalities concerning electrode placement, current intensity and stimulation-rate have not been systematically explored. Aim of this study was to assess efficacy of an alternative stimulation regime on GTS symptoms in a pilot study. To test a treatment protocol with tDCS twice a day, we administered 10 sessions over 5 days of bilateral cathodal tDCS (30 min, 2 mA) over the pre-SMA in three patients with severe GTS. Tic severity as well as obsessive-compulsive (OC) symptoms and affective scales were rated before and after tDCS treatment.Discussion: Only one out of three patients showed a 34.5% reduction in tic severity. The two other patients showed an increase in tic severity. All patients showed a mild increase in positive affect and a reduction in negative affect, OC symptom changes were heterogeneous. Our results do not support earlier findings of extensive therapeutic effects of cathodal tDCS on tics in patients with GTS and show that prediction of stimulation effects on a targeted brain area remains inaccurate.Concluding Remarks: Future research will have to focus on the determination of most effective stimulation modes regarding site, polarity and frequency of tDCS in GTS patients.

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