Bipolar disorder: clinical overview. / Klinik bipolarer Erkrankungen.

Bipolar disorder is a severe psychiatric disorder, characterized by depressive, manic and mixed episodes. The illness affects about 1-2 % of the population. Bipolar I disorders affect both genders equally, whereas bipolar II disorders seem to occur more frequently in women. The classification of the different subtypes of bipolar disorders is done depending on the severity and frequency of the episodes. Other subtypes beside bipolar I and bipolar II disorder are rapid cycling (more than 4 episodes of mania, depression, hypomania or mixed state in one year) and cyclothymia (hypomanic and subdepressive symptoms over a two year period). Besides a thorough psychiatric and neurological examination, further clinical tests should be performed in order to exclude differential diagnosis (psychiatric as well as neurological and somatic diseases). The course of the illness is often negatively affected by the high frequency of psychiatric and somatic comorbidities. After all the prognosis of bipolar disorder is depending on the individual course of the illness. Notably comorbidities and psychotic symptoms seem to have a negative influence on the prognosis.

Basic data for bipolar disorders: genetics, neurobiology and pharmacology. / Bipolare Störungen: Basiswissen Aktueller Forschungsstand zu Genetik, Neurobiologie und Pharmakologie .

Bipolar disorders are quite common (lifetime prevalence 1­2 %) and have a substantial genetic risk (total heritability about 80 %). However, the contribution of individual genes to the total genetic risk is very small. Accordingly, no specific genes are known which show a larger contribution. Nevertheless, many of the known genes involved encode for proteins important for neural plasticity, mitochondrial function, dopaminergic neurotransmission and calcium channels. Similarly, the few data about neurobiological alterations in the brains of bipolar patients also point into the same direction. However, these observations are not very specific. A possible exception might be mitochondrial dysfunction seen in bipolar patients, which could integrate several of the other findings into one concept. The pharmacology of the drugs used to treat bipolar disorders is also not pointing to one common mechanism of action. While the mechanisms of action of antidepressants and antipsychotics probably are not different from the mechanisms relevant to treat depression and schizophrenia, the mechanisms of the anticonvulsants used in bipolar disorders (valproic acid, carbamazepine, lamotrigine) are probably different from their mechanism of action as anticonvulsant drugs. More likely, these drugs improve neuronal plasticity similarly to lithium and antidepressants.

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia.

Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R(2)=0.34-0.55, p⩽0.0001; controls R(2)=0.05-0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p⩽0.001-0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature.

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence.

There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol's antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.