Schizophrenia is a chronic, complex and heterogeneous mental disorder, with pathological features of disrupted neuronal excitability and plasticity within limbic structures of the brain. These pathological features manifest behaviorally as positive symptoms (including hallucinations, delusions and thought disorder), negative symptoms (such as social withdrawal, apathy and emotional blunting) and other psychopathological symptoms (such as psychomotor retardation, lack of insight, poor attention and impulse control). Altered glutamate neurotransmission has for decades been linked to schizophrenia, but all commonly prescribed antipsychotics act on dopamine receptors. LY404039 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors and has shown antipsychotic potential in animal studies. With data from rodents, we provide new evidence that mGlu2/3 receptor agonists work by a distinct mechanism different from that of olanzapine. To clinically test this mechanism, an oral prodrug of LY404039 (LY2140023) was evaluated in schizophrenic patients with olanzapine as an active control in a randomized, three-armed, double-blind, placebo-controlled study. Treatment with LY2140023, like treatment with olanzapine, was safe and well-tolerated; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo (P < 0.001 at week 4). Notably, patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation, extrapyramidal symptoms or weight gain. These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.

Schizophrenia is a socially significant mental disorder characterized by early onset and high time and financial expenditure on treatment. The basic drugs in these patients are antipsychotics that are highly effective against the positive and negative symptoms of schizophrenia, but at the same time have a wide range of adverse reactions (ARs). The clinical effect and tolerability of antipsychotics are variable and depend on the characteristics of genetically determined mechanisms (transportation, biotransformation, and elimination).The paper describes a clinical case of a female patient with schizophrenia who has been noted to be unresponsive to antipsychotic therapy for some years after the onset of the disease. After pharmacogenetic testing, she was found to be homozygous for the nonfunctional allelic variant CYP2D6*4 (1934 G>A, rs3892097), which was the reason for the complete shutdown of isoenzyme 2D6 activity and the development of ARs in the use of initial doses of antipsychotic drugs, as well as for an increase in the severity of ARs with aggravation of psycho-producing symptoms with an even slow titration of the daily dose.

In a cohort of schizophrenia inpatients CYP2D6 metabolic activity affects mean AP daily dose only in the presence of DRD2 Taq1A polymorphic allele. CYP2D6 metabolic activity correlates independently from DRD2 Taq1A polymorphism with hospital stay duration. Subpopulation of schizophrenia inpatients with altered CYP2D6 activity (PMs and UMs) carriers of Taq1A polymorphisms needs special attention of clinicians in aligning of AP treatment.

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Hashimoto thyroiditis is the most common thyroid disease. This form of pathology has a diverse clinical picture, including neuropsychiatric disorders. There are frequent cases of comorbidity of autoimmune thyroiditis and psychiatric forms of pathology, along with such a nosological entity as Hashimotos encephalopathy (aka: Steroid-responsive encephalopathy of autoimmune thyroiditis), characterized by an increased level of antithyroid autoantibodies and various mental disorders, with still unclear pathogenesis. The question arises, how to regard patients with psychiatric disorders and Hashimoto thyroiditis either as patients having autoimmune thyroiditis, comorbid with psychiatric forms of pathology, or as patients with Hashimotos encephalopathy? We studied groups of patients with autoimmune thyroiditis free from any psychiatric disorders, autoimmune thyroiditis comorbid with psychiatric forms of pathology, and a group of healthy donors similar as regards to their age and sex. We also studied medical history, clinical manifestations of the disease, instrumental data and the serum levels of thyrotropin, thyroid hormones, various antithyroid autoantibodies, and prolactin. We analyzed the correlation of laboratory and instrumental parameters and clinical data in all groups of patients. Therewas a significant relationship (p 0,05) between various psychiatric symptoms and a decreased level of free thyroxine, an increased level of thyroid stimulating hormone (TSH), an increased level of prolactin and an increased volume of a thyroid gland. Asignificant relationship (p 0,05) was also found between various symptoms of hypothyroidism and a decreased level of free triiodothyronine (FT3), an increased level of antibodies to thyroglobulin (anti-TG Ab), and an increased level of antibodies to thyroid peroxidase (anti-TPO Ab).