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.

No abstract

Alzheimer′s disease (AD) is a tragic neurodegenerative disease affecting more than 5 million Americans. Circadian disruptions impact nearly all AD patients, with reversal of sleep/wake cycles and agitation in the evening being common disturbances that manifest early in disease. These alterations support a role for circadian dysfunction as a driver of AD, emphasizing a critical need to investigate the therapeutic potential of circadian-modulating interventions. One of the most powerful regulators of the circadian system is the daily feed/fast cycle. Here we show that time-restricted feeding (TRF) without caloric restriction, improved key disease components including behavior, disease pathology and transcription in the APP23 mouse model of Alzheimer′s disease. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and hyperactivity, and normalizing transcription of circadian, AD and neuroinflammation-associated genes in APP23 mice. Thus, our study unveils for the first time that circadian modulation through timed feeding has far-reaching effects beyond metabolism and affects the brain as the substrate for neurodegeneration. Since the pleiotropic effects of TRF can substantially modify disease trajectory, this intervention has immediate translational value, addressing the crucial need for accessible approaches to reduce or halt AD progression.

No abstract