Lyubomir I. Aftanas

Association Study Indicates a Protective Role of Phosphatidylinositol-4-Phosphate-5-Kinase against Tardive Dyskinesia

Background: Tardive dyskinesia is a disorder characterized by involuntary muscle movements that occur as a complication of long-term treatment with antipsychotic drugs. It has been suggested to be related to a malfunctioning of the indirect pathway of the motor part of the cortical-striatal-thalamic-cortical circuit, which may be caused by oxidative stress-induced neurotoxicity. Methods: The purpose of our study was to investigate the possible association between phosphatidylinositol-4-phosphate-5-kinase type IIa (PIP5K2A) function and tardive dyskinesia in 491 Caucasian patients with schizophrenia from 3 different psychiatric institutes in West Siberia. The Abnormal Involuntary Movement Scale was used to assess tardive dyskinesia. Individuals were genotyped for 3 single nucleotide polymorphisms in PIP5K2A gene: rs10828317, rs746203, and rs8341. Results: A significant association was established between the functional mutation N251S-polymorphism of the PIP5K2A gene (rs10828317) and tardive dyskinesia, while the other 2 examined nonfunctional single nucleotide polymorphisms were not related. Conclusions: We conclude from this association that PIP5K2A is possibly involved in a mechanism protecting against tardive dyskinesia-inducing neurotoxicity. This corresponds to our hypothesis that tardive dyskinesia is related to neurotoxicity at striatal indirect pathway medium-sized spiny neurons.

Cytochrome P450 1A2 co-determines neuroleptic load and may diminish tardive dyskinesia by increased inducibility

Abstract Objectives. The aim of this study was to investigate a possible association between tardive dyskinesia (TD) and CYP1A2 (*1F, -163C>А, rs762551) polymorphism in Russian psychiatric inpatients. Methods. TD was assessed cross-sectionally using the Abnormal Involuntary Movement Scale (AIMS). Orofacial and limb-truncal dyskinesia were assessed with AIMS 1–4 and 5–7, respectively. Standard protocols were applied for genotyping. Analysis of covariance (ANCOVA) was used to compare the mean AIMS scores for each of the genotypic classes. Results. A total of 319 Caucasian patients from West Siberia with schizophrenia and 117 healthy volunteers were investigated. No significant differences between the patients and the controls in genotype frequencies were found. Analysis of covariance (ANCOVA) with age, sex, duration of disease, chlorpromazine equivalent (CPZEQ) incorporated as covariates showed that limb-truncal, but not orofacial TD, is associated with CYP1A2 (−163C>, rs762551) polymorphism (F = 3.27, P = 0.039). Patients with the C/C genotype had a higher mean AIMS 5–7 score than those with the A/C or the A/A genotype. Conclusions. Our results support the hypothesis that not only with clozapine, but also with other classical and atypical antipsychotics, smoking may decrease plasma levels; this is most extensively expressed in carriers of the CYP1A2*1F (-163C> A) polymorphism.

Investigation of an Immediate Effect of Bright Light on Oxygen Consumption, Heart Rate, Cortisol, and α-Amylase in Seasonal Affective Disorder Subjects and Healthy Controls

Background: Body (fat) mass has been shown to decrease following bright light treatment for overweight women, irrespective of their seasonal (light) dependence. It is not known if this is due to an (immediate) increase of metabolism. Methods: Ten women with seasonal affective disorder (SAD) and 10 non-SAD women matched by age, body mass index, and menopausal status participated in a laboratory study in the morning, twice within 1-5 days. During one session, bright light (4,300 lx) was presented for 30 min, and during the other session, red light (250 lx “placebo”) was used. After an initial 15 min of sitting quietly in an experimental chamber, 10-min measurements were done before, at the end, and 15 min after light exposure; the subjects remained seated for 80 min in total. The measurements included 5-min oxyspirography (oxygen consumption, carbon dioxide emission, and heart rate), saliva sampling for the estimation of cortisol and α-amylase concentrations, and self-rating of mood, energy, and sleepiness. Results: There was no light-specific effect on the measured variables, except that sleepiness was reduced more with bright light than with red light in the combined group. α-Amylase values were lower in the SAD patients than in the non-SAD controls. Conclusions: Morning artificial bright light, in comparison with dim red light, had no immediate effect on metabolism and resting sympathetic tone, though subjective sleepiness decreased more with bright light. SAD patients have low salivary α-amylase levels, indicating lower sympathetic tone.

Posture-Motor and Posture-Ideomotor Dual-Tasking: A Putative Marker of Psychomotor Retardation and Depressive Rumination in Patients With Major Depressive Disorder

Background: Recent studies have demonstrated that the assessment of postural performance may be a potentially reliable and objective marker of the psychomotor retardation (PMR) in the major depressive disorder (MDD). One of the important facets of MDD-related PMR is reflected in disrupted central mechanisms of psychomotor control, heavily influenced by compelling maladaptive depressive rumination. In view of this we designed a research paradigm that included sequential execution of simple single-posture task followed by more challenging divided attention posture tasks, involving concurring motor and ideomotor workloads. Another difficulty dimension assumed executing of all the tasks with eyes open (EO) (easy) and closed (EC) (difficult) conditions. We aimed at investigating the interplay between the severity of MDD, depressive rumination, and efficiency of postural performance. Methods: Compared with 24 age- and body mass index-matched healthy controls (HCs), 26 patients with MDD sequentially executed three experimental tasks: (1) single-posture task of maintaining a quiet stance (ST), (2) actual posture-motor dual task (AMT); and (3) mental/imaginary posture-motor dual task (MMT). All the tasks were performed in the EO and the EC conditions. The primary dependent variable was the amount of kinetic energy (E) expended for the center of pressure deviations (CoPDs), whereas the absolute divided attention cost index showed energy cost to the dual-tasking vs. the single-posture task according to the formula: ΔE = (EDual-task - ESingle-task). Results: The signs of PMR in the MDD group were objectively indexed by deficient posture control in the EC condition along with overall slowness of fine motor and ideomotor activity. Another important and probably more challenging feature of the findings was that the posture deficit manifested in the ST condition was substantially and significantly attenuated in the MMT and AMT performance dual-tasking activity. A multiple linear regression analysis evidenced further that the dual-tasking energy cost (i.e., ΔE) significantly predicted clinical scores of severity of MDD and depressive rumination. Conclusion: The findings allow to suggest that execution of concurrent actual or imaginary fine motor task with closed visual input deallocates attentional resources from compelling maladaptive depressive rumination thereby attenuating severity of absolute dual-tasking energy costs for balance maintenance in patients with MDD. Significance: Quantitative assessment of PMR through measures of the postural performance in dual-tasking may be useful to capture the negative impact of past depressive episodes, optimize the personalized treatment selection, and improve the understanding of the pathophysiological mechanisms underlying MDD.

The polymorphism of dopamine receptor D4 (DRD4) and dopamine transporter (DAT) genes in the men with antisocial behaviour and mixed martial arts fighters

Abstract Objectives: Variable-number tandem repeat (VNTR) polymorphisms of DRD4 and DAT genes were studied in the Russian and Chechen men convicted of crimes, and two control groups comprised of the MMA fighters and a sample of general population. A group of MMA fighters included only the subjects without history of antisocial behaviour. Methods: DNA was isolated by phenol–chloroform extraction from the blood. Genotyping VNTR polymorphisms of the DRD4 and DAT genes were performed by PCR on published methods. Results: Among those convicted of felonies and most grave crimes, carriers of DRD4 long alleles are found more frequently, similarly to the cohort of MMA fighters (lacking criminal record in both paternal lines). The 9/9 DAT genotype carriers are more frequently encountered among the habitual offenders. A frequency of the combination of the DRD4 genotype 4/7 and DAT genotype 10/10 is clearly higher among the convicts of violent crimes and the MMA fighters. One can speculate the presence of a ‘controlled aggression’ without a predisposition to pathological violence in the MMA fighters. Conclusions: Our study supports the hypothesis of genetic predisposition to different variants of extreme behaviour mediated by genetic determinants involved in the functioning of neuromediator systems including those controlling dopamine pathways.