Neurocognitive profile in HIV subjects on INSTI-regimen- one year follow up: Is there room for optimism?

The introduction of antiretroviral therapy (ART) has successfully changed the clinical course of people with HIV, leading to a significant decline in the incidence of HIV-related neurocognitive disorders. Integrase strand transferase inhibitors (INSTI) are recommended and preferred first-line ART for the treatment of HIV-1 infection in ART-naïve subjects. This type of therapy regimen is expected to have higher CNS penetration, which may bring more cognitive stability or even make significant cognitive improvement in people with HIV. The study aimed to follow up on neurocognitive performance in HIV subjects on two types of INSTI therapy regimens at two-time points, one year apart. The study sample consisted of 61 ART naïve male participants, of which 32 were prescribed raltegravir (RAL) and 29 dolutegravir (DTG). There was no significant difference between subsamples according to the main sociodemographic (age, education level) and clinical characteristics (duration of therapy, nadir CD4 cells level, CD4 cells count, CD8 cells, CD4/CD8 ratio). For neurocognitive assessment, six measures were used: general cognitive ability (MoCA test), verbal fluency (total sum score for phonemic and category fluency), verbal working memory (digit span forward), cognitive capacity (digit span backwards), sustained attention (Color Trail Test 1), and divided attention (Color Trail Test 2). In both therapy groups (RAL and DTG), there was no significant decrease in neurocognitive achievement on all used measures over a one-year follow-up in both therapy groups. A statistically significant interactive effect of time and type of therapy was found on the measure of divided attention-DTG group showed slight improvement, whereas RAL group showed slight decrease in performance. During the one-year follow-up of persons on INSTI-based regimen, no significant changes in cognitive achievement were recorded, which suggests that the existing therapy can have a potentially positive effect on the maintenance of neurocognitive achievement.

Verbal, Figural, and Arithmetic Fluency of Children with Cochlear Implants.

Cochlear implantation gives children with prelingual severe hearing loss and deafness the opportunity to develop their hearing abilities, speech, language, cognitive abilities and academic skills with adequate rehabilitation. The aim of the research was to analyze verbal, figural and arithmetic fluency and their interrelationship in children with a cochlear implant (CI) and children with normal hearing (NH). A total of 46 children with CI and 110 children with NH, aged 9 to 16, participated in the research. Verbal fluency was assessed using phonemic and semantic fluency, and non-verbal fluency using figural fluency. Arithmetic fluency was assessed using simple arithmetic tasks within the number range up to 100. The results showed that children with CI achieved poorer results in phonemic fluency (z = -4.92; p < 0.001), semantic fluency (z = -3.89; p < 0.001), figural fluency (z = -3.07; p = 0.002), and arithmetic fluency (z = -4.27; p < 0.001). In both groups, a positive correlation was obtained between the measured modalities and types of fluency. In the group of children with CI, a sex difference was obtained on the phonemic fluency test, in favor of girls. The age of children with CI was correlated with arithmetic fluency. Verbal, figural and arithmetic fluency of children with CI speak in favor of the importance of early auditory and language experiences.

The Relationship Between Behavior Aspects of Executive Functions and Personality Traits in Healthy Young Adults.

Executive functions (ЕF) are complex cognitive processes that govern our behavior and thoughts. Associations between personality traits and executive functions clarify the mechanisms of a person's ability to function in everyday situations. The main goal of this study was to explore different personality dimensions relevant to the prediction of two different executive functions - Inhibition and Working Memory. The Big Five Inventory and the Adult Executive Functioning Inventory (ADEXI) were administered on a community sample comprising 549 young adults aged 18-35 years (mean age 22.10 years, SD 3.13). After controlling for age, gender and level of education, Conscientiousness and Extraversion were the most predictive personality traits, while Neuroticism and Agreeableness made specific contributions to the prediction of one of the two executive measures: Working Memory or Inhibition. Specifically, high Conscientiousness and Extraversion with low Neuroticism were significant predictors of Working Memory ability. On the other hand, high Conscientiousness and Agreeableness with low Extraversion predicted better Inhibition ability. These findings support the conclusion that these dimensions of individual differences seem to have numerous points of overlap at both psychological and neurobiological levels, but differences between these constructs are still significant.

Latent, genetic, and molecular genetic structure of the Wisconsin Card Sorting Test.

OBJECTIVE: The main goal of this study was to explore the latent structure and genetic basis of cognitive processes involved in the Wisconsin Card Sorting Task (WCST) within phenotypic, behavioral genetic, and molecular genetic research paradigms. METHOD: The sample used in phenotypic and behavioral genetic analyses comprised 468 twins (154 monozygotic and 80 dizygotic twin pairs), while molecular genetic analyses were performed on 404 twins from the same sample. The zygosity of most twin pairs (96.8%) was determined via deoxyribonucleic acid (DNA) analysis of buccal swabs. Trained researchers administered the Wisconsin Card Sorting Test (WCST; Heaton et al., 1993) to the entire sample. RESULTS: A phenotypic factor analysis of WCST variables suggested a single-factor solution. Overall heritability ranged from 0.19 to 0.23 across different measures of the WCST. The presence of a single general genetic factor, which could be identified from different measures of the WCST, indicated the unity of various WCST indicators and the existence of a common basic ability. Performance on the WCST did not reveal significant differences between the three genotypes on catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2). Carriers of the brain-derived neurotrophic factor (BDNF) Met + genotype exhibited better performance in cognitive functions in comparison to the BDNF Met- genotype. CONCLUSIONS: This study highlighted similarities in the phenotypic and genetic structures of the WCST, suggesting one general factor underlying different cognitive functions. The BDNF Met + genotype showed significant main effects on different WCST measures. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity.

Epigenetic modifications of the membrane bound catechol-O-methyltransferase (MB-COMT) gene may affect the enzymatic degradation of dopamine, and consequently, human behavior. This study investigated the association between membrane bound catechol-O-methyltransferase DNA methylation (DNAm) differences in 92 monozygotic (MZ) twins with phenotypic manifestations of cognitive, behavioral, and personality indicators associated with reward-related behaviors and lack of control. We used pyrosequencing to determine DNAm of the regulatory region of membrane bound catechol-O-methyltransferase in saliva DNA. Results of intrapair differences in the percentage of membrane bound catechol-O-methyltransferase DNAm at each of five CpG sites show that there are associations between phenotypic indicators of lack of control and membrane bound catechol-O-methyltransferase DNAm differences on CpG1, CpG2 and CpG4, suggesting the common epigenetic patterns for personality traits, cognitive functions, and risk behaviors.

DEPRESSION, ANXIETY AND QUALITY OF LIFE IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION IN VOJVODINA.

The objective of this study was to investigate the prevalence of depression and anxiety among patients with chronic hepatitis C and how depression and anxiety correlate with respective health-related quality of life (HRQoL) domains, sociodemographic factors, and clinico-epidemiological characteristics. This prospective study involved 150 patients with chronic hepatitis C awaiting interferon treatment for hepatitis C and 150 healthy subjects. All individuals enrolled in the study completed the Short Form 36 (SF-36) questionnaire and Hospital Anxiety Depression Scale. The symptoms showed greater severity/score among patients with chronic hepatitis C for both depression (t=3.37; p<0.01) and anxiety (t=2.35; p<0.05). Regression analysis was used for estimating the relationship between depression and the set of predictors (domains of the SF-36 questionnaire). Three HRQoL domains (Physical Functioning, Vitality, and Mental Health) were found to have the strongest predictive contribution to the occurrence of depression. A series of Kruskal-Wallis and Mann-Whitney tests showed a significant difference in depression level between marital status categories (χ2(2)=7.86, p<0.05). Divorced participants had significantly higher scores compared to married participants (Z=-2.40, p<0.05) and single participants (Z=-2.75, p<0.01). Unemployment was associated with a higher degree of depression and anxiety. There was no association identified between duration of the disease, route of hepatitis C virus transmission, existence of cirrhosis, and depression or anxiety. The findings of this study can assist in developing a standard protocol for the management of chronic hepatitis C that will include psychological assessment and support.

Behavioral aspects of executive functions in young adults with well-controlled epilepsy.

Executive function (EF) skills involve higher-level cognitive functions, such as planning, goal formation, goal-directed behavior, and effective performance. Previous research has shown that these aspects of EF are essential for successful functioning in everyday life. This study aimed to examine differences in the behavioral aspects of EF between young adults with epilepsy and healthy controls. The study involved 62 young adults, aged 18 to 30 years, divided into two groups: a study group of young adults with well-controlled epilepsy and a control group of healthy young adults. The groups were matched according to basic sociodemographic characteristics. The Behavior Rating Inventory of Executive Function - Adult version was used to assess the behavioral aspects of executive functions. A significant difference between groups was only observed on the Organization of Materials scale, where the group with epilepsy achieved better performance. Our findings suggest that self-assessed behavioral control of EF is almost the same in healthy young adults and young adults with epilepsy who have no comorbidities and have good control of the disease as well as preserved intellectual ability and functionality in everyday activities.

Convergent and Discriminant Validity of the Serbian Version of the Central Sensitization Inventory.

OBJECTIVES: The goal of the present study was to explore additional evidence of validity of the Serbian version of the Central Sensitization Inventory (CSI), a patient-reported outcome measure of symptoms that have been found to be associated with central sensitization (CS). The CSI has been found to be psychometrically sound, and has demonstrated evidence of convergent and discriminant validity in numerous published studies and in multiple languages. METHODS: CSI data were collected from 399 patients with chronic pain who had various diagnoses and from 146 pain-free controls. In addition, the patient sample completed a battery of validated patient-reported outcome measures of sleep problems, cognitive problems, pain catastrophizing, pain-related fear-avoidance, decreased quality of life, and decreased perception of social support. Six patient subgroups were formed, with presumably different levels of CS (including those with fibromyalgia, multiple pain sites, and localized pain sites). RESULTS: Significant differences were found in total CSI scores among the controls and patient subgroups. Those with fibromyalgia and multiple pathologies scored highest and the control subjects scored lowest. Other patient-reported CS-related symptom dimensions were significantly correlated with total CSI scores. When the patients were divided into CSI severity subgroups (from subclinical to extreme), the severity of these other symptom dimensions increased with the severity of CSI scores. CONCLUSIONS: The current study successfully demonstrated additional evidence of the convergent and discriminant validity of the Serbian version of the CSI.

Psychometric properties of the Teenage Executive Functioning Inventory (TEXI): A freely available questionnaire for assessing deficits in working memory and inhibition among adolescents.

The Childhood Executive Functioning Inventory (CHEXI) and the Adult Executive Functioning Inventory (ADEXI) are reliable and valid rating instruments for assessing working memory and inhibitory control. However, a teenage version of this instrument has not been available, and the aim of the present study was therefore to investigate the psychometric properties of the Teenage Executive Functioning Inventory (TEXI). After interviewing both researchers/clinicians and adolescents themselves, a questionnaire with 20 items was created. Data from adolescents age 13-19 years (n = 302) and their parents were thereafter collected. Factor analysis showed that the TEXI has two clear factors: working memory and inhibition. Further, the TEXI was shown to have high reliability in terms of internal consistency (≥ .85), split-half reliability (≥ .81) and inter-rater reliability between self-ratings and parent ratings (.82). In sum, the TEXI is a reliable questionnaire for measuring working memory and inhibition in adolescents. The two versions of the TEXI are presented in the appendices of this paper and they will be freely available on the Internet.

Serbian Twin Registry.

The first twin study in Serbia began in 2011 as a part of the research project, 'Psychological Foundations of Mental Health: Hereditary and Environmental Factors'. At the same time, the research team from the Faculty of Philosophy and Faculty of Medicine in Novi Sad established the first Serbian twin registry. The registry is intended primarily for the purpose of the research in behavioral genetics, as well as potential future studies in human genetics. It includes information on 1658 volunteers, including twin-pairs, their parent and siblings. The behavioral genetic study of adult twins has been focused on the hereditary and environmental sources of variance of different psychological characteristics, such as personality traits, cognitive abilities, executive functions and aggression, as well as some anthropometric measures and aspects of mental and physical health. Certain molecular genetic analyses have also been performed. The research team is currently starting the longitudinal twin study of children, which will be focused on different indicators of emotional, cognitive and physical development.

Neurometabolic Remodeling in Chronic Hiv Infection: a Five-Year Follow-up Multi-Voxel Mrs Study.

There is a lack of data about the long-term follow-up changes in neurometabolic profile and neuropsychological performance of HIV-positive subjects under continuous antiretroviral therapy (cART). The aim of the study was to assess changes in neurometabolic profile in chronically-infected, HIV-positive subjects during a five-year follow-up period, using multi-voxel proton magnetic resonance spectroscopy (1H-MRS). Nineteen neurologically asymptomatic, aviremic, HIV-positive subjects, underwent multi-voxel 2D MRS on a 3 T MR unit and synchronous neurocognitive assessment in a five-year follow-up period. Twelve voxels were placed in prefrontal cortices, anterior and posterior cingulate gyrus, intraparietal sulci, and frontal centrum semiovale white matter, to identify peaks of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myoinositol (mI). Ratios of NAA/Cr, NAA/Cho, NAA/mI, mI/Cr, and Cho/Cr were analyzed. Longitudinal differences in ratios and neurocognitive scores were tested with the Wilcoxon signed-rank-test. Statistical significance was set at p ≤ 0.004 significant, and 0.05 > p > 0.004 trending toward significance. A significant longitudinal increase in NAA/Cr ratio was observed in 5/12 voxels, while there was a trend toward significance in an additional three. The increase in Cho/Cr reached statistical significance in one voxel. Changes in the mI/Cr ratio demonstrated a significant increase in 4/12 voxels. A progressive increase in NAA/Cr, followed by better neurocognitive performance, may be an indicator of brain plasticity in the setting of chronic HIV-related neuronal injury. A progressive mI/Cr increase could be partly explained by glial proliferation due to functional compartment remodeling and partly attributable to insufficient control of persistent neuroinflammation by cART.

Evaluation of Symptoms of Depression and Anxiety in Adolescents with Epilepsy in a Tertiary-Level Medical Center in Serbia.

BACKGROUNDS: Even though epilepsy is the most common neurological disorder in adolescence; studies of adolescents with epilepsy are scarce. OBJECTIVE: To evaluate whether adolescents with epilepsy are more likely to develop anxiety and depressive symptoms than their healthy peers and to determine the relationship of depression and anxiety scores to epilepsy-related variables. SETTINGS AND DESIGN: Cross-sectional observational study. METHODS AND PROCEDURES: Ninety adolescents with epilepsy aged 13-19 years were compared with healthy controls using the Beck Depression Inventory II (BDI II) and the Stait Trait Anxiety Inventory (STAI) for assessment of depressive and anxiety symptoms. Within the study group, epilepsy-related variables were also determined using the stated measures. STATISTICAL ANALYSIS USED: The independent sample t-test, One-Way ANOVA, Pearson's correlation coefficient. OUTCOMES AND RESULTS: 23.3% of the study group and 8.3% of the control group had mild to moderate depression. The mean BDI II score was significantly higher in the group of adolescents with epilepsy. Comparing the STAI scores, results on both STAI scales were higher in the study group. Regarding the epilepsy-related variables, a high frequency of seizures, symptomatic etiology and polytherapy showed strong associations with high depression and anxiety scores. CONCLUSION AND IMPLICATIONS: Symptoms of depression and anxiety are not uncommon among adolescents with epilepsy. BDI II and STAI may be used as screening tools to provide useful information to clinicians when assessing adolescents' mental status.

Psychometric validation of the Serbian version of the Fear Avoidance Component Scale (FACS).

OBJECTIVE: The Fear Avoidance Components Scale (FACS) is a new patient-reported outcome (PRO) questionnaire designed to comprehensively evaluate fear avoidance (FA) beliefs and attitudes in persons with painful medical conditions. The original English version has demonstrated acceptable psychometric properties, including concurrent and predictive validity. Two factors have been identified: 1. general fear avoidance; and 2. types of activities that are avoided. METHODS: The FACS was first translated into Serbian, and then psychometrically validated. A cohort of 322 chronic musculoskeletal pain subjects completed the FACS-Serb and additional FA-related patient-reported outcome (PRO) measures. Their FACS-Serb scores were then compared to a cohort of 68 acute pain subjects. RESULTS: Test-retest reliability (ICC2,1 = 0.928) and internal consistency for both Factors (Cronbach α 0.904 and 0,880 respectively) were very good. An acceptable fit was found with a confirmatory factor analysis of the 2-factor model found with the original English version of the FACS. Strong associations were found among FACS-Serb scores and other PRO measures of pain catastrophizing, depressive/anxiety symptoms, perceived disability, and pain intensity (p<0.001 for all analyses). FACS-Serb total scores, separate Factor scores, and subjective pain ratings were significantly higher in the chronic vs. acute pain cohorts (p<0.001 for all analyses). CONCLUSIONS: The FACS-Serb demonstrated strong psychometric properties, including strong reliability and internal consistency, criterion validity (through associations with other FA-related PRO measures), and discriminant validity (through comparisons with a separate acute pain cohort). The FACS-Serb appears to be a potentially useful pain-related assessment tool.

Executive Functions Rating Scale and Neurobiochemical Profile in HIV-Positive Individuals.

The set of complex cognitive processes, that are necessary for the cognitive control of behavior, known as executive functions (EF), are traditionally associated with the prefrontal cortex and commonly assessed with laboratory based tests and conventional neuroimaging. In an effort to produce a more complete and ecologically valid understanding of executive functioning, the rating scales have been developed in order to assess the behavioral aspects of EF within an everyday real-world context. The main objective of this study was to examine the relationship between behavioral aspects of EF measured by rating scale and neurometabolic profile in neurologically asymptomatic HIV-positive individuals under cART, measured using multi-voxel magnetic resonance spectroscopy (mvMRS). The sample comprised 39 HIV-positive adult male participants, stable on cART and 39 healthy HIV-negative volunteers. Both groups completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). HIV-positive group additionally underwent long-echo three-dimensional mvMRS to determine neurobiochemical profile in the anterior cingulate gyrus (ACG) of both hemispheres. Three dominant neurometabolites were detected: N-acetyl aspartate (NAA), the neuronal marker; choline (Cho), the marker of membrane metabolism and gliosis and creatine (Cr), the reference marker. Ratios of NAA/Cr and Cho/Cr were analyzed. The initially detected significant correlations between age, current CD4, BRIEF-A subscales Inhibit, Shift, Emotional Control, Plan/Organize, Self Monitoring and ratios of NAA/Cr and Cho/Cr in the dorsal and ventral part of the ACG, were lost after the introduction of Bonferroni corrections. Also, there were no significant differences between HIV-positive and HIV-negative group on any of BRIEF-A subscales. Such results possibly imply that stable cART regimen contributes to preservation of behavioral aspects of EF in asymptomatic HIV-positive individuals. Even though a subtle deficit in some aspects of EF might exist, it would not be manifest if behavioral aspect was assessed using EF rating scale. Further explanation might be that expected HIV-related changes in neurometabolic profile of the ACG under cART are not reflected in those behavioral aspects that are measurable by EF rating scale.

Neurocognitive profile of HIV-positive adults on combined antiretroviral therapy: A single-centre study in Serbia.

The advent of combined antiretroviral therapy (cART) has prolonged the life expectancy of HIV + individuals and decreased the incidence of HIV-associated dementia. However, milder forms of neurocognitive impairment remain common and are often associated with poor daily functioning and lower medication adherence. This paper presents a research aimed at exploring the cognitive status differences between HIV + subjects (N = 39) on cART therapy and a group of demographically comparable healthy subjects (N = 39) in Serbia. The significance of differences between the HIV + group and the healthy control group in performance in six cognitive domains was tested using the multivariate analysis of variance. Results showed a lower performance of the HIV + group in the domains of attention/working memory, and learning. HIV-related clinical variables were not significantly associated with cognitive performance. An older age in HIV + patients was significantly related to a lower performance in all six cognitive domains, as opposed to healthy subjects, implying a synergistic interaction between HIV and aging, resulting in accentuated cognitive difficulties. Our findings suggest that even with the absence of a subjective experience of cognitive deficits and with a good basic control of the illness, a certain degree of cognitive deficit can be observed in the tested group.