The impact of COVID-19 pandemic on the 2020 hepatitis C cascade of care in the Republic of Georgia.

OBJECTIVES: In 2015, the Republic of Georgia initiated a National Hepatitis C Elimination Program, with a goal of 90% reduction in prevalence of chronic hepatitis C virus (HCV) infections by 2020. In this article, we explore the impact of the COVID-19 pandemic on the 2020 hepatitis C cascade of care in Georgia. STUDY DESIGN: Retrospective analytic study. METHODS: We used a national screening registry that includes hospitals, blood banks, antenatal clinics, harm reduction sites, and other programs and services to collect data on hepatitis C screening. A separate national treatment database was used to collect data on viremia and diagnostic testing, treatment initiation, and outcome including testing for and achieving sustained virologic response (SVR). We used these databases to create hepatitis C care cascades for 2020 and 2019. Bivariate associations for demographic characteristics and screening locations per year and care cascade comparisons were assessed using a chi-squared test. RESULTS: In 2020 compared to 2019, the total number of persons screened for HCV antibodies decreased by 25% (from 975,416 to 726,735), 59% fewer people with viremic infection were treated for HCV infection (3188 vs. 7868), 46% fewer achieved SVR (1345 vs. 2495), a significantly smaller percentage of persons with viremic infection initiated treatment for HCV (59% vs. 62%), while the percentage of persons who achieved SVR (99.2% vs. 99.3%) remained stable. CONCLUSIONS: The COVID-19 pandemic had a negative impact on the hepatitis C elimination program in Georgia. To ensure Georgia reaches its elimination goals, mitigating unintended consequences of delayed diagnosis and treatment of hepatitis C due to the COVID-19 pandemic are paramount.

Genetic modulation of the response bias towards facial displays of anger and happiness.

BACKGROUND: Investigating genetic modulation of emotion processing may contribute to the understanding of heritable mechanisms of emotional disorders. The aim of the present study was to test the effects of catechol-O-methyltransferase (COMT) val158met and serotonin-transporter-linked promoter region (5-HTTLPR) polymorphisms on facial emotion processing in healthy individuals. METHODS: Two hundred and seventy five (167 female) participants were asked to complete a computerized facial affect recognition task, which involved four experimental conditions, each containing one type of emotional face (fearful, angry, sad or happy) intermixed with neutral faces. Participants were asked to indicate whether the face displayed an emotion or was neutral. The COMT-val158met and 5-HTTLPR polymorphisms were genotyped. RESULTS: Met homozygotes (COMT) showed a stronger bias to perceive neutral faces as expressions of anger, compared with val homozygotes. However, the S-homozygotes (5-HTTLPR) showed a reduced bias to perceive neutral faces as expressions of happiness, compared to L-homozygotes. No interaction between 5-HTTLPR and COMT was found. CONCLUSIONS: These results add to the knowledge of individual differences in social cognition that are modulated via serotonergic and dopaminergic systems. This potentially could contribute to the understanding of the mechanisms of susceptibility to emotional disorders.

Resting-state cerebral blood flow in amygdala is modulated by sex and serotonin transporter genotype.

Serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with modulation of resting-state amygdala level, which was considered to underlie a risk for mood and anxiety disorders. The findings however have been inconsistent which could be related to interactions of the genotype with other factors e.g. sex or personality characteristics. Therefore, the aim of the present study was to explore the modulation of the amygdala perfusion in the resting-state by sex and 5-HTTLPR/rs25531 genotype, controlled for personality dimensions assessed by Temperament and Character Inventory (Cloninger et al., 1994). The resting-state cerebral blood flow (rCBF) was examined using an arterial spin labelling technique. All participants were genotyped for the 5-HTTLPR/rs25531 genotype (L/L-L/S-S/S genotypes and LA-LG variants). The study group comprised 81 right-handed Caucasian healthy volunteers (42 females) aged 19-55 years. We measured rCBF in the amygdala and in the whole-brain grey matter. The data of blood-oxygen-level-dependent (BOLD) response in amygdala to fearful dynamic faces in the same sample were also analysed. There was a significant main effect of sex in both the left and right amygdalae, with higher rCBF in males. Main effect of 5-HTTLPR/rs25531 genotype which was significant in the right amygdala only, was accounted for by higher rCBF in S/S vs. L/L homozygotes. An interaction between sex and 5-HTTLPR/rs25531 genotype was observed in rCBF in the right amygdala. This was accounted for by higher values of rCBF in the right amygdala in males' S allele carriers compared with females. In females, there was a significant negative correlation between the rCBF and BOLD response in the right amygdala, and more so in S carriers. In males, there was no significant correlation between rCBF and BOLD response in the right amygdala. The novelty of our results lies in the demonstration of gene by sex interaction with resting blood flow in the amygdala that elucidates sex-related differences in emotional reactivity.

Genetic modulation of neural response during working memory in healthy individuals: interaction of glucocorticoid receptor and dopaminergic genes.

Suboptimal performance in working memory (WM) tasks and inefficient prefrontal cortex functioning are related to dysregulation of dopaminergic (DA) and hypothalamic-pituitary-adrenal systems. The aim of the present study was to investigate the joint effect of genetic polymorphisms coding for DA catabolism and glucocorticoid receptor (GR, NR3C1) on brain functioning. The study group (90 right-handed white Caucasian healthy individuals) underwent functional magnetic resonance imaging experiments to examine blood oxygenation level dependent (BOLD) response during a WM task with varying cognitive load (1-, 2- and 3-back). We have also examined skin conductance response (SCR) during the WM task and resting-state cerebral blood flow with continuous arterial spin labelling. The genetic markers of interest included Catechol-O-Methyl-Transferase (COMT) (Met(158)Val) and NR3C1 single-nucleotide polymorphisms (BclI C/G rs41423247, 9ß A/G rs6198 and rs1866388 A/G). Haplotype-based analyses showed (i) a significant effect of COMT polymorphism on left anterior cingulate cortex, with greater deactivation in Met carriers than in Val/Val homozygotes; (ii) a significant effect of BclI polymorphism on right dorsolateral prefrontal cortex (DLPFC), with greater activation in G/G carriers than in C carriers and (iii) an interactive effect of BclI (G/G) and COMT (Met/Met) polymorphisms, which was associated with greater activation in right DLPFC. These effects remained significant after controlling for whole-brain resting-state blood flow. SCR amplitude was positively correlated with right DLPFC activation during WM. This study demonstrated that GR and COMT markers exert their separate, as well as interactive, effects on DLPFC function. Epistasis of COMT and BclI minor alleles is associated with higher activation, suggesting lower efficiency, of DLPFC during WM.

Gender differences in the sensitivity to negative stimuli: cross-modal affective priming study.

BACKGROUND: There is evidence showing that men and women differ with regard to the processing of emotional information. However, the mechanisms behind these differences are not fully understood. METHOD: The sample comprised of 275 (167 female) right-handed, healthy participants, recruited from the community. We employed a customized affective priming task, which consisted of three subtests, differing in the modality of the prime (face, written word, and sound). The targets were always written words of either positive or negative valence. The priming effect was measured as reaction time facilitation in conditions where both prime and target were emotional (of the same positive or negative valence) compared with conditions where the emotional targets were preceded by neutral primes. RESULTS: The priming effect was observed across all three modalities, with an interaction of gender by valence: the priming effect in the emotionally negative condition in male participants was stronger compared with females. This was accounted for by the differential priming effect within the female group where priming was significantly smaller in the emotionally negative conditions compared with the positive conditions. The male participants revealed a comparable priming effect across both the emotionally negative and positive conditions. CONCLUSION: Reduced priming in negative conditions in women may reflect interference processes due to greater sensitivity to negative valence of stimuli. This in turn could underlie the gender-related differences in susceptibility to emotional disorders.

Interaction of catechol O-methyltransferase and serotonin transporter genes modulates effective connectivity in a facial emotion-processing circuitry.

Imaging genetic studies showed exaggerated blood oxygenation level-dependent response in limbic structures in carriers of low activity alleles of serotonin transporter-linked promoter region (5-HTTLPR) as well as catechol O-methyltransferase (COMT) genes. This was suggested to underlie the vulnerability to mood disorders. To better understand the mechanisms of vulnerability, it is important to investigate the genetic modulation of frontal-limbic connectivity that underlies emotional regulation and control. In this study, we have examined the interaction of 5-HTTLPR and COMT genetic markers on effective connectivity within neural circuitry for emotional facial expressions. A total of 91 healthy Caucasian adults underwent functional magnetic resonance imaging experiments with a task presenting dynamic emotional facial expressions of fear, sadness, happiness and anger. The effective connectivity within the facial processing circuitry was assessed with Granger causality method. We have demonstrated that in fear processing condition, an interaction between 5-HTTLPR (S) and COMT (met) low activity alleles was associated with reduced reciprocal connectivity within the circuitry including bilateral fusiform/inferior occipital regions, right superior temporal gyrus/superior temporal sulcus, bilateral inferior/middle prefrontal cortex and right amygdala. We suggest that the epistatic effect of reduced effective connectivity may underlie an inefficient emotion regulation that places these individuals at greater risk for depressive disorders.

A new meta-analytic method for neuroimaging studies that combines reported peak coordinates and statistical parametric maps.

Meta-analyses are essential to summarize the results of the growing number of neuroimaging studies in psychiatry, neurology and allied disciplines. Image-based meta-analyses use full image information (i.e. the statistical parametric maps) and well-established statistics, but images are rarely available making them highly unfeasible. Peak-probability meta-analyses such as activation likelihood estimation (ALE) or multilevel kernel density analysis (MKDA) are more feasible as they only need reported peak coordinates. Signed-differences methods, such as signed differential mapping (SDM) build upon the positive features of existing peak-probability methods and enable meta-analyses of studies comparing patients with controls. In this paper we present a new version of SDM, named Effect Size SDM (ES-SDM), which enables the combination of statistical parametric maps and peak coordinates and uses well-established statistics. We validated the new method by comparing the results of an ES-SDM meta-analysis of studies on the brain response to fearful faces with the results of a pooled analysis of the original individual data. The results showed that ES-SDM is a valid and reliable coordinate-based method, whose performance might be additionally increased by including statistical parametric maps. We anticipate that ES-SDM will be a helpful tool for researchers in the fields of psychiatry, neurology and allied disciplines.

Insight in eating disorders: clinical and cognitive correlates.

BACKGROUND: The aim of this study was to explore the extent of lack of insight and its components in eating disorders (EDs) and to investigate the relationship between insight and clinical and cognitive characteristics in this group. METHOD: Seventy-five participants were enrolled in the study: 25 with anorexia nervosa (AN), 15 with bulimia nervosa (BN) and 35 healthy controls (HC). Insight was assessed with a modified version of the Schedule for the Assessment of Insight for EDs (SAI-ED) and multi-dimensional scaling (MDS) analysis was used to clarify the internal structure of the scale. Neuropsychological tests included the Trail Making Test (TMT), the Brixton Test and a Verbal Fluency Task. RESULTS: Only a subgroup of AN patients (24%) had severe impairment of insight. Patients with the restricting type of AN (AN-R) had poorer overall insight than patients with the binge-purge type of the disorder (AN-B/P). More of the ED patients displayed a deliberate denial of illness rather than a lack of awareness of the illness. A regression model revealed that only performance in part B of the TMT (TMT-B) was a moderate predictor of insight level. No association was found between insight and other cognitive or clinical variables. CONCLUSIONS: Impaired insight is a significant feature of some ED patients. Insight in EDs seems to be partially dependent on intact mental flexibility.

Backward and forward visual masking in schizophrenia and its relation to global motion and global form perception.

Whilst visual backward masking deficits in schizophrenia have been reliably reported and may reveal magnocellular dysfunction, forward masking, which may rely more heavily on the parvocellular system, has been under investigated. In a group of 64 schizophrenia patients and 65 matched controls we undertook a visual masking paradigm containing both conditions, together with tests of 'global motion' and 'global form' perception, two 'down-stream' visual tasks reflecting later processing linked to magnocellular and parvocellular function respectively. In the patient group, a significant but small deficit on the masking task, equivalent across forward and backward conditions was seen. Correlations between the masking and motion/form tasks supported the predominant theoretical framework describing the neural processes involved in masking. Performance on the motion and form tasks was differentiated by a trend-level motion processing deficit but near-normal form processing. The results suggest an 'early visual' processing deficit in both magno- and parvocellular systems but one which is only transferred to 'down-stream' processing areas with predominantly magnocellular input.

Exaggerated neural response to emotional faces in patients with bipolar disorder and their first-degree relatives.

Neuroimaging studies have demonstrated abnormalities in patients with bipolar disorder, including overactivity in anterior limbic structures in response to fearful or happy facial expressions. We investigated whether such anomalies might constitute heritable deviations underlying bipolar disorder, by virtue of being detectable in unaffected relatives carrying genetic liability for illness. Twenty patients with bipolar I disorder, twenty of their unaffected 1st degree relatives and twenty healthy volunteers participated in functional magnetic resonance imaging experiments of facial emotion processing. In one of these experiments, the participants watched faces expressing fear of varying intensities (moderate and high), intermixed with the non-emotional faces, and in another experiment - faces expressing moderate or high degrees of happiness intermixed with non-emotional faces. Repeated measures 2x3x3 ANOVA with emotion (fear and happy), intensity (neutral, moderate, and high) as within-subjects variables and group (patients, relatives, and controls) as between-subjects variable produced two clusters of differential activation, located in medial prefrontal cortex and left putamen. Activity in medial prefrontal cortex was greater in patients and in relatives compared with healthy volunteers in response to both fearful and happy faces. Activity in left putamen in response to moderate fear was greater in patients and in relatives compared with controls. Patients (but not relatives) showed also a greater activation in response to high intensity happy faces, compared with controls. Region of Interest analysis of amygdala activation showed increased activity in left amygdala in both patients and relatives groups in response to intensively happy faces. Exaggerated medial prefrontal cortical and subcortical (putamen and amygdala) responses to emotional signals may represent heritable neurobiological abnormalities underlying bipolar disorder.

Vulnerability to depression: what is the role of stress genes in gene x environment interaction?

Vulnerability to depression has been linked to the interaction of genetic predisposition with stressful life events. This review considers the associations between serotonergic and hypothalamic-pituitary-adrenal (HPA) systems. We follow the standpoint of a previous Editorial Review (Bhagwagar & Cowen, Psychological Medicine 2008, 38, 307-313) and consider another possible mechanism of vulnerability to depressive disorder, that is we suggest that the gene x environment interaction involves complex participation of serotonergic genes modulating response to stress through the HPA system.

Neural markers of symptomatic improvement during antidepressant therapy in severe depression: subgenual cingulate and visual cortical responses to sad, but not happy, facial stimuli are correlated with changes in symptom score.

Resting state activity in the ventral cingulate may be an important neural marker of symptomatic improvement in depression. The number of task related functional magnetic resonance imaging (fMRI) studies correlating blood oxygenation level dependent (BOLD) response with symptomatic improvement is limited and methodologies are still evolving. We measured BOLD responses to sad and happy facial stimuli in 12 severely depressed individuals in the early stages of antidepressant treatment (Time 1) and 12 weeks later (Time 2) using event-related fMRI. We calculated correlations between temporal changes in BOLD response and changes in symptom scores. Most subjects improved markedly by Time 2. At Time 1, depression severity correlated positively with responses to sad stimuli in the right visual cortex, subgenual cingulate, anterior temporal pole and hippocampus and correlated negatively with responses to happy stimuli in left visual cortex and right caudate. Decreases in individual effect sizes of right subgenual cingulate and right visual cortical responses to sad, but not happy, facial stimuli were correlated with decreases in symptom scores. There are contrasting cortical and subcortical responses to sad and happy stimuli in severe depression. Responses to sad stimuli show the strongest correlates of clinical improvement, particularly in the subgenual cingulate.

Genetic variation in the serotonin transporter modulates neural system-wide response to fearful faces.

A distributed, serotonergically innervated neural system comprising extrastriate cortex, amygdala and ventral prefrontal cortex is critical for identification of socially relevant emotive stimuli. The extent to which a genetic variation of serotonin transporter gene 5-HTTLPR impacts functional connectivity between the amygdala and the other components of this neural system remains little examined. In our study, neural activity was measured using event-related functional magnetic resonance imaging in 29 right-handed, white Caucasian healthy subjects as they viewed mild or prototypical fearful and neutral facial expressions. 5-HTTLPR genotype was classified as homozygous for the short allele (S/S), homozygous for the long allele (L/L) or heterozygous (S/L). S/S showed greater activity than L/L within right fusiform gyrus (FG) to prototypically fearful faces. To these fearful faces, S/S more than other genotype subgroups showed significantly greater positive functional connectivity between right amygdala and FG and between right FG and right ventrolateral prefrontal cortex (VLPFC). There was a positive association between measure of psychoticism and degree of functional connectivity between right FG and right VLPFC in response to prototypically fearful faces. Our data are the first to show that genotypic variation in 5-HTTLPR modulates both the amplitude within and the functional connectivity between different components of the visual object-processing neural system to emotionally salient stimuli. These effects may underlie the vulnerability to mood and anxiety disorders potentially triggered by socially salient, emotional cues in individuals with the S allele of 5-HTTLPR.

The role of 'shared representations' in social perception and empathy: an fMRI study.

Evidence suggests that we use the same mechanisms for both producing and perceiving actions. Such 'shared representations' may also underlie social perception and empathy. However, this idea raises some important and as yet unresolved questions: (i) how do we distinguish other-orientated empathic responses from a self-orientated reactions such as personal distress and (ii) what are the neural substrates underpinning these processes? We employed event-related functional magnetic resonance imaging (fMRI) to explore whether 'shared representations' were recruited to decode dynamic social stimuli in 12 healthy volunteers. We used an adapted version of the Profile of Non-Verbal Sensitivity (Rosenthal, H., Hall, J.A., DiMatteo, M.R., Rogers, P.L., Archer, D., (1979). Sensitivity to nonverbal communication: the PONS test. The Johns Hopkins University Press, Baltimore) which taps social perception using brief silent video clips. Participants chose one of two words that best described the state conveyed by the actor, or in the control condition using the same clips, the word describing which parts of the body were visible (non-social labelling). Off-line self-report measures of empathy and personal distress engendered by thoughts about others, were also given along with an experimentally-derived index of the degree of self-other overlap during social perception. Brain activation specific to the main experimental condition was found in the inferior frontal gyrus (BA44) and premotor areas (BA6) consistent with the use of 'shared representations'. Somatosensory areas such as the insula and supramarginal gyrus (BA40) were also activated suggesting that participants constructed a qualitative representation of the target state. Activity in the rostral anterior cingulate was associated with self-reports of personal distress and increased blood flow to the anterior cingulate (BA24) and inferior parietal cortex (BA40) was related to self-other overlap.

An examination of perceptual and cognitive set shifting tasks in acute anorexia nervosa and following recovery.

OBJECTIVES: People with anorexia nervosa have a broad spread of symptoms including disturbances in perception, cognition, emotions and behaviour. The aim of this study was to examine tests of executive function (in particular, perceptual and cognitive set shifting tasks) in patients with a current or past diagnosis of anorexia nervosa (AN). METHOD: 30 AN patients, 16 subjects recovered from anorexia nervosa (ANR) and 23 healthy controls were examined using tests of executive function (initiation tasks and perceptual and cognitive set shifting). RESULTS: The AN and ANR subjects had significantly higher perceptual and cognitive set shifting scores than the controls. CONCLUSIONS: Impaired executive function in terms of set shifting tasks could represent a vulnerability factor for AN.

Cortical substrates for the perception of face actions: an fMRI study of the specificity of activation for seen speech and for meaningless lower-face acts (gurning).

Can the cortical substrates for the perception of face actions be distinguished when the superficial visual qualities of these actions are very similar? Two fMRI experiments are reported. Compared with watching the face at rest, observing silent speech was associated with bilateral activation in a number of temporal cortical regions, including the superior temporal sulcus (STS). Watching face movements of similar extent and duration, but which could not be construed as speech (gurning; Experiment 1b) was not associated with activation of superior temporal cortex to the same extent, especially in the left hemisphere. Instead, the peak focus of the largest cluster of activation was in the posterior part of the inferior temporal gyrus (right, BA 37). Observing silent speech, but not gurning faces, was also associated with bilateral activation of inferior frontal cortex (BA 44 and 45). In a second study, speechreading and observing gurning faces were compared within a single experiment, using stimuli which comprised the speaker's face and torso (and hence a much smaller image of the speaker's face and facial actions). There was again differential engagement of superior temporal cortex which followed the pattern of Experiment 1. These findings suggest that superior temporal gyrus and neighbouring regions are activated bilaterally when subjects view face actions--at different scales--that can be interpreted as speech. This circuitry is not accessed to the same extent by visually similar, but linguistically meaningless actions. However, some temporal regions, such as the posterior part of the right superior temporal sulcus, appear to be common processing sites for processing both seen speech and gurns.

Audio-visual speech perception in schizophrenia: an fMRI study.

Abnormalities in the integration of auditory and visual language inputs could underlie many core psychotic features. Perceptual confusion may arise because of the normal propensity of visual speech perception to evoke auditory percepts. Recent functional neuroimaging studies of normal subjects have demonstrated activation in auditory-linguistic brain areas in response to silent lip-reading. Three functional magnetic resonance imaging experiments were carried out on seven normal volunteers, and 14 schizophrenia patients, half of whom were actively psychotic. The tasks involved listening to auditory speech, silent lip-reading (visual speech), and perception of meaningless lip movements (visual non-speech). Subjects also undertook a behavioural study of audio-visual word identification designed to evoke perceptual fusions. Patients and controls both showed susceptibility to audio-visual fusions on the behavioural task. The patient group as a whole showed less activation relative to controls in superior and inferior posterior temporal areas while performing the silent lip-reading task. Attending to visual non-speech, the patients activated less posterior (occipito-temporal) and more anterior (frontal, insular and striatal) brain areas than controls. This difference was accounted for largely by the psychotic subgroup. Insular and striatal areas were also activated in both subject groups in the auditory speech perception condition, thus demonstrating the bimodal sensitivity of these regions. The results suggest that schizophrenia patients with psychotic symptoms respond to visually ambiguous stimuli (non-speech) by activation of polysensory structures. This could reflect particular processing strategies and may increase susceptibility to certain paranoid and hallucinatory symptoms.