HCV Genotype Distribution Among People Who Inject Drug in Turkey: Findings from Multicenter and Cross-Sectional Study.

Background: Hepatitis C virus (HCV) infection is very common in people who inject drugs (PWID). Studies about the prevalence and genotype distribution of the HCV among PWID are very crucial for developing strategies to manage HCV infection. This study's objective is to map the distribution of HCV genotypes among PWID from various regions of Turkey. Method: This prospective, multicenter, cross-sectional study involved 197 PWID who tested positive for anti-HCV antibodies from 4 different addiction treatment facilities in Turkey. Interviews were done with people who had anti-HCV antibodies, and blood samples were taken to check the HCV RNA viremia load and genotyping. Results: This study was conducted on 197 individuals with a mean age of 30.3 ± 8.6 years. 9.1% (136/197 patients) had a detectable HCV-RNA viral load. Genotype 3 was the most commonly observed genotype by 44.1%, followed by genotype 1a by 41.9%, genotype 2 by 5.1%, genotype 4 by 4.4%, and genotype 1b by 4.4%. Whereas genotype 3 was dominant with 44.4% at the central Anatolia region of Turkey, the frequencies of genotypes 1a and 3, which were predominantly detected in the south and northwest regions of Turkey, were very close to each other. Conclusion: Although genotype 3 is the predominant genotype in the PWID population in Turkey, the prevalence of HCV genotype varied across the country. To eliminate HCV infection in the PWID, treatment and screening strategies that differ by genotype are essentially required. Especially identification of genotypes will be useful in developing individualized treatments and determining national prevention strategies.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part I: Anxiety disorders.

AIM: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders (published in 2002, revised in 2008). METHOD: A consensus panel of 33 international experts representing 22 countries developed recommendations based on efficacy and acceptability of available treatments. In total, 1007 RCTs for the treatment of these disorders in adults, adolescents, and children with medications, psychotherapy and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medications. RESULT: This paper, Part I, contains recommendations for the treatment of panic disorder/agoraphobia (PDA), generalised anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias, mixed anxiety disorders in children and adolescents, separation anxiety and selective mutism. Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line medications. Cognitive behavioural therapy (CBT) is the first-line psychotherapy for anxiety disorders. The expert panel also made recommendations for patients not responding to standard treatments and recommendations against interventions with insufficient evidence. CONCLUSION: It is the goal of this initiative to provide treatment guidance for these disorders that has validity throughout the world.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part II: OCD and PTSD.

AIM: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008. METHOD: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments. RESULT: The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD (n = 291) and PTSD (n = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders.For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs.Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated.For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option. CONCLUSION: OCD and PTSD can be effectively treated with CBT and medications.

The Development of Psychosis in Patients with Substance Use Disorder and Its Association with Cavum Septum Pellucidum and Adhesio Interthalamica.

Background: It is known that there is a relationship between psychotic disorders and the presence of cerebral midline defects, such as the cavum septum pellucidum and the absence of adhesio interthalamica. This study aims to investigate whether these defects in people with alcohol/substance use disorders are associated with the occurrence and persistence of psychotic symptoms. Methods: The files of the patients who were hospitalized in an addiction inpatient unit were retrospectively scanned. The presence of cavum septum pellucidum and the absence of adhesio interthalamica were determined by evaluation of the magnetic resonance imaging findings. The presence of psychotic symptoms at admission and the persistence of psychotic symptoms after 2 weeks of detoxification treatment were used as dependent variables in different logistic regression models. The presence of cavum septum pellucidum and the absence of adhesio interthalamica were included in 2 separate models as independent variables. Results: The results of the regression analyses showed no significant relationship with respect to cavum septum pellucidum. However, the analyses revealed that the absence of adhesio interthalamica increases the risk of the persistence of psychotic symptoms. Conclusion: Our findings suggest that the absence of adhesio interthalamica can be considered a structural risk factor for the development of psychosis in people receiving treatment for substance use.

Association of BDNF Gene Val66Met Polymorphism with Suicide Attempts, Focused Attention and Response Inhibition in Patients with Schizophrenia.

Introduction: The relationship between BDNF gene Val/Met polymorphism and clinical symptoms, attention and executive functions in patients with schizophrenia was investigated in this study. Also, BDNF Val66Met gene polymorphism was compared between patients and healthy controls. Thus, genetic factors that may affect both the etiology and cognitive functions in schizophrenia were evaluated. Methods: BDNF Val66Met gene polymorphism was investigated in 102 patients with schizophrenia and 98 healthy controls. Cognitive functions were evaluated by the Wisconsin Card Sorting Test (WCST) and Stroop Test. Results: There was no difference in terms of the genotypic or allelic distribution of BDNF Val66Met polymorphism between patients and healthy controls. A significantly higher percentage of suicide attempts were found in the patients having Met allele (Val/Met and Met/Met). Met allele was associated with failure in focused attention and response inhibition in patients with schizophrenia. Conclusion: The presence of the Met allele could be associated with the risk of suicide attempts in patients with schizophrenia. Impairment in executive function areas such as focused attention and response inhibition appears to be related to the Met allele.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies.

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population's economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

Determination of the Relationship Between Craving and 4-repeat Allele of DRD4 Gene Polymorphism in the Early Withdrawal Period of Alcohol Use Disorders.

Objective: Alcohol use disorder (AUD) is a disease with chronic relapses. Risk factors of craving, which is thought to be one of the predictors of relapse, have been studied for a long time. The DRD4 gene is located on chromosome 11p and has a 48-base pair variable number of tandem repeat (VNTR) polymorphisms in the 3rd exon. This study aimed to investigate if a relationship existed between craving and DRD4 VNTR polymorphism and to determine the predictors of craving. Methods: A total of 125 patients with AUD were included in the study. The sociodemographic data form, the Michigan Alcoholism Screening Test (MAST), the Obsessive Compulsive Drinking Scale (OCDS), and the Penn Alcohol Craving Scale (PACS) were applied to the patients. Polymerase chain reaction (PCR) was used to determine the DRD4 VNTR variant of all participants in the peripheral blood sample. Results: In the 4R/4R homozygous group, it was found that the age at first alcohol use was higher and the scores of the OCDS on the seventh day were lower, but this relationship could not be demonstrated in further statistical analyses. In the stepwise linear regression model, the age at first alcohol use, MAST score, duration of AUD, and delirium tremens history were found to be the predictors of craving. Conclusion: DRD4 VNTR polymorphism does not play a role as a predictor of craving. A decrease in age at first alcohol use, an increase in the MAST score, and the presence of delirium tremens were found to be the predictors of craving among the participants of this study.

The Effect of Anger and Family Functions on Bullying Behavior in Individuals with Substance Use Disorder between the Ages of 15 and 25.

Objective: This study aimed to investigate the effects of anger and family functions on bullying behavior in adolescents and young adults who are followed up with the diagnosis of substance use disorder. Methods: A total of 100 patients, whose ages were between 15 and 25 years and who were diagnosed as having substance use disorder, were included as study participants. All participants were subjected to the Sociodemographic Data Form, Family Assessment Device, Trait Anger-Anger Expression Scale, and Bullying Tendency Scale. Results: It was found that there was a positive relationship between bullying tendency scores and trait anger and anger expression outward scores and a negative relationship with anger control scores. It was observed that there was a positive correlation between subdimension scores of problem solving, roles, and showing necessary attention with respect to family function dimensions and bullying tendency scores. In the multivariate regression model evaluating the predictive power of independent factors associated with bullying tendency, it was observed that anger control from anger subdimensions and problem solving from family function subdimensions had a predictive effect on bullying tendency, and the combination of these 2 factors explained 26% of bullying tendency scores. Conclusion: In this study, it was observed that most of the anger and family function dimensions were related to bullying tendency; in particular, the anger control difficulties and the problem-solving skills in the family were the factors that predicted bullying behavior. We think that addressing these factors that have an impact on bullying behavior in the treatment process will be important to regulate the relations with the outside world in this age group.

Health anxiety during the early phases of COVID-19 pandemic in Turkey and its relationship with postpandemic attitudes, hopelessness, and psychological resilience.

PURPOSE: To investigate health anxiety-related factors in the early stages of pandemic in Turkey. DESIGN AND METHODS: This study included 1046 participants who responded to the online survey anonymously between 28 March and 04 April 2020. FINDINGS: Demographic data, postpandemic attitudes towards the elderly and precaution-taking behaviors were health anxiety-related factors. The main predictors of the health anxiety were the level of hopelessness, perception of self, time spent on social media, and following COVID-19 pandemic-related news. PRACTICE IMPLICATIONS: The results of this study are important in terms of understanding the health anxiety during the pandemic and providing data support for the proper interventions.

[Relationship Between Alcohol Dependence and Neuropeptide Y (NPY) Gene Promoter Polymorphisms in A Turkish Sample]. / Türkiye Örnekleminde Nöropeptit Y Geni (NPY) Promotor Polimorfizmleri ve Alkol Bagimliligi Arasindaki Iliski.

OBJECTIVE: Neuropeptide Y (NPY) is a protein widely expressed in the central nervous system and involved in diverse physiological processes, such as emotional regulation, nutritional behavior, and stress. In some populations, studies on alcohol dependence (AD) and the NPY gene have found that NPY variations increase alcohol consumption and thus may potentially be associated with AD. In this study, we investigated the relationship between NPY gene promoter polymorphisms and phenotypes related to alcohol use. METHOD: A total of 417 male participants comprising 252 individuals with AD and 165 healthy individuals were included in this study and phenotypic data were collected. Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) and DNA sequencing METHODS were used for genotyping the rs16147 and rs17149106 polymorphisms in the promoter region of the NPY gene. The data of 384 participants were analysed to evaluate the possible relationship between genotypes and the diagnosis of AD, family history of AD, the severity of AD using the Michigan Alcoholism Screening Test (MAST), the age of onset of problematic alcohol use, the average amount of alcohol consumed per day for the last six months and the lifetime maximum alcohol consumption in one day. RESULTS: A significant difference was found between the AD and control groups concerning rs16147 polymorphism genotype distribution (p=0.025). No association with polymorphisms and alcohol-related phenotypes were demonstrated in the AD group. CONCLUSION: To our knowledge, this study shows for the first time in the literature that alcohol dependence is associated with NPY rs16147 polymorphism in the Turkish population.

Binomial Logistic Regression and Artificial Neural Network Methods to Classify Opioid-Dependent Subjects and Control Group Using Quantitative EEG Power Measures.

Logistic regression (LR) and artificial neural networks (ANNs) are widely referred approaches in medical data classification studies. LR, a statistical fitting model, is suggested in medical problems because of its well-established methodology and coefficients contributing to the evaluation of clinical interpretations. ANNs are graphical models structured with node networks interconnected with arcs each of which is expressed in terms of weights discovered throughout the modeling process. Since ANNs have a complex structure with its layers and nodes in the layers, which provides ANNs the ability to model any data with complex relationships. Among the various models having origins in statistics and computer science, LR and ANNs have prevailed in the area of mass medical data classification. In this study, we introduce the 2 aforementioned approaches in order to generate a model dichotomizing 75 opioid-dependent patients and 59 control subjects from each other. Quantitative electroencephalography (QEEG) absolute power value of each electrode were calculated for 4 consecutive frequency bands namely delta, theta, alpha, and beta with the frequencies, 0.5 to 4, 4 to 8, 8 to 12, and 12 to 20 Hz, respectively. Significant independent variables contributing to the classification were underlined in LR while a feature selection (FS) method, genetic algorithm, is being applied to the ANN model to reveal more informative features. The performances of the classifiers were finally compared considering overall classification accuracies, area under receiver operating characteristic curve scores, and Gini coefficient. Although ANN-based classifier outperformed compared with LR, both models performed satisfactorily for absolute power measure in beta frequency band. Our results underline the potential benefit of the introduced methodology is promising and is to be treated as a clinical interface in dichotomizing substance use disorders subjects and for other medical data analysis studies.

TARC: Turkish aripiprazole consensus report- Aripiprazole use and switching from other antipsychotics to aripiprazole- consensus recommendations by a Turkish multidisciplinary panel.

In this review, we have attempted to share our 10 years' clinical experience with aripiprazole use and switching from other antipsychotics to aripiprazole. There are various reasons for switching, including a partial or complete lack of efficacy, adverse side effects, and partial or noncompliance with medication. Aripiprazole has some unique receptor-binding qualities that provides some advantages over other antipsychotics in certain clinical situations. We have covered potential clinical scenarios for aripiprazole use as a single agent and switching from other agents in inpatient and outpatient settings. Patients switched from other antipsychotics to aripiprazole have been shown to benefit from significant improvements in clinical response and tolerability. This review examines the strategies for switching patients from antipsychotic drugs to aripiprazole.

Volumetric brain abnormalities in polysubstance use disorder patients.

AIM: Polysubstance users represent the largest group of patients seeking treatment at addiction and rehabilitation clinics in Turkey. There is little knowledge about the structural brain abnormalities seen in polysubstance users. This study was conducted to examine the structural brain differences between polysubstance use disorder patients and healthy control subjects using voxel-based morphometry. METHODS: Forty-six male polysubstance use disorder patients in the early abstinence period and 30 healthy male controls underwent structural magnetic resonance imaging scans. Voxel-based morphometry analysis was performed to examine gray matter (GM) abnormality differences. RESULTS: Polysubstance use disorder patients displayed significantly smaller GM volume in the thalamus, temporal pole, superior frontal gyrus, cerebellum, gyrus rectus, occipital lobe, anterior cingulate cortex, superior temporal gyrus, and postcentral gyrus. CONCLUSION: A widespread and smaller GM volume has been found at different regions of the frontal, temporal, occipital, and parietal lobes, cerebellum, and anterior cingulate cortex in polysubstance users.

[µ-Opioid Receptor Gene (OPRM1) Polymorphisms A118G and C17T in Alcohol Dependence: A Turkish Sample]. / Türkiye'de Alkol Bagimliliginda µ-Opioid Reseptör Geni (OPRM1) A118G ve C17T Polimorfizmleri.

OBJECTIVES: Previous investigations on opioid system genetics have identified polymorphisms of the OPRM1 gene expressing µ-opioid receptors to be significantly associated with some features of alcohol dependence (AD). In the present study, we evaluated the relationship between single nucleotide polymorphisms (SNP) in the OPRM1 gene, A118G (rs1799971, Asn40Asp) and C17T (rs1799972, Arg6Val), and AD diagnosis, level of alcohol consumption, and AD severity in a Turkish sample. METHODS: 121 AD patients and 117 healthy male subjects were included in the study. OPRM1 A118G (N40D) and C17T (A6V) polymorphisms were evaluated using PCR - RFLP (polymerase chain reaction - restriction fragment length polymorphism) method. We evaluated the association between the presence of SNPs and AD diagnosis, family history of AD, AD severity evaluated via the Michigan Alcoholism Screening Test (MAST), the daily average and maximum quantity of alcohol consumed. RESULTS: There was no significant difference in OPRM1 A118G genotype frequencies between the AD and control groups. T allele frequency for the OPRM1 C17T SNP was very low (0.006) in the sample population. OPRM1 A118G SNP G118 allele carriers showed significantly higher levels of AD severity as indicated by the MAST. CONCLUSION: The OPRM1 G118 allele was significantly associated with more severe AD in the Turkish population. Similar to other European populations, the frequency of the OPRM1 T17 allele was very low.

Cabergoline-induced manic episode: case report.

Cabergoline is an orally administered synthetic dopamine agonist that is used for the treatment of hyperprolactinemia, Parkinson's disease and antipsychotic-induced prolactin elevation. One of the main characteristics of cabergoline is its long duration of effect. It is highly effective in suppressing prolactin levels up to 21 days after a single 1 mg oral dose. The prolonged elimination half-life offers an advantage of once-daily dosing, but it might be a handicap in terms of washout of adverse effects such as psychosis. Cabergoline has been associated with adverse reactions consistent with other dopaminergic agonists including cardiovascular, gastrointestinal and neuropsychiatric effects. It is known that dopaminergic treatment is a remarkable risk factor for psychosis. A number of reports implicate dopamine agonists in the development of psychosis, but there is no knowledge in the literature of dopamine agonist-induced mania. In this case, we report the first manic episode occurring after cabergoline use for hyperprolactinemia treatment. In susceptible individuals, cabergoline can cause manic episodes and cabergoline should be used more carefully considering the risk-benefit ratio.

A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine.

OBJECTIVE: The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). METHODS: Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤ 5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. RESULTS: Of 396 patients, 65.2% were men, mean age was 40.0 ± 12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥ 20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8 ± 5.2 kg at endpoint, and a clinically relevant weight gain of ≥ 7% occurred in 8.0% of patients. CONCLUSION: Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine.

Metabolic syndrome in drug-naïve and drug-free patients with schizophrenia and in their siblings.

OBJECTIVES: We tested the hypothesis that metabolic disturbances in people with schizophrenia exist as a part of the schizophrenic syndrome, even when the antipsychotic drug effect is eliminated. We aimed to determine the prevalence of metabolic syndrome among patients with schizophrenia who were antipsychotic drug-naive or drug-free and their siblings for comparison with healthy controls. METHODS: One-hundred-two patients with schizophrenia (drug-naïve or drug-free), 64 siblings and 70 age-matched healthy subjects were recruited for this case-control study. Metabolic syndrome was assessed based on Adult Treatment Panel (ATP) III, adapted ATP III and International Diabetes Federation criteria. Student's t-tests, chi-squared tests, Kruskal-Wallis tests and Bonferroni corrections were used as appropriate. RESULTS: The diagnoses of metabolic syndrome and metabolic disturbances as a subsyndromal state were found to be significantly more frequent in patients and their siblings than in the controls. Low levels of high-density lipoprotein cholesterol and disturbances in blood pressure put the patient group at risk for metabolic syndrome even before they were exposed to antipsychotic drugs. CONCLUSIONS: Although antipsychotic drugs have consistently been related to disturbances of glucose and lipid metabolism in patients with schizophrenia, this study showed that patients with schizophrenia and their siblings are already at a high risk for metabolic syndrome independent of any antipsychotic effects. These individuals should be monitored regularly following a diagnosis of schizophrenia.

Thalamic and Cerebellar Gray Matter Volume Reduction in Synthetic Cannabinoids Users.

BACKGROUND: Synthetic cannabinoids are compounds that bind cannabinoid receptors with a high potency and have been used widely in Europe by young people. However, little is known about the pharmacology and morphological effects of this group of substances in the brain. This study is aimed at investigating the morphological differences among synthetic cannabinoids users and healthy controls. METHODS: Voxel-based morphometry was used to investigate the differences in brain tissue composition in 20 patients with synthetic cannabinoids use and 20 healthy controls. All participants were male. RESULTS: Compared to healthy controls, voxel of interest analyses showed that regional grey matter volume in both left and right thalamus and left cerebellum was significantly reduced in synthetic cannabinoids users (p < 0.05). No correlation has been found between the age of first cannabis use, duration of use, frequency of use and grey matter volume. DISCUSSION: These preliminary results suggest an evidence of some structural differences in the brain of synthetic cannabinoids users, and point the need for further investigation of morphological effects of synthetic cannabinoids in the brain.