A case control study investigating the methylation levels of GHRL and GHSR genes in alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) is a relapsing disease described as excessive use of alcohol. Evidence of the role of DNA methylation in addiction is accumulating. Ghrelin is an important peptide known as appetite hormone and its role in addictive behavior has been identified. Here we aimed to determine the methylation levels of two crucial genes (GHRL and GHSR) in ghrelin signaling and further investigate the association between methylation ratios and plasma ghrelin levels. METHODS: Individuals diagnosed with (n = 71) and without (n = 82) AUD were recruited in this study. DNA methylation levels were measured through methylation-sensitive high-resolution melting (MS-HRM). Acylated ghrelin levels were detected by ELISA. The GHRL rs696217 polymorphism was analyzed by the standard PCR-RFLP method. RESULTS: GHRL was significantly hypermethylated (P < 0.0022) in AUD between 25 and 50% methylation than in control subjects but no significant changes of GHSR methylation were observed. Moreover, GHRL showed significant positive correlation of methylation ratio between 25 and 50% with age. A significant positive correlation between GHSR methylation and ghrelin levels in the AUD group was determined (P = 0.037). The level of GHRL methylation and the ghrelin levels showed a significant association in the control subjects (P = 0.042). CONCLUSION: GHSR and GHRL methylation levels did not change significantly between control and AUD groups. However, GHRL and GHSR methylations seemed to have associations with plasma ghrelin levels in two groups. This is the first study investigating the DNA methylation of GHRL and GHSR genes in AUD.

Ghrelin and impulsivity relationship in alcohol-dependent patients and healthy individuals.

AIMS: Abundant research indicates that ghrelin hormone levels are associated with alcohol use and addiction. One of the mediators of this association may be impulsivity, which is one of the common traits observed in alcohol addiction and some eating disorders. This study evaluated participants with alcohol dependency and healthy volunteers to determine whether trait impulsivity and ghrelin levels are associated. METHODS: This study analyzed trait impulsivity scores and fasting serum ghrelin levels of 44 males with alcohol dependency and 48 healthy male participants. The Barratt Impulsiveness Scale and the UPPS Impulsive Behaviour Scale (UPPS) were used to measure trait impulsivity levels. Penn Alcohol Craving Scale and Yale Brown Obsessive Compulsive Drinking Scale for heavy drinking were used to assess craving at the baseline and after the detoxification period. RESULTS: Alcohol-dependent patients' fasting ghrelin levels were significantly higher than that of healthy participants. Ghrelin plasma levels were positively correlated with UPPS total impulsivity scores and sensation-seeking among healthy individuals. In alcohol-dependent participants, there was a positive correlation between UPPS urgency scores obtained at the baseline and fasting ghrelin levels before and after the detoxification period. CONCLUSIONS: Ghrelin-impulsivity relationship could be observed in certain dimensions of impulsivity in both alcohol-dependent and healthy individuals and even independent of the effect of alcohol. Although the associated impulsivity dimensions differ in different groups, the results are parallel to other studies in terms of demonstrating the relationship between ghrelin and impulsivity.

Association of PDYN 68-bp VNTR polymorphism with sublingual buprenorphine/naloxone treatment and with opioid or alcohol use disorder: Effect on craving, depression, anxiety and age onset of first use.

In this case-control study (423 Turkish subjects), the functional pro-dynorphin (PDYN) 68-bp VNTR polymorphism was genotyped in opioid users receiving sublingual buprenorphine/naloxone treatment (SBNT; n = 129, 119 males and 10 females), in opioid users (OUD; n = 99, 90 males and 9 females), in alcohol users (AUD; n = 75, 75 males) and in controls (n = 120, 109 males and 11 females) to determine the effect of this polymorphism on different treatment responses, heroin or alcohol dependence as well as age onset of first use. The PDYN 68-bp alleles were determined based on the number of repeats and genotypes were classified as "short/short (SS)", "short-long (SL)" and "long-long (LL)". The intensity of craving, withdrawal, depression and anxiety were measured by the Substance Craving Scale (SCS), the Clinical Opiate Withdrawal Scale (COWS), the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively. Healthy controls (5.5 ± 5.8) had significantly lower levels of depressive symptoms compared to OUD (25.4 ± 13.5), AUD (22.5 ± 11.3) and SBNT (19.29 ± 12.2) groups. In OUD group, the LL genotype was associated with decreased intensity of anxiety and depressive symptoms than the SS+SL genotype. The BDI-II scores for PDYN VNTR genotypes within the 4 groups were analysed by two-way ANOVA and statistical differences were found for the groups. SBNT group had significantly lower COWS score than OUD group (1.00 versus 3.00). There were statistically significant differences in the median BAI (11 versus 24) and BDI-II scores (17.5 versus 25) between OUD and SBNT groups, supporting the antidepressant and anxiolytic effects of SBNT in persons with OUD.

Cortical activity during social acceptance and rejection task in social anxiety disorder: A controlled functional near infrared spectroscopy study.

BACKGROUND: The cognitive and emotional vulnerability of individuals with social anxiety disorder (SAD) and their response to repeated experiences of social rejection and social acceptance are important factors for the emergence and maintenance of symptoms of the disorder. Functional neuroimaging studies of SAD reveal hyperactivity in regions involved in the fear circuit such as amygdala, insula, anterior cingulate, and prefrontal cortices (PFC) in response to human faces with negative emotions. Observation of brain activity, however, involving studies of responses to standardized human interaction of social acceptance and social rejection have been lacking. METHODS: We compared a group of index subjects with SAD (N = 22, mean age:26.3 ± 5.4, female/male: 7/15) (SADG) with a group of healthy controls (CG) (N = 21, mean age:28.7 ± 4.5, female/male: 14/7) in measures of cortical activity during standardized experiences of human interaction involving social acceptance (SA) and social rejection (SR) video-simulated handshaking tasks performed by real actors. In a third, control condition (CC), the subjects were expected to press a switch button in an equivalent space. Subjects with a concurrent mood episode were excluded and the severity of subclinical depressive symptoms was controlled. 52-channel functional near-infrared spectroscopy (fNIRS) was used to measure cortical activity. RESULTS: Activity was higher in the SAD subjects compared to healthy controls, in particular in channels that project to middle and superior temporal gyri (STG), frontal eye fields (FEF) and dorsolateral prefrontal cortex (DLPFC) in terms of both SA and SR conditions. Cortical activity during the CC was not different between the groups. Only in the SAD-group, activity in the pre-motor and supplementary motor cortices, inferior and middle temporal gyri and fronto-polar area was higher during the rejection condition than the other two conditions. Anxiety scores were correlated with activity in STG, DLPFC, FEF and premotor cortex, while avoidance scores were correlated with activity in STG and FEF. CONCLUSIONS: SA and SR are represented differently in terms of cortical activity in SAD subjects compared to healthy controls. Higher activity in both social conditions in SAD subjects compared to controls may imply biological sensitivity to these experiences and may underscore the importance of increased cortical activity during social interaction experiences as a putative mediator of vulnerability to SAD. Higher cortical activity in the SADG may possibly indicate stronger need for inhibitory control mechanisms and higher recruitment of theory of mind functions during social stress. Higher activity during the SR compared to the SA condition in the SAD subjects may also suggest distinct processing of social cues, whether they involve acceptance or rejection.

Live Donor Assessment Tool (LDAT): A Turkish validity and reliability study.

BACKGROUND/AIMS: Psychosocial and psychiatric evaluations are crucial components of the assessment of a live donor candidate. The Live Donor Assessment Tool (LDAT) was developed for this purpose. This study aims to evaluate the validity and reliability of the Turkish version of LDAT. MATERIALS AND METHODS: 132 live kidney or liver donor were referred to assess their psychosocial/psychiatric appropriateness for donation and were randomized for clinical evaluation as usual or with LDAT. The internal consistency of LDAT was measured by Chronbach's alpha coefficient. Inter-rater reliability was measured by using Spearman's correlation coefficient. The potential validity of LDAT was assessed by comparing LDAT scores to clinical decisions. The Mann-Whitney U test was used to compare LDAT scores across two clinically classified groups (acceptable/declined). Logistic regression was performed using LDAT scores to predict the clinical decision. RESULTS: The Turkish version of LDAT items demonstrate good internal consistency (α=0.773). Inter-rater reliability of LDAT demonstrated strong correlation (ICC=0.72). LDAT scores differentiated the accepted/declined groups, and strongly predicted the clinical decision. With a cut-off score of 60.5, LDAT was found to have high sensitivity and specificity. CONCLUSION: The Turkish version of LDAT was found to be a valid and reliable tool. LDAT could be an appropriate tool to assess live donor candidates.

Risk factors for valproic acid induced hyperammonemia and its association with cognitive functions.

OBJECTIVE: Valproic acid (VPA)-induced hyperammonemia (VIH), is an increase in blood ammonia levels without any alteration of hepatic enzymes, which can occur during VPA treatment. We aimed to determine the prevalence rate and the risk factors for VIH and its association with cognitive functions. METHOD: A prospective, cross-sectional study was conducted. Patients aged between 18 and 64 who were on VPA treatment and who diagnosed with mood disorders or epilepsy were enrolled in this study (n = 107). For cognitive assessment, Serial 7's and Subjective Memory Complaints Questionnaire (SMCQ) were used. Blood samples were collected for blood VPA and ammonia levels along with other laboratory tests. RESULTS: 55,3% of the sample were considered as VIH. Blood ammonia level significantly correlates with VPA blood levels, total daily dose of VPA and total number of medications concurrently used, but no significant correlation was found between blood ammonia level and cognitive test scores. Gender, body weight, blood VPA levels and the total number of medications concurrently used significantly predicted blood ammonia levels (F(4,81) = 2670, p = 0,038, R2 = 0,116). CONCLUSION: VIH is relatively high in our sample. There is a dose-dependent association between VPA and blood ammonia level. No association was found between cognitive functions and hyperammonemia however with some limitations. Future, prospective cohort studies are needed.