DTI-MRI findings in synthetic cannabinoid users

Background/aim: Synthetic cannabinoids (SCs) are full agonists of both cannabinoid receptors. Conventional magnetic resonance imaging (MRI) findings of SC users are mainly defined as diffusion restriction and T2/FLAIR hyperintensity. Diffusion tensor imaging (DTI) studies examining SC users have shown contradictory results. The aim of this study was to define white matter (WM) changes of SC users using DTI. Materials and methods: The study included 22 patients with a history of using SC for 5­37 months, and 22 healthy, age and sex-matched control subjects. A total of 41 diffusion gradient directions were used in the acquisition of diffusion imaging data. Fractional anisotropy (FA) and apparent diffusion coefficients (ADC) values were obtained. ROIs were placed on WM areas of normal appearance. Results: In the SC users, significantly lower FA values were determined in the left temporal lobe (216.2 ± 58.9 vs. 263 ± 27.4; P = 0.002) and right hippocampus (224.5 ± 61.5 vs. 255 ± 24.3; P = 0.040). The ADC values of the hippocampus and temporal lobe were significantly higher than those of the control group on both the left and right sides. Conclusion: The SC use causes WM microstructural changes, especially in the hippocampus and temporal lobes. DTI is a useful tool to reveal WM changes in SC addicts and can be used earlier than conventional MRI.

Association of OPRK1 rs963549 and rs997917 polymorphisms with opioid use disorder and related phenotypes.

Aim: To evaluate the association between OPRK1 rs963549 and rs997917 and opioid use disorder (OUD) and related phenotypes. Methods: A sample of 208 individuals with (n = 100) and without (n = 108) OUD were enrolled. OPRK1 rs963549 and rs997917 were analyzed by PCR-RFLP. Craving, opioid withdrawal and the intensity of depressive and anxiety symptoms were measured by the appropriate scales. Results: OPRK1 rs963549 variation showed a trend of association with decreased opioid withdrawal. No significant associations were found between OPRK1 rs963549 and rs997917 polymorphisms and craving, depression or anxiety symptoms. Neither single OPRK1 SNPs nor OPRK1 haplotypes were associated with OUD. Conclusion: Our results could be useful for treatment failures of individuals who experience greater opioid withdrawal due to their OPRK1 rs963549 genotypes.

Effects of UGT2B7 rs7662029 and rs7439366 polymorphisms on sublingual buprenorphine metabolism in heroin addicts: An improved PCR-RFLP assay for the detection of rs7662029 polymorphism.

This study aimed to determine the effects of UGT2B7 rs7662029 and rs7439366 polymorphisms on plasma buprenorphine (BUP) concentration and different treatment responses in a sample of 109 patients with opioid use disorder (OUD) treated with sublingual BUP/naloxone. Polymorphisms were analysed by PCR-RFLP. Plasma concentrations of BUP and its metabolite norbuprenorphine were detected by LC-MS/MS. Craving, withdrawal, depression and anxiety were measured by appropriate scales. OUD patients with rs7439366 CC or rs7662029 GG genotypes had significantly lower dose-normalized (BUP/D) and dose/kg-normalized BUP (BUP/D.kg-1) levels than those who were CT or AA carriers. Significant associations between UGT2B7 rs7662029 and increased craving (p = 0.037) and withdrawal symptoms (p = 0.029) were detected. Our findings were pointing to an important role of UGT2B7 in the metabolism of sublingual BUP/naloxone in the heroin addicts for the first time. A novel PCR-RFLP assay was developed for the determination of UGT2B7 rs7662029 polymorphism, based on utilizing novel restriction enzyme.

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.

Sublingual buprenorphine/naloxone treatment is not affected by OPRM1 A118G and BDNF Va66Met polymorphisms, but alters the plasma beta-endorphin and BDNF levels in individuals with opioid use disorder.

The study aimed to examine the genetic contribution to buprenorphine (BUP) treatment in individuals with opioid use disorder (OUD), with a specific focus on BDNF and OPRM1 genes. A total of 113 controls and 111 OUD patients receiving sublingual BUP/naloxone were enrolled. OPRM1 A118G and BDNF Val66Met polymorphisms were investigated by PCR-FRLP. Plasma BDNF and beta-endorphin levels were assessed by ELISA kits in both groups. Blood BUP levels were measured by LC-MS/MS and normalized with daily BUP dose (BUP/D). OPRM1 A118G and BDNF Val66Met polymorphisms didn't have an effect on plasma beta-endorphin and BDNF levels in OUD patients, respectively. Interestingly, OUD patients had significantly higher plasma BDNF and lower beta-endorphin levels compared to the controls (p < 0.001). A negative and significant correlation between plasma BUP/D and BDNF levels was found. Age onset of first use was associated with OPRM1 A118G polymorphism. The findings indicated that sublingual BUP/naloxone may increase plasma BDNF levels, but may decrease beta-endorphin levels in individuals with OUD. Plasma BDNF level seemed to be decreased in a BUP/D concentration-dependent manner.

Association of Glial Cell-Line Derived Neurotrophic Factor and Nerve Growth Factor with Duration of Untreated Psychosis and Clinical Symptoms in Drug-Naive Schizophrenia.

Background: The neurodevelopmental hypothesis is one of the most-emphasized hypotheses in the etiology of schizophrenia. Nerve growth factor (NGF) and glial cell-line derived neurotropic factor (GDNF) are neurotrophic factors that provide growth, differentiation, and survival in nerve cells in the development process. In this study, we aimed to compare the GDNF and NGF levels of schizophrenia patients with healthy controls and to analyze the relationship between the Positive and Negative Syndrome Scale (PANSS) scores, serum GDNF and NGF levels and the duration of untreated psychosis (DUP) of the patients. Methods: The study involved 45 patients with a diagnosis of schizophrenia, who had never used any antipsychotic drug, and 45 age- and sex-matched healthy participants. The participants filled a sociodemographic data form. The PANSS was applied to evaluate the clinical conditions. Before the initiation of the treatment, serum samples were collected from the patients. Results: The difference between the GDNF and NGF levels of the patient group and control group was statistically significant. The serum GDNF and NGF levels in schizophrenia patients were lower than healthy controls. No correlation was found between the DUP and serum GDNF and NGF levels. There was a positive correlation between general psychopathology and negative scores of PANSS and the DUP of patients. Conclusion: GDNF and NGF levels seem to be indicators of schizophrenia and its progress; nevertheless, we still do not have sufficient information about these neurotrophic factors. The results of our study indicate that the neurodevelopmental changes occurring at the early stages of the illness prominently affect the progress of disease, highlighting the importance of treatment in the early stages of disease.

Evaluation of the diagnostic performance of an oral fluid screening test device for substance abuse at traffic controls.

INTRODUCTION: The aim of this study was to evaluate the analytical performance of the Kite Biotechnology Oral fluid (OF) screening test device, which is used for roadside screening of cannabis, opiates, amphetamines, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), cocaine and benzodiazepines by comparing samples with matched plasma samples, analysed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for confirmation. METHODS: OF and plasma samples were obtained simultaneously from a total of 100 subjects. OF samples were analysed by OF screening test based on immunochromatography. The OF screening test cut-off values were 50 ng/mL for amphetamines (d-amphetamine) and methamphetamine/MDMA (d-methamphetamine), 30 ng/mL for cocaine (benzoylecgonine), 40 ng/mL for opiates (morphine), 20 ng/mL for benzodiazepines (nordazepam), and 25 ng/mL for cannabis (Δ9-tetrahydrocannabinol). LC-MS/MS method validation was performed according to the CLSI C62-A recommendations with the following parameters: matrix effect, lower limit of quantification (LLOQ), linearity, intra-day and inter-day precision and accuracy. RESULTS: The overall specificity, accuracy and negative predictive values (NPV) were acceptable and met the DRUID standard of >80%. The OF screening test device showed good sensitivity for cocaine, amphetamines and opiates, whereas it indicated poor sensitivity for methamphetamine/MDMA (66.7%) and failed to detect cannabis and benzodiazepines. CONCLUSION: The present study is the first report to evaluate the Kite Biotechnology OF screening test device. The diagnostic performance of the OF screening test device was acceptable for opiates, cocaine and amphetamines, but it was insufficient for methamphetamine/MDMA, benzodiazepines and cannabis because of sensitivity issues.

Association of serum brain derived neurotropic factor with duration of drug-naive period and positive-negative symptom scores in drug naive schizophrenia.

INTRODUCTION: The aim of this study was to compare the serum brain derived neurotropic factor (BNDF) levels of patients with schizophrenia who had never received an antipsychotic treatment with those of a control group. Also, to analyze the relationship between the Positive and Negative Symptom Scale (PANSS) scores and BDNF levels of the patients during the period they were drug-naive. MATERIALS AND METHODS: The sample of the study comprised patients who presentedto the Psychiatry Clinic and were admitted after a distinctive schizophrenia diagnosis was made in accordance with the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) diagnosis classification and who were not using and never had any antipsychotic medicine. A total of 160 participants were included in the study, 80 of whom had schizophrenia patients and 80 constituted the age- and sex-matched healthy control group. Before the start of the treatment, the serum samples to be checked for the BDNF levels were collected from the patients. RESULTS: The difference between the average BDNF levels of the groups were statistically significant (t = -5.25; p˂.001). An analysis as to whether there was a relation between the BDNF levels and the drug-naïve duration indicated no correlations. An examination of the relationship between PANSS scores and BDNF levels of the patients yielded no correlations. DISCUSSION: Serum BDNF levels seem to be one of the indicators of schizophrenia and its progress; nevertheless, we still do not have sufficient information about this neurotropic factor. In light of our study, the neurodevelopmental changes that occur at disease onset of the illness prominently affect the progress of the illness, which highlights the importance of the treatment in the early stages.

TNF-related weak inducer of apoptosis (TWEAK) levels in schizophrenia.

Members of tumor necrosis factor (TNF) superfamily have roles in many biological events and pathogenesis of central nervous system (CNS) diseases. A relatively recently found member of this family, TNF-related weak inducer of apoptosis (TWEAK) have importance both in development of pathological CNS processes and as a target for the treatment of these diseases. The aim of this study was to investigate whether TWEAK's plasma levels are different in patients with schizophrenia. For this purpose plasma TWEAK levels of 44 patients diagnosed with schizophrenia and control group of 40 healthy individuals were compared. Although numerical difference was found between TWEAK levels of patients and controls it was not statistically significant. When we tested for female and male patients and controls seperately, TWEAK levels of male patients were significantly lower than male controls. As far as we know this is the first study that investigates levels of TWEAK in patients with schizophrenia. Although we did not find statistically significant results in our study, we believe that difference could be found in future studies with higher number of subjects. Researches with non-studied TNF superfamily members like TWEAK and TNF-related apoptosis-inducing ligand (TRAIL) could contribute to the understanding of immune-cytokine related hypotheses of schizophrenia.