Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

AIMS: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. METHODS: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. RESULTS: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. CONCLUSIONS: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Sodium oxybate for the maintenance of abstinence in alcohol-dependent patients: An international, multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. AIMS: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. METHODS: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3-3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. RESULTS: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6-68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites (n = 3-66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. CONCLUSIONS: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648423.

Using Biotinylated myo-Inositol Hexakisphosphate to Investigate Inositol Pyrophosphate-Protein Interactions with Surface-Based Biosensors.

Inositol pyrophosphates (PP-InsPs) are highly phosphorylated molecules that have emerged as central nutrient messengers in eukaryotic organisms. They can bind to structurally diverse target proteins to regulate biological functions, such as protein-protein interactions. PP-InsPs are strongly negatively charged and interact with highly basic surface patches in proteins, making their quantitative biochemical analysis challenging. Here, we present the synthesis of biotinylated myo-inositol hexakisphosphates and their application in surface plasmon resonance and grating-coupled interferometry assays, to enable the rapid identification, validation, and kinetic characterization of InsP- and PP-InsP-protein interactions.

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy.

BACKGROUND: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD. METHODS: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis. RESULTS: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months). CONCLUSIONS: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.

Treating alcohol dependence with an abuse and misuse deterrent formulation of sodium oxybate: Results of a randomised, double-blind, placebo-controlled study.

Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen's d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.

Post-marketing and clinical safety experience with sodium oxybate for the treatment of alcohol withdrawal syndrome and maintenance of abstinence in alcohol-dependent subjects.

Introduction: Sodium oxybate (SMO) has been approved in Italy and in Austria for the treatment of alcohol use disorder (AUD). This study describes the cumulative postmarketing and clinical safety experience with SMO in AUD.Areas covered: Safety data for SMO at approved posology in AUD were identified from: (i) the clinical trial registries of the US National Institutes of Health (NIH) and the European Medicines Agency (EMA), (ii) reports from the biomedical literature and (iii) available pharmacovigilance safety information from the EMA.Expert opinion: Safety data from 3 recent large randomized clinical studies (520 participants) and 43 earlier clinical studies (2547 participants) showed that SMO has a good safety profile in AUD patients. The safety profile was confirmed by pharmacovigilance data resulting from 299 013 patients exposed to SMO in Austria and Italy. Main adverse events were transitory dizziness and vertigo. Serious adverse events were rare. No death attributable to SMO has been reported. Risks of abuse or dependence are low in patients without psychiatric comorbidities or poly-drug use. The adverse events of SMO are transitory and do not require discontinuation of treatment. SMO abuse or dependence are extremely rare in patients without psychiatric comorbidities or poly-drug use.

Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level.

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABAB receptors and extrasynaptic GABAA receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL.

No evidence of subgroups found in amphetamine consumers in Iran.

Amphetamine type substances are the second most commonly consumed illicit drug type and their use is an important contributor to the global burden of disease. This investigation set out to determine whether, similar to alcohol or nicotine addiction, subgroups of consumers can also be found in amphetamine addicts. 204 consumers of methamphetamine only (n = 50) or both methamphetamine and heroin (n = 154) have been investigated in Mashhad, Iran by means of "Lesch Alcoholism Typology". No significant differences in consumption pattern or age of onset have been found between the different types. Many subjects, however, reported symptoms of anxiety (n=78) or depression (n = 129) prior to drug use. These findings highlight the need for high quality epidemiological studies further addressing this issue.

Changes in Pro-Inflammatory Markers in Detoxifying Chronic Alcohol Abusers, Divided by Lesch Typology, Reflect Cognitive Dysfunction.

AIM: To investigate pro-inflammatory markers in the blood and associate with cognitive impairment. METHODS: Il-6 and ferritin were assayed in the blood of 27 patients, divided according to Lesch typology, at the commencement and after 21 days of detoxification, together with a battery of cognitive tests. RESULTS: A significantly higher mean level of IL-6 was present in the blood of patients with Lesch typology 1 compared to the other typologies 2 and 3 on admission to the Detoxification Ward which did not alter significantly after detoxification. The mean level of IL-6 was initially elevated in Lesch typology 2 alcohol abusers and declined to the reference range after detoxification. Lesch typology 3 alcohol abusers showed normal levels of IL-6 at both time points. Only in Lesch typology 1 were the levels of ferritin and IL-10 significantly elevated at the start of the detoxification process. Cognitive impairment, as ascertained by Stroop test and Brown-Peterson procedure was greater in Lesch typology 1 than the other 2 patient groups. CONCLUSION: Such data might indicate a greater degree of neuroinflammation in Lesch typology 1 alcoholic patients. SHORT SUMMARY: Dividing a heterogeneous group of alcoholic subjects into homogenous groups according to Lesch typology, identifies a greater pro-inflammatory profile in Lesch typology 1 patients who also showed greater cognitive impairment.

Attention deficit hyperactivity disorder and substance abuse: An investigation in young Austrian males.

BACKGROUND: Many studies have found an association between Substance Use Disorders (SUDs) and Attention Deficit Hyperactivity Disorder (ADHD) in children, adolescents and adults. We intended to determine whether substance abuse and SUDs are associated with former and current ADHD symptomatology in a non-clinical sample of 17 and 18 year old males. METHOD: A representative sample of 3280 young men (6.8% of all males born in Austria in the respective year) was investigated during the examination for military service. We collected data on past (WURS) and current (ADHD symptom checklist) ADHD symptomatology, substance abuse, parental substance use and abuse and motives for substance use. RESULTS: Measured by WURS, 10.1% had scored positive for past ADHD symptoms. 2.7% of all subjects stated that they have been treated for ADHD and 1.5% reported that they had at one point received pharmacological treatment for the condition. Abuse of alcohol, nicotine and illicit substances was significantly (p<.01) more frequent in subjects with ADHD syndrome. Perceived parental alcohol abuse increased the risk for ADHD in the offspring. Motives for substance use differed greatly between groups. LIMITATIONS: The sample consists of men only. Subjects had to be fit enough to be enlisted military service, generating a possible bias towards healthier subjects. The cross-sectional design does not allow conclusions about the temporal relationships between ADHD symptoms and substance abuse. CONCLUSION: Identification of vulnerability factors for comorbid ADHD and SUD in adolescence should be intensified. Preventive strategies ought to be established.

The influence of reported ADHD and substance abuse on suicidal ideation in a non-clinical sample of young men.

This study intended to determine whether former and current ADHD symptomatology is associated with suicidal ideation in a non-clinical sample of 18 year old males. We performed a cross sectional descriptive study of 3280 men during the examination for military service. The investigation included a screening for substance abuse, past (WURS) and current (ADHD symptom checklist) ADHD symptomatology and an interview about suicidal ideations. We found a correlation of suicidal ideations with a history of ADHD symptomatology. ADHD symptoms were strongly consistent over time. These results indicate that a history of (diagnosed or undiagnosed) ADHD could be a predictor for suicidal ideations. Surveying a history of ADHD in primary care might help identify subjects at risk for suicidal tendencies.

Motivational factors and negative affectivity as predictors of alcohol craving.

Craving is thought to play an important role in alcohol use disorders. The recent inclusion of "craving" as a formal diagnostic symptom calls for further investigation of this subjective phenomenon with multiple dimensions. Considering that alcohol-dependent patients compensate negative physical/emotional states with alcohol, the aim of this study is to investigate alcohol craving and its correlation with drinking measures and affective personality dimensions. A sample of 135 alcohol-dependent patients (104 males and 31 females) was collected from a clinical setting. Subjects self-rated their cravings (Penn Alcohol Craving Scale) and the stage of change. Several personality scales were also administered. Craving was related to drinking status, abstinence time, age, and taking steps. After controlling for these conditions, psychological characteristics related to low self-concept, neuroticism, cyclothymic affective temperament, depression, and hostility were found to be predictors of craving in sober alcohol-dependent patients. Our results support craving as a component of the phenomenology of alcohol dependence and highlight the presence of unpleasant feelings as predictors of craving in sober alcohol-dependent patients without co-occurring psychiatric conditions. The predisposition to experience negative emotions may induce a stronger craving response and increase the likelihood of a first drink and a subsequent loss of control.

Sodium oxybate in the treatment of alcohol withdrawal syndrome: a randomized double-blind comparative study versus oxazepam. The GATE 1 trial.

BACKGROUND: Benzodiazepines (BDZs) are the gold standard in the treatment of alcohol withdrawal syndrome (AWS). Sodium oxybate (SMO) has been tested as a treatment for AWS with encouraging results. The aim of this phase IV, multicenter, randomized, double-blind, double-dummy study was to evaluate the efficacy of SMO in comparison with oxazepam in the treatment of uncomplicated AWS. METHODS: Alcohol-dependent outpatients (n = 126) affected by uncomplicated AWS according to the Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) scale were enrolled in the study and randomized in two groups: 61 patients received SMO and 65 patients received oxazepam for 10 days. The primary endpoint was the reduction of symptoms of AWS measured by the change in the total CIWA-Ar score from baseline (day 1) to the end of the study (day 10). This study is registered with ClinicalTrials.gov, number: NCT02090504 RESULTS: A significant decrease of the mean total CIWA-Ar score from baseline to the end of the study was found in both the SMO (p < 0.0001) and the oxazepam group (p < 0.0001), with no significant differences between the two treatments (p = 0.21). Treatment with SMO and oxazepam resulted in a marked decrease in the severity of the mean CIWA subscales, i.e. sweating, tremor, and anxiety, with no significant differences between the two treatments. Both drugs were well tolerated and no severe side effects were reported. CONCLUSION: SMO is as effective as oxazepam, one of the gold standard BDZs, in the treatment of uncomplicated AWS. Due to its tolerability and absence of significant side effects, SMO may be considered a valid alternative choice in the treatment of AWS.

Sodium oxybate in the treatment of alcohol dependence: from the alcohol withdrawal syndrome to the alcohol relapse prevention.

INTRODUCTION: Sodium oxybate (SMO) has been shown to be safe and effective in the treatment of patients with alcohol use disorders (AUDs); it was approved in Italy and Austria for the treatment of alcohol withdrawal syndrome and for relapse prevention. The focus of this review is to discuss the clinical evidence on the therapeutic potential of SMO for AUDs. AREAS COVERED: This review covers the studies in patients with alcohol withdrawal syndrome who received SMO for the treatment of withdrawal symptoms and the studies in patients with AUDs who received SMO to achieve total alcohol abstinence, reduction of alcohol intake, and relapse prevention. Relevant medical literature on SMO was identified by searching databases including MEDLINE and EMBASE (searches last updated 20 September 2013), bibliographies from published literature, clinical trial registries/databases, and websites. EXPERT OPINION: SMO has proved safe and effective in the treatment of alcohol withdrawal syndrome and in the prevention of relapses. Craving for and abuse of SMO have been reported, in particular in some subtypes of alcoholic patients, e.g., those affected by co-addiction and/or psychiatric comorbidity. Future multicenter, multinational, randomized clinical trials should be useful to optimize the treatments in relation with patients' characteristics, for example, pharmacogenetic, neurobiological, and psychological.

Can we predict addiction to opioid analgesics? A possible tool to estimate the risk of opioid addiction in patients with pain.

BACKGROUND: The use of opioid analgesics in the treatment of chronic pain conditions has long been controversial. They have been reported to be relatively safe when prescribed with caution, but a brief and valid instrument to estimate a person's risk of addiction is still missing. OBJECTIVE: The aim of this study was to investigate a self-rating questionnaire allowing an estimation of a person's risk of addiction to opioid analgesics. STUDY DESIGN: Retrospective review. SETTING: Four Austrian hospitals. METHODS: Seven hundred forty-one patients were interviewed. Of these, 634 patients were affected with chronic pain while 107 patients had a history of opioid addiction. Patients were interviewed about alcohol and nicotine consumption and family history of psychiatric disorders. Attitudes towards medication and the origin of pain were examined. We asked patients with an opioid addiction and patients suffering from chronic pain to complete a short questionnaire intended to help screen for addiction potential. RESULTS: Compared to the patients suffering from chronic pain, patients with an opioid addiction significantly more often had alcohol- and nicotine-related pathologies and psychiatric comorbidity. A family history of mental illness and developmental problems were significantly more frequent in this group. Compared to those not addicted, those with an opioid addiction had significantly higher expectations concerning the potential of medication to change one's mental state; they thought that psychological  factors might contribute to the pain they feel. LIMITATIONS: The main limitation of this study is the use of a self-rating instrument which reduces objectivity and introduces the possibility of misreporting. Also, the 2 groups differ in number and are not homogenous. CONCLUSION: We found differences in questionnaire responses between patients with an opioid addiction and patients suffering from chronic pain to be dependent upon the prevalence of current or former addiction, psychiatric history, attitudes towards medication, and ideas about the origin of pain. We believe these factors have predictive value in estimating a patient with pain's risk of addiction.

Adolescence and Alcohol: a review of the literature.

Up to two thirds of adolescents consume alcohol and about a quarter engage in abusive behavior at some point. Many users begin alcohol use at young ages, and binge drinking is a dominant pattern for a proportion of youth. Because neurogenesis is inhibited by ethanol, consequences of adolescent alcohol abuse include changes in brain development and impairment of neurocognitive performance. A variety of mental and psychosocial problems are also often witnessed in alcohol abusing youth. Apart from the influence exerted by genetic and psychosocial factors, the chance of developing problematic alcohol consumption is increased by consumption in a binge drinking manner and by first contact with alcohol at a young age. Discrimination of alcohol consumption within the frames of normal adolescent behavior from problematic use is still a challenging issue. Different prevention programs provide treatment either directly to the adolescent, in the context of the school, or within the frame of the adolescent's family. Although some of these efforts have been shown to be effective in reducing alcohol misuse in youth, hardly any intervention reveals satisfactory outcomes in a long-term prospect. Successful prevention strategies would need to comprise treatment of current neuropsychological impairment as well as of comorbid mental health problems and concurrent other substance misuse.

Serbian and Austrian alcohol-dependent patients: a comparison of two samples regarding therapeutically relevant clinical features.

AIMS: To support the Serbian Expert Board in setting up reimbursement for modern pharmacotherapeutic support, we compared a Serbian sample of alcohol-dependent patients with an Austrian sample, in order to detect differences that might inhibit the introduction of anti-craving medications in Serbia. METHODS: One hundred and twenty-seven (116 males) alcohol-dependent patients in Serbia and 136 in Austria (78 males) were enrolled consecutively from January 2011 to March 2012 and were assessed using the Lesch alcoholism typology instrument (LAT). RESULTS: Age of onset was slightly higher in the Austrian sample (28.5 vs. 30.0; P = 0.10). The Serbian sample showed a higher rate of anxiety disorders than the Austrian sample (89.8 vs. 26.5%, P ≤ 0.0001). Suicidal tendencies, independent of alcohol intake or withdrawal syndrome, were higher in the Austrian sample (1.6 vs. 13.2% P ≤ 0.0001). There was no difference between the two samples in Lesch-Type IV (26 vs 28); there was a slight excess in the Serbian sample of Type I (15 vs. 10). In Austria, significantly more Type II patients (32 vs. 52) had been included, while the Serbian sample comprised significantly more Type III patients. CONCLUSIONS: Austrian and Serbian patients are quite similar, without any showing any factor that would detract from the potential value of modern anti-craving medications in Serbia. The differences in anxiety disorders might be due to the 1990s war and should be investigated further.

Genetic markers of comorbid depression and alcoholism in women.

BACKGROUND: Alcohol dependence (AD) is often accompanied by comorbid depression. Recent clinical evidence supports the benefit of subtype-specific pharmacotherapy in treating the population of alcohol-dependent subjects with comorbid major depressive disorder (MDD). However, in many alcohol-dependent subjects, depression is a reactive response to chronic alcohol use and withdrawal and abates with a period of abstinence. Genetic markers may distinguish alcohol-dependent subjects with MDD not tied chronologically and etiologically to their alcohol consumption. In this work, we investigated the association of adenylyl cyclase genes (ADCY1-9), which are implicated in both AD and mood disorders, with alcoholism and comorbid depression. METHODS: Subjects from Vienna, Austria (n = 323) were genotyped, and single nucleotide polymorphisms (1,152) encompassing the genetic locations of the 9 ADCY genes were examined. The Vienna cohort contained alcohol-dependent subjects differentiated using the Lesch Alcoholism Typology. In this typology, subjects are segregated into 4 types. Type III alcoholism is distinguished by co-occurrence of symptoms of depression and by affecting predominantly females. RESULTS: We identified 4 haplotypes associated with the phenotype of Type III alcoholism in females. One haplotype was in a genomic area in proximity to ADCY2, but actually within a lincRNA gene, 2 haplotypes were within ADCY5, and 1 haplotype was within the coding region of ADCY8. Three of the 4 haplotypes contributed independently to Type III alcoholism and together generated a positive predictive value of 72% and a negative predictive value of 78% for distinguishing women with a Lesch Type III diagnosis versus women designated as Type I or II alcoholics. CONCLUSIONS: Polymorphisms in ADCY8 and ADCY5 and within a lincRNA are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression. Each of these genetic locations can rationally contribute to the polygenic etiology of the alcoholism/depression phenotype, and the use of these genetic markers may aid in choosing appropriate and beneficial treatment strategies.

The concept of temperament in psychoactive substance use among college students.

BACKGROUND: Substance abuse is among the leading causes of preventable diseases and premature death but reasons and conditions leading to substance abuse are complex and multifaceted. Different models of abuse and dependence assume an underlying emotional vulnerability. Individual behavioral and emotional reactivity patterns of personality are considered in the concept of temperament but studies linking different types of temperament with substance use are rare. METHODS: In this study we investigated 1380 inhabitants (59.7% females; 40.3% males) of residential student homes in Austria, using Akiskals TEMPS-M auto-questionnaire. Further, we administered the CAGE- and the HSI-questionnaire and assessed other psychoactive substance use to examine associations between traits of temperament and substance abuse using ordered logistic regression. RESULTS: Temperaments follow different distributions in both genders: Women have higher scores on the depressive, cyclothymic, and anxious subscales and lower scores on the hyperthymic scale than men. The cyclothymic and particularly irritable temperament serve as predictors of self-reported nicotine dependence, alcohol abuse and cannabis use. Interestingly, the depressive temperament seems to be protective against self-reported cannabis use. LIMITATIONS: Substance abuse assessment is based on self-reports only and urine drug and blood tests were not performed. Also, the history of substance abuse is not documented thus temperamental factors could have been influenced by substance abuse if the time of onset was in early adolescence. The study design was cross-sectional, thus limiting causal interpretations. CONCLUSIONS: It might be important to consider temperamental traits as protective- and risk factors in the etiology, prevention and therapy of substance abuse in future.