Excess mortality among people in homelessness with substance use disorders: a Swedish cohort study.

BACKGROUND: People in homelessness have an increased risk of substance use disorders (SUDs) and poor health outcomes. This cohort study aimed to investigate the association between homelessness and mortality in people with SUDs, adjusting for age, sex, narcotic use, intravenous drug use and inpatient care for SUDs. METHODS: Data from the Swedish National Addiction Care Quality Register in the Stockholm region were used to analyse mortality risk in people with SUDs (n=8397), including 637 in homelessness, 1135 in precarious housing and 6625 in stable housing, at baseline. HRs and CIs were calculated using Cox regression. RESULTS: Mortality was increased for people in homelessness (HR 2.30; 95% CI 1.70 to 3.12) and precarious housing (HR 1.23; 95% CI 0.86 to 1.75) compared with those in stable housing. The association between homelessness and mortality decreased (HR 1.27; 95% CI 0.91 to 1.78) after adjusting for narcotic use (HR 1.28; 95% CI 1.00 to 1.63), intravenous drug use (HR 1.98; 95% CI 1.52 to 2.58) and inpatient care for SUDs (HR 1.96; 95% CI 1.57 to 2.45). Standardised mortality ratios (SMRs) showed that mortality among people in homelessness with SUDs was 13.6 times higher than the general population (SMR=13.6; 95% CI 10.2 to 17.9), and 3.7 times higher in people in stable housing with SUDs (SMR=3.7; 95% CI 3.2 to 4.1). CONCLUSION: Homelessness increased mortality, but the risk decreased after adjusting for narcotic use, intravenous drug use and inpatient care for SUDs. Interventions are needed to reduce excess mortality among people in homelessness with SUDs.

Risk of severe mood and anxiety disorders in the adult children of parents with alcohol use disorder: a nationwide cohort study.

BACKGROUND: Growing up with parental alcohol use disorder (AUD) is a risk factor for psychiatric disorders. This study investigated the risk of mood disorders and of anxiety disorders in the adult children of parents with AUD, adjusted for sociodemographic factors. METHODS: Individual-level register data on the total population were linked to follow children of parents with AUD from 1973 to 2018 to assess their risk of mood disorders and of anxiety disorders. AUD, mood disorders and anxiety disorders were defined with International Statistical Classification of Diseases and Related Health Problems codes from the National Patient Register. HRs of outcomes were calculated with Cox regression. Model 1 was adjusted for the child's sex, parental education and death of a parent. Model 2 was adjusted for those factors and parental diagnosis of mood or anxiety disorder. RESULTS: Those with ≥1 parent with AUD (99 723 of 2 421 479 children) had a higher risk of mood disorder and of anxiety disorder than those whose parents did not have AUD (HR mood 2.32, 95% CI 2.26 to 2.39; HR anxiety 2.66, 95% CI 2.60 to 2.72). The risk remained elevated after adjustment for sociodemographic factors and parental psychiatric diagnosis (HR mood 1.67, 95% CI 1.63 to 1.72; HR anxiety 1.74, 95% CI 1.69 to 1.78). The highest risks were associated with AUD in both parents, followed by AUD in mothers and then in fathers. CONCLUSION: Adult children of parents with AUD have a raised risk of mood and anxiety disorders even after adjustment for sociodemographic factors and parental mood or anxiety disorder. These population-level findings can inform future policies and interventions.

From alcohol detoxification to treatment: A qualitative interview study on perceived barriers and assessed potential of mHealth among individuals postdetoxification.

OBJECTIVE: Most individuals attending detoxification clinics do not pursue subsequent treatment. Earlier research has suggested that emerging technologies like mHealth interventions could address the postdetoxification treatment gap, yet it remains unclear whether patients themselves endorse such approaches. Our study aimed to qualitatively explore perceived treatment barriers and assessed potential of mHealth among individuals who have undergone alcohol detoxification. METHOD: We conducted a single-interview-per-participant qualitative study, sampling participants (n = 23) that had visited the Stockholm substance use disorder emergency department for alcohol-related reasons, of whom n = 8 were purposively included due to having missed their scheduled follow-up outpatient appointment. Semistructured telephone interviews were conducted (2021-2022) and then systematically analyzed using reflexive thematic analysis. RESULTS: Across both areas of analysis, we identified six themes in total. We clustered barriers to postdetoxification treatment into three themes (10 subthemes) that may offer a nuancing perspective on previous research: "Misalignment between the treatment system and the individual," "Practical hurdles" and "Between reaching out and retreating." We identified three themes in participants' perspectives on mHealth as aftercare support, revealing expectations that such an approach may promote "self-awareness on own terms," assist in "navigating from solitary substance use struggles to supportive connections," and "offer a lifeline when needed most," thereby potentially resolving several barriers to treatment. CONCLUSIONS: This first qualitative study on barriers to alcohol treatment and mHealth potential postdetoxification offered various insights that may be translated into effective, real-world solutions to bridge the postdetoxification treatment gap. A natural next step for future research is to evaluate the impact of mHealth postdetoxification. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Effect of Methylphenidate on Cognition in Patients with Comorbid Attention Deficit/Hyperactivity Disorder and Amphetamine Use Disorder: An Exploratory Single-Blinded within-Subject Study.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) with co-occurring substance use disorder (SUD) is associated with poor treatment outcomes. Two randomized controlled trials, utilizing robust doses of stimulants, demonstrated a significant effect on treatment outcomes in patients with ADHD/SUD. This study aimed to investigate differences in executive functioning and explore the dose-dependent effect of OROS-methylphenidate (MPH) in patients with comorbid ADHD and amphetamine use disorder (ADHD+AMPH) and patients with ADHD only. METHODS: Three groups (ADHD+AMPH, ADHD only, and healthy controls) were assessed repeatedly with a neuropsychological test battery. An exploratory within-subject single-blinded design was employed where the ADHD only group received a maximum dose of 72 mg OROS-MPH, the ADHD+AMPH group a maximum dose of 180 mg, whereas the healthy subjects did not receive any study medication. Both ADHD groups received the same dose titration up to 72 mg OROS-MPH. RESULTS: The ADHD+AMPH group demonstrated a significantly poorer motor inhibition and spatial working memory and reported more severe ADHD symptoms compared to the ADHD only group. 180 mg OROS-MPH was associated with a significant improvement in executive functioning in the dual diagnosis group. However, the exploratory study design and recruitment issues do not allow for any conclusion to be drawn regarding the effect of 180 mg OROS-MPH. CONCLUSION: Patients with ADHD+AMPH present with more severe neurocognitive deficits compared to ADHD only. The effect of 180 mg OROS-MPH on cognition in patients with ADHD+AMPH was inconclusive. Future studies should consider recruitment issues and high drop-out rates in this study population.

Impulsive choice in individuals with comorbid amphetamine use disorder and attention deficit-hyperactivity disorder.

BACKGROUND: Amphetamine use disorder (AMPH) and attention deficit-hyperactivity disorder (ADHD) often co-occur and are associated with poor treatment outcomes. Elevated impulsivity is a core feature in both disorders. Little is known however about the specific neurocognitive profile regarding different facets of impulsivity, and specifically impulsive choice, in comorbid populations. METHODS: Three groups (ADHD + AMPH, ADHD only and healthy controls (HC)) were assessed with self-reported impulsivity and cognitive tasks of impulsive choice, operationalized as delay aversion (DA) and reflection impulsivity. RESULTS: Twenty-nine participants with comorbid ADHD + AMPH, 25 participants with ADHD only and 116 HC completed screening, including self-rating scales, and cognitive testing. 20, 16 and 114 participants completed computerized cognitive tasks in the ADHD + AMPH group, ADHD group and HC group, respectively. The ADHD + AMPH group reported significantly higher motor, attentional and non-planning impulsiveness, and showed a significantly higher degree of impulsive choice, compared to both groups. There were no differences in task-related impulsiveness between ADHD only and HC. CONCLUSIONS: The current findings suggest that individuals with ADHD + AMPH have overall elevated levels of impulsivity compared to individuals with ADHD only. In addition, that ADHD + AMPH is specifically associated with impairments in task-related impulsive choice, which was not found in ADHD only compared to HC. The neurocognitive profile in this specific patient group may represent a need for more systematic screening within healthcare settings in order to develop effective and targeted treatment for comorbid patients. TRIAL REGISTRATION: EudraCT, 2012-004298-20.

Striatal dopamine D2 receptor availability as a predictor of subsequent alcohol use in social drinkers.

BACKGROUND AND AIMS: Whereas striatal dopamine D2 receptor (D2R) availability has shown to be altered in individuals with alcohol use disorder (AUD) and in healthy individuals with a family history of AUD, the role of D2R in the development of AUD is unknown. In this positron emission tomography (PET) study, we measured whether D2R availability is associated with subsequent alcohol use and alcohol-related factors, at a follow-up 8 to 16 years post-PET scan, in social drinkers. DESIGN: Longitudinal study investigating the association between PET data and later self-report measures in healthy individuals. SETTING: Academic research imaging centre in Stockholm, Sweden. PARTICIPANTS: There were 71 individuals (68 of whom had evaluable PET data, 5 females, 42.0 years mean age) from a series of previous PET studies. MEASUREMENTS: One PET examination with the D2R antagonist radioligand [11 C]raclopride at baseline and self-report measures assessing alcohol use, drug use, impulsivity, reward sensitivity and family history of alcohol or substance use disorder at follow-up. FINDINGS: We found no evidence for an association between D2R availability and later alcohol use (B = -0.019, B 95% CI = -0.043 to -0.006, P = 0.147) nor for the majority of the alcohol-related factors (B 95% CI = -0.034 to 0.004, P = 0.273-0.288). A negative association with a small effect size was found between D2R availability and later impulsivity (B = -0.017, B 95% CI = -0.034 to -0.001, P = 0.046). CONCLUSIONS: Low striatal dopamine D2 receptor availability may not be a strong predictor in the development of alcohol use disorder.

Acute Alcoholic Hallucinosis: A Review.

Acute alcoholic hallucinosis is a psychotic disorder characterized by a predominance of auditory hallucinations with delusions and affective symptoms in the clinical picture. Classically, it develops as part of the alcohol withdrawal syndrome. The prevalence of acute alcoholic hallucinosis ranks second among alcohol-related psychoses after alcohol delirium. The study aimed to systematize the scientific data on the history of alcoholic hallucinosis, its pathogenesis, clinical presentation, and treatment approaches. A literature search was performed in PubMed, Scopus, Google Scholar, and eLibrary. The following words and combinations were used as search strings: (alcoholic hallucinosis OR alcoholic psychosis OR alcohol-related psychosis OR alcohol-induced psychosis OR alcohol-induced psychotic disorder OR complicated alcohol withdrawal syndrome) NOT (animal OR rat OR mouse). The relevant information concerning the history of acute alcoholic hallucinosis, its pathogenesis, clinical picture, and treatment approaches was systematized and summarized. This review presents relevant findings regarding acute alcoholic hallucinosis. Limitations of the review include the use of heterogeneous and mostly descriptive studies and studies on small cohorts of patients.

Alcohol as a risk factor for mortality in liver transplant patients in Sweden.

OBJECTIVES: Liver transplantation (LT) is the only available cure for end-stage liver disease and one of the best treatment options for hepatocellular carcinomas (HCC). Patients with known alcohol-associated cirrhosis (AC) are routinely assessed for alcohol dependence or abuse before LT. Patients with other liver diseases than AC may consume alcohol both before and after LT. The aim of this study was to assess the effects of alcohol drinking before and after LT on patient and graft survival regardless of the etiology of liver disease. MATERIALS AND METHODS: Between April 2012 and December 2015, 200 LT-recipients were interviewed using the Lifetime Drinking History and the Addiction Severity Index questionnaire. Patients were categorized as having AC, n = 24, HCC and/or hepatitis C cirrhosis (HCV), n = 69 or other liver diseases, n = 107. Patients were monitored and interviewed by transplantation-independent staff for two years after LT with questions regarding their alcohol consumption. Patient and graft survival data were retrieved in October 2019. RESULTS: Patients with AC had an increased hazard ratio (HR) for death after LT (crude HR: 4.05, 95% CI: 1.07-15.33, p = 0.04) and for graft loss adjusted for age and gender (adjusted HR: 3.24, 95% CI 1.08-9.77, p = 0.04) compared to the other patients in the cohort. There was no significant effect of the volume of alcohol consumed before or after LT on graft loss or overall survival. CONCLUSION: Patients transplanted for AC have a worse prognosis, but we found no correlation between alcohol consumed before or after LT and graft or patient survival.

Validity of the ADHD module of the Mini International Neuropsychiatric Interview PLUS for screening of adult ADHD in treatment seeking substance use disorder patients: ADHD screening with MINI-Plus.

OBJECTIVE: This study aims to assess the validity of the ADHD module of the Mini-International Neuropsychiatric Interview (MINI-Plus) in patients with substance use disorders (SUD), using the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID) as the external criterion. METHOD: A cross sectional international multi-center study in 10 countries was conducted in treatment seeking SUD patients. A sample of 1263 patients with both MINI-Plus and CAADID was analyzed to determine the psychometric properties of the MINI-Plus. RESULTS: According to the CAADID, 179 patients (14.2%) met criteria for adult ADHD, whereas according to the MINI-Plus 227 patients (18.0%) were identified as having adult ADHD. Sensitivity of the MINI-Plus ADHD module was 74%, specificity was 91%, positive predictive value was 60% and negative predictive value was 96%. Kappa was 0.60. CONCLUSION: The MINI-Plus has acceptable criterion validity for the screening of adult ADHD in treatment seeking SUD patients. SCIENTIFIC SIGNIFICANCE: On the basis of the results, The MINI-Plus may be used for the screening of ADHD in SUD patients.

Meta-analysis of pharmacogenetic clinical decision support systems for the treatment of major depressive disorder.

The study aimed to conduct a meta-analysis of studies comparing pharmacogenetically guided dosing of antidepressants with empiric standard of care. Publications referring to genotype-guided antidepressant therapy were identified via PubMed, Google Scholar, Scopus, Web of Science, Embase, and Cochrane databases from the inception of the databases to 2021. In addition, bibliographies of all articles were manually searched for additional references not identified in primary searches. Studies comparing clinical outcomes between two groups of patients who received antidepressant treatment were included in meta-analysis. Analysis of the data revealed statistically significant differences between the experimental group receiving pharmacogenetically guided dosing and the empirically treated controls. Specifically, genotype-guided treatment significantly improved response and remission of patients after both eight and twelve weeks of therapy, whereas no effect on the development of adverse drug reactions was observed. This meta-analysis indicates that the use of preemptive genotyping to guide dosing of antidepressants might increase treatment efficacy.

CYP3A4*22 and CYP3A5*3 impact efficacy and safety of diazepam in patients with alcohol withdrawal syndrome.

BACKGROUND: Diazepam is one of the most commonly prescribed pharmaceuticals for the treatment of alcohol withdrawal syndrome (AWS). However, diazepam sometimes is ineffective, and some patients experience dose-dependent adverse drug reactions (ADR). Previous studies have shown that diazepam metabolism involves the CYP3A4 and CYP3A5 isoenzymes, whose activity is highly variable between individuals, which may contribute to differences in clinical response. PURPOSE: The study aimed to investigate the effects of the genetic polymorphisms CYP3A4*22 and CYP3A5*3 on the efficacy and safety of diazepam in patients with AWS. MATERIALS AND METHODS: One hundred male AWS patients received 30 mg/day diazepam by intramuscular injections for 5 days. Genotyping for CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) was performed by real-time polymerase chain reaction with allele-specific hybridization. The efficacy and safety assessments were performed using psychometric scales. RESULTS: Patients who carry CT and TT genotypes by polymorphic marker C > T intron 6 (rs35599367) of the CYP3A4 gene had a higher risk for ADR and demonstrated lower safety of diazepam therapy (p < 0.001; two-way ANOVA). CONCLUSION: These results suggest that genotyping for common CYP3A variants might have the potential to guide benzodiazepine withdrawal treatment.

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

BACKGROUND: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. AIMS: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. RESULTS: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. CONCLUSIONS: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. TRIAL REGISTRATION: ISRCTN15998989 20/12/2019.

Gender specific early treatment for women with alcohol addiction (EWA): Impact on work related outcomes. A 25-year registry follow-up of a randomized controlled trial (RCT).

BACKGROUND: Alcohol contributes to substantial economic burden, at both individual and community levels. We investigated the effect of the Early treatment for Women with Alcohol Addiction (EWA) treatment program on sickness leave, income, unemployment and early retirement pension up to 25 years following intake to treatment. METHODS: The EWA RCT included 200 women with alcohol use disorder from 1983 to 1984 at the Karolinska University Hospital, Sweden. Participants were randomized to the EWA program, a two-year specialized woman only treatment including psychiatric, interpersonal and family concerns, or treatment as usual (TAU) in a mixed gender setting. We followed the participants in the RCT from 1985 to 2009 through linkage with a national labor market registry and applied latent growth curve modeling to estimate level and change in sickness leave, income, unemployment and early retirement pension. FINDINGS: Relative to TAU, the EWA group had less increase in sickness leave up to 21 years after treatment. Overall, we found no differences in income between treatment groups, yet, a two-year interval analysis showed greater rise in income up to 8 years after treatment for the EWA group. Level and change in unemployment and early retirement pension did not differ between treatment groups. CONCLUSIONS: Gender specific treatment emphasizing psychiatric, interpersonal and family issues for women with alcohol addiction had long-term positive effects on sickness leave and income. These findings complement positive clinical outcomes of the EWA treatment program on drinking patterns, mental health and mortality.

Mortality in adult children of parents with alcohol use disorder: a nationwide register study.

Research suggests that adult children of parents with harmful alcohol use are at increased risk for premature death. This national cohort study investigated mortality in adult children of parents with alcohol use disorder (AUD), adjusting for sociodemographic variables. The study used 1973 to 2018 data from Swedish national registers to compare mortality risk in children who had ≥ 1 parent with AUD (ICD-10 code F10 and its ICD-8 and ICD-9 equivalents) (n = 122,947) and those who did not (n = 2,298,532). A Cox regression model adjusted for year of birth, sex, parental education, and childhood loss of a parent was used. Before the age of 18 years, about 5% of children born in Sweden lived with ≥ 1 parent who had a clinical diagnosis of AUD. Overall mortality was higher in adult children of parents with AUD: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.71-1.82. Mortality remained elevated after adjustments for sociodemographic factors (HR 1.45, 95% CI 1.40-1.50). Children of parents with AUD had increased mortality from all investigated causes. The highest excess risk was for death from drug-related causes (excluding accidental poisonings) (HR 3.08, 95% CI 2.74-3.46). For most causes, mortality was higher if the mother had AUD than if the father had AUD. Patterns of mortality were similar in both sexes. This study provides evidence that parental AUD raises the risk of offspring mortality from preventable causes such as drug use, suicide (HR 2.16, 95% CI 1.98-2.36), accident (HR 2.00, 95% CI 1.87-2.13), and assault (HR 1.76, 95% CI 1.38-2.24).

Prevalence and comorbidity of psychiatric disorders among treatment-seeking elite athletes and high-performance coaches.

Objectives: Few studies have evaluated the prevalence of psychiatric disorders among treatment-seeking elite athletes (EA) or high-performance coaches (HPC) in psychiatric outpatient settings. Methods: Descriptive overview of EA and HPC with psychiatric disorders at two publicly funded psychiatric outpatient treatment clinics in Stockholm and Malmö, Sweden. Co-occurring psychiatric disorders were illustrated using Venn diagrams for EA and HPC, and male and female EA separately, among patients from the Stockholm clinic (SC) that used standardised diagnostic interviews. Results: Overall, most patients were EA (n=221) compared with HPC (n=34). The mean age was 23.5 (±5.9) years for EA and 42.8 (±8.8) for HPC. Anxiety disorders were most common at the SC in EA and HPC (69% vs 91%, respectively). Stress-related disorders were found in 72% of HPC compared with 25% of EA. Affective disorders were found in 51% of EA and 52% of HPC. Eating disorders were common among EA (26%), especially females (37%). Substance use disorders were found in 17% of HPC. Comorbidity was generally common between affective and anxiety disorders. Conclusion: Stress and adjustment disorders were found in nearly three of the four HPC compared with one in four EA. Eating disorders were prevalent in around one in four athletes and about one in six HPC had a substance use disorder.

Initiation of Opioid Prescription and Risk of Suicidal Behavior Among Youth and Young Adults.

BACKGROUND AND OBJECTIVES: Opioids are involved in an increasing proportion of suicide deaths. This study examined the association between opioid analgesic prescription initiation and suicidal behavior among young people. METHODS: We analyzed Swedish population-register data on 1 895 984 individuals ages 9 to 29 years without prior recorded opioid prescriptions. We identified prescriptions dispensed from January 2007 onward and diagnosed self-injurious behavior and death by suicide through December 2013. We first compared initiators with demographically matched noninitiators. To account for confounding, we applied an active comparator design, which examined suicidal behavior among opioid initiators relative to prescription nonsteroidal antiinflammatory drug (NSAID) initiators while inverse-probability-of-treatment weighting with individual and familial covariates. RESULTS: Among the cohort, 201 433 individuals initiated opioid prescription. Relative to demographically matched noninitiators, initiators (N = 180 808) had more than doubled risk of incident suicidal behavior (hazard ratio = 2.64; 95% confidence interval [CI], 2.47-2.81). However, in the active comparator design, opioid initiators (N = 86 635) had only 19% relatively greater risk of suicidal behavior compared with NSAID initiators (N = 255 096; hazard ratio = 1.19; 95% CI,: 1.11-1.28), corresponding to a weighted 5-year cumulative incidence of 2.2% (95% CI, 2.1-2.4) for opioid and 1.9% (95% CI, 1.9-2.0) for NSAID initiators. Most sensitivity analyses produced comparable results. CONCLUSIONS: Opioid initiation may make only a small contribution to the elevated risk of suicidal behavior among young people receiving pharmacologic pain management. In weighing benefits and harms of opioid initiation, our results suggest that increased risk of suicidal behavior may not be a major concern.

The Hypothesis of Subliminal Cue Reactivity in Addiction Revisited: An fMRI Study.

INTRODUCTION: Exposure to conditioned cues is a common trigger of relapse in addiction. It has been suggested that such cues can activate motivationally relevant neurocircuitry in individuals with substance use disorders even without being consciously perceived. We aimed to see if this could be replicated in a sample with severe amphetamine use disorder and a control group of healthy subjects. METHODS: We used fMRI to test the hypothesis that individuals with amphetamine use disorder, but not healthy controls, exhibit a specific neural reactivity to subliminally presented pictures related to amphetamine use. Twenty-four amphetamine users and 25 healthy controls were recruited and left data of sufficient quality to be included in the final analysis. All subjects were exposed to drug-related and neutral pictures of short duration (13.3 ms), followed by a backward visual mask image. The contrast of interest was drug versus neutral subliminal pictures. RESULTS: There were no statistically significant differences in BOLD signal between the drug and neutral cues, neither in the limbic regions of primary interest nor in exploratory whole-brain analyses. The same results were found both in amphetamine users and controls. DISCUSSION/CONCLUSION: We found no evidence of neural reactivity to subliminally presented drug cues in this sample of subjects with severe amphetamine dependence. These results are discussed in relation to the earlier literature, and the evidence for subliminal drug cue reactivity in substance use disorders is questioned.

Substance Use, Hospitalizations, and Co-Occurring Disorders among Patients Transferred from a Needle Exchange Program to Opioid Maintenance Treatment.

Opioid use disorders (OUD) is a relapsing condition with high mortality. Opioid maintenance treatment (OMT) reduces heroin use, and overall morbidity and mortality. The prevalence of psychiatric and substance use disorders, potential baseline predictors for psychiatric hospitalization, and psychiatric diagnoses at follow-up were investigated and may give hints about possible preventative strategies. The medical records for 71 patients were reviewed 36 months following referral to OMT from a needle exchange program (NEP). Their psychiatric diagnoses and hospitalizations were identified. Their baseline characteristics were assessed for potential differences between hospitalized versus non-hospitalized patients and between patients with and without psychiatric diagnoses in a longitudinal observational study without controls. A regression analysis was performed to identify predictors for hospitalization when controlling for OMT status. Sixty-five percent of the patients were hospitalized at least once with a psychiatric diagnosis. Substance-related reasons were prevalent, and detoxification occurred among 59% of patients, with sedative- hypnotics (benzodiazepines, zopiclone, zolpidem, and pregabalin) being the substance used by 52% of patients. Baseline use of these drugs and/or buprenorphine predicted for hospitalization when controlling for OMT status. During the follow-up period, 72% of patients met the criteria for a psychiatric diagnosis other than OUD. The prevalence of non-substance use disorders overlapping with SUD was 41%, and that overlapping with anxiety disorder was 27% of all participants. Increased attention to psychiatric co-occurring disorders in the treatment of OUD is required and the importance of addressing sedative-hypnotics use when initiating OMT is highlighted.

Plasma concentrations of methylphenidate enantiomers in adults with ADHD and substance use disorder, with focus on high doses and relationship to carboxylesterase activity.

Scarce data are available on methylphenidate (MPH) plasma concentrations reached after doses higher than 180 mg. The interindividual and intraindividual variability in the exposure of MPH and ritalinic acid (RA) enantiomers was examined in 28 patients with ADHD and substance use disorders, with MPH daily doses between 30 and 600 mg (median 160 mg). MPH and RA plasma concentrations were analysed with an enantioselective LC-MS/MS method. d-MPH plasma concentration/dose varied 25-fold between subjects but was reasonably stable within an individual. Twelve subjects had quantifiable l-MPH plasma concentrations, which accounted for up to 48% of the total MPH plasma concentration. The less active l-MPH enantiomer could, in individuals with low carboxylesterase 1 (CES1) activity, contribute significantly to the total MPH plasma drug concentration and hamper the estimation of the exposure to the more active d-MPH enantiomer. However, the high correlation between the total (d + l) RA/MPH metabolic ratio and the d-RA/d-MPH metabolic ratio (rs  = 0.94) indicates that the ratio based on non-enantioselective analysis could be used as a marker of CES1 activity. Whether this holds true for subjects with aberrant metabolism due to genetic variants or during concomitant treatment with inhibitors or inducers of the enzyme remains to be studied.

Effect of alcohol use disorder family history on cognitive function.

BACKGROUND: Alcohol use disorder (AUD) is associated with cognitive deficits but little is known to what degree this is caused by genetically influenced traits, i.e. endophenotypes, present before the onset of the disorder. The aim of the current study was to investigate to what degree family history (FH) of AUD is associated with cognitive functions. METHODS: Case-control cross-sectional study at an outpatient addiction research clinic. Treatment-seeking AUD patients (n = 106) were compared to healthy controls (HC; n = 90), matched for age and sex. The HC group was further subdivided into AUD FH positive (FH+; n = 47) or negative (FH-; n = 39) based on the Family Tree Questionnaire. Participants underwent psychiatric and substance use assessments, completed the Barratt Impulsiveness Scale and performed a comprehensive battery of neuropsychological tests assessing response inhibition, decision making, attention, working memory, and emotional recognition. RESULTS: Compared to HC, AUD patients exhibited elevated self-rated impulsivity (p < 0.001; d = 0.62), as well as significantly poorer response inhibition (p = 0.001; d = 0.51), attention (p = 0.021; d = 0.38) and information gathering in decision making (p = 0.073; d = 0.34). Similar to AUD patients, FH+ individuals exhibited elevated self-rated impulsivity (p = 0.096; d = 0.46), and in addition significantly worse future planning capacity (p < 0.001; d = 0.76) and prolonged emotional recognition response time (p = 0.010; d = 0.60) compared to FH-, while no other significant differences were found between FH+ and FH-. CONCLUSIONS: Elevated impulsivity, poor performance in future planning and emotional processing speed may be potential cognitive endophenotypes in AUD. These cognitive domains represent putative targets for prevention strategies and treatment of AUD.