Browsing by Subject "ABUSE"

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  • Palmu, Raimo; Partonen, Timo; Suominen, Kirsi; Vuola, Jyrki; Isometsä, Erkki (2018)
    Objective: We investigated alcohol use and smoking at time of burn and their relationships with severity of burn and presence of mental disorders. Methods: Consecutive acute burn patients (N = 107) admitted to the Helsinki Burn Center were assessed with the structured clinical interview for mental disorders (SCID) at baseline and after 6 months. Information regarding being under the influence of alcohol and having smoking-related activity at burn as well as about hazardous drinking (Alcohol Use Disorders Identification Test) and heavy smoking before the burn was recorded. Results: Around half (52%) of the acute burn patients were under the influence of alcohol and 19% had been both drinking and smoking at the time of the burn. Patients under the influence at the time of burn had significantly higher prevalence of lifetime mental disorders compared to those patients who were not under the influence of alcohol (73.2% vs. 45.1%, p = 0.003), especially alcohol dependence (55.4% vs. 13.7%, p <0.001) and anxiety disorders (28.6% vs. 9.8%, p = 0.015). Patients who had both alcohol use and smoking at burn had even more often at least one mental disorder (95.0% vs. 51.7%, p <0.001), in specific alcohol dependence (90.0% vs. 23.0%, p <0.001), or psychotic disorder (25.0% vs. 6.9%, p = 0.016). The main characteristics of the burns themselves did not differ significantly between these groups. Conclusion: Half of the burn patients were under the influence of alcohol at the time of the burn in this study. In almost all patients where alcohol and smoking contributed to the burn a diagnosable alcohol use disorder was present. Interventions for those with alcohol use disorders and the associated risk behaviors are important for the prevention of burns. (C) 2017 Published by Elsevier Ltd.
  • Broms, Ulla; Koskenvuo, Karoliina; Sillanmaki, Lauri H.; Mattila, Kari J.; Koskenvuo, Markku (2012)
  • Kivimies, Kristiina; Repo-Tiihonen, Eila; Kautiainen, Hannu; Tiihonen, Jari (2018)
    BackgroundSubstance use disorders are associated with poorer clinical outcomes in patients with schizophrenia. There is no specific treatment for amphetamine or cannabis use disorder, but methadone and buprenorphine are used as replacement therapy in the treatment of opioid dependence. Our aim was to study whether patients with schizophrenia have received opioid replacement therapy for their opioid use disorder.MethodsThe study sample consisted of 148 individuals diagnosed with schizophrenia who were in involuntary psychiatric treatment as forensic patients in Finland in 2012. The proportion of the study sample with comorbid opioid use disorder having received opioid replacement therapy prior to their forensic psychiatric treatment was compared to the available information of opioid dependent patients in general. The data were collected from forensic examination statements, patient files and other medical registers retrospectively.ResultsOf the study sample, 15.6% (23/148) had a history of opioid use disorder, of whom 8.7% (2/23) had received opioid replacement treatment (95% confidence interval (Cl): 1.1-28.0), even though opioid use disorder had been diagnosed in the treatment system. According the available information the corresponding proportion among patients with opioid use disorder and using substance use disorder services was 30.4% (565/1860, 95% Cl: 28.3-32.5). The fraction of patients receiving opioid replacement therapy was significantly lower among patients with schizophrenia (p=0.022).ConclusionsOpioid replacement therapy was seldom used among schizophrenia patients who were later ordered to involuntary forensic psychiatric treatment. More attention should be paid to the possible use of opioids when planning treatment for patients with schizophrenia.Trial registrationOur study is not a randomized controlled trial (but a register-based study); thus the trial registration is not applicable.
  • Nissinen, Niina-Maria; Gissler, Mika; Sarkola, Taisto; Kahila, Hanna; Autti-Rämö, Ilona; Koponen, Anne M. (2021)
    Introduction: The dual impact of prenatal substance exposure (i.e. alcohol/drugs) and adverse postnatal caregiving environment on offspring secondary education completion is an understudied research area. The aim was to investigate the influence of childhood adversities, out-of home care, and offspring's mental and/or behavioural disorders on secondary education completion among prenatally exposed offspring in comparison to matched unexposed offspring. Methods: This is a longitudinal register-based matched cohort study in Finland including offspring with a history of prenatal substance exposure and a matched unexposed cohort. The study sample included 283 exposed and 820 unexposed offspring aged 18-23 years. Results: The results showed a time lag in secondary education completion and lower educational attainment overall among exposed compared with unexposed (37.8% vs. 51.0%, respectively). The results from the multivariate logistic regression models showed that the differences in the secondary education completion between exposed and unexposed were diminished in the presence of covariates. A cumulative childhood adversity score and out-of-home care were not associated with secondary education completion in the multivariate models, whereas the different domains of offspring's mental and/or behavioural disorders including psychiatric disorders (AOR 0.65, 95% CI 0.45-0.96), neuropsychological disorders (AOR 0.35, 95% CI 0.23-0.54) and dual psychiatric and neuropsychological disorder (AOR 0.29, 95% CI 0.18-0.48) showed an independent negative effect on secondary education completion. Conclusions: Inferior educational outcomes may not be directly linked with prenatal substance exposure but may rather reflect the extent of evolving offspring's mental and/or behavioural disorders over time influenced by childhood adversities.
  • Kosola, Jussi; Kaipia, Antti; Laitinen, Minna K.; Nieminen, Jyrki (2017)
    Purpose One-third of hip fractures occur in men. The causes underlying hip fractures in men differ from those in women and include alcohol abuse. This retrospective register study evaluated the trends and results associated with different surgical treatment methods for nondisplaced and displaced femoral neck fractures in male patients with alcohol dependence syndrome. Methods Men with hip fractures were identified from a local district hospital database. Alcohol dependence syndrome was identified as a diagnosis in medical records. Results For displaced fractures, implant survival after total hip arthroplasty was significantly lower compared to hemiarthroplasty. For nondisplaced fractures, implant survival of cannulated screws was significantly lower compared to sliding hip screws. Overall patient survival for males with alcohol dependence syndrome with hip fracture was 62% at 1 year and 49% at 2 years. Patient survival in this population did not differ between displaced and nondisplaced fractures or among different surgical methods. Conclusion Patients with alcoholism who had documented evidence of alcohol dependence syndrome represented nearly half of patients
  • Mariottini, Claudia; Kriikku, Pirkko; Ojanperä, Ilkka (2021)
    Background: Buprenorphine is abused in several countries notwithstanding its benefits as an analgesic and as an opioid agonist treatment medication. Benzodiazepines and alcohol have previously been associated with buprenorphine toxicity. This study elucidates the role of emerging concomitant drugs in different groups of buprenorphine user deaths. Methods: All cases in the Finnish national post-mortem toxicology database from 2016-2019 in which buprenorphine or norbuprenorphine was a laboratory finding in any post-mortem specimen and age at death of 15-64 years were investigated for cause and manner of death, concurrent drug and alcohol findings, age, and gender. Results: There were 792 deaths with a buprenorphine finding, of which buprenorphine was implicated in poisoning without other opioids in 271 cases (34 %). In this group of buprenorphine poisoning deaths, concomitant benzodiazepines were found in 94 % (clonazepam 53 %), illicit drugs in 63 %, gabapentinoids in 50 % (pregabalin 41 %), alcohol in 41 %, antidepressants in 32 %, and antipsychotics in 28 % of cases; only three deaths showed no benzodiazepines, alcohol, or gabapentinoids. Polydrug use was common regardless of the cause of death. In the age group 15 to 24 years, concomitant use of benzodiazepines and illicit drugs, and buprenorphine poisoning were more prevalent than in the age group 25-64 years. Conclusions: The unprecedentedly high concomitant use of benzodiazepines in buprenorphine user deaths obscures other possible pharmacological risk factors for buprenorphine poisoning that could be relevant for prevention. Higher mortality in the younger age group suggests particularly unsafe drug use patterns that should be addressed.
  • Kopra, Jaakko; Villarta-Aguilera, Marian; Savolainen, Mari; Weingerl, Samo; Myohänen, Timo T.; Rannanpää, Saara; Salvatore, Michael E.; Andressoo, Jaan-Olle; Piepponen, T. Petteri (2018)
    Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons. (C) 2017 Elsevier Ltd. All rights reserved.
  • Mynttinen, Elsi; Wester, Niklas; Lilius, Tuomas; Kalso, Eija; Mikladal, Bjorn; Varjos, Ilkka; Sainio, Sami; Jiang, Hua; Kauppinen, Esko I.; Koskinen, Jari; Laurila, Tomi (2020)
    Oxycodone is a strong opioid frequently used as an analgesic. Although proven efficacious in the management of moderate to severe acute pain and cancer pain, use of oxycodone imposes a risk of adverse effects such as addiction, overdose, and death. Fast and accurate determination of oxycodone blood concentration would enable personalized dosing and monitoring of the analgesic as well as quick diagnostics of possible overdose in emergency care. However, in addition to the parent drug, several metabolites are always present in the blood after a dose of oxycodone, and to date, there is no electrochemical data available on any of these metabolites. In this paper, a single-walled carbon nanotube (SWCNT) electrode and a Nafion-coated SWCNT electrode were used, for the first time, to study the electrochemical behavior of oxycodone and its two main metabolites, noroxycodone and oxymorphone. Both electrode types could selectively detect oxycodone in the presence of noroxycodone and oxymorphone. However, we have previously shown that addition of a Nafion coating on top of the SWCNT electrode is essential for direct measurements in complex biological matrices. Thus, the Nafion/SWCNT electrode was further characterized and used for measuring clinically relevant concentrations of oxycodone in buffer solution. The limit of detection for oxycodone with the Nafion/SWCNT sensor was 85 nM, and the linear range was 0.5-10 mu M in buffer solution. This study shows that the fabricated Nafion/SWCNT sensor has potential to be applied in clinical concentration measurements.
  • Alasaari, Jukka S.; Lagus, Markus; Ollila, Hanna M.; Toivola, Auli; Kivimäki, Mika; Vahtera, Jussi; Kronholm, Erkki; Harma, Mikko; Puttonen, Sampsa; Paunio, Tiina (2012)
  • Ojanpera, Ilkka; Kriikku, Pirkko; Vuori, Erkki (2016)
    The fatal toxicity index (FTI) is the absolute number of fatal poisonings caused by a particular drug divided by its consumption figure. Consequently, it is a useful measure in evaluating toxicity of the drug and its relevance in fatal poisonings. In this study, we assessed the FTI of medicinal drugs in 3 years (2005, 2009, and 2013) in Finland. As the measure of drug consumption, we used the number of defined daily doses (DDD) per population in each year. There were 70 medicinal drugs in Finland for which the mean FTI expressed as the number of deaths per million DDD over the three study years was higher or equal to 0.1. The Anatomical Therapeutic Chemical (ATC) classification system was used for the classification of the active ingredients of medicinal drugs according to the organ or system which they act on. Of these 70 drugs, 55 drugs (78.6 %) acted on the nervous system (denoted by ATC code N), 11 (15.7 %) on the cardiovascular system (C), three (4.3 %) on the alimentary tract and metabolism (A), and one (1.4 %) on the musculoskeletal system (M). The nervous system drugs consisted of 20 psycholeptics, (ATC code N05), 20 psychoanaleptics (N06), eight analgesics (N02), six antiepileptics (N03), and one other nervous system drug (N07). The highest individual FTIs were associated with the opioids methadone, dextropropoxyphene, oxycodone, tramadol, and morphine; the antipsychotics levomepromazine and chlorprothixene; and the antidepressants doxepin, amitriptyline, trimipramine, and bupropion. Buprenorphine was not included in the study, because most of the fatal buprenorphine poisonings were due to smuggled tablets. A clearly increasing trend in FTI was observed with pregabalin and possibly with bupropion, both drugs emerging as abused substances.
  • Wang, Cuicui; Luo, Jie; Nie, Peixin; Wang, Daoyang (2019)
    The present study examined the relationship between substance use and reasoning in adolescents, and further investigated the modulation role of growth mindset on this relationship. A total of 1759 adolescents in China with substance use experience were investigated. The results showed that substance use (smoking, drinking, and illicit drug use) was negatively correlated with reasoning (r = -0.24 similar to -0.39, p <0.01) and growth mindset (r = -0.18 similar to -0.32, p <0.01). Regression analysis revealed that after controlling for the background variables (i.e., age, family annual income, and parents' educational level), only illicit drug use was the significant predictor of reasoning (beta = -0.325, t = -14.28, p <0.001). The interaction effect between growth mindset and illicit drug use was also a significant predictor of reasoning (beta = -0.067, t = -2.92, p = 0.004), indicating growth mindset modulated the relationship between illicit drug use and reasoning ability. Further analysis found that the negative correlation between frequency of illicit drug use and reasoning in high growth mindset group was weaker than that of low growth mindset group (F-(3.1733) = 332.51, p <0.001, f(2) = 0.22). This suggests that growth mindset plays a significant moderating role in the relationship between substance use and reasoning. Overall, substance use has adverse effect on adolescent reasoning, however, growth mindset could reduce this adverse effect.
  • Jokela, Markus; García-Velázquez, Regina; Gluschkoff, Kia; Airaksinen, Jaakko; Rosenström, Tom (2020)
    Objectives Smoking rates have declined with a slower pace among those with psychological distress compared to those without. We examined whether other health behaviors (heavy alcohol consumption, physical inactivity, short sleep duration) showed similar trends associated with sychological distress. We also examined differences by age and birth cohort. Methods Data were from the annually repeated cross-sectional U.S. National Health Interview Surveys (NHIS) of 1997-2016 (total n = 603,518). Psychological distress was assessed with the 6-item Kessler Psychological Distress Scale (K6). Results Psychological distress became more strongly associated with smoking (OR 1.09 per 10 years; 95% CI 1.07, 1.12), physical inactivity (OR 1.08; 1.05, 1.11), and short sleep (OR 1.12; 1.06, 1.18), but less strongly associated with heavy alcohol consumption (OR 0.93; 0.89, 0.98). The associations of smoking and alcohol consumption attenuated with age, whereas the association with physical inactivity strengthened with age. Compared to older birth cohorts, smoking became more strongly associated with psychological distress among younger birth cohorts up to those born in the 1980s. Conclusions The strength of associations between psychological distress and health behaviors may vary by time period, age, and birth cohort.
  • Kriikku, Pirkko; Hakkinen, Margareeta; Ojanpera, Ilkka (2018)
    Sublingual buprenorphine is used in opioid maintenance treatment but buprenorphine is also widely abused and causes fatal poisonings. The aim of this study was to investigate buprenorphine-positive fatalities in order to gain novel information on the magnitude and nature of buprenorphine abuse. All post-mortem toxicology cases positive for urinary buprenorphine, including fatal poisonings caused by buprenorphine and fatalities in which the cause of death was unrelated to buprenorphine, in the five year period of 2010-2014 in Finland were characterized according to urine buprenorphine and naloxone concentrations (n = 775). Urine concentrations were used to assess which buprenorphine preparation had been used; mono-buprenorphine or a buprenorphine-naloxone combination, and whether they had been administered parenterally. In at least 28.8% of the buprenorphine-positive cases the drug had been administered parenterally. The majority of the parenteral users (68.6%) had taken mono-buprenorphine. Fatal poisoning was significantly more common among the identified parenteral users (65.5%) than among other users of buprenorphine products (45.3%). The proportion of buprenorphine-related poisoning was similar in identified parenteral users of mono-buprenorphine (68.6%) and buprenorphine-naloxone (64.1%). In nearly all of the fatal poisoningss the deceased had used other drugs and/or alcohol along with buprenorphine (98.7%). The median age of the deceased increased significantly over the study period, from 32 to 38 years. Our results show that there is ongoing parenteral abuse of both mono-buprenorphine and buprenorphine-naloxone combination. Parenteral users of buprenorphine put themselves into a great risk of fatal poisoning or other accidental injury death which is further exacerbated by the frequent polydrug use. (c) 2018 Elsevier B.V. All rights reserved.
  • Kaakinen, Markus; Koivula, Aki; Savolainen, Iina; Sirola, Anu; Mikkola, Marko; Zych, Izabela; Paek, Hye-Jin; Oksanen, Atte (2021)
    Based on lifestyle exposure theory (LET), this study examined online dating application (ODA) use and victimization experiences among adolescents using large cross-national samples of Finnish, American, Spanish, and South Korean young people between ages 15 and 18. According to logistic regression analyses in two substudies, ODA use was associated with more likely victimization to online harassment, online sexual harassment, and other cybercrimes and sexual victimization by adults and peers. According to mediation analyses, this relationship was mainly accounted for by the fact that ODA users engage in more risky activities in online communication and information sharing. Attention should be paid to the risks ODAs pose to vulnerable groups, such as young people, with insufficient skills to regulate their social relationships online.
  • Pulkki-Raback, Laura; Elovainio, Marko; Hakulinen, Christian; Lipsanen, Jari; Kubzansky, Laura D.; Hintsanen, Mirka; Savelieva, Kateryna; Serlachius, Anna; Magnussen, Costan G.; Sabin, Matthew A.; Burgner, David P.; Lehtimaki, Terho; Jokinen, Eero; Ronnemaa, Tapani; Mikkila, Vera; Jula, Antti; Hutri-Kahonen, Nina; Viikari, Jorma; Keltikangas-Jarvinen, Liisa; Raitakari, Olli; Juonala, Markus (2017)
    Introduction: Type 2 diabetes is a public health concern, but psychosocial factors that may protect against the disease are unknown. This study examines whether a positive psychosocial environment in childhood is associated with lower risk for Type 2 diabetes in adulthood or healthier glucose trajectories over the life course, and whether BMI mediates the associations. Methods: A cohort of 3,596 Finnish children was followed into adulthood over 32 years. An overall positive psychosocial score, consisting of six subdomains, was measured at study baseline (1980). Relative risk ratios and multilevel growth curve modeling were used to examine associations of the psychosocial score with Type 2 diabetes (2012) and glucose trajectories (1986-2012). The mediating effect by BMI was examined using mediation analysis. The analyses were conducted between June 2015 and January 2016. Results: There was a 21% decrease in the rate of Type 2 diabetes (relative risk ratio, 0.79; 95% CI = 0.66, 0.94) for each 1-SD increase in the positive psychosocial score after adjustment for childhood cardiovascular risk factors and dietary behaviors. Adult BMI mediated 52% and weight gain mediated 25% of the association. The growth curve model showed healthier glucose trajectories (age X psychosocial score interaction, b = -0.01; p = 0.010) for participants with higher versus lower positive psychosocial score in childhood. Conclusions: Positive psychosocial environment in childhood seems to have beneficial influences on the risk for Type 2 diabetes over the life span. RCTs will be required to see if interventions directed at early-life circumstances are warranted. (C) 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
  • Vaaramo, Kalle; Puljula, Jussi; Tetri, Sami; Juvela, Seppo; Hillbom, Matti (2014)
  • Koponen, Anne M.; Nissinen, Niina-Maria; Gissler, Mika; Autti-Rämö, Ilona; Sarkola, Taisto; Kahila, Hanna (2020)
    Both prenatal substance exposure (PSE, alcohol/drugs) and experiences during the first years of life have powerful effects on brain development. However, only a few studies have investigated the combined effect of PSE and adverse childhood experiences (ACEs) on mental and behavioral disorders among exposed adolescents and adults. This longitudinal register-based cohort study 1) compared the nature and extent of diagnosed mental and behavioral disorders among youth with PSE and matched unexposed controls, and 2) investigated the influence of PSE, health in infancy and ACEs (maternal risk factors and out-of-home care, OHC) on diagnoses of mental and behavioral disorders. The data consisted of 615 exposed youth aged 15-24 years and 1787 matched unexposed controls. Data from hospital medical records and nine registers were merged for the analysis. Descriptive analysis methods and Cox regression were used. The results showed that the prevalence of mental and behavioral disorders was twice as high among exposed compared with controls. The highest levels of mental and behavioral disorders and ACEs were found among exposed with at least one OHC episode. The difference in the risk of mental and behavioral disorders between exposed and controls diminished after controlling for the effect of ACEs. Low birth weight, maternal risk factors, and OHC were the strongest predictors of mental and behavioral disorders. The results suggest that PSE alone does not explain poorer mental health among exposed youth. Risk factors accumulate, and low birth weight and ACEs are strongly associated with increased risk of mental and behavioral disorders.
  • Kakko, Johan; Gedeon, Charlotte; Sandell, Mikael; Grelz, Henrik; Birkemose, Inge; Clausen, Thomas; Runarsdottir, Valgerour; Simojoki, Kaarlo; Littlewood, Richard; Alho, Hannu; Nyberg, Fred (2018)
    Background: Long-term use of opioid analgesics (OA) for chronic pain may result in opioid use disorder (OUD). This is associated with adverse outcomes for individuals, families and society. Treatment needs of people with OUD related to chronic pain are different compared to dependence related to use, and also injection, of illicit opioids. In Nordic countries, day-to-day practical advice to assist clinical decision-making is insufficient. Aim: To develop principles based on expert clinical insights for treatment of OUD related to the long-term use of OA in the context of chronic pain. Methods: Current status including an assessment of barriers to effective treatment in Finland, Denmark, Iceland, Norway, Sweden was defined using a patient pathway model. Evidence to describe best practice was identified from published literature, clinical guidelines and expert recommendations from practice experience. Results: Availability of national treatment guidelines for OUD related to chronic pain is limited across the Nordics. Important barriers to effective care identified: patients unlikely to present for help, healthcare system set up limits success, diagnosis tools not used, referral pathways unclear and treatment choices not elucidated. Principles include the development of a specific treatment pathway, awareness/education programs for teams in primary care, guidance on use of diagnostic tools and a flexible treatment plan to encourage best practice in referral, treatment assessment, choice and ongoing management via an integrated care pathway. Healthcare systems and registries in Nordic countries offer an opportunity to further research and identify population risks and solutions. Conclusions: There is an opportunity to improve outcomes for patients with OUD related to chronic pain by developing and introducing care pathways tailored to specific needs of the population.
  • Orsolini, Laura; Rojnic Palavra, Irena; Papanti, Gabriele Duccio; Potocan, Matej; Quattrone, Diego; Martens, Matis; Sklenarova, Sandra; Levola, Jonna; Grichy, Leslie; Naughton, Sean; Grineviciene, Indre Kotryna; Kuiters, Jelly Petra; Gondek, Tomasz M.; Panfil, Anca-Livia; Borovcanin, Milica M.; San Roman Uria, Alberto; Biskup, Ewelina; Sonmez Gungor, Ekin; Casanova Dias, Marisa; Tomori, Sonila; Banjac, Visnja; Marinova-Djambazova, Petra; Pinto da Costa, Mariana (2021)
    Background: Although psychoactive substance use disorders (PSUDs) are a domain of mental health, addiction psychiatry is only formally recognized as a subspecialty in a few European countries, and there is no standardized training curriculum. Methods: A 76-item questionnaire was developed and disseminated through an online anonymous data-collecting system and hand-to-hand amongst psychiatric trainees from the 47 European countries of the Council of Europe plus Israel and Belarus. Results: 1,049/1,118 psychiatric trainees from 30 European countries completed the questionnaire. Fifty-nine-point nine percent of trainees stated to have training in addictions. Amongst the trainees who described having training in addictions, 43% documented a not well-structured training and 37% an unsatisfactory training, mainly due to poor acquired knowledge. Overall, 97% of trainees stated that addiction represents a core curriculum for their training. Overall, general adult psychiatric trainees reported a better knowledge in addictions, compared to trainees in child and adolescent psychiatry. Conclusion: Despite a growing spread of PSUDs in European countries, addiction psychiatry is a relatively poorly trained field within psychiatry training programs. Further research should investigate reasons for poor training and timings of the educational activities to optimize experiential education training in addiction psychiatry.
  • Orcholski, Mark E.; Khurshudyan, Artyom; Shamskhou, Elya A.; Yuan, Ke; Chen, Ian Y.; Kodani, Sean D.; Morisseau, Christophe; Hammock, Bruce D.; Hong, Ellen M.; Alexandrova, Ludmila; Alastalo, Tero-Pekka; Berry, Gerald; Zamanian, Roham T.; Perez, Vinicio A. de Jesus (2017)
    Pulmonary arterial hypertension is a complication of methamphetamine use (METH-PAH), but the pathogenic mechanisms are unknown. Given that cytochrome P450 2D6 (CYP2D6) and carboxylesterase 1 (CES1) are involved in metabolism of METH and other amphetamine-like compounds, we postulated that loss of function variants could contribute to METH-PAH. Although no difference in CYP2D6 expression was seen by lung immunofluorescence, CES1 expression was significantly reduced in endothelium of METH-PAH microvessels. Mass spectrometry analysis showed that healthy pulmonary microvascular endothelial cells (PMVECs) have the capacity to both internalize and metabolize METH. Furthermore, whole exome sequencing data from 18 METH-PAH patients revealed that 94.4% of METH-PAH patients were heterozygous carriers of a single nucleotide variant (SNV; rs115629050) predicted to reduce CES1 activity. PMVECs transfected with this CES1 variant demonstrated significantly higher rates of METH-induced apoptosis. METH exposure results in increased formation of reactive oxygen species (ROS) and a compensatory autophagy response. Compared with healthy cells, CES1-deficient PMVECs lack a robust autophagy response despite higher ROS, which correlates with increased apoptosis. We propose that reduced CES1 expression/activity could promote development of METH-PAH by increasing PMVEC apoptosis and small vessel loss.