“I feel good when I drink”—detecting childhood-onset alcohol abuse and dependence in a Ugandan community trial cohort

Background Alcohol, substance use, and mental health disorders constitute major public health issues worldwide, including in low income and lower middle-income countries, and early initiation of use is an important predictor for developing substance use disorders in later life. This study reports on the existence of childhood alcohol abuse and dependence in a sub-study of a trial cohort in Eastern Uganda. Methods The project SeeTheChild—Mental Child Health in Uganda (STC) included a sub-study of the Ugandan site of the study PROMISE SB: Saving Brains in Uganda and Burkina Faso. PROMISE SB was a follow-up study of a trial birth cohort (PROMISE EBF) that estimated the effect that peer counselling for exclusive breast-feeding had on the children’s cognitive functioning and mental health once they reached 5–8 years of age. The STC sub-study (N = 148) used the diagnostic tool MINI-KID to assess mental health conditions in children who scored medium and high (≥ 14) on the Strengths and Difficulties Questionnaire (SDQ) in the PROMISE SB cohort N = (119/148; 80.4%). Another 29/148 (19.6%) were recruited from the PROMISE SB cohort as a comparator with low SDQ scores (< 14). Additionally, the open-ended questions in the diagnostic history were analysed. The MINI-KID comprised diagnostic questions on alcohol abuse and dependence, and descriptive data from the sub-study are presented in this paper. Results A total of 11/148 (7.4%) children scored positive for alcohol abuse and dependence in this study, 10 of whom had high SDQ scores (≥ 14). The 10 children with SDQ-scores ≥ 14 had a variety of mental health comorbidities of which suicidality 3/10 (30.0%) and separation anxiety disorder 5/10 (50.0%) were the most common. The one child with an SDQ score below 14 did not have any comorbidities. Access to homemade brew, carer’s knowledge of the drinking, and difficult household circumstances were issues expressed in the children’s diagnostic histories. Conclusions The discovery of alcohol abuse and dependence among 5–8 year olds in clinical interviews from a community based trial cohort was unexpected, and we recommend continued research and increased awareness of these conditions in this age group. Trial registration Trial registration for PROMISE SB: Saving Brains in Uganda and Burkina Faso: Clinicaltrials.gov (NCT01882335), 20 June 2013. Regrettably, there was a 1 month delay in the registration compared to the commenced re-inclusion in the follow-up study: https://clinicaltrials.gov/ct2/show/NCT01882335?term=saving+brains&draw=2&rank=1

Population Attributable Fraction of Early Age of Onset of Alcohol Use in Alcohol Abuse and Dependence: A 3-Year Follow-Up Study in University Students

Background: we aimed to determine the risk factors and associated population attributable fractions (PAFs) for the age of onset of alcohol use and also to identify protective factors. Methods: we analyzed follow-up data collected between autumn 2011 and spring 2016 (n = 5170) from the first two cohorts (2011, 2012) of the Spit for ScienceTM project. The dependent variables were alcohol abuse and dependence, and the independent variables were age of drinking onset, residence, ethnicity, religiosity, sexual orientation and work status. We determined the odds ratios (OR) using multilevel logistic regression for repeated measures in SPSSv.20. Results: the early onset of alcohol use was associated with an increased risk of alcohol abuse and dependence among females (OR = 14.98; OR = 11.83) and males (OR = 7.41; OR = 6.24). The PAFs for the early onset of alcohol use in alcohol abuse and dependence were respectively 80.9% and 71.7% in females and 71.0% and 63.5% in males. Among females, being white (OR = 1.58; OR = 1.51), living off-campus (OR = 1.73; OR = 2.76) and working full-time (OR = 1.69; OR = 1.78) were also risk factors. Strong religious beliefs were found to protect males from alcohol abuse (OR = 0.58), while same-gender sexual orientation increased the risk among females (OR = 2.09). Conclusion: delaying the age of onset by one year would reduce alcohol abuse among young adults.

Сравнительный анализ экспрессии генов опиоидной системы в мозге крыс с различным уровнем предпочтения алкоголя

Введение. Среди факторов риска формирования алкогольной зависимости важное место занимает высокая гедоническая ценность алкоголя. Активация двух подтипов опиоидных рецепторов - каппа- (KOP) и ноцицептинового (NOP) сопровождается снижением уровня дофамина в прилежащем ядре системы расширенной миндалины мозга. Можно предполагать, что экспрессия эндогенных лигандов рецепторов динорфина и ноцицептина является гомеостатическим механизмом отрицательной обратной связи в системе «награды», а ее нарушение - один из патогенетических механизмов формирования зависимости. Цель исследования - выявление различий в уровнях мРНК генов, кодирующих KOP и NOP рецепторы и их эндогенные лиганды - препродинорфин (ppDyn) и препроноцицептин (ppNoc) в ключевых областях мезолимбической дофаминергической системы у хронически алкоголизировнных животных с различным уровнем потребления алкоголя. Методы. Половозрелые крысы-самцы Wistar содержались 15 сут. (60-х по 85-е сут. жизни) в условиях «свободного выбора» между 10% раствором этанола и водой. Уровень экспрессии мРНК генов определяли методом ПЦР в реальном времени. Результаты. Были выделены 2 группы животных - со стабильно низким (группа А; n = 14) и неуклонно растущим (группа А; n = 12) уровнем предпочтения алкоголя. Животные группы А характеризовались статистически значимо сниженной экспрессией мРНК генов, кодирующих ppDyn и ppNoc в стриатуме, а также ppDyn и опиоидные рецепторы (KOP и NOP) - в миндалине мозга. Заключение. Предполагается, что низкий уровень экспрессии генов «антигедонических» опиоидных рецепторов (KOP и NOP) и их эндогенных лигандов (ppDyn и ppNoc) в лимбических структурах мозга может рассматриваться в качестве этиопатогенетического механизма, лежащего в основе положительного подкрепляющего действия алкоголя у животных с высоким уровнем его предпочтения. Background. High hedonic value of alcohol is one of important risk factors for alcohol abuse and dependence. Activation of dynorphin and nociceptin opioidergic neurotransmission is suggested to be a homeostatic mechanism of negative feedback loop to arrest excessive mesolimbic dopamine release and thus, to decrease the rewarding effects of drugs of abuse and alcohol. Decreased tone of these evolutionarily closely related «anti-reward» opioidergic systems may result in increased hedomimetic properties of alcohol and thus, represent a principal pathogenetic mechanism of substance abuse. The aim of this study was to analyze opioid gene (KOP, NOP, ppDyn and ppNoc) expression in mesolimbic areas (mesencephalon, striatum and amygdala) in two groups of animals with different levels of alcohol preference. Methods. Using a 25-day-long (postnatal days [PND] 60 to 85) two-bottle free choice regimen (10% ethanol/water) in male Wistar rats we identified two groups of animals: low-drinking (A-) and low-drinking under the initial ethanol exposure but increasing the alcohol intake over the course of experiment (A+). mRNA levels were evaluated on PND 85 using a quantitative real-time reverse-transcription polymerase chain reaction procedure. Results. The А+ rats were found to have statistically significantly lower levels of ppDyn and ppNoc mRNA in the striatum and ppDyn, KOP and NOP mRNA in the amygdala than А- rats. Conclusions. We suggested that low levels of these «anti-hedonic» opioid gene expression in the striatum and amygdala may result in increased rewarding properties of alcohol in А+ rats and thus, may represent one of the principal mechanisms underlying high alcohol preference.