Children born to women in opioid maintenance treatment: A longitudinal study of child behavioral problems and parenting stress

© 2022 Sarfi, Eikemo and Konijnenberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.In the wake of the “opioid epidemic”, there is considerable concern regarding potential harmful long-term effects of prenatal opioid exposure. Opioid misuse and addiction confer increased exposure to lifestyle stressors and health burdens. Accordingly, it is challenging to disentangle effects of prenatal opioid exposure per se from factors related to maternal stress. In this study, we followed 36 women enrolled in comprehensive opioid maintenance treatment (OMT) program and their children alongside 36 age-matched mother-child dyads from a community sample (COMP) from pregnancy until child-age 8 years. Across five sessions, we used a battery of well-established questionnaires to investigate trajectories of parenting stress and mental health symptoms as well as child behavior problems. The 8-year retention was relatively high (OMT: 72%, COMP: 67%), and the OMT sample remarkably stable and well-functioning, with minimal concomitant illicit drug use. Mixed effects regressions showed significantly different trajectories of child behavior problems (F = 3.8, p = 0.024) and parenting stress (F = 3.1, p = 0.016) in the two groups. Differences in experienced stress were largely explained by more distress specifically related to the parenting role in the OMT group (F = 9.7, p = 0.003). The OMT sample also reported higher psychological distress (F = 15.6, p < 0.001) than the comparison group, but notably few participants presented with problems that warranted clinical intervention. The results underscore the benefits of tailored follow-up of children prenatally exposed to opioids and their families beyond infancy and toddlerhood. Long-term direct effects of prenatal opioid exposure on behavior problems are likely modest, given an otherwise stable caregiving environment conducive to healthy development.publishedVersio

Mental health and use of health care services in opioid‑exposed school‑aged children compared to foster children

Given the concerns raised regarding the effects of prenatal exposure to methadone and buprenorphine on the developmental outcomes of the children, this study assessed mental health and use of services in a national sample of school-aged children (N = 78) born to women enrolled in opioid maintenance treatment during pregnancy, compared with a group of foster children (N = 140). The majority of the opioid-exposed children lived with their birth parent(s) at the time of assessment (N = 62), while 16 lived in foster homes. Caregivers completed the Strengths and Difficulties Questionnaire (SDQ) and the Reactive Attachment Disorder scale. Teachers completed the SDQ. Three kinds of services were included in measuring service use: school-based education services, child mental health services, and hospital-based habilitation services. The main finding of the study is that children prenatally exposed to methadone or buprenorphine living with their family of origin had significantly better mental health status than their foster-placed counterparts and that of the comparison group of foster children. In addition, the exposed children living at home had less child welfare involvement, and only half of them were using any of the three services measured. The odds for using services increased significantly in accordance with increasing mental health problems, independent of group affiliation, indicating a need-based access to services. In line with other studies, we found that the odds for using one or more services was 2.3 times greater for boys than for girls. Our results contribute to a more-nuanced understanding of the developmental outcomes of prenatal exposure to methadone and buprenorphine, and factors associated with increased service use in groups of at-risk children.publishedVersio

Sweet taste pleasantness is modulated by morphine and naltrexone

Rodent models highlight the key role of µ-opioid receptor (MOR) signaling in palatable food consumption. In humans however, the effects of MOR stimulation on eating and food liking remain unclear. In a bidirectional psychopharmacological cross-over study, 49 healthy men underwent a sweet taste paradigm following double-blind administration of the MOR agonist morphine, placebo, and the opioid antagonist nalt rexone. We hypothesized that behaviors regulated by the endogenous MOR system would be enhanced by MOR agonism, and decreased by antagonism. The strongest drug effects were expected for the sweetest (high-calorie) sucrose solution, as reported in rodents. However, very sweet sucrose-water solutions are considered sickly and aversive by many people (called sweet dislikers). Since both sweet likers and dislikers were tested, we were able to assess whether MOR manipulations affect pleasantness ratings differently depending on both subjective and objective value. As hypothesized, MOR stimulation with morphine increased pleasantness of the sweetest of five sucrose solutions, without enhancing pleasantness of the lower-sucrose solutions. For opioid antagonism, an opposite pattern was observed for the sweetest drink only. This bidirectional effect of agonist and antagonist treatment is consistent with rodent findings that MOR manipulations most strongly affect the highest-calorie foods. Importantly, the observed drug effects on pleasantness of the sweetest drink did not differ between sweet likers and dislikers. We speculate that the MOR system promotes survival in part by increasing concordance between the objective (caloric) and subjective (hedonic) value of food stimuli, so that feeding behaviour becomes more focused on the richest food available

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

The Role of the Opioid System in Reward Responsiveness

Studies of non-human animals have provided ample evidence that opioids are involved in reward processes. Less is known about the role of the opioid system for human reward processes. We hypothesized that an opioid agonist would increase, and an opioid antagonist would decrease responsiveness to rewards in healthy humans. We tested 30 healthy male participants on a reward responsiveness task using a randomized, placebo-controlled double-blind design. Participants received oral treatment with a µ-opioid agonist (morphine, 10mg), a non-selective opioid antagonist (naltrexone, 50mg) or placebo on three separate days. One-two hours after drug administration, one of three locally developed versions of a reward responsiveness task was completed. The task was a two-alternative signal detection task with a skewed reward schedule. Stimuli were schematic faces which differed in the size or position of the mouth. Reward responsiveness was operationalized as a bias towards choosing the most frequently rewarded response option. In line with our hypothesis, the results showed that morphine significantly increased and that naltrexone significantly decreased bias relative to placebo. These effects could be due to either a direct effect of opioid agonism/antagonism on the neural reward system, or due to indirect effects, e.g. via opioid effects on striatal dopamine functioning. Notably, although our naltrexone condition would be expected to block endogenous opioid function, reward responsiveness was not completely eliminated. This could indicate that opioids may be involved in, but not necessary for, this effect. Overall, our findings confirm a role for the opioid system in human reward responsiveness

The role of the opioid system in decision making and cognitive control: A review

The opioid system regulates affective processing, including pain, pleasure, and reward. Restricting the role of this system to hedonic modulation may be an underestimation, however. Opioid receptors are distributed widely in the human brain, including the more “cognitive” regions in the frontal and parietal lobes. Nonhuman animal research points to opioid modulation of cognitive and decision-making processes. We review emerging evidence on whether acute opioid drug modulation in healthy humans can influence cognitive function, such as how we choose between actions of different values and how we control our behavior in the face of distracting information. Specifically, we review studies employing opioid agonists or antagonists together with experimental paradigms of reward-based decision making, impulsivity, executive functioning, attention, inhibition, and effort. Although this field is still in its infancy, the emerging picture suggests that the mu-opioid system can influence higher-level cognitive function via modulation of valuation, motivation, and control circuits dense in mu-opioid receptors, including orbitofrontal cortex, basal ganglia, amygdalae, anterior cingulate cortex, and prefrontal cortex. The framework that we put forward proposes that opioids influence decision making and cognitive control by increasing the subjective value of reward and reducing aversive arousal. We highlight potential mechanisms that might underlie the effects of mu-opioid signaling on decision making and cognitive control and provide directions for future research

Effects of opioid receptor stimulation and blockade on touch pleasantness: a double-blind randomised trial

The μ-opioid receptor (MOR) system has long been thought to underpin the rewarding properties of pleasant touch. Numerous non-human animal studies implicate MORs in social behaviours involving touch, but little is currently known about MOR involvement in human touch reward. Here, we employed a bi-directional pharmacological double-blind crossover design to assess the role of the human MOR system for touch pleasantness and motivation. Forty-nine male volunteers received 10 mg per-oral morphine, 50 mg per-oral naltrexone and placebo before being brushed on their forearm at three different velocities (0.3, 3 and 30 cm/s). In a touch liking task, pleasantness ratings were recorded after each 15 s brushing trial. In a touch wanting task, participants actively manipulated trial duration through key presses. As expected, 3 cm/s was the preferred velocity, producing significantly higher pleasantness ratings and wanting scores than the other stimuli. Contrary to our hypothesis, MOR drug manipulations did not significantly affect either touch pleasantness or wanting. The null effects were supported by post hoc Bayesian analyses indicating that the models with no drug effect were more than 25 times more likely than the alternative models given the data. We conclude that μ-opioid signalling is unlikely to underpin non-affiliative touch reward in humans

Mental health and use of health care services in opioid‑exposed school‑aged children compared to foster children

Given the concerns raised regarding the effects of prenatal exposure to methadone and buprenorphine on the developmental outcomes of the children, this study assessed mental health and use of services in a national sample of school-aged children (N = 78) born to women enrolled in opioid maintenance treatment during pregnancy, compared with a group of foster children (N = 140). The majority of the opioid-exposed children lived with their birth parent(s) at the time of assessment (N = 62), while 16 lived in foster homes. Caregivers completed the Strengths and Difficulties Questionnaire (SDQ) and the Reactive Attachment Disorder scale. Teachers completed the SDQ. Three kinds of services were included in measuring service use: school-based education services, child mental health services, and hospital-based habilitation services. The main finding of the study is that children prenatally exposed to methadone or buprenorphine living with their family of origin had significantly better mental health status than their foster-placed counterparts and that of the comparison group of foster children. In addition, the exposed children living at home had less child welfare involvement, and only half of them were using any of the three services measured. The odds for using services increased significantly in accordance with increasing mental health problems, independent of group affiliation, indicating a need-based access to services. In line with other studies, we found that the odds for using one or more services was 2.3 times greater for boys than for girls. Our results contribute to a more-nuanced understanding of the developmental outcomes of prenatal exposure to methadone and buprenorphine, and factors associated with increased service use in groups of at-risk children

Assessment of Anhedonia in Adults With and Without Mental Illness A Systematic Review and Meta-analysis

This systematic review and meta-analysis assesses levels of anhedonia in healthy individuals and patients with mental illness according to the Snaith-Hamilton Pleasure Scale. Question Does anhedonia severity differ among patients with different types of mental illness typically associated with this symptom, and what is considered healthy hedonic functioning? Findings In this systematic review and meta-analysis of 168 studies including more than 16000 participants, anhedonia as measured by the Snaith-Hamilton Pleasure Scale was significantly elevated in patients with major depressive disorder, schizophrenia, substance use disorders, Parkinson disease, and chronic pain. Compared with ongoing major depressive disorder, all other patient groups displayed significantly lower anhedonia. Meaning The findings of this meta-analysis provide a possible set of reference values for anhedonia severity across healthy populations and those with mental illness; these results may have utility for researchers and clinicians evaluating new and existing treatments for anhedonia. Importance Anhedonia, a reduced capacity for pleasure, is described for many psychiatric and neurologic conditions. However, a decade after the Research Domain Criteria launch, whether anhedonia severity differs between diagnoses is still unclear. Reference values for hedonic capacity in healthy humans are also needed. Objective To generate and compare reference values for anhedonia levels in adults with and without mental illness. Data Sources Web of Science, Scopus, PubMed, and Google Scholar were used to list all articles from January 1, 1995 to July 2, 2019, citing the scale development report of a widely used anhedonia questionnaire, the Snaith-Hamilton Pleasure Scale (SHAPS). Searches were conducted from April 5 to 11, 2018, and on July 2, 2019. Study Selection Studies including healthy patients and those with a verified diagnosis, assessed at baseline or in a no-treatment condition with the complete 14-item SHAPS, were included in this preregistered meta-analysis. Data Extraction and Synthesis Random-effects models were used to calculate mean SHAPS scores and 95% CIs separately for healthy participants and patients with current major depressive disorder (MDD), past/remitted MDD, bipolar disorder, schizophrenia, substance use disorders, Parkinson disease, and chronic pain. SHAPS scores were compared between groups using meta-regression, and traditional effect size meta-analyses were conducted to estimate differences in SHAPS scores between healthy and patient samples. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Main Outcomes and Measures Self-reported anhedonia as measured by 2 different formats of the SHAPS (possible ranges, 0-14 and 14-56 points), with higher values on both scales indicating greater anhedonia symptoms. Results In the available literature (168 articles; 16494 participants; 8058 [49%] female participants; aged 13-72 years), patients with current MDD, schizophrenia, substance use disorder, Parkinson disease, and chronic pain scored higher on the SHAPS than healthy participants. Within the patient groups, those with current MDD scored considerably higher than all other groups. Patients with remitted MDD scored within the healthy range (g = 0.1). This pattern replicated across SHAPS scoring methods and was consistent across point estimate and effect size analyses. Conclusions and Relevance The findings of this meta-analysis indicate that the severity of anhedonia may differ across disorders associated with anhedonia. Whereas anhedonia in MDD affects multiple pleasure domains, patients with other conditions may experience decreased enjoyment of only a minority of lifes many rewards. These findings have implications for psychiatric taxonomy development, where dimensional approaches are gaining attention. Moreover, the SHAPS reference values presented herein may be useful for researchers and clinicians assessing the efficacy of anhedonia treatments.Funding Agencies|South-Eastern Norway Regional Health Authority [2018035]; European Research Council under the European UnionEuropean Research Council (ERC) [802885]</p

Morphine reduced perceived anger from neutral and implicit emotional expressions

The μ-opioid system modulates responses to pain and psychosocial stress and mediates non-social and social reward. In humans, the μ-opioid agonist morphine can increase overt attention to the eye-region and visual exploration of faces with neutral expressions. However, little is known about how the human μ-opioid system influences sensitivity to and appraisal of subtle and explicit cues of social threats and reward. Here, we examined the effects of selective μ-opioid stimulation on perception of anger and happiness in faces with explicit, neutral or implicit emotion expressions. Sixty-three healthy adults (32 females) attended two sessions where they received either placebo or 10 mg per oral morphine in randomised order under double-blind conditions. Based on the known μ-opioid reduction of pain and discomfort, as well as reports suggesting that the non-specific partial agonist buprenorphine or the non-specific antagonist naltrexone affect appraisal of social emotional stimuli, we hypothesised that morphine would reduce threat sensitivity and enhance perception of happy facial expressions. While overall perception of others’ happiness was unaffected by morphine treatment, morphine reduced perception of anger in stimuli with neutral and implicit expressions without affecting perception of explicit anger. This effect was statistically unrelated to gender, subjective drug effects, mood and autism trait measures. The finding that a low dose of μ-agonist reduced the propensity to perceive anger in photos with subtle facial expressions is consistent with the notion that μ-opioids mediate social confidence and reduce sensitivity to threat cues