Adult self-reported childhood maltreatment types are associated with treatment satisfaction and alcohol relapse in patients with comorbid substance use and mental health disorders.

BACKGROUND AND OBJECTIVES: Individuals with comorbid substance use and mental health disorders (concurrent disorders; CD) report poor treatment outcomes, high prevalence of childhood maltreatment, and mostly negative experiences with treatment. No studies to date have examined childhood maltreatment and treatment outcomes in CD. This study investigated self-reported childhood maltreatment as it relates to treatment satisfaction and substance use relapse among CD patients. METHODS: The 258 CD inpatients completed a self-report questionnaire package, comprising the Childhood Trauma Questionnaire and the Inpatient Consumer Survey (ICS). Childhood maltreatment was assessed according to five subtypes and self-perceived treatment satisfaction was rated across six ICS domains. Psychiatric diagnoses, substance use status and relapse data were retrieved via patient medical charts. RESULTS: Emotional neglect was associated with lower ratings across all ICS domains and physical neglect was associated with a lower rating for 'outcome of care'. Childhood sexual abuse was associated with a greater likelihood of alcohol relapse. No other relationships were statistically significant. DISCUSSION AND CONCLUSIONS: The presence of childhood neglect (but not abuse) was more associated with overall treatment dissatisfaction, and sexual abuse alone increased the likelihood of alcohol relapse. These findings suggest some early adverse experiences in CD patients may increase negative experiences in treatment while others contribute to the risk of substance use. Broader longitudinal research is needed to examine the trajectory leading to negative outcomes. SCIENTIFIC SIGNIFICANCE: This is the first study to report differential patterns of association by type of childhood maltreatment on negative outcomes in treatment among CD patients.

Laboratory method to induce state boredom increases impulsive choice in people who use cocaine and controls.

Background: Impulsive choice is associated with both cocaine use and relapse. Little is known about the influence of transient states on impulsive choice in people who use cocaine (PWUC).Objective: This study investigated the direct effects of induced boredom on impulsive choice (i.e., temporal discounting) in PWUC relative to well-matched community controls.Methods: Forty-one PWUC (≥1× cocaine use in past 3 months; 7 females) and 38 demographically matched controls (5 females) underwent two experimental conditions in counterbalanced order. Temporal discounting was assessed immediately after a standardized boredom induction task (peg-turning) and a self-selected video watched for the same duration (non-boredom). Subjective mood state and perceived task characteristics were assessed at baseline, during experimental manipulations, and after the choice task.Results: PWUC and controls were well matched on sex, age, and socioeconomic status. Groups were also similar in reported use of drugs other than cocaine, except for recent cigarette and alcohol use (PWUC > controls). As expected, peg-turning increased boredom in the sample overall, with higher boredom reported during peg-turning than the video (p < .001, η2p = .20). Participants overall exhibited greater impulsive choice after boredom than non-boredom (p = .028, η2p = .07), with no preferential effects in PWUC (p > .05, BF01 = 2.9).Conclusion: Experimentally induced boredom increased state impulsivity irrespective of cocaine use status - in PWUC and carefully matched controls - suggesting a broad link between boredom and impulsive choice. This is the first study to show that transient boredom directly increases impulsive choice. Data support a viable laboratory method to further parse the effects of boredom on impulsive choice.

Associations of the P300 Event-Related Potentials and Self-Reported Craving in Substance Use Disorders: A Systematic Review.

INTRODUCTION: The phenomenon of craving and attention bias towards drug cues is theorized to operate cooperatively, owing to the principles of associative learning. In this context, the conditioned response to drug-related stimuli activates reward mechanisms within the brain, consequently inducing craving and fostering the underlying mechanisms that contribute to relapse in individuals with substance use disorders. Multiple studies have assessed the relationship between attention to substance-related cues and subjective craving through electroencephalography (EEG), but their findings have yet to be synthesized and examined. This review summarizes the association between the amplitude of the P300 event-related potential (ERP) and substance use craving, compares discrepancies in results by type of substance, and discusses gaps in the literature to inform future research. METHODS: A systematic search was conducted on Embase, Web of Science, CINAHL, and PsychINFO databases. Studies were published in English and included peer-reviewed human research investigating the relationship between EEG P300 ERP and self-reported substance use craving. The included study samples comprised of in treatment or non-treatment-seeking participants who use substances. The primary outcomes of interest were those derived from inferential statistics assessing P300 amplitude and substance use craving. RESULTS: Ten studies were included in the final search and were organized by substance type: three alcohol, three cocaine, two tobacco, one heroin, and one cannabis. Results were mixed for alcohol and cocaine. Studies on tobacco, heroin, and cannabis use were congruent for associations between the P300 amplitude and craving. CONCLUSIONS: Overall findings are mixed between studies addressing the association of the EEG P300 amplitude and craving. These results should be considered in the context of the limited sample size, underpowered analyses, and methodological differences that potentially contribute to discrepancies in outcomes. Further research is required to assess the role of craving assessment, EEG methodology, and substance-related factors on the association between P300 amplitude and self-reported craving.

Astrogliosis marker 11C-SL25.1188 PET in traumatic brain injury with persistent symptoms.

Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in the brain of humans with TBI and persistent symptoms is lacking. Astroglial marker monoamine oxidase B (MAO-B) total distribution volume (11C-SL25.1188 VT), an index of MAO-B density, was measured in 29 TBI and 29 similarly aged healthy control cases with 11C-SL25.1188 PET, prioritizing prefrontal cortex (PFC) and cortex proximal to cortical convexity. Correlations of PFC 11C-SL25.1188 VT with psychomotor and processing speed; and serum blood measures implicated in astrogliosis were determined. 11C-SL25.1188 VT was greater in TBI in PFC (P = 0.00064) and cortex (P = 0.00038). PFC 11C-SL25.1188 VT inversely correlated with Comprehensive Trail Making Test psychomotor and processing speed (r = -0.48, P = 0.01). In participants scanned within 2 years of last TBI, PFC 11C-SL25.1188 VT correlated with serum glial fibrillary acid protein (r = 0.51, P = 0.037) and total tau (r = 0.74, P = 0.001). Elevated 11C-SL25.1188 VT argues strongly for astrogliosis and therapeutics modifying astrogliosis towards curative phenotypes should be tested in TBI with persistent symptoms. Given substantive effect size, astrogliosis PET markers should be applied to stratify cases and/or assess target engagement for putative therapeutics targeting astrogliosis.

Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms.

Importance: Persistent depressive symptoms, often accompanied by cognitive symptoms, commonly occur after COVID-19 illness (hereinafter termed COVID-DC, DC for depressive and/or cognitive symptoms). In patients with COVID-DC, gliosis, an inflammatory change, was suspected, but measurements of gliosis had not been studied in the brain for this condition. Objective: To determine whether translocator protein total distribution volume (TSPO VT), a marker of gliosis that is quantifiable with positron emission tomography (PET), is elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of persons with COVID-DC. Design, Setting, and Participants: This case-control study conducted at a tertiary care psychiatric hospital in Canada from April 1, 2021, to June 30, 2022, compared TSPO VT of specific brain regions in 20 participants with COVID-DC with that in 20 healthy controls. The TSPO VT was measured with fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) PET. Main Outcomes and Measures: The TSPO VT was measured in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus. Symptoms were measured with neuropsychological and psychological tests, prioritizing outcomes related to striatal function. Results: The study population included 40 participants (mean [SD] age, 32.9 [12.3] years). The TSPO VT across the regions of interest was greater in persons with COVID-DC (mean [SD] age, 32.7 [11.4] years; 12 [60%] women) compared with healthy control participants (mean [SD] age, 33.3 [13.9] years; 11 [55%] women): mean (SD) difference, 1.51 (4.47); 95% CI, 0.04-2.98; 1.51 divided by 9.20 (17%). The difference was most prominent in the ventral striatum (mean [SD] difference, 1.97 [4.88]; 95% CI, 0.36-3.58; 1.97 divided by 8.87 [22%]) and dorsal putamen (mean difference, 1.70 [4.25]; 95% CI, 0.34-3.06; 1.70 divided by 8.37 [20%]). Motor speed on the finger-tapping test negatively correlated with dorsal putamen TSPO VT (r, -0.53; 95% CI, -0.79 to -0.09), and the 10 persons with the slowest speed among those with COVID-DC had higher dorsal putamen TSPO VT than healthy persons by 2.3 (2.30 divided by 8.37 [27%]; SD, 2.46; 95% CI, 0.92-3.68). Conclusions and Relevance: In this case-control study, TSPO VT was higher in patients with COVID-DC. Greater TSPO VT is evidence for an inflammatory change of elevated gliosis in the brain of an individual with COVID-DC. Gliosis may be consequent to inflammation, injury, or both, particularly in the ventral striatum and dorsal putamen, which may explain some persistent depressive and cognitive symptoms, including slowed motor speed, low motivation or energy, and anhedonia, after initially mild to moderate COVID-19 illness.

Predictors of therapeutic alliance, treatment feedback, and clinical outcomes among African American women in treatment for co-occurring PTSD and SUD.

INTRODUCTION: Black women are at heightened risk for trauma exposure, post-traumatic stress disorder (PTSD), and substance use disorders (SUDs), compared to White women and the general population. However, disparities in treatment engagement and retention persist, particularly for Black women with co-occurring PTSD+SUD. Although therapeutic alliance is an important predictor and mediator of treatment retention and outcomes, we know little about predictors of alliance and the mediating role of alliance for PTSD+SUD outcomes among Black women. METHODS: This study utilized data previously collected for the National Drug Abuse Treatment Clinical Trials Network (CTN) Women and Trauma Study. Participants were 88 Black/African American women (Mage = 41.90, SD = 7.72) participating in a clinical trial comparing Seeking Safety (a cognitive-behavioral intervention for PTSD+SUD) to Women's Health Education (control). This study includes participants from both arms. Measures included the Helping Alliance Questionnaire, Addiction Severity Index-Lite, and Clinician Administered PTSD Scale. Women in the intervention arm also completed the Seeking Safety Feedback Questionnaire. RESULTS: Stepwise, hierarchical linear regressions indicated that years of education and previous alcohol/drug treatment attempts significantly predicted early alliance in the second week of therapy (ß = 0.411, p = .021 and ß = 0.383, p = .011, respectively), but not late alliance in the last week of therapy (ps > .794). Greater education and more treatment attempts were associated with higher early alliance. Alliance did not mediate relationships between these significant predictors and treatment outcomes (e.g., attendance, post-treatment PTSD and SUD symptoms) or treatment feedback in the Seeking Safety group. CONCLUSIONS: Education and prior treatment attempts predicted early alliance among Black/African American women in PTSD+SUD group treatment, and higher education level was associated with poorer Seeking Safety feedback topic ratings. Educational level and treatment history should be considered during alliance building in therapeutic interventions with Black women. Clinicians may consider the integration of pre-treatment alliance-building strategies with Black female patients who have lower levels of education. This study provides insight into the relative impact of several important factors that influence early alliance among Black women with co-occurring PTSD+SUD.

Responses to social evaluative stress in regular cannabis smokers.

BACKGROUND: Aspects of the canonical stress response differ in stimulant, opioid, and alcohol users relative to controls, and dysregulated responses to stress may contribute to continued use of these drugs. Little prior research has focused on stress responses in regular cannabis smokers. We assessed responses to a standardized laboratory social stress assay (the Trier Social Stress Task; TSST) in regular cannabis smokers (CANs) compared with controls (CONs). METHODS: Healthy, non-treatment-seeking adult CANs (⩾4×/week; smoking cannabis as usual) and demographically matched CONs completed the TSST. Outcome measures were subjective mood, heart rate, and salivary cortisol. RESULTS: Nineteen CANs (1 female) and 20 CONs (2 female) participated; groups were matched on trauma exposure, sex, race, and age. CANs smoked cannabis 6.4 ± 1.1 days/week. Eight CANs and one CON smoked tobacco cigarettes daily. Overall, the TSST produced expected increases in anxiety, negative mood states, cortisol, and heart rate. CANs had blunted subjective response to stress relative to CONs, but they did not differ in physiological (cortisol and cardiovascular) stress responding. CONCLUSION: These results indicate that CANs have blunted mood responses to social stress, but normative physiological stress responding. Observed differences could be due to residual effects of cannabis, reluctance to endorse negative mood states, or to issues related to identifying (i.e., emotional identification) or feeling (i.e., interoception) stress-related affective states. Further research is warranted to characterize the mechanisms of these differences and assess implications for daily functioning and treatment outcomes.

Changes in Loss Sensitivity During Treatment in Concurrent Disorders Inpatients: A Computational Model Approach to Assessing Risky Decision-Making.

BACKGROUND: Recent studies have employed computational modeling to characterize deficits in aspects of decision-making not otherwise detected using traditional behavioral task outcomes. While prospect utility-based modeling has shown to differentiate decision-making patterns between users of different drugs, its relevance in the context of treatment has yet to be examined. This study investigated model-based decision-making as it relates to treatment outcome in inpatients with co-occurring mental health and substance use disorders. METHODS: 50 patients (Mage = 38.5, SD = 11.4; 16F) completed the Cambridge Gambling Task (CGT) within 2 weeks of admission (baseline) and 6 months into treatment (follow-up), and 50 controls (Mage = 31.9, SD = 10.0; 25F) completed CGT under a single outpatient session. We evaluated 4 traditional CGT outputs and 5 decisional processes derived from the Cumulative Model. Psychiatric diagnoses and discharge data were retrieved from patient health records. RESULTS: Groups were similar in age, sex, and premorbid IQ. Differences in years of education were included as covariates across all group comparisons. All patients had ≥1 mental health diagnosis, with 80% having >1 substance use disorder. On the CGT, patients showed greater Deliberation Time and Delay Aversion than controls. Estimated model parameters revealed higher Delayed Reward Discounting, and lower Probability Distortion and Loss Sensitivity in patients relative to controls. From baseline to follow-up, patients (n = 24) showed a decrease in model-derived Loss Sensitivity and Color Choice Bias. Lastly, poorer Quality of Decision-Making and Choice Consistency, and greater Color Choice Bias independently predicted higher likelihood of treatment dropout, while none were significant in relation to treatment length of stay. CONCLUSION: This is the first study to assess a computational model of decision-making in the context of treatment for concurrent disorders. Patients were more impulsive and slower to deliberate choice than controls. While both traditional and computational outcomes predicted treatment adherence in patients, findings suggest computational methods are able to capture treatment-sensitive aspects of decision-making not accessible via traditional methods. Further research is needed to confirm findings as well as investigate the relationship between model-based decision-making and post-treatment outcomes.

Pharmacotherapeutic strategies for treating cocaine use disorder-what do we have to offer?

BACKGROUND: Cocaine use contines to be a significant public health problem world-wide. However, despite substantial research efforts, no pharmacotherapies are approved for the treatment of cocaine use disorder (CUD). ARGUMENT: Studies have identified positive signals for a range of medications for treating CUD. These include long-acting amphetamine formulations, modafinil, topiramate, doxazosin and combined topiramate and mixed amphetamine salts extended-release (MAS-ER). However, valid conclusions about a medication's clinical efficacy require nuanced approaches that take into account behavioural phenotypes of the target population (frequency of use, co-abuse of cocaine and other substances, genetic subgroups, psychiatric comorbidity), variables related to the medication (dose, short-/long-acting formulations, titration speed, medication adherence) and other factors that may affect treatment outcomes. Meta-analyses frequently do not account for these co-varying factors, which contributes to a somewhat nihilistic view on pharmacotherapeutic options for CUD. In addition, the predominant focus on abstinence, which is difficult for most patients to achieve, may overshadow more nuanced therapeutic signals. CONCLUSION: While there is an emphasis on finding new medications with novel mechanisms of action for treating CUD, currently available medications deserve further investigation based on the existing literature. Evaluating refined metrics of treatment success in well-defined subgroups of patients, and further exploring combination therapies and their synergy with behavioural/psychosocial interventions, are promising avenues to establishing effective therapies for CUD.

Cognitive function in aging cocaine smokers.

BACKGROUND: Little is known about the functional status of older drug users, who may pose challenges to public health systems in coming years. Here, we assessed cognitive function in aging cocaine smokers compared to demographically matched controls. METHODS: A total of 22 non-treatment-seeking aging (50-60 years old) cocaine smokers (⩾twice/week; ⩾15 years of weekly use) and 19 controls completed a comprehensive cognitive battery. Controls with cannabis, tobacco, and alcohol use were included to better match the cocaine users. All cocaine users, and current cannabis- or alcohol-using controls, completed testing after 4 drug-free inpatient days to better control for acute and residual drug effects. RESULTS: Cocaine users (52.9 ± 2.5 years old, four female; cocaine use 3.9 ± 1.4 days/week) and controls (52.7 ± 2.6 years old, four female) were well matched demographically, but cocaine users reported a more extensive substance use profile. Cocaine users showed marginally worse verbal learning than controls, recalling on average one word fewer across immediate and delayed word recall trials. Their performance was intact relative to controls across all other measures of cognitive function. Bayesian analysis indicated the absence of group differences was not due to power limitations. CONCLUSION: These data suggest that aging, long-term cocaine users have similar cognitive functioning to appropriately matched controls when tested under drug-free conditions, with only marginal decreases in verbal learning. Findings, although reassuring with regard to broad cognitive capacities in aging cocaine smokers, suggest that future investigations of cognitive function in aging drug users are warranted.

Stress responding in cannabis smokers as a function of trauma exposure, sex, and relapse in the human laboratory.

BACKGROUND: Stress responding is linked to drug use, but little is known about stress responses in cannabis smokers. We investigated acute stress responding in cannabis smokers as a function of trauma exposure and sex, and relationships between stress responses and cannabis relapse. METHODS: 125 healthy, non-treatment-seeking daily cannabis smokers (23F, 102 M) completed the Trier Social Stress Task (TSST), a standardized laboratory stressor; subsets also completed a trauma questionnaire (n = 106) and a laboratory cannabis relapse measure (n = 54). Stress responding was assessed with heart rate (HR), salivary cortisol (CORT), and self-rated mood. RESULTS: Cannabis smokers reporting at least one trauma exposure had higher CORT and anxiety overall compared to those reporting no trauma. Stress responding did not differ as a function of binary trauma exposure, although total number of exposures correlated positively with CORT and anxiety during stress. Females reported increased nervousness after stress relative to males matched to the females for cannabis and cigarette use. An interactive effect of sex and trauma on HR suggested that females with trauma exposure have increased cardiovascular stress responding relative to those without such exposure, with no differential effect in males. Stress responding did not predict laboratory cannabis relapse. CONCLUSION: We report differences in acute stress responding as a function of trauma, sex, and their interaction in a large sample of relatively homogenous cannabis smokers. Further investigation of how trauma impacts stress responding in male and female cannabis smokers, and how this relates to different aspects of cannabis use, is warranted.

Genome re-sequencing reveals the history of apple and supports a two-stage model for fruit enlargement.

Human selection has reshaped crop genomes. Here we report an apple genome variation map generated through genome sequencing of 117 diverse accessions. A comprehensive model of apple speciation and domestication along the Silk Road is proposed based on evidence from diverse genomic analyses. Cultivated apples likely originate from Malus sieversii in Kazakhstan, followed by intensive introgressions from M. sylvestris. M. sieversii in Xinjiang of China turns out to be an "ancient" isolated ecotype not directly contributing to apple domestication. We have identified selective sweeps underlying quantitative trait loci/genes of important fruit quality traits including fruit texture and flavor, and provide evidences supporting a model of apple fruit size evolution comprising two major events with one occurring prior to domestication and the other during domestication. This study outlines the genetic basis of apple domestication and evolution, and provides valuable information for facilitating marker-assisted breeding and apple improvement.Apple is one of the most important fruit crops. Here, the authors perform deep genome resequencing of 117 diverse accessions and reveal comprehensive models of apple origin, speciation, domestication, and fruit size evolution as well as candidate genes associated with important agronomic traits.