Karen D. Ersche

Despite rising global rates for cocaine addiction, treatments options are limited. Psychological treatments remain the standard option but have only modest effectiveness. One major barrier to treatment success is that patients often make disadvantageous decisions that go against recovery, highlighting the need for strategies to support decision-making. Converging evidence indicates that decision-making deficits in cocaine addiction are driven by impaired processing of outcomes and risks. We investigated how patients with cocaine addiction use explicit outcomes and risk information to guide decision-making. One-hundred-and-five patients with moderate-to-severe cocaine use disorder (CUD) and 80 healthy control volunteers completed a decision-making task in which reward, loss, and probability information were provided explicitly. A subset of participants underwent diffusion-weighted magnetic resonance imaging to investigate the orbitofronto-striatal white matter tracts that underpin decision-making. We used generalized linear mixed-effects models to determine how rewards, losses, and probability influence decisions, and combined probabilistic tractography with principal component analysis to characterize the white matter tracts. We found that patients incorporated explicit probability information into their decisions to the same degree as control participants but showed reduced integration of outcomes. Notably, patients were less likely to integrate losses into their decisions than rewards. Although orbitofronto-striatal white matter tracts did not differ between groups, individual variability predicted the extent to which reward and loss information guided decisions, irrespective of diagnosis. Overall, these findings reveal fundamental challenges in using outcomes, particularly negative ones, to guide decision-making in patients with CUD, emphasizing the need for additional support to promote adaptive choices during recovery.

Introduction: Objective measures for the severity of addiction are needed to identify and appropriately stratify patients into effective treatment groups for intervention and recovery. Our aim was to determine if blood-derived, dopamine-related biomarkers hold predictive validity in patients with cocaine use disorder (CUD). Methods: A total of 349 participants (163 patients with moderate-to-severe CUD and 186 healthy control participants without a history of substance use disorder) were recruited for a cross-sectional case-control study in the East of England, UK. Data on individual differences in CUD-related traits, e.g., impulsivity, sensation-seeking, were collected. Measurements included mRNA transcription of dopamine-related genes (DRD2, DRD3, DRD4, and COMT) and risk alleles (rs6277, rs1800497, rs12364283, rs6280, and rs4680). Results: CUD patients showed elevated DRD2 mRNA in peripheral blood (B0 = 0.43, 95% CI [0.13, 0.73], pFDR = 0.020) and the DRD2-related rs6277 risk allele was associated with CUD diagnosis (odds ratio = 2.16, 95% CI [1.15, 4.17], p = 0.02). DRD2 mRNA levels related to self-reported impulsivity (B0 = −0.17, 95% CI [−0.32, −0.03], p = 0.013). Conclusions: Blood-based expression of DRD2 may be a useful biomarker related to CUD diagnosis and related traits.

Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7 T QSM data from 30 patients, scanned 93–548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients’ QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.

Introduction: Regular cocaine use has been associated with hormonal dysfunction including hypogonadism, which can lead to fatigue, reduced stamina, sexual dysfunction, and impaired quality of life. However, cocaine’s endocrine effects are largely under-reported in the scientific addiction literature and, in many cases, are not addressed within treatment services. The low profile of these adverse effects might be attributable to a lack of awareness and linkage with cocaine use, such that they are recognized only when an acute/emergency problem arises. Methods: We assessed endocrine diurnal function (adrenocorticotrophic hormone [ACTH], cortisol, and testosterone) in 26 healthy and 27 cocaine-dependent men and examined changes in hormone levels in response to a single 40 mg dose of the noradrenaline re-uptake inhibitor atomoxetine in a double-blind, placebo-controlled experimental medicine study. Results: When compared with healthy controls, diurnal and atomoxetine-induced changes in ACTH and cortisol showed greater variability in cocaine-dependent men. Interestingly, despite an exaggerated rise in ACTH following atomoxetine, an attenuated cortisol response was observed, and one-third of cocaine-dependent men had subnormal testosterone levels. Conclusion: Our findings point to a potential disconnection between the pituitary and adrenal responses in cocaine-dependent men, a higher rate of hypogonadism, and a pressing need for more research into the endocrine effects of cocaine and their clinical implications.

Introduction: Chronotype describes a person’s preferential activity pattern during a 24-hour period, which may not be in line with their social lifestyle. A mismatch between biological and social time is known as “social jetlag,” which has negative effects on wellbeing. Cocaine influences a person’s activity levels, but very little is known about possible changes in chronotype of patients with cocaine use disorder (CUD). Here, we aimed to shed light on self-reported changes in chronotype in patients with CUD and the clinical implications. Methods: A total of 90 men from the local community were recruited; about half of the sample met the criteria for CUD, while the other half were healthy without a personal history of substance use disorder. Participants completed the Munich Chronotype Questionnaire along with questionnaires about mental health, daily fatigue, and drug/alcohol use. Results: Half of the CUD patients fell into the category of late chronotype – a significantly larger proportion than their healthy peers. Late “night owls” tended to have started using cocaine at an earlier age than other chronotypes; a finding that was not observed with tobacco, cannabis, or alcohol. Drug use severity in CUD patients did not differ across chronotypes. CUD patients (52%) did not have a preferred time of day to use cocaine. The mismatch between social and biological time was significantly greater in CUD patients and unrelated to drug use or mental health status. Conclusion: CUD appears to be associated with disruptions in chronotype which are, contrary to a widely held view, not reflected by using patterns or addiction severity.