The coronavirus disease 2019 (Covid-19) pandemic intensified the already catastrophic drug overdose and substance use disorder (SUD) epidemic, signaling a syndemic as social isolation, economic and ...mental health distress, and disrupted treatment services disproportionally impacted this vulnerable population. Along with these social and societal factors, biological factors triggered by intense stress intertwined with incumbent overactivity of the immune system and the resulting inflammatory outcomes may impact the functional status of the central nervous system (CNS). We review the literature concerning SARS-CoV2 infiltration and infection in the CNS and the prospects of synergy between stress, inflammation, and kynurenine pathway function during illness and recovery from Covid-19. Taken together, inflammation and neuroimmune signaling, a consequence of Covid-19 infection, may dysregulate critical pathways and underlie maladaptive changes in the CNS, to exacerbate the development of neuropsychiatric symptoms and in the vulnerability to develop SUD.
This article is part of the special Issue on ‘Vulnerabilities to Substance Abuse’.
•Co-morbidities contribute to severe Covid-19, potentially due to inflammation.•Inflammation and the kynurenine pathway during SUD may add to Covid-19 severity.•Neuroimmune signaling during Covid-19 dysregulates tryptophan metabolism.•Increased levels of kynurenine destabilize normal neurotransmitter levels.•Altered neurotransmitters are related to drug use and misuse and increased SUDs.
This study aimed to examine friendship networks and social support outcomes for mothers according to patterns of playgroup participation.
Data from the Longitudinal Study of Australian Children were ...used to examine the extent to which patterns of playgroup participation across the ages of 3-19 months (Wave 1) and 2-3 years (Wave 2) were associated with social support outcomes for mothers at Wave 3 (4-5 years) and four years later at Wave 5 (8-9 years). Analyses were adjusted for initial friendship attachments at Wave 1 and other socio-demographic characteristics.
Log-binomial regression models estimating relative risks showed that mothers who never participated in a playgroup, or who participated at either Wave 1 or Wave 2 only, were 1.7 and 1.8 times as likely to report having no support from friends when the child was 4-5 years, and 2.0 times as likely to have no support at age 8-9 years, compared with mothers who persistently participated in playgroup at both Wave 1 and Wave 2.
These results provide evidence that persistent playgroup participation may acts as a protective factor against poor social support outcomes. Socially isolated parents may find playgroups a useful resource to build their social support networks.
Increasing numbers of young people living with HIV (YPLWH) have unaddressed mental health challenges. Such challenges are associated with poor antiretroviral therapy (ART) adherence and high ...mortality. Few evidence-based mental health interventions exist to improve HIV outcomes among YPLWH.
This pilot group treatment trial individually randomized YPLWH from two clinical sites in Tanzania, evaluated acceptability, feasibility, and preliminary effectiveness of a mental health intervention, Sauti ya Vijana (SYV; The Voice of Youth), was compared to the local standard-of-care (SOC) for improving ART adherence and virologic suppression. Enrolled YPLWH were 12-24 years of age and responded to mental health and stigma questionnaires, self-reported adherence, objective adherence measures (ART concentration in hair), and HIV RNA at baseline and 6-months (post-intervention). Feasibility and acceptability were evaluated, and potential effectiveness was assessed by comparing outcomes between arms using mixed effects modeling.
Between June 2016 and July 2017, 128 YPLWH enrolled; 105 were randomized and 93 (55 in SYV) followed-up at 6-months and were thereby included in this analysis. Mean age was 18.1 years; 51% were female; and 84% were HIV-infected perinatally. Attendance to intervention sessions was 86%; 6-month follow-up was 88%, and fidelity to the protocol approached 100%. Exploratory analyses of effectiveness demonstrated self-reported adherence improved by 7.3 percentage points (95% CI: 2.2, 12.3); and the pooled standard deviation for all ART concentration values increased by 0.17 units (95% CI: - 0.52, 0.85) in the SYV arm compared to SOC. Virologic suppression rates (HIV RNA < 400 copies/mL) at baseline were 65% in both arms but increased to 75% in the SYV arm while staying the same in the SOC arm (RR 1.13; 95% CI: 0.94, 1.36).
YPLWH often have poor HIV outcomes, making interventions to improve outcomes in this population critical. This pilot trial of the Tanzania-based SYV intervention demonstrated trends towards improvement in ART adherence and virologic outcomes among YPLWH, supporting efforts to scale the intervention into a fully-powered effectiveness trial.
ClinicalTrials.gov Identifier: NCT02888288 . Registered August 9, 2016. Retrospectively registered as first participant enrolled June 16, 2016.
Abstract Serotonin 2C receptors (5-HT2C R) appear to exert tonic inhibitory influence over dopamine (DA) neurotransmission in the ventral tegmental area (VTA), the origin of the mesolimbic DA system, ...thought to be important in psychiatric disorders including addiction and schizophrenia. Current literature suggests that the inhibitory influence of 5-HT2C R on DA neurotransmission occurs via indirect activation of GABA inhibitory neurons, rather than via a direct action of 5-HT2C R on DA neurons. The present experiments were performed to establish the distribution of 5-HT2C R protein on DA and GABA neurons in the VTA of male rats via double-label immunofluorescence techniques. The 5-HT2C R protein was found to be co-localized with the GABA synthetic enzyme glutamic acid decarboxylase (GAD), confirming the presence of the 5-HT2C R on GABA neurons within the VTA. The 5-HT2C R immunoreactivity was also present in cells that contained immunoreactivity for tyrosine hydroxylase (TH), the DA synthetic enzyme, validating the localization of 5-HT2C R to DA neurons in the VTA. While the degree of 5-HT2C R+GAD co-localization was similar across the rostro-caudal levels of VTA subnuclei, 5-HT2C R+TH co-localization was highest in the middle relative to rostral and caudal levels of the VTA, particularly in the paranigral, parabrachial, and interfascicular subnuclei. The present results suggest that the inhibitory influence of the 5-HT2C R over DA neurotransmission in the VTA is a multifaceted and complex interplay of 5-HT2C R control of the output of both GABA and DA neurons within this region.
Although 85% of HIV-positive adolescents reside in sub-Saharan Africa, little is known about the psychosocial and mental health factors affecting their daily well-being. Identifying these contextual ...variables is key to development of culturally appropriate and effective interventions for this understudied and high-risk population. The purpose of this study was to identify salient psychosocial and mental health challenges confronted by HIV-positive youth in a resource-poor Tanzanian setting. A total of 24 qualitative interviews were conducted with a convenience sample of adolescents aged 12-24 receiving outpatient HIV care at a medical center in Moshi, Tanzania. All interviews were audio-recorded, transcribed, and coded using thematic analysis. Psychosocial challenges identified included loss of one or more parents, chronic domestic abuse, financial stressors restricting access to medical care and education, and high levels of internalized and community stigma among peers and other social contacts. Over half of youth (56%) reported difficulties coming to terms with their HIV diagnosis and espoused related feelings of self-blame. These findings highlight the urgent need to develop culturally proficient programs aimed at helping adolescents cope with these manifold challenges. Results from this study guided the development of Sauti ya Vijana (The Voice of Youth), a 10-session group mental health intervention designed to address the psychosocial and mental health needs of HIV-positive Tanzanian youth.
Highlights • Cue reactivity incubates during forced abstinence from cocaine- or sucrose-taking. • Incubation aligns with lower potency of 5-HT2C R agonist to suppress cocaine cue reactivity. • ...Incubation of cocaine cue reactivity associates with lower 5-HT2C R expression in mPFC. • Membrane to cytoplasmic 5-HT2C R ratio inversely correlates with cocaine cue reactivity.
Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality.
Plasma viremia (lower ...limit of detection, <2 copies/mL), T-cell activation, HIV-1-specific immune responses, and the persistence of cells carrying replication-competent virus were quantified during long-term effective combination antiretroviral therapy (cART) in 4 perinatally HIV-1-infected youth who received treatment early (the ET group) and 4 who received treatment late (the LT group). Decay in peripheral blood mononuclear cell (PBMC) proviral DNA levels was also measured over time in the ET youth.
Plasma viremia was not detected in any ET youth but was detected in all LT youth (median, 8 copies/mL; P = .03). PBMC proviral load was significantly lower in ET youth (median, 7 copies per million PBMCs) than in LT youth (median, 181 copies; P = .03). Replication-competent virus was recovered from all LT youth but only 1 ET youth. Decay in proviral DNA was noted in all 4 ET youth in association with limited T-cell activation and with absent to minimal HIV-1-specific immune responses.
Initiation of early effective cART during infancy significantly limits circulating levels of proviral and replication-competent HIV-1 and promotes continuous decay of viral reservoirs. Continued cART with reduction in HIV-1 reservoirs over time may facilitate HIV-1 eradication strategies.
Clinical investigators in Japan have long suggested that exposure to methamphetamine might cause a persistent schizophrenia-like psychosis. This possibility is discounted in the Western literature. ...To investigate the relationship between drug use and later schizophrenia, the authors conducted a large-scale cohort study of drug users initially free of persistent psychosis.
A population-based cohort study was conducted using data from California inpatient hospital discharge records from 1990 through 2000. Patients with methamphetamine-related conditions (N=42,412) and those with other drug use disorders (cannabis, cocaine, alcohol, and opioids) were propensity score-matched to individuals with primary appendicitis who served as a population proxy comparison group; the methamphetamine cohort was also matched to the other drug cohorts. Cox modeling was used to estimate differences between matched groups in the rates of subsequent admission with schizophrenia diagnoses.
The methamphetamine cohort had a significantly higher risk of schizophrenia than the appendicitis group (hazard ratio=9.37) and the cocaine, opioid, and alcohol groups (hazard ratios ranging from 1.46 to 2.81), but not significantly different from that of the cannabis group. The risk of schizophrenia was higher in all drug cohorts than in the appendicitis group.
Study limitations include difficulty in confirming schizophrenia diagnoses independent of drug intoxication and the possibility of undetected schizophrenia predating drug exposure. The study's findings suggest that individuals with methamphetamine-related disorders have a higher risk of schizophrenia than those with other drug use disorders, with the exception of cannabis use disorders. The elevated risk in methamphetamine users may be explained by shared etiological mechanisms involved in the development of schizophrenia.
Recently discovered relativistic spin torques induced by a lateral current at a ferromagnet/paramagnet interface are a candidate spintronic technology for a new generation of electrically controlled ...magnetic memory devices. The focus of our work is to experimentally disentangle the perceived two model physical mechanisms of the relativistic spin torques, one driven by the spin-Hall effect and the other one by the inverse spin-galvanic effect. Here, we show a vector analysis of the torques in a prepared epitaxial transition-metal ferromagnet/semiconductor-paramagnet single-crystal structure by means of the all-electrical ferromagnetic resonance technique. By choice of our structure in which the semiconductor paramagnet has a Dresselhaus crystal inversion asymmetry, the system is favourable for separating the torques due to the inverse spin-galvanic effect and spin-Hall effect mechanisms into the field-like and antidamping-like components, respectively. Since they contribute to distinct symmetry torque components, the two microscopic mechanisms do not compete but complement each other in our system.
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