General lifestyle factors explain young athletes’ mental health more than perceived coach autonomy support: a cross-sectional study on basketball players and gymnasts aged 10–22

Objectives This study described differences in lifestyle factors (sleeping problems/fatigue, pressure/activation), perceived coach autonomy support and indicators of mental health (well-being and poor general mental health) across various age groups (children ≤12 years, youths 13–15 years, junior to senior ≥16 years) and sports (basketball and gymnastics). Second, the relationships between lifestyle factors and mental health indicators were explored, hypothesising that the relationships would be mediated by perceived coach autonomy support.Methods A cross-sectional study design was implemented by using an online survey which assessed lifestyle and environmental factors as well as mental health indicators. Participants were recruited through sports clubs in basketball and gymnastics. A total of 209 athletes (77 basketball players and 132 gymnasts) in the age range of 10–22 (median=13) years volunteered to complete the survey.Results Separate two-way analyses of variance showed significant main effects for age group on sleeping problems/fatigue, sleep quantity, pressure/activation, well-being and poor general mental health, with higher scores reported for older age groups of athletes. Path analysis displayed sleeping problems/fatigue and pressure/activation to significantly affect decreased well-being and poor general mental health; however, the relationships were not mediated by perceived coach autonomy support.Conclusion Lifestyle factors play a prominent role in mental health outcomes. Researchers studying athlete mental health should consider both general lifestyle and sports-related factors, considering developmental phases in the young athlete’s sporting context and overall life

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

BACKGROUND: Posttraumatic stress disorder, an area of large unmet medical needs, is characterized by persistence of fear memories and maladaptive stress responses. In rodents, elevation of the endocannabinoid anandamide due to inhibition of fatty acid amide hydrolase (FAAH) facilitates fear extinction and protects against the anxiogenic effects of stress. We recently reported that elevated anandamide levels in people homozygous for a loss-of-function FAAH mutation are associated with a similar phenotype, suggesting a translational validity of the preclinical findings. METHODS: In this double-blind, placebo-controlled experimental medicine study, healthy adults were randomized to an FAAH inhibitor (PF-04457845, 4 mg orally, once daily; n = 16) or placebo (n = 29) for 10 days. On days 9 and 10, participants completed a task battery assessing psychophysiological indices of fear learning, stress reactivity, and stress-induced affective responses. RESULTS: FAAH inhibition produced a 10-fold increase in baseline anandamide. This was associated with potentiated recall of fear extinction memory when tested 24 hours after extinction training. FAAH inhibition also attenuated autonomic stress reactivity, assessed via electrodermal activity, and protected against stress-induced negative affect, measured via facial electromyography. CONCLUSIONS: Our data provide preliminary human evidence that FAAH inhibition can improve the recall of fear extinction memories and attenuate the anxiogenic effects of stress, in a direct translation of rodent findings. The beneficial effects of FAAH inhibition on fear extinction, as well as stress- and affect-related behaviors, provide a strong rationale for developing this drug class as a treatment for posttraumatic stress disorder.Funding Agencies|Swedish Research CouncilSwedish Research Council [2013-07434]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR)</p

Stress recovery with social support : A dyadic stress and support task

How does social support bolster resilience? Here, we present a new dyadic paradigm to study causal mechanisms of acute and ecologically valid social support in the laboratory. The Dyadic Stress and Support Task (DSST) consists of a psychosocial stress phase and a recovery phase. During DSST stress, a pair of participants take turns to perform public speaking and mental arithmetic in front of a panel. Unable to see or touch each other, they witness each others performance and feedback. During DSST recovery, the pair either interact freely with each other for 5 min (social support condition) or interact separately with an experimenter (non-support condition). To establish the validity of the DSST, we tested 21 pairs of long-term close friends in a pilot study. Primary outcome measures were ratings of affective state and bodily arousal (VAS scales 0-100). Secondary outcome measures were heart rate and salivary cortisol. DSST stress successfully induced subjective Stress Activation, increased Negative Affect and decreased Positive Affect. We also observed increased heart rate and salivary cortisol. After DSST recovery, Stress Activation and Negative Affect ratings were reduced in both groups. Positive Affect was completely restored to pre-stress baseline levels in the Social support group, while remaining significantly lower in the Non-support group. The DSST successfully induced stress and negative affect and captured stress recovery in both groups. Free-form interaction with the friend enhanced recovery of affective state, supporting the validity of spontaneous interaction between friends as a model of social support.Funding Agencies|European Research Council under the European Unions Horizon 2020 research and innovation program [802885]; South-Eastern Norway Regional Health Authority [2020087, 2018035]</p

Stress-induced escalation of alcohol self-administration, anxiety-like behavior, and elevated amygdala Avp expression in a susceptible subpopulation of rats

Comorbidity between alcohol use and anxiety disorders is associated with more severe symptoms and poorer treatment outcomes than either of the conditions alone. There is a well-known link between stress and the development of these disorders, with post-traumatic stress disorder as a prototypic example. Post-traumatic stress disorder can arise as a consequence of experiencing traumatic events firsthand and also after witnessing them. Here, we used a model of social defeat and witness stress in rats, to study shared mechanisms of stress-induced anxiety-like behavior and escalated alcohol self-administration. Similar to what is observed clinically, we found considerable individual differences in susceptibility and resilience to the stress. Both among defeated and witness rats, we found a subpopulation in which exposure was followed by emergence of increased anxiety-like behavior and escalation of alcohol self-administration. We then profiled gene expression in tissue from the amygdala, a key brain region in the regulation of stress, alcohol use, and anxiety disorders. When comparing "comorbid" and resilient socially defeated rats, we identified a strong upregulation of vasopressin and oxytocin, and this correlated positively with the magnitude of the alcohol self-administration and anxiety-like behavior. A similar trend was observed in comorbid witness rats. Together, our findings provide novel insights into molecular mechanisms underpinning the comorbidity of escalated alcohol self-administration and anxiety-like behavior.Funding Agencies|Wallenberg FoundationEuropean Commission [KAW 2018.0322]; Region Ostergotland; Stiftelsen psykiatriska forskningsfonden; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2013-07434]</p

Peripheral and central kynurenine pathway abnormalities in major depression

Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an index of metabolic disturbance associated with atypical depression. Plasma levels of picolinic acid (PIC), the kynurenic/quinolinic acid ratio (KYNA/QUIN), and PIC/QUIN were lower in MDD, but QUIN levels were increased. In the CSF, we found lower PIC in MDD. Confirming previous work, MDD patients had lower hippocampal, and amygdalar volumes. Hippocampal and amygdalar volumes were correlated positively with plasma KYNA/QUIN ratio in MDD patients. BMI was increased in the MDD group relative to the control group. Moreover, BMI was inversely correlated with plasma and CSF PIC and PIC/QUIN, and positively correlated with plasma QUIN levels in MDD. Our results partially confirm previous peripheral KP findings and extend them to the CSF in MDD. We present the novel finding that abnormalities in KP metabolites are related to metabolic disturbances in depression, but the relation between KP metabolites and depression-associated brain atrophy might not be as direct as previously hypothesized.Funding Agencies|Johnson &amp; Johnson Innovation; Swedish Medical Research CouncilSwedish Medical Research Council (SMRC)European Commission [2017-00875, 2013-07434, 2019-01138]; ALF Grants, Region Ostergotland; National Institutes of HealthUnited States Department of Health &amp; Human ServicesNational Institutes of Health (NIH) - USA [R01 CA193522, R01 NS073939]; MD Anderson Cancer Support Grant [P30 CA016672]</p

A randomized controlled experimental medicine study of ghrelin in value-based decision making

BACKGROUND. The stomach-derived hormone ghrelin stimulates appetite, but the ghrelin receptor is also expressed in brain circuits involved in motivation and reward. We examined ghrelin effects on decision making beyond food or drug reward using monetary rewards. METHODS. Thirty participants (50% women and 50% men) underwent 2 fMRI scans while receiving i.v. ghrelin or saline in a randomized counterbalanced order. RESULTS. Striatal representations of reward anticipation were unaffected by ghrelin, while activity during anticipation of losses was attenuated. Temporal discounting rates of monetary reward were lower overall in the ghrelin condition, an effect driven by women. Discounting rates were inversely correlated with neural activity in a large cluster within the left parietal lobule that included the angular gyrus. Activity in an overlapping cluster was related to behavioral choices and was suppressed by ghrelin. CONCLUSION. This is, to our knowledge, the first human study to extend the understanding of ghrelins significance beyond the canonical feeding domain or in relation to addictive substances. Contrary to our hypothesis, we found that ghrelin did not affect sensitivity to monetary reward anticipation, but rather resulted in attenuated loss aversion and lower discounting rates for these rewards. Ghrelin may cause a motivational shift toward caloric reward rather than globally promoting the value of reward. TRIAL REGISTRATION. EudraCT 2018-004829-82.Funding Agencies|Swedish Research Council [2013-07434]; Marcus and Marianne Wallenberg foundatio [2014.0187]; National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism Intramural Research Program</p

Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation

Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD. Four groups were defined across the dimensions of CM and lifetime SUD (N = 101 in total). After screening, participants completed two experimental sessions on separate days, aimed at assessing the behavioral, physiological, and neural mechanisms involved in emotion regulation. In the first session, participants engaged in tasks assessing biochemical (i.e., cortisol, endocannabinoids), behavioral, and psychophysiological indices of stress and affective reactivity. During the second session, the behavioral and brain mechanisms associated with emotion regulation and negative affect were investigated using magnetic resonance imaging. CM-exposed adults who did not develop SUD, operationally defined as resilient to developing SUD, had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress exposure, compared to controls. Similarly, this group had increased activity in salience and emotion regulation regions in task-based measures of emotion regulation compared to controls, and CM-exposed adults with lifetime SUD. At rest, the resilient group also showed significantly greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to controls and CM-exposed adults with lifetime SUD. Collectively, these peripheral and central findings point to mechanisms of potential resilience to developing SUD after documented CM exposure.Funding Agencies|Swedish Research Council for Infrastructures and Science for Life Laboratory, Sweden; Swedish Research Council [2013-07434]; Medical Training and Research Agreement in Ostergotland Region [ALF 2017: LIO-599451, ALF 2018: LIO-692621, ALF 2019: LIO-791581, ALF 2020: RO-888021, ALF 2021: RO-935602]; Systembolagets alkoholforskningsrad [2016-0018, 2017-0075, 2018-0030, 2019-0007]; Brain &amp; Behavior Research Foundation NARSAD Young Investigator Grant [27094]</p