Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of Anabolic-Androgenic Steroids.

AIM: In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodeling and their association with hormones and echocardiographic myocardial pathology in weightlifters. METHODS: In a cross-sectional study, 93 weightlifting AAS-users, of which 62 were current and 31 were past users, with at least one-year cumulative AAS-use (mean 11±7 accumulated years of AAS-use), were compared to 54 non-using weightlifting controls (WLC) using clinical interview, blood pressure measurements, and echocardiography. RESULTS: Serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF), interferon (IFN)γ, growth differentiation factor (GDF)-15 and matrix metalloproteinase (MMP-9), sex hormones and lipids were analyzed. Serum levels of IL-8, GDF-15 and MMP-9 were significantly increased in current AAS users compared to former users and WLC. MMP-9, but not IL-8, correlated consistently with sex-hormone levels, and sex-hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current versus former AAS users, in significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP9 also with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users. CONCLUSION: In conclusion, long-term AAS is associated with increased levels of markers of inflammation and extracellular matrix remodeling, which seems to have a hormone-dependent (MMP-9) and hormone-independent (IL-8) association with markers of myocardial dysfunction.

Long-term use of anabolic-androgenic steroids (AAS) can increase inflammation and mediators of extracellular matrix (ECM) remodeling which potentially could be involved in myocardial pathology seen in these individuals. AAS use increased levels of inflammatory marker IL-8 and marker of ECM remodeling MMP-9.IL-8 and MMP-9 were both associated with myocardial pathology in current, but not former users, suggesting that these markers are association with risk of myocardial damage during AAS use.

Sleep pathology and use of anabolic androgen steroids among male weightlifters in Norway.

Use of anabolic androgenic steroids (AAS) causes drastic changes in hormonal milieu and is associated with a range of medical and psychological consequences. Sleep pathology is a common side-effect of AAS use but few have studied these relations. This study examined the relationship between AAS use, psychological distress and sleep quality, and how phases of heavy use and abstinence influence sleep. The Pittsburgh-Sleep-Quality-Index (PSQI) and Jenkins Sleep Scale (JSS) were used to assess sleep quality, and psychological distress was measured with the Hopkins Symptoms Checklist (HSCL). Participants comprised men who have previous or current long-term use of AAS (n = 68) and non-using weightlifting controls (WLC) (n = 58), where a subgroup of participants (n = 22) was monitored over ~ 6 months during phases of AAS use and withdrawal. Group differences on PSQI and JSS were evaluated with Kruskal-Wallis H tests, and the mediating role of psychological distress was evaluated using structural equation modeling. Linear mixed models were used to assess the role of AAS use and withdrawal on sleep quality. Among the AAS group, 66% reported sleep problems as a side effect, and 38% had used sleep medication. PSQI scores showed significantly lower sleep quality in the AAS group compared to WLC (p < 0.001) on all subscales except "sleep latency". Furthermore, sleep quality was significantly poorer during withdrawal-phases than periods with AAS use (p < .001). Our findings provide key insight into sleep disturbances among men who use AAS, suggesting a link between sleep disturbances and hormone levels that deviate from physiologically normal levels in both directions.

Supraphysiological testosterone levels from anabolic steroid use and reduced sensitivity to negative facial expressions in men.

RATIONALE: Anabolic-androgenic steroids (AAS) are used to improve physical performance and appearance, but have been associated with deficits in social cognitive functioning. Approximately 30% of people who use AAS develop a dependence, increasing the risk for undesired effects. OBJECTIVES: To assess the relationship between AAS use (current/previous), AAS dependence, and the ability to recognize emotional facial expressions, and investigate the potential mediating role of hormone levels. METHODS: In total 156 male weightlifters, including those with current (n = 45) or previous (n = 34) AAS use and never-using controls (n = 77), completed a facial Emotion Recognition Task (ERT). Participants were presented with faces expressing one out of six emotions (sadness, happiness, fear, anger, disgust, and surprise) and were instructed to indicate which of the six emotions each face displayed. ERT accuracy and response time were recorded and evaluated for association with AAS use status, AAS dependence, and serum reproductive hormone levels. Mediation models were used to evaluate the mediating role of androgens in the relationship between AAS use and ERT performance. RESULTS: Compared to never-using controls, men currently using AAS exhibited lower recognition accuracy for facial emotional expressions, particularly anger (Cohen's d = -0.57, pFDR = 0.03) and disgust (d = -0.51, pFDR = 0.05). Those with AAS dependence (n = 47) demonstrated worse recognition of fear relative to men without dependence (d = 0.58, p = 0.03). Recognition of disgust was negatively correlated with serum free testosterone index (FTI); however, FTI did not significantly mediate the association between AAS use and recognition of disgust. CONCLUSIONS: Our findings demonstrate impaired facial emotion recognition among men currently using AAS compared to controls. While further studies are needed to investigate potential mechanisms, our analysis did not support a simple mediation effect of serum FTI.

Clustering psychopathology in male anabolic-androgenic steroid users and nonusing weightlifters.

INTRODUCTION: Prior research has demonstrated that personality disorders and clinical psychiatric syndromes are common among users of anabolic-androgenic steroids (AAS). However, the prevalence, expression, and severity of psychopathology differ among AAS users and remain poorly understood. In this study, we examine the existence of potential clinically coherent psychopathology subgroups, using cluster procedures. METHODS: A sample of 118 male AAS users and 97 weightlifting nonusers was assessed using the Millon Clinical Multiaxial Inventory-III (MCMI-III), measuring personality disorders and clinical syndromes. Group differences in MCMI-III scales were assessed using Wilcoxon-Mann-Whitney tests and Fisher's exact test. Agglomerative hierarchical clustering was used to identify clusters based on MCMI-III scale scores from the whole sample. RESULTS: AAS users displayed significantly higher scores on all personality disorder (except narcissistic) and clinical syndrome scales compared to nonusing weightlifters. The clustering analysis found four separate clusters with different levels and patterns of psychopathology. The "no psychopathology" cluster was most common among nonusing weightlifters, while the three other clusters were more common among AAS users: "severe multipathology," "low multipathology," and "mild externalizing." The "severe multipathology" cluster was found almost exclusively among AAS users. AAS users also displayed the highest scores on drug and alcohol dependence syndromes. CONCLUSIONS: AAS users in our sample demonstrated greater psychopathology than the nonusing weightlifters, with many exhibiting multipathology. This may pose a significant challenge to clinical care for AAS users, particularly as there appears to be significant variation in psychopathology in this population. Individual psychiatric profiles should be taken into consideration when providing treatment to this group. SIGNIFICANT OUTCOMES: As a group, AAS users displayed markedly greater psychopathology than nonusing weightlifters. Multipathology was common among AAS users. Four different subgroups of personality profiles were identified with distinct patterns of pathology and severity. LIMITATIONS: The cross-sectional nature of the study precludes inferences about causality. The study is limited by possible selection bias, as participants choosing to be involved in research may not be entirely representative for the group as a whole. The study is vulnerable to information bias, as the results are based on self-report measures and interviews.

Investigating anabolic-androgenic steroid dependence and muscle dysmorphia with network analysis among male weightlifters.

BACKGROUND: Anabolic-androgenic steroid (AAS) dependence has numerous adverse health consequences, and may be driven in part by body image concerns, primarily muscle dysmorphia. This study aims to further understand and identify potential clinical targets using network analyses of AAS dependence and muscle dysmorphia symptoms in males who used AAS and weightlifting controls. METHODS: A sample of 153 men who currently or previously used AAS and 88 weight-lifting controls were recruited through social media and relevant online forums, and via posters and flyers distributed in select gyms in Oslo, Norway. Symptoms of AAS dependence and muscle dysmorphia were assessed using clinical interviews and standardized questionnaires. Severity of muscle dysmorphia symptoms were compared between the groups using independent samples t-tests. The following symptom networks were computed using Gaussian graphical modeling or mixed graphical modeling: (1) AAS dependence symptoms among men with AAS use (2) muscle dysmorphia symptoms among men with AAS use and weight-lifting controls in two separate networks, which were compared using a network comparison test, and (3) AAS dependence and muscle dysmorphia symptoms among men with AAS use. RESULTS: In a network of AAS dependence symptoms, continuing use despite physical and mental side effects, using longer than planned, tolerance, and work/life interference were the most central symptoms. When comparing symptom structures of muscle dysmorphia between those who used AAS and controls, the most central symptoms in each group were exercise dependence and size/symmetry concerns, respectively. Men with AAS use demonstrated elevated muscle dysmorphia symptoms compared to controls, indicating that both the severity and structure of symptoms differ between these groups. In a network including both AAS dependence and muscle dysmorphia symptoms, no significant connections between symptom groups were identified. CONCLUSIONS: AAS dependence is complex, with correlated somatic and psychological challenges driving the symptom network, indicating that alleviating physical and mental health concerns during both AAS use and cessation is an important clinical target. Muscle dysmorphia symptoms related to taking action (diet, exercise, and supplement use) appear to cluster together more for those who use AAS than those who do not.

Use of High-Dose Androgens Is Associated with Reduced Brain-Derived Neurotrophic Factor in Male Weightlifters.

INTRODUCTION: Use of high-dose androgens causes drastic changes in hormonal milieu and is associated with adverse medical, psychological, and cognitive effects. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors plays a critical role in neuroplasticity, with implications for cognitive function and mental health. The impact of long-term, high-dose androgen use on BDNF in a natural setting has not been investigated. This study examined the association between long-term androgen exposure and BDNF levels, and the links between BDNF, heavy resistance exercise, hormones, androgens, and mental health. METHODS: We measured serum levels of BDNF and sex steroid hormones in male weightlifters (N = 141) with a history of current (n = 59), past (n = 29), or no (n = 52) androgen use. All participants completed questionnaires assessing maximum strength and measures of anxiety and depression. Group differences in BDNF were tested using general linear models adjusting for age and associations between BDNF and strength, anxiety, and depression using Pearson's or Kendall's correlations. RESULTS: Both current (mean: 44.1 ng/mL [SD: 12.7]) and past (39.5 ng/mL [SD: 13.9]) androgen users showed lower serum BDNF levels compared to nonusing controls (51.5 [SD: 15.3], p < 0.001, ηp2 = 0.10). BDNF levels were negatively related to maximal strength, and with hormonal status in past androgen users, but no significant associations were found with measures of depression and anxiety. CONCLUSION: Lower circulating BDNF concentrations in current and past androgen users suggest that high-dose androgen exposure triggers persistent changes in BDNF expression. Further studies are needed to verify the relationship and its potential clinical implications.

Psychopathology among anabolic-androgenic steroid using and non-using female athletes in Norway.

Anabolic-androgenic steroids (AAS) are primarily used to improve physical appearance and increase lean muscle mass. Due to their masculinizing properties, the majority of people using AAS are men; however, AAS use among females may increase with changing body ideals trending towards a more muscular appearance. AAS use among males have been associated with risk-taking behavior, and increased prevalence of personality disorders and psychopathology. As a result of low perceived prevalence and stigma among females who use AAS, the relationship between AAS use and psychopathology in this population is not well-known. AAS using women (n = 16) and weight-lifting controls (WLC) (n = 16) completed questionnaires regarding AAS use, health and training information. Psychopathology was evaluated using the Millon Clinical Multiaxial Inventory-III (MCMI-III). Group differences on demographic variables and scores on MCMI-III scales were evaluated with Mann-Whitney U tests. The clinical cut-off was then applied to all MCMI-III scales and groups were compared using Fisher's exact test. AAS consumers demonstrated significantly greater psychopathology than WLC on several scales. Externalizing personality disorder scales were elevated among those who use AAS relative to controls, such as borderline (p < 0.001), antisocial (p = 0.007) and sadistic (p = 0.002), and in addition depressive (p = 0.012), negativistic (p = 0.001) and masochistic (p = 0.029) personality disorders scales. Furthermore, all clinical syndromes were elevated among AAS consumers. AAS consumers thus demonstrated multi-pathology, and 56% (n = 9) of the group met the clinical criteria for six or more disorders. Females who use AAS experience in general increased levels of psychopathology compared to WLC. Clinicians should be aware of these traits and the challenges they present in providing care to this population.

Severity of anabolic steroid dependence, executive function, and personality traits in substance use disorder patients in Norway.

INTRODUCTION: Anabolic androgenic steroids (AAS), including testosterone and synthetic derivatives, are typically used to increase muscle mass. Many users develop a dependence on these substances, contributing to worsened physical and mental health outcomes. Aspects of personality and executive dysfunction may represent underlying vulnerabilities for developing dependence. OBJECTIVE: To identify levels of AAS dependence within substance use disorder (SUD) treatment patients and assess the relationship between dependence severity and personality traits and executive function (EF). METHODS: Data were collected from patients at 38 SUD treatment facilities in Norway. Questionnaires were completed for measures of personality and EF. Measures of symptoms of AAS dependence were used in latent class analysis to identify sub-groups of patients, which were evaluated for association with EF and personality traits, and compared with a group of non-AAS using SUD patients. RESULTS: Three classes were identified; largely reflecting low, moderate, and high symptoms of dependence. Multinomial regression analyses indicated that moderate and high symptoms were associated with several measures of EF and personality traits, particularly self-monitoring, antagonism, disinhibition, and rigid perfectionism while users with low symptoms exhibited higher capacities for emotional control and shift, and lower negative affectivity, relative to non-AAS using SUD patients. Backward stepwise regressions indicated antagonism, and decreased self-monitoring as key personality and cognitive characteristics of SUD patients with severe AAS dependence. CONCLUSION: Our findings indicate that specific executive dysfunctions and personality features, particularly those associated with poor emotional control, reduced empathy, and impulsivity are associated with more severe AAS dependence in the SUD population.

Association of childhood maltreatment and cortisol with the severity and stability of depression symptoms.

BACKGROUND: Little is known about patterns of depression symptoms over time in older adults. This study aims to assess the association of childhood maltreatment and cortisol levels with latent classes of depression symptoms over ten years in older adults. METHODS: A total of 752 participants (mean age 61.7±9.5, female 18%) in the Second Manifestations of ARTerial disease-Memory, depression and aging (SMART-Medea) study provided up to twenty measures of depression symptoms over ten years based on the Patient Health Questionnaire-9 (PHQ-9). At baseline, salivary cortisol was measured, and childhood maltreatment was assessed. Responses to the PHQ-9 were indicators in a latent class analysis. Multinomial regression determined associations between class membership and cortisol and maltreatment, adjusting for age, sex, and education. RESULTS: Four distinct classes were identified; never depressed (n=275, 37%), energy/sleep difficulties (n=237, 32%), mild depression symptoms (n=152, 20%) and fluctuating severe depression (n=88, 12%). Childhood maltreatment was associated with mild depression symptoms (OR=1.95, 95% CI: 1.17-3.25) and fluctuating severe depression (OR=3.50, 95% CI: 1.99-6.15). Blunted morning cortisol was associated with energy/sleep difficulties (OR=0.98, 95% CI: 0.95-1.00) and fluctuating severe depression (OR=0.96, 95% CI: 0.92-0.99). There was no evidence for interaction between maltreatment and cortisol. LIMITATIONS: There is limited generalizability due to the cohort consisting of participants with atherosclerosis and being mostly male. This study utilizes retrospective self-reporting of childhood maltreatment. CONCLUSION: Childhood maltreatment and blunted morning cortisol independently contribute to a worse depression course. Blunted morning cortisol may contribute to sub-clinical depression symptoms, specifically difficulties with energy levels and sleep.

Androgen abuse and the brain.

PURPOSE OF REVIEW: The purpose of this review is to examine the recent evidence regarding the effects of exogenous androgens on the brain. Understanding these effects is of high importance, as the consequences of androgens on the reproductive and endocrine system are well documented, while fewer studies have focused on the neural and cerebral consequences of androgen use. RECENT FINDINGS: Supraphysiological doses of androgens have been shown to contribute to neurodegeneration, decreased brain-derived neurotrophic factor, increased inflammation and decreased neuronal density in animal studies, which may correspond to changes in mood, cognition and aggression. Findings from human studies suggest that similar behavioural and cognitive deficits may occur as a result of prolonged use of androgens. Additional evidence suggests that androgen use, particularly in high doses, may contribute to brain ageing and cerebrovascular problems. SUMMARY: Findings from recent human and animal studies indicate that androgen use likely contributes to brain alterations, which may cause the frequently observed deficits in cognitive and emotional functioning. Although exogenous testosterone in appropriate doses for therapeutic purposes likely have some neurobiological benefits for certain populations, supraphysiological doses may cause multiple mental and physical health problems, indicating a need for additional large-scale studies in humans.

Biomarkers of Alzheimer's Disease and Cerebrovascular Lesions and Clinical Progression in Patients with Subjective Cognitive Decline: A Systematic Review.

BACKGROUND: Early identification of Alzheimer's disease (AD) may be extremely beneficial for delaying disease progression. Subjective cognitive decline (SCD) may be an early indicator of AD pathology. Not all individuals with SCD will eventually develop AD, making it critical to identify biomarkers during the SCD stage which indicate likely clinical progression. OBJECTIVE: The present review aims to summarize available data on structural MRI and cerebrospinal fluid (CSF) biomarkers and their association with clinical progression to mild cognitive impairment (MCI) or AD in people with SCD. METHODS: Database searches were conducted using Embase and PubMed until June 2020. Longitudinal studies assessing biomarkers in individuals with SCD and assessing clinical progression to MCI/AD were included. Two assessors performed data extraction and assessed the risk of bias in the included studies. Data were synthesized narratively. RESULTS: An initial search identified 1,065 papers; after screening and review 14 studies were included. Sample size of the included studies ranged from 28-674, mean age was 60.0-68.6 years, and 10.2%-52%of participants converted to MCI/AD. Lower levels of CSF Aß42 were consistently associated with clinical progression. Combination measures identifying an AD-like profile of Aß42 and tau levels were strongly associated with clinical progression. Biomarkers identified with structural MRI were less conclusive, as some studies found significant associations while others did not. CONCLUSION: Biomarkers may be able to predict clinical progression in those with cognitive complaints. Aß42, or combinations of Aß42 and tau may be useful biomarkers in identifying individuals with SCD who will progress to MCI/AD.