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.

Severe biventricular cardiomyopathy in both current and former long-term users of anabolic-androgenic steroids.

AIMS: This study aims to explore the cardiovascular effects of long-term anabolic-androgenic steroid (AAS) use in both current and former weightlifting AAS users and estimate the occurrence of severe reduced myocardial function and the impact of duration and amount of AAS. METHODS AND RESULTS: In this cross-sectional study, 101 weightlifting AAS users with at least 1 year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use) were compared with 71 non-using weightlifting controls (WLC) using clinical data and echocardiography. Sixty-nine were current, 30 former (>1 year since quitted), and 2 AAS users were not available for this classification. Anabolic-androgenic users had higher left ventricular mass index (LVMI) (106 ± 26 vs. 80 ± 15 g/m2, P < 0.001), worse left ventricular ejection fraction (LVEF) (49 ±7 vs. 59 ± 5%, P < 0.001) and right ventricular global longitudinal strain (-17.3 ± 3.5 vs. -22.8 ± 2.0%, P < 0.001), and higher systolic blood pressure (141 ± 17 vs. 133 ± 11 mmHg, P < 0.001) compared with WLC. In current users, accumulated duration of AAS use was 12 ± 7 years and in former 9 ± 6 years (quitted 6 ± 6 years earlier). Compared with WLC, LVMI and LVEF were pathological in current and former users (P < 0.05) with equal distribution of severely reduced myocardial function (LVEF ≤40%) (11 vs. 10%, not significant (NS)). In current users, estimated lifetime AAS dose correlated with reduced LVEF and LVGLS, P < 0.05, but not with LVMI, P = 0.12. Regression analyses of the total population showed that the strongest determinant of reduced LVEF was not coexisting strength training or hypertension but history of AAS use (ß -0.53, P < 0.001). CONCLUSION: Long-term AAS users showed severely biventricular cardiomyopathy. The reduced systolic function was also found upon discontinued use.

In this, to date, largest cardiovascular study comparing 101 weightlifting long-term anabolic­androgenic steroid (AAS) users (11 ± 7 accumulated years of AAS use), with 71 weightlifting controls, we conclude that non-medical use of AAS is associated with adverse cardiovascular effects including enlarged heart muscle, seriously reduced heart function, and increased blood pressure. Both current and former users with accumulated years of AAS use of respectively 12 ± 7 years and 9 ± 6 years (former quitted 6 ± 6 years earlier) had biventricular cardiomyopathy with severely affected left and right myocardium. Of note, 11% of AAS users (10% of current and 11% of former) had severely reduced left ventricular systolic function with ejection fraction < 40%, consistent with heart failure.Regression analyses of the total population showed that the strongest determinant of reduced left ventricle ejection fraction was not coexisting strength training or hypertension but history of AAS use (ß −0.53, P < 0.001).

Screening of attention and executive functions in pediatric patients at a tertiary epilepsy center.

OBJECTIVE: Executive dysfunction is prevalent in children with epilepsy, and associated with poor psychosocial outcome. Sensitive and time effective tools are needed, which capture executive dysfunction across a wide range of impairment. The present study evaluates the applicability of EpiTrack Junior® (EpiTrackJr) as a screening tool at a tertiary epilepsy center, and explore how EpiTrackJr in combination with a subjective measure of everyday attention and executive functions (EFs) may provide clinically important information. METHODS: Retrospective study including 235 pediatric patients admitted to the Norwegian National Centre for Epilepsy. EpiTrackJr and Behavioral Rating Inventory of Executive Functioning (BRIEF) were used to assess attention and EFs. RESULTS: 27,7% obtained a score categorized as "average/unimpaired", 23% as "mildly impaired", and 47.7% as "significantly impaired" on EpiTrackJr. The distribution of age-corrected EpiTrackJr scores was satisfactory. Performance was related to numbers of anti-seizure medication (ASM load), comorbidity and IQ. We found a significant, but weak correlation between EpiTrackJr performance and the BRIEF Metacognitive Index (r = -0.236, n = 108, p=.014), but no significant correlation with the Behavioral Regulation Index (r = -0.178, n = 108, p=.065). SIGNIFICANCE: Our results indicate that EpiTrackJr is applicable as a screening tool for attention and EFs in pediatric patients at a tertiary epilepsy center. Impaired test performance was associated with greater ASM load, comorbidity and lower IQ. Performance based measures and behavior ratings likely capture different aspects of EFs. In combination, the two provide important and nonredundant information about the child's EFs in different settings.

Long-term Anabolic-Androgenic Steroid Use Is Associated With Deviant Brain Aging.

BACKGROUND: High-dose long-term use of anabolic-androgenic steroids (AASs) may cause a range of adverse effects, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging. METHODS: T1-weighted magnetic resonance imaging (3D MPRAGE [magnetization-prepared rapid acquisition gradient-echo]) scans were obtained from male weightlifters with a history of prolonged AAS use (n = 130) or no AAS use (n = 99). We trained machine learning models on combinations of regional brain volumes, cortical thickness, and surface area in an independent training set of 1838 healthy male subjects (18-92 years of age) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval = 3.5 years, n = 76) magnetic resonance imaging data, we used linear mixed-effects models to compare the gap between chronological age and predicted brain age (the brain age gap [BAG]) for the two groups and tested for group differences in the rate of change in BAG. We tested for associations between apparent brain aging and AAS use duration, pattern of administration, and dependence. RESULTS: AAS users had higher BAG compared with weightlifting control subjects, which was associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities, or depression. While longitudinal analysis revealed no evidence of increased brain aging in the overall AAS group, accelerated brain aging was seen with longer AAS exposure. CONCLUSIONS: The findings suggest that long-term high-dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AASs.

Anabolic androgenic steroids, antisocial personality traits, aggression and violence.

BACKGROUND: Anabolic androgenic steroid (AAS) use is associated with a wide range of adverse physical, psychological and social effects. While some experience few side effects, others might experience severe consequences. Aggression and violence are among the often-cited side effects associated with high-dose AAS use; however, most of the knowledge is generated from subgroups, such as prison populations. A likely hypothesis is that AAS use is associated with aggression and violence, but that these associations are complex and may be mediated by several factors, such as substance use, AAS dependence and personality traits. METHODS: In the present study, we tested this hypothesis by examining the relations between long-term AAS use and AAS dependence, aggression, interpersonal violence and potential mediating factors in a sample of male AAS exposed and non-exposed weightlifting controls (WLC), using self-report questionnaires. Based upon AAS dependence criteria, a sample of male AAS users and WLC (N = 139) were stratified into three groups: WLC (n = 66), AAS dependents (n = 41) and AAS non-dependents (n = 32). RESULTS: The results demonstrate that AAS dependents reported significantly higher levels of aggression compared to WLC and AAS non-dependents. While interpersonal violence was reported in all three groups, the highest percentage was found in the AAS dependent group. CONCLUSION: In summary, our study confirms a link between AAS use, aggression and violence in a weightlifting population. However, the association is foremost seen in AAS dependent users and it seems that antisocial personality traits are an important mediator.

Theory of mind in users of anabolic androgenic steroids.

RATIONALE: Anabolic androgenic steroids are used to improve physical performance or increase lean muscle mass. About one-third of users develop a dependency syndrome, which is characterized by elevated rates of psychopathology, cognitive impairments, and aggressive and antisocial behaviors. The mechanisms behind these intra- and interpersonal problems are not known. OBJECTIVE: To examine theory of mind (ToM), i.e., the ability to infer the mental state of others, in users of anabolic androgenic steroids. Reduced ToM may be one factor underlying the interpersonal problems that have been reported with prolonged use of anabolic androgenic steroids. METHODS: The Movie for the Assessment of Social Cognition (MASC) was used to assess ToM. Study participants were male/female weightlifters who used anabolic androgenic steroids (AAS, n = 34/9), who were dependent on anabolic androgenic steroids (AASdep, n = 44/7), and a non-using weightlifting comparison group (WLC, n = 69/16). RESULTS: Analyses of variance showed that the AASdep group performed significantly worse than the WLC group, for all MASC measures (total ToM, cognitive ToM, affective ToM, overmentalizing/undermentalizing errors). Sex and sex x group interaction effects were non-significant. CONCLUSIONS: Male and female weightlifters who were dependent on anabolic androgenic steroids had impaired ToM. Their reduced social cognition may be one contributing factor to the elevated rates of antisocial behavior reported in this population.

Anabolic androgenic steroid dependence is associated with executive dysfunction.

BACKGROUND: Anabolic androgenic steroid (AAS) dependence is associated with a high prevalence of intra- and interpersonal problems, hence it is central to identify cognitive factors related to the development and maintenance of dependence. METHODS: The study explores executive functions (EFs) in a sample of 174 male weightlifters, divided into three groups; 1) AAS dependents; n = 58, 2) AAS non-dependents; n = 38 and 3) AAS non-users; n = 78, using a targeted battery of neuropsychological (NP) tests, and self-report questionnaires assessing EFs in everyday life, ADHD symptoms and psychological distress. RESULTS: Multivariate analysis of variance showed significant between-group differences on several EFs, including working memory [F (2, 169) = 13.79, p < .001, ηp² = 0.14], mental flexibility [F (2, 169) = 4.82, p = .009, ηp² = 0.05], problem-solving [F (2, 169) = 4.77 p = .010, ηp² = 0.05] and inhibition [F (2, 163) = 4.15, p = .017, ηp² = 0.05]. Additionally, significant between-group differences were seen for self-reported problems with EFs [F (2, 124) = 4.38 p = .015, ηp² = 0.07], ADHD symptoms [F (2, 124) = 7.02 p = .001, ηp² = 0.10], and psychological distress [F (2, 124) = 4.11 p = .019, ηp² = 0.06]. Post hoc tests showed that AAS dependents exhibited poorer EFs and reported more psychological distress compared to non-users. CONCLUSION: AAS dependence is associated with executive dysfunction, which might be related to continued abuse despite adverse side-effects and social consequences. Increased awareness of executive dysfunction could have important implications for treatment and rehabilitation.

Structural brain characteristics of anabolic-androgenic steroid dependence in men.

AIM: To identify differences in brain morphology between dependent and non-dependent male anabolic-androgenic steroid (AAS) users. DESIGN: This study used cross-sectional data from a longitudinal study on male weightlifters. PARTICIPANTS: Oslo University Hospital, Norway. SETTING: Eighty-one AAS users were divided into two groups; AAS-dependent (n = 43) and AAS-non-dependent (n = 38). MEASUREMENTS: Neuroanatomical volumes and cerebral cortical thickness were estimated based on magnetic resonance imaging (MRI) using FreeSurfer. Background and health information were obtained using a semi-structured interview. AAS-dependence was evaluated in a standardized clinical interview using a version of the Structured Clinical Interview for DSM-IV, adapted to apply to AAS-dependence. FINDINGS: Compared with non-dependent users, dependent users had significantly thinner cortex in three clusters of the right hemisphere and in five clusters of the left hemisphere, including frontal, temporal, parietal and occipital regions. Profound differences were seen in frontal regions (left pars orbitalis, cluster-wise P < 0.001, right superior frontal, cluster-wise P < 0.001), as has been observed in other dependencies. Group differences were also seen when excluding participants with previous or current non-AAS drug abuse (left pre-central, cluster-wise P < 0.001, left pars orbitalis, cluster-wise P = 0.010). CONCLUSION: Male dependent anabolic-androgenic steroid users appear to have thinner cortex in widespread regions, specifically in pre-frontal areas involved in inhibitory control and emotional regulation, compared with non-dependent anabolic-androgenic steroid users.

Anabolic androgenic steroid dependence is associated with impaired emotion recognition.

RATIONALE: Illicit use of anabolic androgenic steroids (AAS) has grown into a serious public health concern throughout the Western World. AAS use is associated with adverse medical, psychological, and social consequences. Around 30% of AAS users develop a dependence syndrome with sustained use despite adverse side effects. AAS dependence is associated with a high frequency of intra- and interpersonal problems, and it is central to identify factors related to the development and maintenance of dependence. METHODS: The present study investigated the ability to recognize emotion from biological motion. The emotional biological motion task was administered to male AAS dependent users (AAS dependents; n = 45), AAS non-dependent users (AAS non-dependents; n = 38) and a comparison-group of non-using weightlifters (non-users; n = 69). RESULTS: Multivariate analysis of variance showed a general impairment in emotion recognition in AAS dependents, compared to the non-using weightlifters, whereas no significant impairment was observed in AAS non-dependents. Furthermore, AAS dependents showed impaired recognition of fearful stimuli compared to both AAS non-dependents and non-using weightlifters. The between-group effect remained significant after controlling for Intelligence Quotient (IQ), past 6 months of non-AAS drug use, antisocial personality problems, anxiety, and depression. CONCLUSION: AAS dependents show impaired emotion recognition from body movement, fear in particular, which could potentially contribute to higher frequency of interpersonal problems and antisocial behaviors in this population.