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But this hypothesis remains uncertain. In an analysis of preliminary data from an ongoing study of AAS users conducted by three of the present authors (see (8)), it appears that adolescent body image disorder is strongly associated with initiation of AAS use. However, among AAS users, those who progressed to AAS dependence did not show a greater level of body image disturbance than those who did not. In other words, concerns about muscularity may bring an individual to the threshold of initially using AAS, but beyond this effect, these concerns may not determine whether that individual progresses onward to AAS dependence (Kanayama G, Hudson JI, Pope HG Jr, 2009, unpublished data). A second possible hypothesis is that individuals who progress to AAS dependence are more biologically vulnerable to the dysphoric effects of AAS withdrawal. As noted, AAS produce a characteristic withdrawal syndrome, with both affective and hypogonadal symptoms (65, 130’132). Individuals with more severe withdrawal symptoms after initial cycles of AAS use might become increasingly prone to resume AAS to prevent these symptoms. As implied above, this possible biological vulnerability might be related to the HPT axis, to opioidergic pathways, or to other neurotransmitter mechanisms. A third possible hypothesis is suggested by the apparent overlap of AAS dependence with other forms of substance dependence and with conduct disorder. An evolving neuropsychological literature has shown that individuals with many other forms of substance dependence exhibit a cluster of cognitive attributes that might be summarized as ‘risk-taking/decision-making deficits,’ such as elevated rates of delay discounting (133, 134); increased impulsivity (135’137); and deficits in decision-making, as illustrated by performance on gambling tasks and other measures of risk-taking (135, 138’140). These deficits are also associated with antisocial or ‘psychopathic’ traits (141’144), including conduct disorder (145’147). Conduct disorder in turn appears to be associated with AAS dependence (8), and other studies have documented criminality and so-called Cluster B personality traits, including antisocial personality, among AAS users (121, 148’155). These features may collectively mark an endophenotype (156) that plays a causal role in the development of substance dependence (135). With AAS, the direction of causality might well go both ways: in individuals with these hypothesized underlying deficits, use of testosterone and presumably other AAS may shift the balance even further towards an increased sensitivity for reward and decreased sensitivity for threat or punishment, as suggested by both animal (157, 158) and human studies (159, 160). No studies, to our knowledge, have assessed the possible role of such deficits in individuals with AAS dependence, but this possibility would seem to deserve further investigation. A growing literature of human and animal studies suggests that AAS dependence is a valid diagnostic entity, often associated with conduct disorder and other forms of substance abuse. The prevalence of AAS dependence may be rising, as increasing numbers of AAS users are growing old enough to have established a dependence pattern. The diagnosis of AAS dependence requires some modest adaptations of standard diagnostic criteria for substance dependence, since these criteria were designed primarily for acutely intoxicating drugs, and are not optimally suited for cumulatively acting drugs such as AAS. However, as suggested above, such criteria can be easily adapted for the diagnosis of AAS dependence. AAS dependence is arguably the only major form of worldwide substance dependence that remains largely unexplored. In particular, it remains unclear why some AAS users progress from more benign initial use to more malignant AAS dependence ‘ and the observed overlap between AAS and opioids, in both men and animals, might possibly hold a key to this explanation. Understanding the nature and etiology of AAS dependence is a matter of growing public health importance, since individuals with dependence likely account for the great majority of the public health problems associated with AAS, including the cardiovascular, neuroendocrine, and psychiatric complications of long-term AAS exposure (9). With an improved understanding of AAS dependence, we may be able to better identify those at risk and better able to develop appropriate treatment. Supported in part by NIDA Grant DA 016744 (to Drs. Pope, Kanayama, and Hudson) and NIDA Grant DA 12843 (to Dr, buy trenbo a 100 mg injectable steroids $62.00 trenbolone acetate. undefined Anabolic steroid treatment did not affect the rate of skeletal muscle protein. 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