Somatic effects of AAS abuse: A 30-years follow-up study of male former power sports athletes.

OBJECTIVES: The aim of the present study was to investigate the association between somatic health and former abuse of AAS in former elite male athletes 30 years after the end of their active sports career. DESIGN: Retrospective follow-up study. METHODS: N=996 former elite male athletes were sent a questionnaire concerning sociodemographic variables, previous and past sport activity and lifetime prevalence of seeking professional help for health problems. N=683 (68.6%) answered the questionnaire. The lifetime prevalence of AAS-abuse was 21% (n=143), while 79% (n=540) did not admit having ever used AAS. RESULTS: Former AAS-abuse was associated with tendon ruptures (p=0.01), depression (p=0.001), anxiety (p=0.01) and lower prevalence of prostate hypertrophy (p=0.01) and decreased libido (p=0.01). Former advanced AAS-abusers had higher anxiety (p=0.004) compared to the former less advanced AAS-abusers. Moreover, former advanced AAS-abusers, compared to AAS-naïves, reported more psychiatric problems (p=0.002), depression (p=0.003) and anxiety (p=0.00). CONCLUSIONS: A former AAS-abuse seems to be associated with some somatic and mental health problem, although a former less advanced AAS-abuse is related to lower incidence of prostate hypertrophy. The results raise the question whether some of these associations might be dose- and frequency dependent. These findings should however be seen as hypothesis generating and further studies are needed.

Increased mortality rate and suicide in Swedish former elite male athletes in power sports.

Physical training has been shown to reduce mortality in normal subjects, and athletes have a healthier lifestyle after their active career as compared with normal subjects. Since the 1950s, the use of anabolic androgenic steroids (AAS) has been frequent, especially in power sports. The aim of the present study was to investigate mortality, including causes of death, in former Swedish male elite athletes, active 1960-1979, in wrestling, powerlifting, Olympic lifting, and the throwing events in track and field when the suspicion of former AAS use was high. Results indicate that, during the age period of 20-50 years, there was an excess mortality of around 45%. However, when analyzing the total study period, the mortality was not increased. Mortality from suicide was increased 2-4 times among the former athletes during the period of 30-50 years of age compared with the general population of men. Mortality rate from malignancy was lower among the athletes. As the use of AAS was marked between 1960 and 1979 and was not doping-listed until 1975, it seems probable that the effect of AAS use might play a part in the observed increased mortality and suicide rate. The otherwise healthy lifestyle among the athletes might explain the low malignancy rates.

A retrospective 30-year follow-up study of former Swedish-elite male athletes in power sports with a past anabolic androgenic steroids use: a focus on mental health.

BACKGROUND: The knowledge concerning the long-term effect of former anabolic androgenic steroids (AAS)-use on mental health is sparse. AIM: This study aims to investigate whether previous AAS-use affects mental health, present sociodemographic data, sport activity and substance abuse in a retrospective 30-year follow-up study of former elite athletes. METHODS: Swedish male-elite power sport athletes (n=683) on the top 10 national ranking lists during any of the years 1960-1979 in wrestling, Olympic lifting, powerlifting and the throwing events in track and field answered a questionnaire. RESULTS: At least 20% of the former athletes admitted previous AAS-use. They had more often sought professional expertise for mental problems and had used illicit drugs compared to those not having used AAS. The AAS-users also differed in former sport activity pattern compared to non AAS-users. CONCLUSIONS: It is clear that a relationship exists between use of AAS and mental-health problems. Further studies need to be done in order to clarify this relationship.

Inverse relationship between central serotonergic neurotransmission and blood pressure in alcohol-dependent male subjects.

Data has accumulated indicating an inverse relation between central serotonergic (5-HT) neurotransmission and blood pressure in hypertensive rats and in healthy individuals. The present study aimed to elucidate whether an inverse relation exists between systolic (SBP) and diastolic (DBP) blood pressure levels and central 5-HT neurotransmission also in a group of alcohol-dependent individuals. Central 5-HT neurotransmission was assessed by using the maximum prolactin (PRL) responses to the 5-HT probe DL-fenfluramine (DL-FEN; 60 mg po) in 17 alcohol-dependent male subjects investigated during a period of on-going alcohol intake. BP was measured immediately before all time points for blood sampling, and readings before DL-FEN administration were used as the subjects resting BP. Results showed that there were inverse correlations between the maximum PRL responses to DL-FEN and the SBP levels (r = -0.57, p < 0.002) and with the DBP levels (r = -0.52, p < 0.05), respectively. The present study suggests the existence of an association between central 5-HT neurotransmission and blood pressure regulation also in alcohol-dependent individuals.

Personality profile in type I alcoholism: long duration of alcohol intake and low serotonergic activity are predictive factors of anxiety proneness.

The aim of the present study was to further investigate personality profiles in male type I alcohol-dependent subjects (n = 33), in relation to central serotonergic neurotransmission, history of excessive alcohol consumption and present use of tobacco. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to D-fenfluramine. By using the Temperament and Character Inventory and the Karolinska Scales of Personality, all subjects self-rated their personality profile. The results showed that individuals with low PRL response and long duration of excessive alcohol consumption had significantly higher anxiety proneness, and that years of excessive alcohol consumption was the strongest predictor. Long duration of excessive alcohol consumption thus appears to have an influence on personality traits in male type I alcohol-dependent individuals and these personality traits may therefore be a consequence of, rather than preceding, alcoholism in these individuals.

Platelet monoamine oxidase B (MAO-B) activity and its relationship to DL-fenfluramine-induced prolactin response in healthy men.

Several techniques are used to assess central serotonergic neurotransmission in man, e.g. challenge tests (hormonal and physiological responses to serotonin active drugs), platelet MAO-B activity as well as brain imaging techniques. Little is known about how these tests relate to each other. The aim of the present study was therefore to investigate if platelet MAO-B activity could be related to hormonal and temperature responses to the serotonin active drug DL-fenfluramine in healthy men. Twelve male subjects without any history of psychiatric disorders or drug abuse/dependencies were recruited. Prior to the challenge with 60 mg DL-fenfluramine, which was given orally, blood for determination of platelet MAO-B activity was drawn. Blood samples for determination of serum prolactin and serum cortisol were drawn at baseline and thereafter every hour for the following six hours. In addition, body temperature was measured at the same time-points. Delta-values were calculated as the difference between the baseline values and the highest (prolactin and cortisol) or lowest value (temperature) thereafter. There was a strong positive correlation (r = 0.75, p < 0.02) between platelet MAO-B activity and Delta-prolactin. No correlations were found to Delta-cortisol, Delta-temperature or any of the baseline values. The results support the notion that the peripheral marker platelet MAO-B activity is related to the function of the central serotonergic neurotransmitter system as assessed by the prolactin response to 60 mg DL-fenfluramin.

No effect of the cortisol-synthesis inhibitor metyrapone on alcohol drinking: a pilot study.

Two bases for this study were the theory of stress as a provoking factor for high alcohol consumption in human being and findings that the stress hormones stimulate ethanol intake in rats. We therefore investigated whether the cortisol-synthesis inhibitor metyrapone could reduce high alcohol consumption in socially stable subjects who reported drinking mainly for relaxation purposes. Most of the investigated subjects were found to be alcohol dependent (81%), with moderately high levels of intake, yet they had not reported more severe life problems. All subjects reported their daily alcohol consumption during 2-week baseline, medication, and postmedication periods. Sixteen subjects were given 1 g of metyrapone orally daily for 14 days, and 15 subjects received placebo. Morning serum cortisol concentration was assessed four times in the course of the study period. Metyrapone treatment was not found to reduce alcohol consumption more than placebo. Serum cortisol concentrations remained within the laboratory reference interval during the study and did not differ between the study groups. In this study, we found that a cortisol-synthesis inhibitor had no effect on alcohol consumption. One reason may be that cortisol secretion has no role in the maintenance of high alcohol consumption. On the other hand, because this study is the first of its kind, further studies using other doses of treatment and treatment schedules are suggested.

Relationship between central serotonergic neurotransmission and reduction in alcohol intake by citalopram.

The relationship between the effect of citalopram on alcohol intake and central serotonergic neurotransmission, as assessed by prolactin (PRL) response to fenfluramine, was investigated in 17 male heavy drinkers. A positive correlation was obtained, suggesting that the status of central serotonergic neurotransmission in individuals is associated with the treatment response to citalopram. When the group of subjects were divided into those with high and low PRL response (above and below median, respectively) to fenfluramine, those with high PRL response had a significant reduction in alcohol intake during citalopram treatment, whereas those with low PRL response had no such effect. Thus, in subjects with evidence of unimpaired or only slightly impaired central serotonergic neurotransmission (high PRL response) citalopram may have beneficial effect on alcohol consumption, whereas in those with more evidently impaired serotonergic neurotransmission (low PRL response) citalopram treatment may have no effect on or may even increase the alcohol consumption.

Ion permeation and selectivity in ClC-type chloride channels.

Voltage-gated anion channels are present in almost every living cell and have many physiological functions. Recently, a novel gene family encoding voltage-gated chloride channels, the ClC family, was identified. The knowledge of primary amino acid sequences has allowed for the study of these anion channels in heterologous expression systems and made possible the combination of site-directed mutagenesis and high-resolution electrophysiological measurements as a means of gaining insights into the molecular basis of channel function. This review focuses on one particular aspect of chloride channel function, the selective transport of anions through biological membranes. I will describe recent experiments using a combination of cellular electrophysiology, molecular genetics, and recombinant DNA technology to study the molecular basis of ion permeation and selection in ClC-type chloride channels. These novel tools have provided new insights into basic mechanisms underlying the function of these biologically important channels.

Residues lining the inner pore vestibule of human muscle chloride channels.

Chloride channels belonging to the ClC family are ubiquitous and participate in a wide variety of physiological and pathophysiological processes. To define sequence segments in ClC channels that contribute to the formation of their ion conduction pathway, we employed a combination of site-directed mutagenesis, heterologous expression, patch clamp recordings, and chemical modification of the human muscle ClC isoform, hClC-1. We demonstrate that a highly conserved 8-amino acid motif (P3) located in the linker between transmembrane domains D2 and D3 contributes to the formation of a wide pore vestibule facing the cell interior. Similar to a previously defined pore region (P1 region), this segment functionally interacts with the corresponding segment of the contralateral subunit. The use of cysteine-specific reagents of different size revealed marked differences in the diameter of pore-forming regions implying that ClC channels exhibit a pore architecture quite similar to that of certain cation channels, in which a narrow constriction containing major structural determinants of ion selectivity is neighbored by wide vestibules on both sides of the membrane.

Anabolic androgenic steroids affects alcohol intake, defensive behaviors and brain opioid peptides in the rat.

The present study investigated whether a relationship exists between nandrolone decanoate and voluntary ethanol intake in laboratory rats. Animals were subjected to daily subcutaneous injections with nandrolone decanoate (15 mg/kg) during 2 weeks. One group of animals was tested for voluntary alcohol intake 1 week after the end of the 2-week treatment period and another group received alcohol 3 weeks after the treatment. In addition, assessment of defensive behaviors and immunoreactivity (ir) levels of the brain opioid peptides dynorphin B and Met-enkephalin-Arg-Phe (MEAP) were performed. The nandrolone decanoate-treated animals were significantly more aggressive and showed lower fleeing and freeezing reaction than the oil-treated controls. Treatment with nandrolone decanoate enhanced voluntary alcohol intake, regardless if it was presented 1 or 3 weeks after end of the treatment period. These animals had a decreased activity of dynorphin B-ir in the nucleus accumbens, decreased levels of MEAP-ir in the periaqueductal gray (PAG) and higher levels of MEAP-ir in the hypothalamus compared to controls. In line with previous studies, this suggests that the altered dynorphin B-ir activity may promote the rewarding effects of ethanol and thereby increasing alcohol intake, whereas MEAP-ir may be associated with the ability to control the aggressive reaction. Abuse of nandrolone decanoate may thus constitute a risk factor for increased alcohol consumption and defensive aggression. In human, this constellation of behavioral symptoms is closely related to acts of crimes and violence and is often observed among those abusing anabolic androgenic steroids.

Cardiovascular responses to clonidine in alcohol withdrawal: are they related to psychopathology and mental well-being?

The possible relationships between alpha-2-adrenoceptor function, as assessed by blood pressure, heart rate, and sedative responses to clonidine (CLON; 1.5 microg/kg, i.v.), and psychopathology and mental well-being were investigated in 19 patients with alcohol-dependence in the early withdrawal period (days 1 and 7). An age-matched control group was used (n=17). CLON-induced maximum reduction of systolic blood pressure was less day 1 in the alcohol-dependent patients compared to controls. CLON was found to induce less sedation at day 7 compared to day 1 and to controls. No relationships were seen between the parameters for alpha-2-adrenoceptor function and psychopathology and mental well-being. These findings suggest that CLON-induced changes in blood pressures and heart rate reflect the cardiovascular situation in alcohol withdrawal and not aspects of behavior.

Alcoholics with the dopamine receptor DRD2 A1 allele have lower platelet monoamine oxidase-B activity than those with the A2 allele: a preliminary study.

Low platelet monoamine oxidase B (MAO-B) activity and the presence of the Taq1 A1 allele of the dopamine D2 receptor (DRD2) gene have independently been proposed as 'biological/genetic' markers for alcoholism. In the present study, the relationship between these two markers was investigated in a group of socially stable Caucasian middle-aged men with a mean (+/-SD) daily ethanol consumption of 85 +/- 57 g. The platelet MAO-B activity was significantly lower in individuals with the DRD2 A1 allele (n = 8), compared to those without it (n = 29). This relationship remained unchanged when including only subjects who fulfilled DSM-IV criteria for alcohol dependence (n = 27). The finding suggests that alcoholics who are carriers of the DRD2 A1 allele may have lower platelet MAO-B activity.

Transient increase in platelet monoamine oxidase b activity during early abstinence in alcoholics: implications for research.

Some earlier studies have suggested that platelet monoamine oxidase (MAO)-B activity should be determined at time points other than early in the abstinence phase. However, the optimal times for blood sampling have not been precisely defined. We therefore assessed platelet MAO-B activity repeatedly in 13 male alcohol-dependent patients over the 2 months after the end of a period of heavy alcohol intake. Twelve healthy men were used as controls. In the alcohol-dependent patients, platelet MAO-B activity was transiently increased from 2 to 6 weeks after the end of alcohol intake and the values during this time period were not different from those of controls. Platelet MAO-B activity was, however, significantly lower in the alcohol-dependent patients at 1 week and at 2 months after the end of alcohol intake, in comparison to controls. It is concluded that the transient increase in platelet MAO-B activity after the end of alcohol intake in alcohol-dependent patients may conceal a difference from a control group. Therefore, it is suggested that when platelet MAO-B activity is determined, the preferential time point for obtaining those values in alcohol-dependent patients is after 2 months of abstinence.

Rearing experiences and stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates.

BACKGROUND: The purpose of this study was to assess the impact of early rearing and stress-induced rise of plasma cortisol collected during infancy as a biological predictors of adult alcohol consumption in nonhuman primates. METHODS: Ninety-seven female and male rhesus macaques (Macaca mulatta) were investigated. They were reared for their first 6 months of life either without mothers or other adults but with constant access to same-aged peers (peer-reared), or as controls with their mothers (mother-reared). When subjects reached 6 months of age, they underwent a series of four sequential weeks of 4-day social separations. Blood was drawn 1 and 2 hr after initiation of the 4-day separation periods, and the plasma was assayed for plasma cortisol concentrations. When the subjects were young adults (approximately 50 months of age), they were tested for voluntary intake of alcohol for 1 hr per day, 4 days a week, during a period of 5 to 7 weeks under normal living conditions. RESULTS: The social separation challenge increased infant plasma cortisol concentrations, with peer-reared subjects exhibiting higher stress-induced cortisol concentrations than mother-reared animals. Subjects that responded to the social separation challenge with high cortisol levels consumed significantly more alcohol per kilogram of body weight as adults than subjects with a low cortisol response to the separation challenge, regardless of rearing condition. In addition, male and peer-reared subjects consumed significantly more alcohol than female and mother-reared subjects, respectively. CONCLUSIONS: These findings suggest that early rearing experiences, such as adult absence, and high plasma cortisol concentrations early in life after a social separation stressor, are useful psychobiological predictors of future high alcohol consumption among nonhuman primates.

Effect of adrenalectomy and exposure to corticosterone on alcohol intake in alcohol-preferring and alcohol-avoiding rat lines.

The daily fluid intake of male rats of the alcohol-preferring (AA) and alcohol-avoiding (ANA) lines with simultaneous access to 10% (v/v) ethanol and water was determined during a baseline period (2 weeks), following adrenalectomy (1 week), and for 2 weeks following corticosterone treatment. The results showed that adrenalectomized AA rats decreased their ethanol intake compared to the sham-operated AA controls and that treatment with corticosterone restored the intake of ethanol to that observed during the baseline period. In contrast to the AA rats, there were no alterations in ethanol intake after adrenalectomy and following corticosterone replacement in the ANA rats. These results suggest that corticosterone stimulates ethanol intake in animals with pronounced high preference for ethanol.

Molecular mechanisms of ion conduction in ClC-type chloride channels: lessons from disease-causing mutations.

The muscle Cl- channel, ClC-1, is a member of the ClC family of voltage-gated Cl- channels. Mutations in CLCN1, the gene encoding this channel, cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen). The functional characterization of these naturally occurring mutations not only allowed a better understanding of the pathophysiology of myotonia, it also provided important insights into the structure and function of the entire ClC channel family. This review describes recent experiments using a combination of cellular electrophysiology, molecular genetics, and recombinant DNA technology to study the molecular basis of ion permeation and selection in ClC-type chloride channels.