Adult attention-deficit/hyperactivity disorder and its association with substance use and substance use disorders in young men.

BACKGROUND: Functional and mental health impairments that adults with attention-deficit/hyperactivity disorder (ADHD) experience may be exacerbated by regular substance use and co-morbidity with substance use disorders (SUD). This may be especially true during young adulthood, which represents a critical stage of life associated with increased substance use and associated problems. However, previous studies investigating the association between ADHD and substance use and SUD have demonstrated inconsistent results, probably due to methodological limitations (e.g., small and non-representative samples). Thus, the relationship of ADHD with substance use and related disorders remains unclear. The aim of the present study was to examine the association between ADHD and both the use of licit and illicit substances and the presence of SUD in a large, representative sample of young men. METHOD: The sample included 5677 Swiss men (mean age 20 ± 1.23 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed using the adult ADHD Self Report Screener (ASRS). The association between ADHD and substance use and SUD was assessed for alcohol, nicotine, cannabis and other illicit drugs, while controlling for socio-demographic variables and co-morbid psychiatric disorders (i.e., major depression (MD) and anti-social personality disorder (ASPD)). RESULTS: Men with ADHD were more likely to report having used nicotine, cannabis and other illicit drugs at some time in their life, but not alcohol. ADHD was positively associated with early initiation of alcohol, nicotine and cannabis use, the risky use of these substances, and the presence of alcohol use disorders, and nicotine and cannabis dependence. Additionally, our analyses revealed that these patterns are also highly associated with ASPD. After adjusting for this disorder, the association between ADHD and licit and illicit substance use and the presence of SUDs was reduced, but remained significant. CONCLUSIONS: Our findings suggest that adult ADHD is significantly associated with a propensity to experiment with licit and illicit substances, especially at earlier ages, to exhibit risky substance use patterns, and to subsequently develop SUDs. Preventive strategies that include early intervention and addressing co-morbidity with ASPD may be crucial to reducing substance use and the development of pathological substance use patterns in young men affected by ADHD and, thus, helping to prevent further illness burden later in life.

Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder.

While the neurobiological basis and developmental course of attention-deficit/hyperactivity disorder (ADHD) have not yet been fully established, an imbalance between inhibitory/excitatory neurotransmitters is thought to have an important role in the pathophysiology of ADHD. This study examined the changes in cerebral levels of GABA+, glutamate and glutamine in children and adults with ADHD using edited magnetic resonance spectroscopy. We studied 89 participants (16 children with ADHD, 19 control children, 16 adults with ADHD and 38 control adults) in a subcortical voxel (children and adults) and a frontal voxel (adults only). ADHD adults showed increased GABA+ levels relative to controls (P = 0.048), while ADHD children showed no difference in GABA+ in the subcortical voxel (P > 0.1), resulting in a significant age by disorder interaction (P = 0.026). Co-varying for age in an analysis of covariance model resulted in a nonsignificant age by disorder interaction (P = 0.06). Glutamine levels were increased in children with ADHD (P = 0.041), but there was no significant difference in adults (P > 0.1). Glutamate showed no difference between controls and ADHD patients but demonstrated a strong effect of age across both groups (P < 0.001). In conclusion, patients with ADHD show altered levels of GABA+ in a subcortical voxel which change with development. Further, we found increased glutamine levels in children with ADHD, but this difference normalized in adults. These observed imbalances in neurotransmitter levels are associated with ADHD symptomatology and lend new insight in the developmental trajectory and pathophysiology of ADHD.

Age dependent electroencephalographic changes in attention-deficit/hyperactivity disorder (ADHD).

OBJECTIVE: Objective biomarkers for attention-deficit/hyperactivity disorder (ADHD) could improve diagnostics or treatment monitoring of this psychiatric disorder. The resting electroencephalogram (EEG) provides non-invasive spectral markers of brain function and development. Their accuracy as ADHD markers is increasingly questioned but may improve with pattern classification. METHODS: This study provides an integrated analysis of ADHD and developmental effects in children and adults using regression analysis and support vector machine classification of spectral resting (eyes-closed) EEG biomarkers in order to clarify their diagnostic value. RESULTS: ADHD effects on EEG strongly depend on age and frequency. We observed typical non-linear developmental decreases in delta and theta power for both ADHD and control groups. However, for ADHD adults we found a slowing in alpha frequency combined with a higher power in alpha-1 (8-10Hz) and beta (13-30Hz). Support vector machine classification of ADHD adults versus controls yielded a notable cross validated sensitivity of 67% and specificity of 83% using power and central frequency from all frequency bands. ADHD children were not classified convincingly with these markers. CONCLUSIONS: Resting state electrophysiology is altered in ADHD, and these electrophysiological impairments persist into adulthood. SIGNIFICANCE: Spectral biomarkers may have both diagnostic and prognostic value.

Methadone maintenance treatment and St. John's Wort - a case report.

St. John's wort, a popular over-the-counter drug for treatment of depression, might reduce concentrations of drugs such as cyclosporin and indinavir and lead to drug resistance and treatment failure. No studies as yet have examined its influence on methadone plasma levels. The trough methadone plasma levels were measured in four patients (2 males, median age: 31 years; range 19 - 40 years) in methadone maintenance treatment just before the introduction of St. John's wort (900 mg/d) and after a median period of 31-day treatment (range 14 - 47). The study was proposed to addict patients about to start an antidepressant therapy. Introduction of St. John's wort resulted in a strong reduction of (R,S)-methadone concentration-to-dose ratios in the four median patients included, with a median decrease to 47 % of the original concentration (range: 19 % - 60 % of the original concentration). Two patients reported symptoms that suggested a withdrawal syndrome. Thus, prescription of St. John's wort might decrease methadone blood levels and induce withdrawal symptoms which, if not correctly identified and handled (by changing the antidepressant or by increasing the methadone dose), might cause unnecessary discomfort to the patient, lead to resumption of illicit drug uses, or be a risk factor for discontinuation of the methadone or antidepressant treatment.

[Are there predictors for sexual risk behavior in HIV-infected patients?]. / Gibt es Prädiktoren für sexuelles Risikoverhalten bei HIV-Infizierten?

The influence of four coping strategies ("rumination," "search for affiliation," "threat minimization," and "search for information"), four social network dimensions ("affectively positive," "affectively negative," "accepting confidants," and "liking confidants") and sociodemographics on the sexual risk behavior of HIV-infected persons were analyzed in sexual encounters with steady and casual partners. The analysis examines bi- and multivariately the predictors for sexual risk behavior. The study population consisted of 103 asymptomatic HIV-infected persons (80 men, 23 women, mean age 34 years, range 21-69 years) who participated in our prospective study and reported their sexual contacts during the previous 6 months. In sexual encounters with steady partners, the risk of unprotected behavior increased with the frequency of sexual contact. In these encounters, coping strategies and social network had no influence on sexual risk behavior. In sexual contacts with casual partners, the number of contacts with these partners was also of importance. The coping strategy "rumination" correlates significantly with enhanced risk behavior. In sexual contacts with casual partners, there was no correlation between sexual risk behavior and the three other coping strategies or social network. In multivariate analysis, the number of sexual contacts was the only significant predictor for sexual risk behavior with steady partners as well as casual ones. As sexual activity with HIV-infected persons is not absolutely safe, further prevention campaigns have to focus more on the motivation for safe sex, its situational aspects, and partners' responsibility.

Predictors of unprotected sexual contacts in HIV-infected persons in Switzerland.

Predictors of sexual risk behavior with regular and casual partners among HIV-infected heterosexual and gay persons were addressed. Sociodemographic data as well as self- and interviewer-reported data on sexual behavior were obtained from 117 asymptomatic HIV-infected persons enrolled in the Zurich part of the Swiss HIV Cohort Study (SHCS). Participants who reported sexual intercourse at least once (vaginal and/or anal) without condom use in the 6 months prior to interview were considered to have risk behavior. Sexual risk behavior was analyzed separately in contacts with regular and casual partners. In the 6-month preinterview period, 92% (108 of 117) of the HIV-infected study population reported sexual contacts, and 30/117 (26%) had at least one unprotected vaginal and/or anal contact. Among 93 persons using condoms, 25% of the heterosexual and 10% of the homosexual participants reported breakage of the condom. The main predictor for unprotected sexual behavior with regular partners was an elevated number of contacts. Predictors for sexual risk behavior with casual partners were the combination of alcohol and sexual encounters and the change of sexual behavior since the epidemic of AIDS. These findings did not differ between persons with hetero- and homosexual behavior. Considering that these contacts may have passed the virus on to the seronegative population, that the probability of unsafe sex increased with the growing number of contacts, and that the number of condom breakages was remarkable, it is imperative that this group be educated and motivated to take the active role in insisting on safer sex practices in each encounter.

[Is there a correlation between alcohol drinking and sexual risk taking? A discussion of conceptional aspects exemplified by HIV infected men with homosexual behavior]. / Besteht ein Zusammnenhang von Alkoholkonsum und sexuellem Risikoverhalten? Eine Diskussion konzeptioneller Aspekte am Beispiel HIV-infizierter Männer mit homosexuellem Verhalten.

Does sexual risk behavior and alcohol consumption correlate or is sexual risk behavior due to alcohol consumption? These questions are controversially discussed in the literature. We investigated whether the two different methodological concepts (global association, e.g. not specific to the critical incident and situational association) cause these discrepancies in a sample of 64 HIV-infected gay men. There was no significant global association between alcohol consumption and sexual risk behavior. Using the situational approach, drinking was not related to sexual risk behavior. The combination of these two concepts may help to identify persons at risk.

[Are there factors which maintain a subjective symptom-free psychological state? A study exemplified with HIV-infected subjects]. / Gibt es Einflussfaktoren, welche die subjektive psychische Symptomfreiheit aufrechterhalten? Eine Untersuchung am Beispiel HIV-infizierter Personen.

AIMS: In the absence of curative treatment, the diagnosis of HIV infection imposes a heavy burden. Infected persons are therefore confronted with psychological, social and physical problems and cope with them via different strategies and social resources. We investigated the question of what factors help to maintain a psychologically symptom-free state. METHODS: A sample of 117 asymptomatic HIV-infected persons was recruited out of the Swiss HIV Cohort Study (Part A) in 1989 and 1990. The psychological symptoms were assessed with a self-rating questionnaire (SCL-90-R). The structured interview focused on social network, social support (SONET), and coping strategies (FEKB). RESULTS: 79% of the asymptomatic persons did not report psychological symptoms. In multivariate analyses, "rumination" (= preoccupational thinking), female gender, and affectively negative relationships correlated with more, but affectively positive relationships and the strategy "defence against threat" with fewer, psychological symptoms. Additionally, there was no significant correlation between the immunological markers (CD4-, CD8-cell count, p24 antigen) and psychological complaints. CONCLUSIONS: The low number of asymptomatic HIV-infected persons with psychological symptoms (21%) is in accordance with other studies. Psychological symptoms and rumination correlate significantly in our sample. As rumination is difficult to recognize, HIV-infected patients should be directly questioned about rumination and their defence against threat should be supported in order to prevent the development of psychological symptoms.

Loss of muscle oxidative capacity after an extreme endurance run: the Paris-Dakar foot-race.

We measured changes in maximal oxygen uptake capacity (VO2max), ventilation, heart rate, plasma lactate and speed at the end of an incremental exercise test as a consequence of a relay foot race from Paris to Dakar in 6 subjects. Additionally, anthropometric measurements were taken and muscle biopsies from M. vastus lateralis were obtained before and after the race. The latter were analyzed with morphometric methods for fiber size, capillarity and muscle ultrastructural composition. Weight specific VO2max was significantly reduced from 62.4 to 60.5 ml/min.kg after the race while absolute VO2max and the other endurance related functional variables remained unchanged. Body fat, thigh cross-sectional area and thigh volume showed tendential reduction immediately after the race but regained pre-race values within a few days. Fiber size and capillarity were not affected by the race. Volume density of total mitochondria was significantly reduced from 6.98 to 4.89% of fiber volume. Both subsarcolemmal and interfibrillar mitochondria were significantly reduced by 59 and 21%, respectively. The volume density of satellite cell was increased about three-fold whereas the content of lipofuscin remained constant. It is concluded that extreme endurance events such as a multi-stage relay race may induce a considerable loss of oxidative capacity of skeletal muscle tissue.

The cholinergic rapid eye movement sleep induction test with RS-86. State or trait marker of depression?

Rapid eye movement (REM) sleep disinhibition at the beginning of the night is one of the most frequently described biologic abnormalities in depression. As REM sleep in animals and humans seems to be facilitated by cholinergic neuronal activity, it has been postulated that REM sleep disinhibition in depression is a consequence of cholinergic neuronal overactivity. The current study with the newly available cholinergic agonist RS-86, which is orally active, has a half-life of six to eight hours, and exhibits only minor peripheral side effects, supports this assumption. The application of this compound before sleep led to a significantly faster induction of REM sleep at the beginning of the night in patients with major depressive disorders compared with healthy subjects and patients with other nondepressive psychiatric diseases, such as eating disorders. Whereas 14 of 16 depressed patients displayed sleep-onset REM periods after the administration of RS-86, this happened only in three of the 16 healthy controls and in one of the 20 patients with other diagnoses. The increased susceptibility of REM sleep to cholinergic stimulation was limited to the state of depression and was not observed in a group of remitted depressed patients.

Influence of the cholinergic agonist RS 86 on normal sleep: sex and age effects.

In 36 healthy control subjects (21 females, 15 males; age range 18-65 years; mean age 41.8 years, SD 15.6 years), a bedtime dose of 1.5 mg RS 86, an orally acting cholinergic agonist, shortened rapid eye movement (REM) latency, increased REM sleep, and decreased slow-wave sleep. Six of the subjects (greater than 40 years old) even displayed sleep-onset REM periods after the drug. Results of the present study agree well with those of studies using other cholinomimetics (i.e., physostigmine, arecholine) and confirm the importance of the cholinergic system for REM sleep regulation. Since RS 86 mimicked some of the REM sleep abnormalities specific for patients with depressive disorders, the cholinergic system may play a role in the pathogenesis and pathophysiology of depressive diseases.

Is there a relationship between response to total sleep deprivation and efficacy of clomipramine treatment in depressed patients?

Total sleep deprivation (TSD) and tricyclic medication are successful treatment modalities for patients with a major depressive disorder. Recent studies have suggested a positive relationship between TSD response and succeeding tricyclic treatment, even on a very specific level, thus supporting the assumption of two distinct biochemical subtypes of depression. The present study tested this hypothesis by treating 10 inpatients with a major depressive disorder first with TSD and succeedingly with clomipramine. Contrary to expectation, a negative relationship between clinical response to the two treatment modalities was found.