Physiological and psychological stress responses in adults with attention-deficit/hyperactivity disorder (ADHD).

According to self-report and unsystematic observational data adult patients with attention-deficit/hyperactivity disorder suffer from increased vulnerability to daily life stressors. The present study examined psychological and physiological stress responses in adult ADHD subjects in comparison to healthy controls under laboratory conditions. Thirty-six subjects (18 patients with DSM-IV ADHD diagnosis, 18 sex- and age-matched healthy controls) underwent the Trier Social Stress Test (TSST; Kirschbaum, C., Pirke, K.-M., Hellhammer, D.H., 1993. The "Trier Social Stress Test"--a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28, 76-81), a standardized psychosocial stress protocol which contains a stress anticipation phase and a stress phase with a free speech assignment and subsequent performance of a mental arithmetic. Physiological stress measures were salivary cortisol as an indicator of the HPA axis, heart rate (HR), and time- and frequency-domain heart rate variability (HRV) parameters. Subjective stress experience was measured via self-report repeatedly throughout the experimental session. In line with previous theoretical and empirical work in the field of childhood ADHD, it was hypothesized that the ADHD and control group would exhibit comparable baseline levels in all dependent variables. For ADHD subjects, we expected attenuated responses of the physiological parameters during anticipation and presence of the standardized stressor, but elevated subjective stress ratings. Hypotheses were confirmed for the baseline condition. Consistent with our assumptions in regard to the psychological stress response, the ADHD group experienced significantly greater subjective stress. The results for the physiological variables were mixed. While ADHD subjects revealed an attenuated HR during the stress phase, no significant group differences were found for the other parameters, although a trend was observed for both the low frequency/high frequency (LF/HF) ratio of the HRV power spectral analysis and salivary cortisol (the latter possibly indicating generally lower cortisol levels in ADHD subjects). In summary, the present findings are the first to demonstrate a significant alteration of a specific physiological stress measure (HR) and, more clearly, of psychological aspects of the stress response in adults suffering from ADHD. In regard to the physiological stress response, it is recommended that future studies employ larger sample sizes and a more comprehensive range of physiological stress parameters. Additionally, the issue of transferability of laboratory results to real life stressors needs to be addressed.

Reduced oxidative damage in ALS by high-dose enteral melatonin treatment.

Amyotrophic lateral sclerosis (ALS) is the collective term for a fatal motoneuron disease of different etiologies, with oxidative stress as a common molecular denominator of disease progression. Melatonin is an amphiphilic molecule with a unique spectrum of antioxidative effects not conveyed by classical antioxidants. In preparation of a possible future clinical trial, we explored the potential of melatonin as neuroprotective compound and antioxidant in: (1) cultured motoneuronal cells (NSC-34), (2) a genetic mouse model of ALS (SOD1(G93A)-transgenic mice), and (3) a group of 31 patients with sporadic ALS. We found that melatonin attenuates glutamate-induced cell death of cultured motoneurons. In SOD1(G93A)-transgenic mice, high-dose oral melatonin delayed disease progression and extended survival. In a clinical safety study, chronic high-dose (300 mg/day) rectal melatonin was well tolerated during an observation period of up to 2 yr. Importantly, circulating serum protein carbonyls, which provide a surrogate marker for oxidative stress, were elevated in ALS patients, but were normalized to control values by melatonin treatment. This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS.

Very early treatment with fluoxetine and reboxetine causing long-lasting change of the serotonin but not the noradrenaline transporter in the frontal cortex of rats.

Interactions of the serotonergic and noradrenergic system at different sites of the brain may be important for efficacy and side effects of antidepressant drugs. Further, serotonin and noradrenaline play a critical role in the development of neurons during brain maturation. To gain further insight how brain maturation and the two monoaminergic systems are influenced by drug treatment during early postnatal development, this animal study investigated possible effects on the noradrenaline and serotonin transporter density of the frontal cortex very early in postnatal life. Rats were treated from postnatal day 2 to 5 either with fluoxetine (5 mg/kg per day s.c.) or with reboxetine (10 mg/kg per day s.c.). At day 90 the serotonin and noradrenaline transporter density in the frontal cortex was measured by ligand binding assay. Fluoxetine treatment led to a significant long-lasting increase of serotonin (not noradrenaline) transporter density (Bmax = 1231 +/- 34) in the frontal cortex (compared with saline-treated controls (Bmax = 1112 +/- 58)). Reboxetine treatment (surprisingly) led to an even more enhanced serotonin transporter density (Bmax = 1322 +/- 46), while noradrenaline transporter density seemed to be unaffected. There were no significant differences for KD values. The results support the idea that serotonin seems to play an important role during early brain development. Moreover, drug-related modulation of the noradrenergic system during brain maturation seems to cross-influence the serotonergic system.

[Successful coping and experience-dependent brain plasticity]. / Uber die Kunst, gute Erfahrungen im Gehirn zu verankern.

Recent progress in brain research has shown that the human brain, i.e., the neuronal and synaptic connectivity especially in higher cortical association centres, is much more plastic and use-dependent than previously thought. This contribution summarizes the present knowledge about this phenomenon of experience-dependent plasticity. Irritation, anxiety and the activation of the neuroendocrine stress-response-system is the most important trigger for the adaptive modification and reorganization of neuronal networks and synaptic connectivity. The experience and successful mastery of a large spectrum of different challenges already during early childhood and during later life diminish the risk of the acquisition and facilitation of maladaptive coping-strategies. Once established, the strongly facilitated neuronal networks involved in the generation of maladaptive behavioural patterns are difficult to reorganize. The experience of loss of control and the long-lasting activation of an uncontrollable stress response may contribute to the destabilization of the neuronal connectivity established in the course of acquisition of such maladaptive coping strategies.