Attention-deficit/hyperactivity disorder symptoms and stress-related biomarkers.

OBJECTIVE: The current study examined whether (a) Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms were associated with dysregulation of stress-related mechanisms, and (b) whether ADHD symptoms interact with affective disorders in their association with dysregulated stress-related mechanisms. METHODS: Data were obtained from 2307 subjects participating in the Netherlands Study of Depression and Anxiety. Stress-related mechanisms were reflected by the following biomarkers: (1) hypothalamic-pituitary-adrenal axis indicators (salivary cortisol awakening curve, evening cortisol, cortisol suppression after a 0.5mg dexamethasone suppression test (DST)); (2) autonomic nervous system measures (heart rate, pre-ejection period, respiratory sinus arrhythmia); (3) inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha); (4) brain-derived neurotrophic factor. ADHD symptoms were measured using Conners' Adult ADHD Rating Scale and used both dichotomous (High ADHD symptoms (yes/no)) and continuous (Inattentive symptoms, Hyperactive/Impulsive symptoms, and the ADHD index). RESULTS: Regression analyses showed associations between High ADHD symptoms, Inattentive symptoms, the ADHD index and a higher cortisol awakening curve, between Hyperactive/Impulsive symptoms and less cortisol suppression after DST, and between Inattentive symptoms and a longer pre-ejection period. However, the associations with the cortisol awakening curve disappeared after adjustment for depressive and anxiety disorders. No associations were observed between ADHD symptoms and inflammatory markers or BDNF. ADHD symptoms did not interact with affective disorders in dysregulation of stress-related mechanisms. CONCLUSION: Some associations were observed between ADHD symptoms, the HPA-axis, and the pre-ejection period, but these were mostly driven by depressive and anxiety disorders. This study found no evidence that ADHD symptomatology was associated with dysregulations in inflammatory markers and BDNF. Consequently, ADHD symptoms did not confer an added risk to the disturbances of stress-related mechanisms in an - already at-risk - population with affective disorders.

Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are involved in MDD's etiology. These same mechanisms, however, are less important in clinical progression from first to later MDD episodes and toward chronicity.

Wave function control over a single donor atom.

Single donor atoms in semiconductor nanostructures are attractive basic components for quantum device applications. In this work, we demonstrate the ability to manipulate the wave function of a single donor electron with an electric field. The deformation of the wave function is probed by the tunnel current which, furthermore, allows for the determination of the location of the atom in the device. This experiment demonstrates the control necessary for the utilization of single donors in quantum electronics.

Magnetic-field probing of an SU(4) Kondo resonance in a single-atom transistor.

Semiconductor devices have been scaled to the point that transport can be dominated by only a single dopant atom. As a result, in a Si fin-type field effect transistor Kondo physics can govern transport when one electron is bound to the single dopant. Orbital (valley) degrees of freedom, apart from the standard spin, strongly modify the Kondo effect in such systems. Owing to the small size and the s-like orbital symmetry of the ground state of the dopant, these orbital degrees of freedom do not couple to external magnetic fields which allows us to tune the symmetry of the Kondo effect. Here we study this tunable Kondo effect and demonstrate experimentally a symmetry crossover from an SU(4) ground state to a pure orbital SU(2) ground state as a function of magnetic field. Our claim is supported by theoretical calculations that unambiguously show that the SU(2) symmetric case corresponds to a pure valley Kondo effect of fully polarized electrons.

Lifetime-enhanced transport in silicon due to spin and valley blockade.

We report the observation of lifetime-enhanced transport (LET) based on perpendicular valleys in silicon by transport spectroscopy measurements of a two-electron system in a silicon transistor. The LET is manifested as a peculiar current step in the stability diagram due to a forbidden transition between an excited state and any of the lower energy states due to perpendicular valley (and spin) configurations, offering an additional current path. By employing a detailed temperature dependence study in combination with a rate equation model, we estimate the lifetime of this particular state to exceed 48 ns. The two-electron spin-valley configurations of all relevant confined quantum states in our device were obtained by a large-scale atomistic tight-binding simulation. The LET acts as a signature of the complicated valley physics in silicon: a feature that becomes increasingly important in silicon quantum devices.

Integrated logic circuits using single-atom transistors.

Scaling down the size of computing circuits is about to reach the limitations imposed by the discrete atomic structure of matter. Reducing the power requirements and thereby dissipation of integrated circuits is also essential. New paradigms are needed to sustain the rate of progress that society has become used to. Single-atom transistors, SATs, cascaded in a circuit are proposed as a promising route that is compatible with existing technology. We demonstrate the use of quantum degrees of freedom to perform logic operations in a complementary-metal-oxide-semiconductor device. Each SAT performs multilevel logic by electrically addressing the electronic states of a dopant atom. A single electron transistor decodes the physical multivalued output into the conventional binary output. A robust scalable circuit of two concatenated full adders is reported, where by utilizing charge and quantum degrees of freedom, the functionality of the transistor is pushed far beyond that of a simple switch.

Tunable Kondo effect in a single donor atom.

The Kondo effect has been observed in a single gate-tunable atom. The measurement device consists of a single As dopant incorporated in a silicon nanostructure. The atomic orbitals of the dopant are tunable by the gate electric field. When they are tuned such that the ground state of the atomic system becomes a (nearly) degenerate superposition of two of the silicon valleys, an exotic and hitherto unobserved valley Kondo effect appears. Together with the "regular" spin Kondo, the tunable valley Kondo effect allows for reversible electrical control over the symmetry of the Kondo ground state from an SU(2) to an SU(4) configuration.

[Pharmacotherapeutic compass 1998]. / Farmacotherapeutisch kompas 1998.

The Central Medical Pharmaceutical Committee of the Health Insurance Council informs the medical profession annually about the effects of drugs through the Pharmacotherapeutical Compass. The 1998 edition now contains a chapter on pharmacokinetics as well. Compared with previous editions the main alterations of the contents concern an introduction and advice on the antidepressants, two protocols with respect to the medical treatment of patients suffering from epilepsy, advice with respect to oral drugs for the treatment of inflammatory bowel disease, an introduction and advice regarding the treatment of allergic rhinitis, the treatment of patients suffering from AIDS with antiretroviral drugs, the treatment of genital herpes, the taking of insulin lispro by patients with diabetes and the taking of bisphosphonates to prevent or to treat osteoporosis. Two corrections to the 1998 edition are given.