Volume 8, Issue 3, September 2006

Editoral in Hungarian

Gábor Kovács

The intimate relationship between depressive disorders and biological rhythm disturbances has long been known. One major component in diurnal rhythm regulation in mammals, like humans, is the melatonin axis and its close connections with serotonergic and noradrenergic structures. In major depression various functional anomalies have been shown in all of these systems. Agomelatine is a novel antidepressant with direct agonist activity at the melatonin MT1 and MT2 receptors, and a selective antagonist action at the serotonin 5HT2C receptor. It has no measurable affinity to any other known receptor. In animal models agomelatine has antidepressant-like and anxiolytic-like properties, it promotes sleep, and is able to resynchronize various experimentally uncoupled or phase-shifted biological rhythms. In randomized and controlled clinical trials agomelatine appears to be an effective antidepressant, comparable to standard SSRI/SNRI drugs, with excellent safety and tolerability profile. It usually produces mild and transient side effects, similar to those seen in patients receiving placebo. Sleep architecture and subjective measures of sleep quality may also respond favorably. Agomelatine causes significantly less sexual dysfunction than a reference SNRI. No discontinuation symptoms have been observed upon abrupt withdrawal. The overall dropout rates in the clinical trials have been remarkably low, suggesting good acceptability and compliance. Even though most current antidepressants are effective, they also have weaknesses; therefore we still need innovative drugs with novel biochemical actions, faster efficacy and/or better tolerability.

Keywords: depression, melatonin, circadian rhythms, agomelatin

As binding sites of the alpha-amino butyric acid receptor complexes benzodiazepine-receptors offer a possibility to enhance hyperpolarization-based inhibition by allosteric modulation. Most of the hypnotic drugs are compounds that bind to benzodiazepine receptors. The effects of these drugs are usually characterized at a descriptive level, without deliberation of the basic processes involved in sleep regulation. This review follows the analysis of hypnotic’s effect from a perspective of homeostatic, circadian, ultradian and microstructural regulation of sleep. In contrast to their expected effect benzodiazepines produce a decrease in most of the markers of homeostatic sleep regulation. Ligands with non-benzodiazepine structure (cyclopyrrolones, imidazopyridines, pyrazolopyrimidines) have a permissive or even stimulating effect in some measures of homeostatic sleep regulation. Some benzodiazepines have marked chronobiotic effects, while others interfere with circadian rhythms. The non- benzodiazepine-type hypnotics are mostly free of chronobiotic effects, although zaleplon may increase melatonin release. Given their acute hypothermic effect all hypnotic sedatives mimic the circadian signal of sleep initiation. Ultradian sleep regulation is largely unaffected by hypnotics. The microstructure of sleep as quantified by arousal instability is a sensitive measure of the effect of most of the hypnotics. Hypnotic sedatives decrease arousal instability. Zolpidem has the strongest effects in microstructural terms.

Keywords: slow-wave sleep – REM sleep – insomnia – hypnotics – circadian rhythm – benzodiazepines – zolpidem, zaleplon, zopiclone

The authors in a review article deal with characteristic cognitive and behavioral features appearing in mental retardations, which later are referred as behavioral phenotypes. Nyhan (1972) introduced the term “behavioral phenotype” to describe outwardly observable behavior so characteristic of children with genetic disorders that its presence suggests the underlying genetic condition. The behavioral phenotype is a characteristic pattern of motor, cognitive, linguistic and social abnormalities that is consistently associated with a biological/neurodevelopmental disorder. This does not mean that the behavior is present in all instances but that the probability of its occurrence is increased. In the future, more may be learned about brain mechanisms and gene-brain interactions by comparing those with behavioral involvement with others with the same syndrome but without the behavioral features.

Keywords: mental retardation – behavioral phenotypes – biologial markers – cognitive deficits – neurodevelopment


Linking of pharmacotherapy and physiotherapy is considered the most effective approach in psychiatry of our days. While pharmacotherapy is mainly based on research of the monoaminergic systems, the focus of psychotherapy is on stress. The distinct neuronal mechanisms targeted by the two therapeutic modalities are in close affiliation with each other. The aim of this current paper is to highlight basic characteristics and conjunctions of these two systems and to pinpoint core interaction between pharmacotherapy and psychotherapy.

Keywords: monoaminergic systems, stress mechanism


The prevailing neuroscientific paradigm considers information processing within the central nervous system as occurring through hierarchically organized and interconnected neural networks. The hierarchy of neural networks doesn’t end at the neuroaxonal level; it incorporates subcellular mechanisms as well. When the size of the hierarchical components reaches the nanometer range and the number of elements exceeds that of the neuroaxonal system, an interface emerges for a possible transition between neurochemical and quantum physical events. “Signal nonlocality”, accessed by means of quantum entanglement is an essential feature of the quantum physical domain. The presented interface may imply that some manifestations of altered states of consciousness, unconscious/conscious shifts have quantum origin with significant psychosomatic implications. Healing methods based on altered states of consciousness and common in spiritual or shamanic traditions escape neuroscientific explanations based on classical cognition denoted here as “perceptual-cognitive-symbolic” (characteristic of ordinary states of consciousness). Another channel of information processing, called “direct-intuitive-nonlocal” (characteristic of non-ordinary states of consciousness) is required to be introduced for interpretation. The first one is capable of modeling via symbolism and is more culturally bound due to its psycholinguistic features. The second channel lacks the symbolic mediation, therefore it has more transcultural similarity and practically ineffable for the first one, though culture specific transliteration may occur. Different traditional healing rituals pursue the same end: to destroy “profane” sensibility. The ritual use of hallucinogens, the monotonous drumming, the repeated refrains, the fatigue, the fasting, the dancing and so forth, create a sensory condition which is wide open to the so-called “supernatural”. According to contemporary anthropological views, the breakdown of ordinary sensibility/cognition is not the ultimate goal, but the way to accomplish healing, that is psychointegration in the widest sense. From the perspective of system theory, integration needs information to be brought into the system. According to the presented model, when the coping capability of the “perceptual-cognitive-symbolic” processing is exhausted in a stressful, unmanageable situation, or its influence is eliminated by the use of hallucinogens or in case of transcendental meditation, a frame shift occurs, and the “spiritual universe” opens up through the “direct-intuitive-nonlocal” channel. There is little chance either for a psychointegrative effect, or for a meaningful “opening” without ritual context, and with the recreational use of mind altering strategies.

Keywords: altered states of consciousness – cognition – cytoskeleton – dimethyltryptamine – ethnopharmacology – hallucinogenic agents – ritual healing


Some authors treated two groups of patients with postpsychotic depression in a group of patients with schizophrenia. Sertraline proved better than imipramine in view of earlier onset of action and lower incidence, intensity and duration of adverse effects and lower risk of schizophrenic symptom recurrence.

Keywords: postpsychotic depression – sertraline – perphenazine – lithium carbonate – lorazepamum