Social psychiatry and schizophrenia--changes and perspectives

There will be an enormous change for general as well as social psychiatry in the next decade. With regard to schizophrenia it is apparent that only innovative research strategies and practical care together may be able to improve the clinical outcome of these disabled persons in the long term. Definitely, a modern social psychiatry does need a better understanding of different aspects of schizophrenia, which includes comprehensive knowledge about its ethiological genetic- and cognitive-based hypotheses as well as awareness of modern drug strategies and effective rehabilitation programs. Alike health economic aspects will reform social psychiatry as its own concepts have to prove their efficacy not only from a therapeutical view but also with respect to its short-, middle- and long-term cost effectiveness.     

Differentialdiagnostic problems of frontotemporal dementia--a case study

A case study on the clinical picture of frontotemporal dementia and the differential diagnostic problems will be described.     

Psychotherapy units in Bavarian state mental hospitals

OBJECTIVE AND METHOD: In this paper we report about the situation of psychotherapeutic inpatient treatment in Bavarian state mental hospitals, based on data coming from surveys in those hospitals. RESULTS AND CONCLUSION: 22 State mental hospitals in Bavaria have 1217 beds for acute psychotherapy, proofed on the basis of quality criteria. More than 50 per cent of all psychotherapy beds are located in those hospitals.     

Noise trauma alters D-[3H]aspartate release and AMPA binding in chinchilla cochlear nucleus

Exposure of adults to loud noise can overstimulate the auditory system, damage the cochlea, and destroy cochlear nerve axons and their synaptic endings in the brain. Cochlear nerve loss probably results from the death of cochlear inner hair cells (IHC). Additional degeneration in the cochlear nucleus (CN) is hypothesized to stem from overstimulation of the system, which may produce excitotoxicity. This study tested these predictions by exposing one ear of anesthetized adult chinchillas to a loud noise, which damaged the ipsilateral cochlea and induced degeneration in the glutamatergic cochlear nerve. During the first postexposure week, before cochlear nerve axons degenerated, glutamatergic synaptic release in the ipsilateral CN was elevated and uptake was depressed, consistent with hyperactivity of glutamatergic transmission and perhaps with the operation of an excitotoxic mechanism. By 14 days, when cochlear nerve fibers degenerated, glutamatergic synaptic release and uptake in the CN became deficient. By 90 days, a resurgence of transmitter release and an elevation of AMPA receptor binding suggested transmission upregulation through plasticity that resembled changes after mechanical cochlear damage. These changes may contribute to tinnitus and other pathologic symptoms that precede and accompany hearing loss. In contrast, the other ear, protected with a silicone plug during the noise exposure, exhibited virtually no damage in the cochlea or the cochlear nerve. Altered glutamatergic release and AMPA receptor binding activity in the CN suggested upregulatory plasticity driven by signals emanating from the CN on the noise-exposed side.     

Quantitative study of degeneration and new growth of axons and synaptic endings in the chinchilla cochlear nucleus after acoustic overstimulation

To determine if acoustic overstimulation altered synaptic connections in the cochlear nucleus, anesthetized adult chinchillas, with one ear protected by a silicone plug, were exposed for 3 hr to a 108-dB octave-band noise, centered at 4 kHz, and allowed to survive for periods up to 32 weeks. This exposure led to cochlear damage in the unprotected ear, mainly in the basal regions of the organ of Corti. The anterior part of the ipsilateral posteroventral cochlear nucleus consistently contained a band of degenerating axons and terminals, in which electron microscopic analysis revealed substantial losses of axons and synaptic terminals with excitatory and inhibitory cytology. The losses were significant after 1 week's survival and progressed for 16-24 weeks after exposure. By 24-32 weeks, a new growth of these structures produced a resurgence in the number of axons and terminals. The net number of excitatory endings fully recovered, but the quantity with inhibitory cytology was only partially recouped. Neuronal somata lost both excitatory and inhibitory endings at first and later recovered a full complement of excitatory but not inhibitory terminals. Dendrites suffered a net loss of both excitatory and inhibitory endings. Excitatory and inhibitory terminals with unidentified postsynaptic targets in the neuropil declined, then increased in number, with excitatory terminals exhibiting a greater recovery. These findings are consistent with a loss and regrowth of synaptic endings and with a reorganization of synaptic connections that favors excitation.     

Extratemporal resection for childhood epilepsy

There have been relatively few studies reporting the safety, efficacy, and outcome in children undergoing extratemporal resection for epilepsy. We reviewed the pediatric cases of extratemporal resection for intractable epilepsy performed by the Comprehensive Epilepsy Program at the University of Alberta Hospitals between 1988-1998. Thirty-five patients were studied, 14 male and 21 female. The age at operation ranged from 6 months to 16 years. The operations included frontal excisions (12), parietal (8), occipital (4), hemispherectomies or multilobar resections (10), and one removal of a hypothalamic hamartoma. The pathology at surgery included patients with focal cortical dysplasia (8), brain tumors (6), neurocutaneous syndrome (7), Rasmussen's encephalitis (2), porencephalic cysts (4), hypothalamic hamartoma (1), and nonspecific gliosis (6). Twenty-four of 35 patients (68.5%) had an Engel Class I outcome after surgery and an additional six patients (11%) had a significant decrease in seizure frequency (Engel Class III). Complications were observed in two patients (5%) and there were no deaths. Extratemporal resection is a safe and effective treatment for children with intractable epilepsy. Overall, 68% of patients were seizure-free after surgery, although outcome may be dependent on site and pathology. A wide range of developmental pathology was observed including focal cortical dysplasia, brain tumors, and lesions with neurocutaneous syndromes. Many families reported improvement in behavior and psychosocial function after surgery.     

Funded research in psychosomatic medicine, medical psychology, and psychotherapy

This paper, summarizing the activities of the research task force of the German College of Psychosomatic Medicine (DKPM), reviews how research in psychosomatic medicine, medical psychology and psychotherapy has been funded by different institutions. The review reveals that psychosocial research has received considerable grants especially by the German Research Council and the Federal Ministry of Education and Research but also from other funding institutions. Besides an overview of potential sources for funding in the psychosocial disciplines, recommendations are formulated that might be helpful for raising research funds in the future.     

Substance identification by quantitative characterization of oscillatory activity in murine spinal cord networks on microelectrode arrays

This paper presents a novel and comprehensive method to identify substances on the basis of electrical activity and is a substantial improvement for drug screening. The spontaneous activity of primary neuronal networks is influenced by neurotransmitters, ligands, and other substances in a similar fashion as known from in vivo pharmacology. However, quantitative methods for the identification of substances through their characteristic effects on network activity states have not yet been reported. We approached this problem by creating a database including native activity and five drug-induced oscillatory activity states from extracellular multisite recordings from microelectrode arrays. The response profiles consisted of 30 activity features derived from the temporal distribution of action potentials, integrated burst properties, calculated coefficients of variation, and features of Gabor fits to autocorrelograms. The different oscillatory states were induced by blocking neurotransmitter receptors for: (i) GABA(A); (ii) glycine; (iii) GABA(A) and glycine; (iv) all major synaptic types except AMPA, and (v) all major synapses except NMDA. To test the identification capability of the six substance-specific response profiles, five blind experiments were performed. The response features from the unknown substances were compared to the database using proximity measures using the normalized Euclidian distance to each activity state. This process created six identification coefficients where the smallest correctly identified the unknown substances. Such activity profiles are expected to become substance-specific 'finger prints' that classify unique responses to known and unknown substances. It is anticipated that this kind of approach will help to quantify pharmacological responses of networks used as biosensors.     

Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease

Minocycline has been shown to exert anti-inflammatory effects underlying its putative neuroprotective properties in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease and in the R6/2 mouse model of Huntington's disease (HD). However, contradictory results have recently been reported. We report deleterious effects of minocycline in two phenotypic (toxic) models of Parkinson's disease and HD in monkey and mouse. Of seven MPTP-intoxicated female cynomolgus monkeys (0.2 mg/kg, i.v. until day 15), three received minocycline (200 mg b.i.d.). While placebo-MPTP-treated animals displayed mild parkinsonism at day 15, the minocycline/MPTP-treated animals tended to be more affected (P = 0.057) and showed a greater loss of putaminal dopaminergic nerve endings (P < 0.0001). In the 3-nitropropionic acid (3-NP) mouse model of HD, minocycline (45 mg/kg i.p.) was administered 30 min before each i.p. injection of 3-NP (b.i.d., cumulated dose, 360 mg/kg in 5 days). Mice receiving minocycline exhibited a worsening of the mean motor score with a slower recovery slope, more impaired general activity and significantly deteriorated performances on the rotarod, pole test and beam-traversing tasks. The histopathological outcome demonstrated that minocycline-treated mice presented significantly more severe neuronal cell loss in the dorsal striatum. The effect of minocycline vs. 3-NP was also investigated on hippocampal and cortical cell cultures. minocycline blocked 3-NP-induced neurotoxicity at certain doses (1 mm cortical neurons) but not at higher doses (10 mm). Thus, minocycline may have variable and even deleterious effects in different species and models according to the mode of administration and dose.     

The effectiveness of stimulants of retard forms in children and adolescents with ADHD--a systematic overview

Stimulants are the matter of choice to treat attention deficit/hyperactivity disorder (ADHD) pharmacologically. The period of effectiveness of immediate release stimulants is, however, often not satisfying. Currently a variety of retarded forms of methylphenidate and also amphetamine were developed in order to minimize the problems involved in a daily dose. This paper presents the clinical studies on effectiveness, period of effectiveness and the profile of side effects of different forms of stimulants. In the clinical practice the new retard products are effective alternatives. There is an advantage in giving this drug in a once daily single dose. At the same time, the side effects that are caused by an extended period of being effective have to be studied in detail. A more exact adaptation to the requirements of daily obligations and needs of children and adolescents is difficult to realize. Future research is supposed to test schemes of titration including immediate and sustained released stimulants.