[Internet-based self-management interventions : Quality criteria for their use in prevention and treatment of mental disorders]. / Internetbasierte Selbstmanagementinterventionen : Qualitätskriterien für ihren Einsatz in Prävention und Behandlung psychischer Störungen.

BACKGROUND: Internet-based self-management interventions are effective in the prevention and treatment of mental disorders; however, for those affected as well as treating clinicians and decision makers in the healthcare sector, it is difficult to identify safe and effective interventions. AIM: Development of quality criteria for self-management interventions. METHODS: Based on a non-specific assessment matrix, a task force from two scientific societies formulated specific quality criteria for self-management interventions for mental disorders. Patients and other relevant stakeholders were involved in the process. RESULTS: A total of 8 key criteria with 17 subordinate points were developed. These must be met for the certification of an intervention. The criteria focus on therapeutic quality requirements, patient safety, data protection and security as well as proof of efficacy in at least one randomized study. A further five criteria are only descriptive and are not required for certification. DISCUSSION: These quality criteria serve as a starting point for the establishment of a certification process. This could help to make internet-based self-management interventions for mental disorders part of routine care in the German healthcare system.

[Internet-based interventions in the treatment of mental disorders : Overview, quality criteria, perspectives]. / Internetbasierte Interventionen in der Behandlung psychischer Störungen : Überblick, Qualitätskriterien, Perspektiven.

BACKGROUND: Mental disorders are frequently not or only insufficiently treated. Internet-based interventions offer the potential of closing the existing gaps in the treatment of mental disorders; however, it is very difficult for patients and providers to choose from the numerous interventions available. OBJECTIVE: The aim of this study was to develop a set of quality criteria that can help patients and care providers to identify recommendable internet-based interventions. METHODS: A selective literature search was carried out and the existing evidence on internet-based interventions in the treatment of mental disorders was collated. A panel of experts then developed quality criteria based on existing models for the systematic assessment of telemedicine applications. RESULTS: Internet-based interventions are effective in the treatment of a broad range of mental disorders. The best evidence is available for depression and anxiety disorders. A set of criteria is proposed for the evaluation of available internet-based interventions using a checklist. These criteria have to be developed further with input from other stakeholders. DISCUSSION: When taking these quality criteria into account, evidence-based interventions available on the internet can make an important contribution to improvement of the care of patients with mental disorders.

Morphology of embryonic hippocampus transplants and generation of long-distance extrinsic graft fiber connections to the lateral septum and the entorhinal cortex in the mature rat brain.

Pyramidal neurons inside transplants of embryonic nervous tissue are capable of generating axonal extrinsic hippocampal fiber connections over considerable distances to appropriate target areas in the mature brain. The establishment of long-distance graft efferents to the lateral septum and to the entorhinal cortex was shown by retrograde transport of the tracers HRP and bisbenzimide which were injected into these areas after bilateral neurotoxic lesions of the hippocampus. Additional AChE-staining demonstrated the presence of an afferent cholinergic graft input mainly from the medial septum via the fornix. Morphological analysis of the transplants grafted as cell suspensions showed typical details of the original hippocampus cytoarchitecture with bands of pyramidal and granule cells.

Attenuation of hippocampal kainic acid-induced seizures by substance P treatment.

Adult male Wistar rats (n = 21) received bilateral kainic acid lesions of their hippocampi. Over a period of 9 weeks the animals received daily IP injections of either 5 micrograms/kg or 50 micrograms/kg substance P (SP) or vehicle. Seizures provoked by the lesions were suppressed by the daily administration of the neuropeptide SP in a dose of 50 micrograms/kg for the whole period of observation. The neurokinin significantly (p < 0.01) reduced the number of seizures compared to the vehicle-treated animals.

Effects of chronic substance P treatment and intracranial fetal grafts on learning after hippocampal kainic acid lesions.

The purpose of this experiment was to investigate whether the neurokinin substance P (SP) can enhance adaptive graft effects on learning and memory functions in animals with lesions of the hippocampus. Adult male Wistar rats received a bilateral kainic acid (KA) lesion of the dorsal hippocampus. One week postlesion, bilateral grafts of fetal hippocampal tissue suspension were applied into the damaged region in half of the animals, whereas the other half received sham transplants (physiological saline). Animals of the control group received a bilateral sham lesion of the hippocampus and sham transplants. One week after transplantation surgery, the rats were tested in the place version of the Morris water maze over a period of 9 weeks. Then they were tested for SP-induced conditioned place preference and on a step-through inhibitory avoidance task. All animals received IP injections of either SP (5 or 50 micrograms/kg) or the SP vehicle (0.5 ml/kg). The treatment with SP or the vehicle was begun 1 week after transplantation and was performed 5 days a week over a period of 10 weeks. During behavioral tests in the water maze and avoidance task, application of the substances was performed 5 h after testing. For the conditioned place preference test, the conditioning trials were performed immediately after drug administration; the test trials were given 24 h later. Chronic administration of 50 micrograms/kg SP, but not 5 micrograms/ kg SP, was found to improve water maze performance in lesioned animals with and without grafts. Unexpectedly, the lesion group with the graft without additional SP treatment was not superior to the lesion group devoid of the graft in this task. The rats without lesions of the hippocampus still showed a conditioned place preference to 50 micrograms/kg SP after 9 weeks of repeated SP applications. In the inhibitory avoidance task, the grafts facilitated retention performance independent of whether SP treatment was given. The morphological analysis of the transplants revealed higher graft volumes and a higher diameter of large pyramidal neurons (> 10 microns) in rats chronically treated with 50 micrograms/kg SP.

Long-term tracing of vital neurons with Hoechst 33342 in transplantation studies.

Hippocampal nerve cells of rats taken from embryonic donors were stained with the fluorescent dye bisbenzimide (Hoechst 33342) and grafted to the brains of adult rats. The numbers of labelled neurons inside the transplants were determined after 6 different intervals, ranging from 2 days to 6 months. Numerous labelled neurons were found inside the grafts up to 6 months after grafting. The results demonstrate that bisbenzimide is a suitable vital cell tracer for long-term grafting experiments.

Functional aspects of the involvement of the hippocampus in behavior and memory functions.

In order to outline the involvement of the hippocampus in behavior and memory functions the results of grafting experiments in the hippocampal formation are presented in addition to former lesion and stimulation studies. Grafts of fetal hippocampal tissue were found to induce short-term beneficial effects on learning and memory. Functional efficiency of the grafts could be substantially improved by additional subcutaneous administration of carbachol over a period of 6 months. As carbachol does not cross the blood-brain barrier (BBB) due to its polar structure the data support the view that grafts of fetal neuronal tissue may induce a prolonged permeability of the BBB over a long period of time which could also be shown by HRP-histochemistry.

Transient and long-lasting beneficial behavioral effects of grafts in the damaged hippocampus of rat.

One week after receiving bilateral neurotoxic lesions of their dorsal hippocampi, adult Wistar rats were bilaterally grafted with fetal hippocampal tissue suspensions. The behavior of the animals was tested during a period of 5 months after grafting to determine changes in lesion-induced deficits. The transplants caused various behavioral effects with different time courses. Grafted animals showed an early, however, transient amelioration of behavioral deficits in a T-maze alternation task and they performed with a long-lasting improvement in the alcove-test. Transplant histology demonstrated high levels of AChE-activity in patches correlating with clusters or rudimentary layers of pyramidal neurons.

Subcutaneous injection of carbachol enhances brain graft-induced recovery of memory-function by circumventing the blood-brain barrier.

After bilateral neurotoxic hippocampectomy adult rats received bilateral fetal suspension grafts at the lesion sites. Functional efficacy of fetal grafted tissue was substantially improved by subcutaneous administration of carbachol at a dose of 0.01 mg/kg s.c. The drug caused an almost complete restitution of performance in grafted animals in a Morris water-maze test. The progress of behavioral recovery was studied over 3 months postoperatively. Grafts of fetal hippocampal neurons alone improved lesion-induced spatial learning deficits to a limited degree. These results suggest that peripheral administration of carbachol may be of use in the treatment of central lesions associated with cognitive impairments, allowing or enhancing the development of graft-induced amelioration of behavioral deficits. The data also support the view that grafts of embryonic neural tissue may produce a local opening of the blood-brain barrier allowing drugs which normally act only peripherally to exert central effects. These central effects are probably limited to the graft site because the rest of the brain has a blood-brain barrier which is still intact.

Spreading depression induced by microinjection of enkephalins into the hippocampus and neocortex.

The opioid peptides Leu-enkephalin, Met-enkephalin and D-Ala2-Met-enkephalinamide were injected at various concentrations into the neocortex and hippocampus of rats to examine their effects on EEG activity and DC potentials. All three compounds were found to elicit spreading depression (SD) in both structures. Higher doses of Met-enkephalin were required to elicit SD as well as seizure activity. In the hippocampus the wave of SD was frequently preceded by seizure activity which was antagonized by naloxone pretreatment (40 mg/kg i.p.). Naloxone also prevented Leu-enkephalin-induced SD in the neocortex (but not in the hippocampus) and Met-enkephalin-induced SD in the hippocampus (but not in the neocortex). It failed to block SD elicited by D-Ala2-Met-enkephalinamide in both structures. Some of the various reported behavioral effects of intracranial injections of enkephalins could be artefacts of hippocampal and/or cortical spreading depression.

Lateral hypothalamic self-stimulation persists in rats after destruction of lateral hypothalamic neurons by kainic acid or ibotenic acid.

Bilateral injections of 1 microgram/microliter of kainic or ibotenic acid into the lateral hypothalamus (LH) of rats destroyed most of the cells in the LH. This treatment did not prevent electrical self-stimulation from electrodes placed in the LH, indicating that intrinsic neurons of the LH alone are not crucial elements of the neural system that mediates reinforcing hypothalamic stimulation.

Energy metabolism and structural factors of long-term grafts in the CNS of rat correlate with graft induced recovery of function.

The oxidative energy metabolism and cytoarchitecture of fetal grafts in the neurotoxically damaged hippocampus of adult rats were investigated over a period of 6 months and correlated with adaptive behavioral effects on spatial memory in the Morris water-maze. Three to 6 months postoperatively grafted animals showed significantly lower latency scores in the water-maze compared to lesioned animals with sham grafts. The oxidative metabolism did not show predictory properties for functional efficiency during the first 3 months after grafting. Six months postoperatively the distribution of the cytochrome-c-oxidase reaction product highly correlated with the efficiency of the graft to compensate behavioral deficits as animals with grafts showing a high cytochrome-c-oxidase activity and a high degree of homotypic cytoarchitectural differentiation showed best recovery of functional deficits with only few errors in the maze. There was no significant difference between lesioned and grafted animals during the acquisition phase 1 week after grafting. The histological evaluation revealed that the distribution of cytochrome-c-oxidase was not homogeneous within the grafts. Patches of pyramidal neurons stained with cresylviolet in parallel slices correlated with clusters of high cytochrome-c-oxidase activity.