GDNF-mediated rescue of the nigrostriatal system depends on the degree of degeneration.

Glial cell-line derived neurotrophic factor (GDNF) is a promising therapeutic molecule to treat Parkinson's disease. Despite an excellent profile in experimental settings, clinical trials testing GDNF have failed. One of the theories to explain these negative outcomes is that the clinical trials were done in late-stage patients that have advanced nigrostriatal degeneration and may therefore not respond to a neurotrophic factor therapy. Based on this idea, we tested if the stage of nigrostriatal degeneration is important for GDNF-based therapies. Lentiviral vectors expressing regulated GDNF were delivered to the striatum of rats to allow GDNF expression to be turned on either while the nigrostriatal system was degenerating or after the nigrostriatal system had been fully lesioned by 6-OHDA. In the group of animals where GDNF expression was on during degeneration, neurons were rescued and there was a reversal of motor deficits. Turning GDNF expression on after the nigrostriatal system was lesioned did not rescue neurons or reverse motor deficits. In fact, these animals were indistinguishable from the control groups. Our results suggest that GDNF can reverse motor deficits and nigrostriatal pathology despite an ongoing nigrostriatal degeneration, if there is still a sufficient number of remaining neurons to respond to therapy.

A patient perspective on recurrent or prolonged contact with psychiatric inpatient care for affective disorder.

BACKGROUND: The aim of this qualitative study was to explore why some patients receive recurrent or prolonged psychiatric inpatient care, based on the experiences of the patients themselves. METHODS: The participants were recruited at an outpatient clinic at the department of psychiatry for patients with affective disorders at Sahlgrenska University Hospital, Sweden. Ten patients, nine women and one man, aged 22-61 years, agreed to participate. A semi-structured interview guide was used during the interviews, which were audiotaped, transcribed, and analyzed using interpretative phenomenological analysis. RESULTS: The four themes that emerged were Difficulties in affective regulation, where the informants reported difficulty in managing their emotions, with the possible consequence of admission to inpatient care; Relational sensitivity, concerning a sensitivity to relationships with healthcare professionals and a need for a secure therapeutic rapport; Resignation, characterized by passivity and depression; and Ambivalence towards responsibility, where ambivalence about their responsibility could lead to failure to initiate change. CONCLUSIONS: More options beside inpatient care should be available in cases of an urgent need for help. A stable care structure, good cooperation, and long-term planning based on individual needs are pivotal. In the planning of psychiatric care, consideration must be given to the patient's relational sensitivity. By encouraging patients to actively seek help, we can counteract their resistance and achieve a more effective contact with psychiatric services.