TY  - JOUR
A1  - Coenen, Volker A.
A1  - Amtage, Florian
A1  - Volkmann, Jens
A1  - Schläpfer, Thomas E.
T1  - Deep Brain Stimulation in Neurological and Psychiatric Disorders
JF  - Deutsches Ärzteblatt International
N2  - Background: 
Deep brain stimulation (DBS) is the chronic electrical stimulation of selected target sites in the brain through stereotactically implanted electrodes. More than 150 000 patients around the world have been treated to date with DBS for medically intractable conditions. The indications for DBS include movement disorders, epilepsy, and some types of mental illness. 

Methods: 
This review is based on relevant publications retrieved by a selective search in PubMed and the Cochrane Library, and on the current guidelines of the German Neurological Society (Deutsche Gesellschaft fur Neurologie, DGN). 

Results: DBS is usually performed to treat neurological diseases, most often movement disorders and, in particular, Parkinson's disease. Multiple randomized controlled trials (RCTs) have shown that DBS improves tremor, dyskinesia, and quality of life in patients with Parkinson's disease by 25% to 50%, depending on the rating scales used. DBS for tremor usually involves stimulation in the cerebello-thalamo-cortical regulatory loop. In an RCT of DBS for the treatment of primary generalized dystonia, the patients who underwent DBS experienced a 39.3% improvement of dystonia, compared to only 4.9% in the control group. Two multicenter trials of DBS for depression were terminated early because of a lack of efficacy. 

Conclusion: 
DBS is an established treatment for various neurological and psychiatric diseases. It has been incorporated in the DGN guidelines and is now considered a standard treatment for advanced Parkinson's disease. The safety and efficacy of DBS can be expected to improve with the application of new technical developments in electrode geometry and new imaging techniques. Controlled trials would be helpful so that DBS could be extended to further indications, particularly psychiatric ones.
KW  - treatment-resistant depression
KW  - randomized controlled trial
KW  - parkinsons disease
KW  - essential tremor
KW  - pallidal stimulation
KW  - nucleus ventralis intermedius
KW  - term follow-up
KW  - subthalamic nucleus
KW  - cervical dystonia
KW  - major depression
Y1  - 2015
U6  - https://doi.org/10.3238/arztebl.2015.0519
VL  - 112
SP  - 519
EP  - 526
ER  - 
TY  - JOUR
A1  - Wiese, Teresa
A1  - Dennstädt, Fabio
A1  - Hollmann, Claudia
A1  - Stonawski, Saskia
A1  - Wurst, Catherina
A1  - Fink, Julian
A1  - Gorte, Erika
A1  - Mandasari, Putri
A1  - Domschke, Katharina
A1  - Hommers, Leif
A1  - Vanhove, Bernard
A1  - Schumacher, Fabian
A1  - Kleuser, Burkard
A1  - Seibel, Jürgen
A1  - Rohr, Jan
A1  - Buttmann, Mathias
A1  - Menke, Andreas
A1  - Schneider-Schaulies, Jürgen
A1  - Beyersdorf, Niklas
T1  - Inhibition of acid sphingomyelinase increases regulatory T cells in humans
JF  - Brain Communications
N2  - Genetic deficiency for acid sphingomyelinase or its pharmacological inhibition has been shown to increase Foxp3\(^+\) regulatory T-cell frequencies among CD4\(^+\) T cells in mice. We now investigated whether pharmacological targeting of the acid sphingomyelinase, which catalyzes the cleavage of sphingomyelin to ceramide and phosphorylcholine, also allows to manipulate relative CD4\(^+\) Foxp3\(^+\) regulatory T-cell frequencies in humans. Pharmacological acid sphingomyelinase inhibition with antidepressants like sertraline, but not those without an inhibitory effect on acid sphingomyelinase activity like citalopram, increased the frequency of Foxp3\(^+\) regulatory T cell among human CD4\(^+\) T cells in vitro. In an observational prospective clinical study with patients suffering from major depression, we observed that acid sphingomyelinase-inhibiting antidepressants induced a stronger relative increase in the frequency of CD4\(^+\) Foxp3\(^+\) regulatory T cells in peripheral blood than acid sphingomyelinase-non- or weakly inhibiting antidepressants. This was particularly true for CD45RA\(^-\) CD25\(^{high}\) effector CD4\(^+\) Foxp3\(^+\) regulatory T cells. Mechanistically, our data indicate that the positive effect of acid sphingomyelinase inhibition on CD4\(^+\) Foxp3\(^+\) regulatory T cells required CD28 co-stimulation, suggesting that enhanced CD28 co-stimulation was the driver of the observed increase in the frequency of Foxp3+ regulatory T cells among human CD4\(^+\) T cells. In summary, the widely induced pharmacological inhibition of acid sphingomyelinase activity in patients leads to an increase in Foxp3+ regulatory T-cell frequencies among CD4\(^+\) T cells in humans both in vivo and in vitro.
KW  - acid sphingomyelinase
KW  - antidepressants
KW  - major depression
KW  - regulatory T cells
KW  - sphingolipids
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259868
VL  - 3
IS  - 2
ER  -