TY  - JOUR
A1  - Brunkhorst-Kanaan, Nathalie
A1  - Trautmann, Sandra
A1  - Schreiber, Yannick
A1  - Thomas, Dominique
A1  - Kittel-Schneider, Sarah
A1  - Gurke, Robert
A1  - Geisslinger, Gerd
A1  - Reif, Andreas
A1  - Tegeder, Irmgard
T1  - Sphingolipid and endocannabinoid profiles in adult attention deficit hyperactivity disorder
JF  - Biomedicines
N2  - Genes encoding endocannabinoid and sphingolipid metabolism pathways were suggested to contribute to the genetic risk towards attention deficit hyperactivity disorder (ADHD). The present pilot study assessed plasma concentrations of candidate endocannabinoids, sphingolipids and ceramides in individuals with adult ADHD in comparison with healthy controls and patients with affective disorders. Targeted lipid analyses of 23 different lipid species were performed in 71 mental disorder patients and 98 healthy controls (HC). The patients were diagnosed with adult ADHD (n = 12), affective disorder (major depression, MD n = 16 or bipolar disorder, BD n = 6) or adult ADHD with comorbid affective disorders (n = 37). Canonical discriminant analysis and CHAID analyses were used to identify major components that predicted the diagnostic group. ADHD patients had increased plasma concentrations of sphingosine-1-phosphate (S1P d18:1) and sphinganine-1-phosphate (S1P d18:0). In addition, the endocannabinoids, anandamide (AEA) and arachidonoylglycerol were increased. MD/BD patients had increased long chain ceramides, most prominently Cer22:0, but low endocannabinoids in contrast to ADHD patients. Patients with ADHD and comorbid affective disorders displayed increased S1P d18:1 and increased Cer22:0, but the individual lipid levels were lower than in the non-comorbid disorders. Sphingolipid profiles differ between patients suffering from ADHD and affective disorders, with overlapping patterns in comorbid patients. The S1P d18:1 to Cer22:0 ratio may constitute a diagnostic or prognostic tool.
KW  - attention deficit hyperactivity disorder
KW  - endocannabinoids
KW  - ceramides
KW  - bipolar disorder
KW  - major depression
KW  - tandem mass spectrometry
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246080
SN  - 2227-9059
VL  - 9
IS  - 9
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  - 
TY  - JOUR
A1  - Zapf, Ludwig
A1  - Finze, Maik
T1  - The crystal structure of poly[(μ \(_3\)-imidazolato-κ \(^3\) N:N:N′)(tetrahydrofuran- κ \(^1\) O)lithium(I)], C\(_7\)H\(_{11}\)LiN\(_2\)O
JF  - Zeitschrift für Kristallographie - New Crystal Structures
N2  - C\(_7\)H\(_{11}\)LiN\(_2\)O, monoclinic, P2\(_1\)/c (no. 14), a = 8.9067(1) angstrom, b = 8.6975(1) angstrom, c = 10.2398(1) angstrom, beta = 101.900(3)degrees, V = 770.491(15) angstrom(3), Z = 4, R-gt (F) = 0.0338, wR(ref) (F\(^2\)) = 0.0925, T = 100 K.
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-260745
VL  - 236
IS  - 5
ER  -