Sphingolipid and Endocannabinoid Profiles in Adult Attention Deficit Hyperactivity Disorder
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants and Biomaterial Sampling
2.2. Clinical Assessment and Questionnaires
2.3. Analysis of Lipid Signaling Molecules
2.4. Statistical Analyses
3. Results
3.1. Canonical Discriminant Analysis Separate ADHD from MD/BD and Healthy Controls
3.2. Influence of Age and Sex and Drug Treatments
3.3. Switch of Lipid Profiles from high S1P d18:1, High AEA towards High Long Chain-Ceramides
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Salum, G.A.; Sonuga-Barke, E.; Sergeant, J.; Vandekerckhove, J.; Gadelha, A.; Moriyama, T.S.; Graeff-Martins, A.S.; Manfro, G.G.; Polanczyk, G.; Rohde, L.A. Mechanisms underpinning inattention and hyperactivity: Neurocognitive support for adhd dimensionality. Psychol. Med. 2014, 44, 3189–3201. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thapar, A.; Cooper, M.; Eyre, O.; Langley, K. What have we learnt about the causes of adhd? J. Child Psychol. Psychiatry 2013, 54, 3–16. [Google Scholar] [CrossRef] [Green Version]
- Polanczyk, G.V.; Willcutt, E.G.; Salum, G.A.; Kieling, C.; Rohde, L.A. Adhd prevalence estimates across three decades: An updated systematic review and meta-regression analysis. Int. J. Epidemiol. 2014, 43, 434–442. [Google Scholar] [CrossRef] [PubMed]
- Franke, B.; Michelini, G.; Asherson, P.; Banaschewski, T.; Bilbow, A.; Buitelaar, J.K.; Cormand, B.; Faraone, S.V.; Ginsberg, Y.; Haavik, J.; et al. Live fast, die young? A review on the developmental trajectories of adhd across the lifespan. Eur. Neuropsychopharmacol. 2018, 28, 1059–1088. [Google Scholar] [CrossRef]
- Schiweck, C.; Arteaga-Henriquez, G.; Aichholzer, M.; Edwin Thanarajah, S.; Vargas-Cáceres, S.; Matura, S.; Grimm, O.; Haavik, J.; Kittel-Schneider, S.; Ramos-Quiroga, J.A.; et al. Comorbidity of adhd and adult bipolar disorder: A systematic review and meta-analysis. Neurosci. Biobehav. Rev. 2021, 124, 100–123. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.H.; Ripke, S.; Neale, B.M.; Faraone, S.V.; Purcell, S.M.; Perlis, R.H.; Mowry, B.J.; Thapar, A.; Goddard, M.E.; Witte, J.S.; et al. Genetic relationship between five psychiatric disorders estimated from genome-wide snps. Nat. Genet. 2013, 45, 984–994. [Google Scholar]
- Gamazon, E.R.; Zwinderman, A.H.; Cox, N.J.; Denys, D.; Derks, E.M. Multi-tissue transcriptome analyses identify genetic mechanisms underlying neuropsychiatric traits. Nat. Genet. 2019, 51, 933–940. [Google Scholar] [CrossRef]
- Legge, S.E.; Jones, H.J.; Kendall, K.M.; Pardiñas, A.F.; Menzies, G.; Bracher-Smith, M.; Escott-Price, V.; Rees, E.; Davis, K.A.S.; Hotopf, M.; et al. Association of genetic liability to psychotic experiences with neuropsychotic disorders and traits. JAMA Psychiatry 2019, 76, 1256–1265. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Landau, Z.; Pinhas-Hamiel, O. Attention deficit/hyperactivity, the metabolic syndrome, and type 2 diabetes. Curr. Diab. Rep. 2019, 19, 46. [Google Scholar] [CrossRef]
- Henriquez-Henriquez, M.; Acosta, M.T.; Martinez, A.F.; Vélez, J.I.; Lopera, F.; Pineda, D.; Palacio, J.D.; Quiroga, T.; Worgall, T.S.; Deckelbaum, R.J.; et al. Mutations in sphingolipid metabolism genes are associated with adhd. Transl. Psychiatry 2020, 10, 231. [Google Scholar] [CrossRef]
- Ahmadalipour, A.; Mehdizadeh Fanid, L.; Zeinalzadeh, N.; Alizadeh, M.; Vaezi, H.; Hassanpour Aydinlou, Z.; Noorazar, S.G. The first evidence of an association between a polymorphism in the endocannabinoid-degrading enzyme faah (faah rs2295633) with attention deficit hyperactivity disorder. Genomics 2020, 112, 1330–1334. [Google Scholar] [CrossRef]
- Ryberg, E.; Larsson, N.; Sjogren, S.; Hjorth, S.; Hermansson, N.O.; Leonova, J.; Elebring, T.; Nilsson, K.; Drmota, T.; Greasley, P.J. The orphan receptor gpr55 is a novel cannabinoid receptor. Br. J. Pharmacol. 2007, 152, 1092–1101. [Google Scholar] [CrossRef]
- Ross, R.A. The enigmatic pharmacology of gpr55. Trends Pharmacol. Sci. 2009, 30, 156–163. [Google Scholar] [CrossRef]
- Bradshaw, H.B.; Lee, S.H.; McHugh, D. Orphan endogenous lipids and orphan gpcrs: A good match. Prostaglandins Other Lipid Mediat. 2009, 89, 131–134. [Google Scholar] [CrossRef] [Green Version]
- O’Sullivan, S.E. Cannabinoids go nuclear: Evidence for activation of peroxisome proliferator-activated receptors. Br. J. Pharmacol. 2007, 152, 576–582. [Google Scholar] [CrossRef] [Green Version]
- Wilson, R.I.; Nicoll, R.A. Endocannabinoid signaling in the brain. Science 2002, 296, 678–682. [Google Scholar] [CrossRef] [Green Version]
- Whiting, P.F.; Wolff, R.F.; Deshpande, S.; Di Nisio, M.; Duffy, S.; Hernandez, A.V.; Keurentjes, J.C.; Lang, S.; Misso, K.; Ryder, S.; et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA 2015, 313, 2456–2473. [Google Scholar] [CrossRef] [PubMed]
- Black, N.; Stockings, E.; Campbell, G.; Tran, L.T.; Zagic, D.; Hall, W.D.; Farrell, M.; Degenhardt, L. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: A systematic review and meta-analysis. Lancet Psychiatry 2019, 6, 995–1010. [Google Scholar] [CrossRef]
- Di Marzo, V.; Despres, J.P. Cb1 antagonists for obesity–What lessons have we learned from rimonabant? Nat. Rev. Endocrinol. 2009, 5, 633–638. [Google Scholar] [CrossRef] [PubMed]
- Cristino, L.; Bisogno, T.; Di Marzo, V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat. Rev. Neurol. 2020, 16, 9–29. [Google Scholar] [CrossRef]
- Micale, V.; Di Marzo, V.; Sulcova, A.; Wotjak, C.T.; Drago, F. Endocannabinoid system and mood disorders: Priming a target for new therapies. Pharmacol Ther. 2013, 138, 18–37. [Google Scholar] [CrossRef]
- Lu, A.T.; Ogdie, M.N.; Jarvelin, M.R.; Moilanen, I.K.; Loo, S.K.; McCracken, J.T.; McGough, J.J.; Yang, M.H.; Peltonen, L.; Nelson, S.F.; et al. Association of the cannabinoid receptor gene (cnr1) with adhd and posttraumatic stress disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008, 147b, 1488–1494. [Google Scholar] [CrossRef] [Green Version]
- Cooper, R.E.; Williams, E.; Seegobin, S.; Tye, C.; Kuntsi, J.; Asherson, P. Cannabinoids in attention-deficit/hyperactivity disorder: A randomised-controlled trial. Eur. Neuropsychopharmacol. 2017, 27, 795–808. [Google Scholar] [CrossRef]
- Navarrete, F.; García-Gutiérrez, M.S.; Jurado-Barba, R.; Rubio, G.; Gasparyan, A.; Austrich-Olivares, A.; Manzanares, J. Endocannabinoid system components as potential biomarkers in psychiatry. Front. Psychiatry 2020, 11, 315. [Google Scholar] [CrossRef]
- Centonze, D.; Bari, M.; Di Michele, B.; Rossi, S.; Gasperi, V.; Pasini, A.; Battista, N.; Bernardi, G.; Curatolo, P.; Maccarrone, M. Altered anandamide degradation in attention-deficit/hyperactivity disorder. Neurology 2009, 72, 1526–1527. [Google Scholar] [CrossRef] [PubMed]
- Muhle, C.; Reichel, M.; Gulbins, E.; Kornhuber, J. Sphingolipids in psychiatric disorders and pain syndromes. Handb. Exp. Pharmacol. 2013, 431–456. [Google Scholar] [CrossRef]
- Gracia-Garcia, P.; Rao, V.; Haughey, N.J.; Bandaru, V.V.; Smith, G.; Rosenberg, P.B.; Lobo, A.; Lyketsos, C.G.; Mielke, M.M. Elevated plasma ceramides in depression. J. Neuropsychiatry Clin. Neurosci. 2011, 23, 215–218. [Google Scholar] [CrossRef]
- Kurz, J.; Parnham, M.J.; Geisslinger, G.; Schiffmann, S. Ceramides as novel disease biomarkers. Trends Mol. Med. 2019, 25, 20–32. [Google Scholar] [CrossRef] [PubMed]
- Brunkhorst-Kanaan, N.; Klatt-Schreiner, K.; Hackel, J.; Schroter, K.; Trautmann, S.; Hahnefeld, L.; Wicker, S.; Reif, A.; Thomas, D.; Geisslinger, G.; et al. Targeted lipidomics reveal derangement of ceramides in major depression and bipolar disorder. Metabolism 2019, 95, 65–76. [Google Scholar] [CrossRef]
- Hammerschmidt, P.; Ostkotte, D.; Nolte, H.; Gerl, M.J.; Jais, A.; Brunner, H.L.; Sprenger, H.G.; Awazawa, M.; Nicholls, H.T.; Turpin-Nolan, S.M.; et al. Cers6-derived sphingolipids interact with mff and promote mitochondrial fragmentation in obesity. Cell 2019, 177, 1536–1552.e1523. [Google Scholar] [CrossRef]
- Turpin, S.M.; Nicholls, H.T.; Willmes, D.M.; Mourier, A.; Brodesser, S.; Wunderlich, C.M.; Mauer, J.; Xu, E.; Hammerschmidt, P.; Brönneke, H.S.; et al. Obesity-induced cers6-dependent c16:0 ceramide production promotes weight gain and glucose intolerance. Cell Metab. 2014, 20, 678–686. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Raichur, S.; Brunner, B.; Bielohuby, M.; Hansen, G.; Pfenninger, A.; Wang, B.; Bruning, J.C.; Larsen, P.J.; Tennagels, N. The role of c16:0 ceramide in the development of obesity and type 2 diabetes: Cers6 inhibition as a novel therapeutic approach. Mol. Metab. 2019, 21, 36–50. [Google Scholar] [CrossRef] [PubMed]
- Goni, F.M.; Alonso, A. Sphingomyelinases: Enzymology and membrane activity. FEBS Lett. 2002, 531, 38–46. [Google Scholar] [CrossRef] [Green Version]
- Merrill, A.H., Jr.; Jones, D.D. An update of the enzymology and regulation of sphingomyelin metabolism. Biochim. Biophys. Acta 1990, 1044, 1–12. [Google Scholar] [CrossRef]
- Mullen, T.D.; Hannun, Y.A.; Obeid, L.M. Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem. J. 2012, 441, 789–802. [Google Scholar] [CrossRef] [Green Version]
- Kitatani, K.; Idkowiak-Baldys, J.; Hannun, Y.A. The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell Signal. 2008, 20, 1010–1018. [Google Scholar] [CrossRef] [Green Version]
- Kang, S.S.; Kurti, A.; Fair, D.A.; Fryer, J.D. Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring. J. Neuroinflamm. 2014, 11, 156. [Google Scholar] [CrossRef]
- Schmitz, K.; Brunkhorst, R.; de Bruin, N.; Mayer, C.A.; Haussler, A.; Ferreiros, N.; Schiffmann, S.; Parnham, M.J.; Tunaru, S.; Chun, J.; et al. Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis. Acta Neuropathol. Commun. 2017, 5, 42. [Google Scholar] [CrossRef]
- Klatt-Schreiner, K.; Valek, L.; Kang, J.S.; Khlebtovsky, A.; Trautmann, S.; Hahnefeld, L.; Schreiber, Y.; Gurke, R.; Thomas, D.; Wilken-Schmitz, A.; et al. High glucosylceramides and low anandamide contribute to sensory loss and pain in parkinson’s disease. Mov. Disord. 2020, 35, 1822–1833. [Google Scholar] [CrossRef]
- Young, R.C.; Biggs, J.T.; Ziegler, V.E.; Meyer, D.A. A rating scale for mania: Reliability, validity and sensitivity. Br. J. Psychiatry 1978, 133, 429–435. [Google Scholar] [CrossRef]
- Ramos-Quiroga, J.A.; Chalita, P.J.; Vidal, R.; Bosch, R.; Palomar, G.; Prats, L.; Casas, M. Diagnosis and treatment of attention deficit hyperactivity disorder in adults. Rev. Neurol. 2012, 54 (Suppl. 1), S105–S115. [Google Scholar] [PubMed]
- Ramos-Quiroga, J.A.; Nasillo, V.; Richarte, V.; Corrales, M.; Palma, F.; Ibáñez, P.; Michelsen, M.; Van de Glind, G.; Casas, M.; Kooij, J.J.S. Criteria and concurrent validity of diva 2.0: A semi-structured diagnostic interview for adult adhd. J. Atten. Disord. 2019, 23, 1126–1135. [Google Scholar] [CrossRef] [PubMed]
- Retz-Junginger, P.; Giesen, L.; Philipp-Wiegmann, F.; Rösler, M.; Retz, W. Wender-reimherr self-report questionnaire on adult adhd. Nervenarzt 2017, 88, 797–801. (in German). [Google Scholar] [CrossRef] [PubMed]
- Rösler, M.; Retz, W.; Retz-Junginger, P.; Stieglitz, R.D.; Kessler, H.; Reimherr, F.; Wender, P.H. Attention deficit hyperactivity disorder in adults. Benchmarking diagnosis using the wender-reimherr adult rating scale. Nervenarzt 2008, 79, 320–327. [Google Scholar] [CrossRef]
- Retz-Junginger, P.; Retz, W.; Blocher, D.; Stieglitz, R.D.; Georg, T.; Supprian, T.; Wender, P.H.; Rösler, M. Reliability and validity of the wender-utah-rating-scale short form. Retrospective assessment of symptoms for attention deficit/hyperactivity disorder. Nervenarzt 2003, 74, 987–993. [Google Scholar] [CrossRef] [PubMed]
- Gurke, R.; Thomas, D.; Schreiber, Y.; Schafer, S.M.G.; Fleck, S.C.; Geisslinger, G.; Ferreiros, N. Determination of endocannabinoids and endocannabinoid-like substances in human k3edta plasma–lc-ms/ms method validation and pre-analytical characteristics. Talanta 2019, 204, 386–394. [Google Scholar] [CrossRef]
- Hahnefeld, L.; Gurke, R.; Thomas, D.; Schreiber, Y.; Schäfer, S.M.G.; Trautmann, S.; Snodgrass, I.F.; Kratz, D.; Geisslinger, G.; Ferreirós, N. Implementation of lipidomics in clinical routine: Can fluoride/citrate blood sampling tubes improve preanalytical stability? Talanta 2020, 209, 120593. [Google Scholar] [CrossRef]
- Craft, R.M.; Marusich, J.A.; Wiley, J.L. Sex differences in cannabinoid pharmacology: A reflection of differences in the endocannabinoid system? Life Sci. 2013, 92, 476–481. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Walter, C.; Ferreiros, N.; Bishay, P.; Geisslinger, G.; Tegeder, I.; Lotsch, J. Exogenous delta(9)-tetrahydrocannabinol influences circulating endogenous cannabinoids in humans. J. Clin. Psychopharmacol. 2013, 33, 699–705. [Google Scholar] [CrossRef] [PubMed]
- Vogel, A.; Wilken-Schmitz, A.; Hummel, R.; Lang, M.; Trautmann, S.; Gurke, R.; Schäfer, M.K.E.; Tegeder, I. Low brain endocannabinoids associated with persistent non-goal directed nighttime hyperactivity after traumatic brain injury in mice. Sci. Rep. 2020. [Google Scholar] [CrossRef]
- Cohen, J.; Wei, Z.; Phang, J.; Laprairie, R.B.; Zhang, Y. Cannabinoids as an emerging therapy for posttraumatic stress disorder and substance use disorders. J. Clin. Neurophysiol. 2020, 37, 28–34. [Google Scholar] [CrossRef]
- Hill, M.N.; Kumar, S.A.; Filipski, S.B.; Iverson, M.; Stuhr, K.L.; Keith, J.M.; Cravatt, B.F.; Hillard, C.J.; Chattarji, S.; McEwen, B.S. Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure. Mol. Psychiatry 2013, 18, 1125–1135. [Google Scholar] [CrossRef] [PubMed]
- Lomazzo, E.; Bindila, L.; Remmers, F.; Lerner, R.; Schwitter, C.; Hoheisel, U.; Lutz, B. Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain. Neuropsychopharmacology 2015, 40, 488–501. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Danandeh, A.; Vozella, V.; Lim, J.; Oveisi, F.; Ramirez, G.L.; Mears, D.; Wynn, G.; Piomelli, D. Effects of fatty acid amide hydrolase inhibitor urb597 in a rat model of trauma-induced long-term anxiety. Psychopharmacology 2018, 235, 3211–3221. [Google Scholar] [CrossRef] [PubMed]
- Gunduz-Cinar, O.; Hill, M.N.; McEwen, B.S.; Holmes, A. Amygdala faah and anandamide: Mediating protection and recovery from stress. Trends Pharmacol. Sci. 2013, 34, 637–644. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bortolato, M.; Mangieri, R.A.; Fu, J.; Kim, J.H.; Arguello, O.; Duranti, A.; Tontini, A.; Mor, M.; Tarzia, G.; Piomelli, D. Antidepressant-like activity of the fatty acid amide hydrolase inhibitor urb597 in a rat model of chronic mild stress. Biol. Psychiatry 2007, 62, 1103–1110. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pardini, M.; Krueger, F.; Koenigs, M.; Raymont, V.; Hodgkinson, C.; Zoubak, S.; Goldman, D.; Grafman, J. Fatty-acid amide hydrolase polymorphisms and posttraumatic stress disorder after penetrating brain injury. Transl. Psychiatry 2012, 2, e75. [Google Scholar] [CrossRef] [Green Version]
- Sipe, J.C.; Scott, T.M.; Murray, S.; Harismendy, O.; Simon, G.M.; Cravatt, B.F.; Waalen, J. Biomarkers of endocannabinoid system activation in severe obesity. PLoS ONE 2010, 5, e8792. [Google Scholar] [CrossRef] [Green Version]
- Lazary, J.; Eszlari, N.; Juhasz, G.; Bagdy, G. Genetically reduced faah activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma. Eur. Neuropsychopharmacol. 2016, 26, 1020–1028. [Google Scholar] [CrossRef]
- Zhang, W.; Liu, H.; Deng, X.D.; Ma, Y.; Liu, Y. Faah levels and its genetic polymorphism association with susceptibility to methamphetamine dependence. Ann. Hum. Genet. 2020, 84, 259–270. [Google Scholar] [CrossRef]
- Bioque, M.; Mas, S.; Costanzo, M.C.; Cabrera, B.; Lobo, A.; González-Pinto, A.; Rodriguez-Toscano, E.; Corripio, I.; Vieta, E.; Baeza, I.; et al. Gene-environment interaction between an endocannabinoid system genetic polymorphism and cannabis use in first episode of psychosis. Eur. Neuropsychopharmacol. 2019, 29, 786–794. [Google Scholar] [CrossRef] [PubMed]
- Monteleone, P.; Bifulco, M.; Di Filippo, C.; Gazzerro, P.; Canestrelli, B.; Monteleone, F.; Proto, M.C.; Di Genio, M.; Grimaldi, C.; Maj, M. Association of cnr1 and faah endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: Evidence for synergistic effects. Genes Brain Behav. 2009, 8, 728–732. [Google Scholar] [CrossRef]
- Jacobson, M.R.; Watts, J.J.; Da Silva, T.; Tyndale, R.F.; Rusjan, P.M.; Houle, S.; Wilson, A.A.; Ross, R.A.; Boileau, I.; Mizrahi, R. Fatty acid amide hydrolase is lower in young cannabis users. Addict. Biol. 2021, 26, e12872. [Google Scholar] [CrossRef]
- Kim, H.; Mittal, D.P.; Iadarola, M.J.; Dionne, R.A. Genetic predictors for acute experimental cold and heat pain sensitivity in humans. J. Med. Genet. 2006, 43, e40. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dincheva, I.; Drysdale, A.T.; Hartley, C.A.; Johnson, D.C.; Jing, D.; King, E.C.; Ra, S.; Gray, J.M.; Yang, R.; DeGruccio, A.M.; et al. Faah genetic variation enhances fronto-amygdala function in mouse and human. Nat. Commun. 2015, 6, 6395. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Henríquez-Henríquez, M.P.; Solari, S.; Quiroga, T.; Kim, B.I.; Deckelbaum, R.J.; Worgall, T.S. Low serum sphingolipids in children with attention deficit-hyperactivity disorder. Front. Neurosci. 2015, 9, 300. [Google Scholar] [CrossRef] [Green Version]
- Wu, H.; Wang, X.; Gao, J.; Liang, S.; Hao, Y.; Sun, C.; Xia, W.; Cao, Y.; Wu, L. Fingolimod (fty720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism. Life Sci. 2017, 173, 43–54. [Google Scholar] [CrossRef] [PubMed]
- Sontag, T.A.; Tucha, O.; Walitza, S.; Lange, K.W. Animal models of attention deficit/hyperactivity disorder (adhd): A critical review. Atten. Defic. Hyperact. Disord. 2010, 2, 1–20. [Google Scholar] [CrossRef] [PubMed]
- Lotsch, J.; Schiffmann, S.; Schmitz, K.; Brunkhorst, R.; Lerch, F.; Ferreiros, N.; Wicker, S.; Tegeder, I.; Geisslinger, G.; Ultsch, A. Machine-learning based lipid mediator serum concentration patterns allow identification of multiple sclerosis patients with high accuracy. Sci. Rep. 2018, 8, 14884. [Google Scholar] [CrossRef] [PubMed]
- Gurke, R.; Etyemez, S.; Prvulovic, D.; Thomas, D.; Fleck, S.C.; Reif, A.; Geisslinger, G.; Lötsch, J. A data science-based analysis points at distinct patterns of lipid mediator plasma concentrations in patients with dementia. Front. Psychiatry 2019, 10, 41. [Google Scholar] [CrossRef] [Green Version]
Female | Male | ||||||||
---|---|---|---|---|---|---|---|---|---|
HC | ADHD | ADHD+ | MD/BD | HC | ADHD | ADHD+ | MD/BD | ||
Mean age (years) | 35.45 | 26.00 | 36.67 | 43.36 | 36.88 | 29.00 | 36.23 | 47.00 | |
Age range (years) | 21–65 | 20–32 | 20–66 | 26–67 | 23–66 | 26–34 | 26–54 | 26–59 | |
Age class | 20–30 | 27 | 5 | 6 | 2 | 12 | 3 | 6 | 2 |
31–40 | 20 | 2 | 4 | 3 | 12 | 2 | 10 | 1 | |
41–50 | 8 | 0 | 1 | 2 | 3 | 0 | 3 | 1 | |
>50 | 10 | 0 | 4 | 4 | 6 | 0 | 3 | 7 | |
Mean BMI | 22.82 | 25.39 | 23.68 | 24.58 | 23.61 | 25.82 | 27.50 | 29.43 | |
BMI range | 18.8–36.1 | 20.0–35.7 | 19.2–35.9 | 16.4–35.5 | 18.8–28.1 | 19.8–37.0 | 19.7–38.8 | 22.2–46.4 | |
BMI class | ≤21.0 | 24 | 3 | 6 | 3 | 5 | 1 | 1 | 0 |
21.1–24.0 | 23 | 1 | 4 | 3 | 14 | 2 | 5 | 1 | |
24.1–28.0 | 13 | 1 | 3 | 3 | 13 | 0 | 7 | 5 | |
28.1+ | 5 | 2 | 2 | 2 | 1 | 2 | 9 | 5 |
Sex and Comorbidities | HC | ADHD | ADHD+ | MD/BD | |
---|---|---|---|---|---|
Sex | male | 33 | 5 | 22 | 11 |
female | 65 | 7 | 15 | 11 | |
total | 98 | 12 | 37 | 22 | |
Smoking | yes | 6 | 4 | 8 | 10 |
no | 92 | 8 | 29 | 12 | |
Type-II diabetes mellitus | yes | 0 | 1 | 2 | 4 |
no | 98 | 11 | 35 | 18 | |
Hypertension | yes | 1 | 1 | 7 | 6 |
no | 97 | 11 | 30 | 16 | |
L-Thyroxin supplementation | yes | 0 | 1 | 11 | 2 |
no | 98 | 11 | 26 | 20 |
ECT and Drug Treatment | HC | ADHD | ADHD+ | MD/BD | |
---|---|---|---|---|---|
Electroconvulsion therapy | yes | 0 | 0 | 1 | 1 |
no | 98 | 12 | 36 | 21 | |
ADHD (MPH, Lisdexamfetamine, Atomoxetine, Guanfacine) | HC | 98 | 0 | 0 | 0 |
yes | 0 | 7 | 16 | 0 | |
no | 0 | 5 | 21 | 22 | |
SNRI, NDRI (Venlafaxine, Bupropion) | HC | 98 | 0 | 0 | 0 |
yes | 0 | 0 | 0 | 10 | |
no | 0 | 12 | 37 | 12 | |
TCA & related compounds | HC | 98 | 0 | 0 | 0 |
yes | 0 | 0 | 3 | 4 | |
no | 0 | 12 | 34 | 18 | |
SSRI (Sertraline, Citalopram, Paroxetine) | HC | 98 | 0 | 0 | 0 |
yes | 0 | 0 | 1 | 3 | |
no | 0 | 12 | 36 | 19 | |
Atypical antipsychotics (Quetiapine, Risperidone, Aripiprazole) | HC | 98 | 0 | 0 | 0 |
yes | 0 | 0 | 3 | 7 | |
no | 0 | 12 | 34 | 15 | |
Antiepileptic (Lamotrigine, Valproic acid) | HC | 98 | 0 | 0 | 0 |
yes | 0 | 0 | 0 | 2 | |
no | 0 | 12 | 37 | 20 |
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Brunkhorst-Kanaan, N.; Trautmann, S.; Schreiber, Y.; Thomas, D.; Kittel-Schneider, S.; Gurke, R.; Geisslinger, G.; Reif, A.; Tegeder, I. Sphingolipid and Endocannabinoid Profiles in Adult Attention Deficit Hyperactivity Disorder. Biomedicines 2021, 9, 1173. https://doi.org/10.3390/biomedicines9091173
Brunkhorst-Kanaan N, Trautmann S, Schreiber Y, Thomas D, Kittel-Schneider S, Gurke R, Geisslinger G, Reif A, Tegeder I. Sphingolipid and Endocannabinoid Profiles in Adult Attention Deficit Hyperactivity Disorder. Biomedicines. 2021; 9(9):1173. https://doi.org/10.3390/biomedicines9091173
Chicago/Turabian StyleBrunkhorst-Kanaan, Nathalie, Sandra Trautmann, Yannick Schreiber, Dominique Thomas, Sarah Kittel-Schneider, Robert Gurke, Gerd Geisslinger, Andreas Reif, and Irmgard Tegeder. 2021. "Sphingolipid and Endocannabinoid Profiles in Adult Attention Deficit Hyperactivity Disorder" Biomedicines 9, no. 9: 1173. https://doi.org/10.3390/biomedicines9091173