Gamma-Hydroxybutyrate (GHB) Content in Hair Samples Correlates Negatively with Age in Succinic Semialdehyde Dehydrogenase Deficiency

  • S. S. Johansen
  • X. Wang
  • D. Sejer Pedersen
  • P. L. Pearl
  • J.-B. Roullet
  • G. R. Ainslie
  • K. R. Vogel
  • K. M. GibsonEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 36)


Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). Our laboratory seeks to identify surrogate biomarkers in SSADHD that can shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD. We quantified GHB in hair derived from ten patients with SSADHD, and documented a significant negative age correlation. These findings are consistent with recent results in patient biological fluids, including plasma and red blood cells. These findings may provide additional insight into the developmental course of SSADHD (Jansen et al., J Inherit Metab Dis 39:795–800, 2016).


GABA metabolism Gamma-hydroxybutyrate (GHB) Hair analysis Succinic semialdehyde dehydrogenase (SSADH) Succinic semialdehyde dehydrogenase deficiency (SSADHD) Tandem mass spectrometry 



The authors gratefully acknowledge the patients and families who contributed hair samples for this study. The ongoing support of the SSADH association ( and Speragen, Inc., for longitudinal analyses of patient biological samples, is gratefully acknowledged.


  1. Absalom N, Eghorn LF, Villumsen IS, Karim N, Bay T, Olsen JV, Knudsen GM, Bräuner-Osborne H, Frølund B, Clausen RP, Chebib M, Wellendorph P (2012) α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB). Proc Natl Acad Sci U S A 109:13404–13409CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ainslie GR, Gibson KM, Vogel KR (2016) A pharmacokinetic evaluation and metabolite identification of the GHB receptor antagonist NCS-382 in mouse informs novel therapeutic strategies for the treatment of GHB intoxication. Pharmacol Res Perspect 4(6):e00265CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bertol E, Mari F, Vaiano F, Romano G, Zaami S, Baglìo G, Busardò FP (2015) Determination of GHB in human hair by HPLC-MS/MS: development and validation of a method and application to a study group and three possible single exposure cases. Drug Test Anal 7:376–384CrossRefPubMedGoogle Scholar
  4. Brenneisen R, Elsohly MA, Murphy TP, Passarelli J, Russmann S, Salamone SJ, Watson DE (2004) Pharmacokinetics and excretion of gamma-hydroxybutyrate (GHB) in healthy subjects. J Anal Toxicol 28:625–630CrossRefPubMedGoogle Scholar
  5. Busardò FP, Vaiano F, Mannocchi G, Bertol E, Zaami S, Marinelli E (2016) Twelve months monitoring of hair GHB decay following a single dose administration in a case of facilitated sexual assault. Drug Test Anal. doi: 10.1002/dta.2100 [Epub ahead of print]
  6. Buzzi A, Wu Y, Frantseva MV, Perez Velazquez JL, Cortez MA, Liu CC, Shen LQ, Gibson KM, Snead OC (2006) Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function. Brain Res 1090:15–22CrossRefPubMedGoogle Scholar
  7. Cooper GAA, Kronstrand R, Kintz P (2012) Society of Hair Testing (SoHT) guidelines for drug testing in hair. Forensic Sci Int 218:20–24CrossRefPubMedGoogle Scholar
  8. Gibson KM, Jakobs C, Ogier H, Hagenfeldt L, Eeg-Olofsson KE, Eeg-Olofsson O, Aksu F, Weber H-P, Rossier E, Vollmer B, Lehnert W (1995) Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis 18:143–146CrossRefPubMedGoogle Scholar
  9. Goullé JP, Chèze M, Pépin G (2003) Determination of endogenous levels of GHB in human hair. Are there possibilities for the identification of GHB administration through hair analysis in cases of drug-facilitated sexual assault? J Anal Toxicol 27:574–580CrossRefPubMedGoogle Scholar
  10. Hillmer AT, Mason GF, Fucito LM, O'Malley SS, Cosgrove KP (2015) How imaging glutamate, γ-aminobutyric acid, and dopamine can inform the clinical treatment of alcohol dependence and withdrawal. Alcohol Clin Exp Res 39:2268–2282CrossRefPubMedPubMedCentralGoogle Scholar
  11. Jagerdeo E, Montgomery MA, LeBeau MA (2015) An improved method for the analysis of GHB in human hair by liquid chromatography tandem mass spectrometry. J Anal Toxicol 39:83–88CrossRefPubMedGoogle Scholar
  12. Jansen EE, Struys E, Jakobs C, Hager E, Snead OC, Gibson KM (2008) Neurotransmitter alterations in embryonic succinate semialdehyde dehydrogenase (SSADH) deficiency suggest a heightened excitatory state during development. BMC Dev Biol 8:112CrossRefPubMedPubMedCentralGoogle Scholar
  13. Jansen EE, Vogel KR, Salomons GS, Pearl PL, Roullet J-B, Gibson KM (2016) Correlation of blood biomarkers with age informs pathomechanisms in succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism. J Inherit Metab Dis 39:795–800CrossRefPubMedPubMedCentralGoogle Scholar
  14. Maitre M, Klein C, Mensah-Nyagan AG (2016) Mechanisms for the specific properties of γ-hydroxybutyrate in brain. Med Res Rev 36:363–388CrossRefPubMedGoogle Scholar
  15. Malaspina P, Roullet JB, Pearl PL, Ainslie GR, Vogel KR, Gibson KM (2016) Succinic semialdehyde dehydrogenase deficiency (SSADHD): pathophysiological complexity and multifactorial trait associations in a rare monogenic disorder of GABA metabolism. Neurochem Int 99:72–84CrossRefPubMedPubMedCentralGoogle Scholar
  16. Parviz M, Vogel K, Gibson KM, Pearl PL (2014) Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies. J Pediatr Epilepsy 3(4):217–227CrossRefPubMedPubMedCentralGoogle Scholar
  17. Pearl PL, Gibson KM, Quezado Z, Dustin I, Taylor J, Trzcinski S, Schreiber J, Forester K, Reeves-Tyer P, Liew C, Shamim S, Herscovitch P, Carson R, Butman J, Jakobs C, Theodore W (2009) Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. Neurology 73:423–429CrossRefPubMedPubMedCentralGoogle Scholar
  18. Reis J, Cohen LG, Pearl PL, Fritsch B, Jung NH, Dustin I, Theodore WH (2012) GABAB-ergic motor cortex dysfunction in SSADH deficiency. Neurology 79:47–54CrossRefPubMedPubMedCentralGoogle Scholar
  19. Shi Y, Cui X, Shen M, Xiang P (2016) Quantitative analysis of the endogenous GHB level in the hair of the Chinese population using GC/MS/MS. J Forensic Leg Med 39:10–15CrossRefPubMedGoogle Scholar
  20. Staeheli SN, Baumgartner MR, Gauthier S, Gascho D, Jarmer J, Kraemer T, Steuer AE (2016) Time-dependent postmortem redistribution of butyrfentanyl and its metabolites in blood and alternative matrices in a case of butyrfentanyl intoxication. Forensic Sci Int 266:170–177CrossRefPubMedGoogle Scholar
  21. Talaei SA, Azami A, Salami M (2016) Postnatal development and sensory experience synergistically underlie the excitatory/inhibitory features of hippocampal neural circuits: glutamatergic and GABAergic neurotransmission. Neuroscience 318:230–243CrossRefPubMedGoogle Scholar
  22. Vogel KR, Ainslie GR, Gibson KM (2016) mTOR inhibitors rescue premature lethality and attenuate dysregulation of GABAergic/glutamatergic transcription in murine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism. J Inherit Metab Dis 39:877–886CrossRefPubMedPubMedCentralGoogle Scholar
  23. Wang X, Linnet K, Johansen SS (2016) Development of a UPLC–MS/MS method for determining γ-hydroxybutyric acid (GHB) and GHB glucuronide concentrations in hair and application to forensic cases. Forensic Toxicol 34:51–60CrossRefGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • S. S. Johansen
    • 1
  • X. Wang
    • 1
  • D. Sejer Pedersen
    • 2
  • P. L. Pearl
    • 3
  • J.-B. Roullet
    • 4
  • G. R. Ainslie
    • 4
  • K. R. Vogel
    • 4
  • K. M. Gibson
    • 4
    Email author
  1. 1.Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Drug Design and Pharmacology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of Neurology, Harvard Medical SchoolBoston Children’s HospitalBostonUSA
  4. 4.Section of Experimental and Systems Pharmacology, College of PharmacyWashington State UniversitySpokaneUSA

Personalised recommendations