Skip to main content
SpringerLink
Log in

Psychiatric and neuropsychological changes in growth hormone-deficient patients after traumatic brain injury in response to growth hormone therapy

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Objective: Traumatic brain injury (TBI) has been recently recognized as a risk factor for cognitive impairment and hypopituitarism, presented most frequently with GH deficiency (GHD). GHD is associated not only with changes in body composition, but also with impaired quality of life, cognitive dysfunctions and some psychiatric sequelae, usually classified as “depression” or “atypical depression”. The impact of GH therapy on mental status in TBI patients is still unknown. Design: Psychiatric and cognitive functions were tested in 6 GHD patients at baseline (minimum 3 yr after TBI), reassessed after 6 months of GH therapy as well as 12 months after discontinuation of GH therapy. Psychiatric and cognitive examinations included semi-structured interviews and 3 instruments: Symptom-checklist (SCL-90-R), Zung Depression Inventory, and standard composite neuropsychological battery. Results: Six months of GH therapy in GHD TBI patients improved cognitive abilities (particularly verbal and non-verbal memory) and significantly improved psychiatric functioning. Severity of depression decreased, as well as intensity of interpersonal sensitivity, hostility, paranoid ideation, anxiety, and psychoticism. Somatization, obsessive-compulsive symptoms and phobic anxiety decreased in all except in one patient. In 3 GHD patients who stopped GH therapy for 12 months we registered worsening of the verbal and non-verbal memory, as well symptoms in 3 SCL dimensions: inter-personal sensitivity, anxiety, and paranoid ideation. Conclusion: GH-deficient TBI patients are depressed and have cognitive impairment. GH therapy induced reduction of depression, social dysfunction, and certain cognitive domains. Our preliminary data support the necessity of conducting randomized placebo-controlled trials on the effects of GH therapy on neuropsychological and psychiatric status in GHD TBI patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aimaretti G, Ambrosio M, Di Somma C, et al. Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury. Clin Endocrinol (Oxf) 2004, 61: 320–6.

    Article  CAS  Google Scholar 

  2. Popovic V, Pekic S, Pavlovic D, et al. Hypopituitarism as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress. J Endocrinol Invest 2004, 11: 1048–54.

    Article  Google Scholar 

  3. Agha A, Rogers B, Sherlock M, et al. Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab 2004, 89: 4929–36.

    Article  PubMed  CAS  Google Scholar 

  4. Deijen JB, de Boer H, van der Veen EA. Cognitive changes during growth hormone replacement in adult men. Psychoneuroendocrinology 1998, 23: 45–55.

    Article  PubMed  CAS  Google Scholar 

  5. Soares CN, Musolino NR, Cunha NM, et al. Impact of recombinant human growth hormone (RH-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults. A placebo-controlled trial. Art Neuropsiquiatr 1999, 57: 182–9.

    Article  CAS  Google Scholar 

  6. Oertel H, Schneider HJ, Stalla GK, et al. The effect of growth hormone substitution on cognitive performance in adult patients with hypopituitarism. Psychoneuroendocrinology 2004, 29: 839–50.

    Article  PubMed  CAS  Google Scholar 

  7. Arwert LI, Deijen JB, Witlox J, Drent ML. The influence of growth hormone (GH) substitution on patient-reported outcomes and cognitive functions in GH-deficient patients: a meta-analysis. Growth Horm IGF Res 2005, 15: 47–54.

    Article  PubMed  CAS  Google Scholar 

  8. Springer J, Chollet A. A traumatic car crash. Lancet 2001, 357: 1848.

    Article  PubMed  CAS  Google Scholar 

  9. Ho KK, 2007 GH Deficiency Consensus Workshop Participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endcocrinol 2007, 157: 695–700.

    Article  CAS  Google Scholar 

  10. Popovic V, Leal A, Micic D, et al. GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults. Lancet 2000, 356: 1137–42.

    Article  PubMed  CAS  Google Scholar 

  11. Zung WWK. A self-rating depression scale. Arch Gen Psychiatry 1965, 12: 63–70.

    Article  PubMed  CAS  Google Scholar 

  12. Derogatis LR, Rickels K, Rock AF. The SCL-90 and the MMPI: A step in the validation of a new self-report scale. Br J Psychiatry 1976, 128: 280–9.

    Article  PubMed  CAS  Google Scholar 

  13. Hoofien D, Barak O, Vakil E, Gilboa A. Symptom checklist-90 revised scores in persons with traumatic brain injury: affective reactions or neurobehavioral outcomes of the injury?. Appl Neuropsychol 2005, 12: 30–9.

    Article  PubMed  Google Scholar 

  14. Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975, 12: 189–98.

    Article  PubMed  CAS  Google Scholar 

  15. Rey A. L’examen clinique en psychologie. Paris: Presses Universitaires de France 1964.

    Google Scholar 

  16. Reitan RM, Wolfson D. The Halstead-Reitan Neuropsychological Test Battery: Theory and clinical interpretation. Tucson, AZ: Neuropsychology Press, 1993.

    Google Scholar 

  17. Kaplan EF, Goodglass H, Weintraub S. The Boston Naming Test. Boston MA: Kaplan and Goodglass, 1978.

    Google Scholar 

  18. Heaton RK. A manual for the Wisconsin Card Sorting Test. Odessa Fl: Psychological Assessment Resources Inc, 1981.

    Google Scholar 

  19. Adem A, Jossan SS, d’Argy R, et al. Insulin-like growth factor I (IGF-I) receptors in the human brain: quantitative autoradiographic localization. Brain Res 1989, 503: 299–303.

    Article  PubMed  CAS  Google Scholar 

  20. Creyghton WM, van Dam PS, Koppeschaar HP. The role of the somatotropic system in cognition and other cerebral functions. Semin Vasc Med 2004, 4: 167–72.

    Article  PubMed  Google Scholar 

  21. Ranganath C, Heller A, Cohen MX, et al. Functional connectivity with the hippocampus during successful memory formation. Hippocampus 2005, 15: 997–1005.

    Article  PubMed  Google Scholar 

  22. Bonne O, Vythilingam M, Inagaki M, et al. Reduced posterior hippocampal volume in posttraumatic stress disorder. J Clin Psychiatry 2008, 69: 1087–91.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Johansson J, Larson G, Andersson M,et al. Treatment of growth hormone-deficient adults with recombinant human growth hormone increases concentration of growth hormone in cerebrospinal fluid and affects neurotransmitters. Neuroendocrinology 1995, 61: 57–66.

    Article  PubMed  CAS  Google Scholar 

  24. Schneider HJ, Pagotto U, Stalla GK. Central effects of the somatotropic system. Eur J Endocrinol 2003, 149: 377–92.

    Article  PubMed  CAS  Google Scholar 

  25. Newcomer J, Krystal J. NMDA receptor regulation of memory and behaviour in humans. Hippocampus 2001, 11: 529–42.

    Article  PubMed  CAS  Google Scholar 

  26. Lasaite L, Bunevicius R, Lasiene D, et al. Psychological functioning after growth hormone therapy in adult growth hormone deficient patients: endocrine and body composition correlates. Medicina (Kaunas) 2004, 40: 740–4.

    Google Scholar 

  27. Clayton P, Gleeson H, Monson J, et al. Growth hormone replacement throughout life: insights into age-related responses to treatment. Growth Horm IGF Res 2007, 17: 369–82.

    Article  PubMed  CAS  Google Scholar 

  28. Nilsson AG, Svensson JJ, Johannsson G. Management of growth hormone deficiency in adults. Growth Horm IGF Res 2007, 17: 441–62.

    Article  PubMed  CAS  Google Scholar 

  29. Huisman J, Aukema EJ, Deijen JB, et al. The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia: an open-label study. BMC Pediatrics 2008, 8: 25–32.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Psychiatry, UCC, Pasterova 2, Belgrade, 11000, Serbia

    Nadja P. Maric & M. Jasovic-Gasic

  2. School of Medicine, University of Belgrade, Belgrade, Serbia

    Nadja P. Maric, M. Doknic, D. Pavlovic, S. Pekic, M. Jasovic-Gasic & V. Popovic

  3. Institute for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center Belgrade, Belgrade, Serbia

    M. Doknic, S. Pekic, M. Stojanovic & V. Popovic

  4. Institute of Neurology, University Clinical Center Belgrade, Belgrade, Serbia

    D. Pavlovic

Authors
  1. Nadja P. Maric
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Doknic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Pavlovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Pekic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Stojanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Jasovic-Gasic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. Popovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nadja P. Maric.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maric, N.P., Doknic, M., Pavlovic, D. et al. Psychiatric and neuropsychological changes in growth hormone-deficient patients after traumatic brain injury in response to growth hormone therapy. J Endocrinol Invest 33, 770–775 (2010). https://doi.org/10.1007/BF03350340

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03350340

Key-words

Search

Navigation