Emerging data indicate that growth hormone (GH) therapy could have a role in improving cognitive function. GH replacement therapy in experimental animals and human patients counteracts the dysfunction of many behaviours related to the central nervous system (CNS). Various behaviours, such as cognitive behaviours related to learning and memory, are known to be induced by GH; the hormone might interact with specific receptors located in areas of the CNS that are associated with the functional anatomy of these behaviours. GH is believed to affect excitatory circuits involved in synaptic plasticity, which alters cognitive capacity. GH also has a protective effect on the CNS, as indicated by its beneficial effects in patients with spinal cord injury. Data collected from animal models indicates that GH might also stimulate neurogenesis. This Review discusses the mechanisms underlying the interactions between GH and the CNS, and the data emerging from animal and human studies on the relationship between GH and cognitive function. In this article, particular emphasis is given to the role of GH as a treatment for patients with cognitive impairment resulting from deficiency of the hormone.
Growth hormone has profound effects on brain function in both humans and experimental animals; in humans, this effect is particularly seen in patients receiving growth hormone replacement therapy
Growth hormone receptors are present in the brain, particularly in areas of importance for cognition, as shown in humans and rodents
Treatment with growth hormone can improve certain components of cognition in growth-hormone-deficient individuals
The effects of growth hormone on cognitive function are mediated through interactions with the N-methyl-D-aspartate receptor complex, which leads to an increase in long-term potentiation
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Pavelic, J., Matijevic, T. & Knezevic, J. Biological & physiological aspects of action of insulin-like growth factor peptide family. Indian J. Med. Res. 125, 511–522 (2007).
Chao, W. & D'Amore, P. A. IGF2: epigenetic regulation and role in development and disease. Cytokine Growth Factor Rev. 19, 111–120 (2008).
Nyberg, F. The role of the somatotrophic axis in neuroprotection and neuroregeneration of the addictive brain. Int. Rev. Neurobiol. 88, 399–427 (2009).
Aberg, D. Role of the growth hormone/insulin-like growth factor 1 axis in neurogenesis. Endocr. Dev. 17, 63–76 (2010).
Bengtsson, B. A. et al. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J. Clin. Endocrinol. Metab. 76, 309–317 (1993).
van Nieuwpoort, I. C. & Drent, M. L. Cognition in the adult with childhood-onset GH deficiency. Eur. J. Endocrinol. 159 (Suppl. 1), S53–S57 (2008).
Burman, P. & Deijen, J. B. Quality of life and cognitive function in patients with pituitary insufficiency. Psychother. Psychosom. 67, 154–167 (1998).
Maruff, P. & Falleti, M. Cognitive function in growth hormone deficiency and growth hormone replacement. Horm. Res. 64 (Suppl. 3), 100–108 (2005).
Salvatori, R. Clinical management of growth hormone therapy in adults. Manag. Care 18 (Suppl. 6), 10–16 (2009).
Deijen, J. B., de Boer, H. & van der Veen, E. A. Cognitive changes during growth hormone replacement in adult men. Psychoneuroendocrinology 23, 45–55 (1998).
Le Greves, M. et al. Growth hormone replacement in hypophysectomized rats affects spatial performance and hippocampal levels of NMDA receptor subunit and PSD-95 gene transcript levels. Exp. Brain Res. 173, 267–273 (2006).
Sathiavageeswaran, M. et al. Effects of GH on cognitive function in elderly patients with adult-onset GH deficiency: a placebo-controlled 12-month study. Eur. J. Endocrinol. 156, 439–447 (2007).
Johansson, J. O. et al. Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters. Neuroendocrinology 61, 57–66 (1995).
Burman, P. et al. Growth hormone treatment affects brain neurotransmitters and thyroxine [see comment]. Clin. Endocrinol. (Oxf.) 44, 319–324 (1996).
Nyberg, F. Growth hormone in the brain: characteristics of specific brain targets for the hormone and their functional significance. Front. Neuroendocrinol. 21, 330–348 (2000).
Zhai, Q., Lai, Z., Roos, P. & Nyberg, F. Characterization of growth hormone binding sites in rat brain. Acta Paediatr. Suppl. 406, 92–95 (1994).
Kwak, M. J. et al. Comparative study of the effects of different growth hormone doses on growth and spatial performance of hypophysectomized rats. J. Korean Med. Sci. 24, 729–736 (2009).
Eichenbaum, H. Declarative memory: insights from cognitive neurobiology. Annu. Rev. Psychol. 48, 547–572 (1997).
Eichenbaum, H. & Fortin, N. J. The neurobiology of memory based predictions. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 1183–1191 (2009).
Bliss, T. V. & Cooke, S. F. Long-term potentiation and long-term depression: a clinical perspective. Clinics (Sao Paulo) 66 (Suppl. 1), 13–17 (2011).
Kenney, J. W. & Gould, T. J. Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol. Neurobiol. 38, 101–121 (2008).
Santini, E., Muller, R. U. & Quirk, G. J. Consolidation of extinction learning involves transfer from NMDA-independent to NMDA-dependent memory. J. Neurosci. 21, 9009–9017 (2001).
Glannon, W. Psychopharmacology and memory. J. Med. Ethics 32, 74–78 (2006).
Kim, J. & Lee, I. Hippocampus is necessary for spatial discrimination using distal cue-configuration. Hippocampus 21, 609–621 (2011).
Andersson, K. et al. Rat growth hormone and hypothalamic catecholamine nerve terminal systems. Evidence for rapid and discrete reductions in dopamine and noradrenaline levels and turnover in the median eminence of the hypophysectomized male rat. Eur. J. Pharmacol. 95, 271–275 (1983).
Frohman, L. A., Nernardis, L. L. & Kant, K. J. Hypothalamic stimulation of growth hormone secretion. Science 162, 580–582 (1968).
van Houten, M., Posner, B. I. & Walsh, R. J. Radioautographic identification of lactogen binding sites in rat median eminence using 125I-human growth hormone: evidence for a prolactin “short-loop” feedback site. Exp. Brain Res. 38, 455–461 (1980).
Lai, Z. et al. Age-related reduction of human growth hormone-binding sites in the human brain. Brain Res. 621, 260–266 (1993).
Thornwall-Le Greves, M. et al. Morphine decreases the levels of the gene transcripts of growth hormone receptor and growth hormone binding protein in the male rat hippocampus and spinal cord. Neurosci. Lett. 304, 69–72 (2001).
Enhamre-Brolin, E., Carlsson, A., Hallberg, M. & Nyberg, F. Growth hormone reverses streptozotocin-induced cognitive impairments in male mice. Behav. Brain Res. 238, 273–278 (2012).
Enhamre, E. et al. The expression of growth hormone receptor gene transcript in the prefrontal cortex is affected in male mice with diabetes-induced learning impairments. Neurosci. Lett. 523, 82–86 (2012).
Coculescu, M. Blood-brain barrier for human growth hormone and insulin-like growth factor-I. J. Pediatr. Endocrinol. Metab. 12, 113–124 (1999).
Pan, W. et al. Permeation of growth hormone across the blood-brain barrier. Endocrinology 146, 4898–4904 (2005).
Pan, W. & Kastin, A. J. Interactions of IGF-1 with the blood-brain barrier in vivo and in situ. Neuroendocrinology 72, 171–178 (2000).
McGauley, G. A. Quality of life assessment before and after growth hormone treatment in adults with growth hormone deficiency. Acta Paediatr. Scand. Suppl. 356, 70–72 (1989).
Jorgensen, J. O. et al. Adult growth hormone deficiency. Horm. Res. 42, 235–241 (1994).
Rosen, T., Wiren, L., Wilhelmsen, L., Wiklund, I. & Bengtsson, B. A. Decreased psychological well-being in adult patients with growth hormone deficiency. Clin. Endocrinol. (Oxf.) 40, 111–116 (1994).
McGauley, G., Cuneo, R., Salomon, F. & Sonksen, P. H. Growth hormone deficiency and quality of life. Horm. Res. 45, 34–37 (1996).
Burman, P., Johansson, A. G., Siegbahn, A., Vessby, B. & Karlsson, F. A. Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J. Clin. Endocrinol. Metab. 82, 550–555 (1997).
Falleti, M. G., Maruff, P., Burman, P. & Harris, A. The effects of growth hormone (GH) deficiency and GH replacement on cognitive performance in adults: a meta-analysis of the current literature. Psychoneuroendocrinology 31, 681–691 (2006).
Webb, S. M. Measurements of quality of life in patients with growth hormone deficiency. J. Endocrinol. Invest. 31 (9 Suppl.), 52–55 (2008).
Geisler, A. et al. Quality of life in children and adolescents with growth hormone deficiency: association with growth hormone treatment. Horm. Res. Paediatr. 78, 94–99 (2012).
Chaplin, J. E. et al. Improvements in behaviour and self-esteem following growth hormone treatment in short prepubertal children. Horm. Res. Paediatr. 75, 291–303 (2011).
Deijen, J. B., de Boer, H., Blok, G. J. & van der Veen, E. A. Cognitive impairments and mood disturbances in growth hormone deficient men. Psychoneuroendocrinology 21, 313–322 (1996).
Arwert, L. I. et al. Growth hormone deficiency and memory functioning in adults visualized by functional magnetic resonance imaging. Neuroendocrinology 82, 32–40 (2005).
Arwert, L. I., Veltman, D. J., Deijen, J. B., van Dam, P. S. & Drent, M. L. Effects of growth hormone substitution therapy on cognitive functioning in growth hormone deficient patients: a functional MRI study. Neuroendocrinology 83, 12–19 (2006).
Schneider-Rivas, S., Rivas-Arancibia, S., Vazquez-Pereyra, F., Vazquez-Sandoval, R. & Borgonio-Perez, G. Modulation of long-term memory and extinction responses induced by growth hormone (GH) and growth hormone releasing hormone (GHRH) in rats. Life Sci. 56, PL433–PL441 (1995).
Ariznavarreta, C. et al. Growth hormone and aging. Homo 54, 132–141 (2003).
Molina, D. P., Ariwodola, O. J., Weiner, J. L., Brunso-Bechtold, J. K. & Adams, M. M. Growth hormone and insulin-like growth factor-I alter hippocampal excitatory synaptic transmission in young and old rats. Age (Dordr) http://dx.doi.org/10.1007/s11357-012-9460-4.
Sonntag, W. E. et al. The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing. J. Anat. 197, 575–585 (2000).
Schliebs, R. & Arendt, T. The cholinergic system in aging and neuronal degeneration. Behav. Brain Res. 221, 555–563 (2011).
Magnusson, K. R. Aging of the NMDA receptor: from a mouse's point of view. Future Neurol. 7, 627–637 (2012).
Stanley, E. M., Fadel, J. R. & Mott, D. D. Interneuron loss reduces dendritic inhibition and GABA release in hippocampus of aged rats. Neurobiol. Aging 33, e431–e413 (2012).
Li, E. et al. Hippocampus-dependent spatial learning and memory are impaired in growth hormone-deficient spontaneous dwarf rats. Endocr. J. 58, 257–267 (2011).
Witty, C. F., Gardella, L. P., Perez, M. C. & Daniel, J. M. Short-term estradiol administration in aging ovariectomized rats provides lasting benefits for memory and the hippocampus: a role for insulin-like growth factor-I. Endocrinology 154, 842–852 (2013).
Le Greves, M. et al. Growth hormone enhances cognitive functions in hypophysectomized rats. Am. J. Neuroprot. Neuroregen 3, 53–58 (2011).
Gronbladh, A., Johansson, J., Nostl, A., Nyberg, F. J. & Hallberg, M. Growth hormone improves spatial memory and reverses certain anabolic androgenic steroid-induced effects in intact rats. J. Endocrinol. 216, 31–41 (2013).
Li, R. C. et al. Exogenous growth hormone attenuates cognitive deficits induced by intermittent hypoxia in rats. Neuroscience 196, 237–250 (2011).
Abel, T. & Lattal, K. M. Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr. Opin. Neurobiol. 11, 180–187 (2001).
Sonntag, W. E., Ramsey, M. & Carter, C. S. Growth hormone and insulin-like growth factor-1 (IGF-1) and their influence on cognitive aging. Ageing Res. Rev. 4, 195–212 (2005).
Kim, E., Grover, L. M., Bertolotti, D. & Green, T. L. Growth hormone rescues hippocampal synaptic function after sleep deprivation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298, R1588–R1596 (2010).
Park, S. W. et al. Differential effects of insufflated, subcutaneous, and intravenous growth hormone on bone growth, cognitive function, and NMDA receptor subunit expression. Endocrinology 151, 4418–4427 (2010).
Magnusson, K. R., Das, S. R., Kronemann, D., Bartke, A. & Patrylo, P. R. The effects of aging and genotype on NMDA receptor expression in growth hormone receptor knockout (GHRKO) mice. J. Gerontol. A Biol. Sci. Med. Sci. 66, 607–619 (2011).
Monaghan, D. T. & Cotman, C. W. Distribution of N-methyl-D-aspartate-sensitive L-[3H]glutamate-binding sites in rat brain. J. Neurosci. 5, 2909–2919 (1985).
Conti, F., Minelli, A., DeBiasi, S. & Melone, M. Neuronal and glial localization of NMDA receptors in the cerebral cortex. Mol. Neurobiol. 14, 1–18 (1997).
Lynch, G., Kessler, M., Arai, A. & Larson, J. The nature and causes of hippocampal long-term potentiation. Prog. Brain Res. 83, 233–250 (1990).
Kang, S. J. et al. Plasticity of metabotropic glutamate receptor-dependent long-term depression in the anterior cingulate cortex after amputation. J. Neurosci. 32, 11318–11329 (2012).
Zorumski, C. F. & Izumi, Y. NMDA receptors and metaplasticity: mechanisms and possible roles in neuropsychiatric disorders. Neurosci. Biobehav. Rev. 36, 989–1000 (2012).
Kauer, J. A., Malenka, R. C. & Nicoll, R. A. NMDA application potentiates synaptic transmission in the hippocampus. Nature 334, 250–252 (1988).
MacDonald, J. F., Jackson, M. F. & Beazely, M. A. Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors. Crit. Rev. Neurobiol. 18, 71–84 (2006).
Zhao, M. G. et al. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron 47, 859–872 (2005).
Cui, Y. et al. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice. PLoS ONE 6, e20312 (2011).
Morris, R. G., Anderson, E., Lynch, G. S. & Baudry, M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319, 774–776 (1986).
Bashir, Z. I., Alford, S., Davies, S. N., Randall, A. D. & Collingridge, G. L. Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus. Nature 349, 156–158 (1991).
Mallon, A. P., Auberson, Y. P. & Stone, T. W. Selective subunit antagonists suggest an inhibitory relationship between NR2B and NR2A-subunit containing N-methyl-D: -aspartate receptors in hippocampal slices. Exp. Brain Res. 162, 374–383 (2005).
Ogden, K. K. & Traynelis, S. F. New advances in NMDA receptor pharmacology. Trends Pharmacol. Sci. 32, 726–733 (2011).
Henson, M. A., Roberts, A. C., Pérez-Otaño, I. & Philpot, B. D. Influence of the NR3A subunit on NMDA receptor functions. Prog. Neurobiol. 91, 23–27 (2010).
Lee, Y. S. & Silva, A. J. The molecular and cellular biology of enhanced cognition. Nat. Rev. Neurosci. 10, 126–140 (2009).
Le Greves, M., Steensland, P., Le Greves, P. & Nyberg, F. Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N-methyl-D-aspartate receptor subunits gene transcripts in male rats. Proc. Natl Acad. Sci. USA 99, 7119–7123 (2002).
Mahmoud, G. S. & Grover, L. M. Growth hormone enhances excitatory synaptic transmission in area CA1 of rat hippocampus. J. Neurophysiol. 95, 2962–2974 (2006).
Le Greves, M., Le Greves, P. & Nyberg, F. Age-related effects of IGF-1 on the NMDA-, GH- and IGF-1-receptor mRNA transcripts in the rat hippocampus. Brain Res. Bull. 65, 369–374 (2005).
Tang, Y. P. et al. Genetic enhancement of learning and memory in mice. Nature 401, 63–69 (1999).
Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P. & Grant, S. G. Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat. Neurosci. 3, 661–669 (2000).
Sheng, M. The postsynaptic NMDA-receptor--PSD-95 signaling complex in excitatory synapses of the brain. J. Cell Sci. 114, 1251 (2001).
Muller, B. M. et al. SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo. Neuron 17, 255–265 (1996).
Kornau, H. C., Schenker, L. T., Kennedy, M. B. & Seeburg, P. H. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269, 1737–1740 (1995).
O'Brien, R. J., Lau, L. F. & Huganir, R. L. Molecular mechanisms of glutamate receptor clustering at excitatory synapses. Curr. Opin. Neurobiol. 8, 364–369 (1998).
Muller, D., Toni, N. & Buchs, P. A. Spine changes associated with long-term potentiation. Hippocampus 10, 596–604 (2000).
Medvedev, N. I. et al. The N-methyl-D-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat. Neuroscience 165, 1170–1181 (2010).
Ramsey, M. M., Weiner, J. L., Moore, T. P., Carter, C. S. & Sonntag, W. E. Growth hormone treatment attenuates age-related changes in hippocampal short-term plasticity and spatial learning. Neuroscience 129, 119–127 (2004).
Helm, K. A. et al. GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. Neuropharmacology 48, 956–964 (2005).
Lasarge, C. L., Banuelos, C., Mayse, J. D. & Bizon, J. L. Blockade of GABA(B) receptors completely reverses age-related learning impairment. Neuroscience 164, 941–947 (2009).
Gronbladh, A., Johansson, J., Nyberg, F. & Hallberg, M. Recombinant human growth hormone affects the density and functionality of GABA(B) receptors in the male rat brain. Neuroendocrinology http://dx.doi.org/10.1159/000339821.
Johansson, J., Gronbladh, A., Nyberg, F. & Hallberg, M. Application of in vitro [35S]GTPγ-S autoradiography in studies of growth hormone effects on opioid receptors in the male rat brain. Brain Res. Bull. 90, 100–106 (2013).
Persson, A. I. et al. Differential regulation of hippocampal progenitor proliferation by opioid receptor antagonists in running and non-running spontaneously hypertensive rats. Eur. J. Neurosci. 19, 1847–1855 (2004).
Aberg, N. D., Brywe, K. G. & Isgaard, J. Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the adult brain. ScientificWorldJournal 6, 53–80 (2006).
Ransome, M. I., Goldshmit, Y., Bartlett, P. F., Waters, M. J. & Turnley, A. M. Comparative analysis of CNS populations in knockout mice with altered growth hormone responsiveness. Eur. J. Neurosci. 19, 2069–2079 (2004).
Svensson, A. L., Bucht, N., Hallberg, M. & Nyberg, F. Reversal of opiate-induced apoptosis by human recombinant growth hormone in murine foetus primary hippocampal neuronal cell cultures. Proc. Natl Acad. Sci. USA 105, 7304–7308 (2008).
Zhu, T., Goh, E. L., Graichen, R., Ling, L. & Lobie, P. E. Signal transduction via the growth hormone receptor. Cell Signal. 13, 599–616 (2001).
Orellana, D. I., Quintanilla, R. A., Gonzalez-Billault, C. & Maccioni, R. B. Role of the JAKs/STATs pathway in the intracellular calcium changes induced by interleukin-6 in hippocampal neurons. Neurotox. Res. 8, 295–304 (2005).
Kasagi, Y., Tokita, R., Nakata, T., Imaki, T. & Minami, S. Human growth hormone induces SOCS3 and CIS mRNA increase in the hypothalamic neurons of hypophysectomized rats. Endocr. J. 51, 145–154 (2004).
Scott, H. J. et al. Differential effects of SOCS2 on neuronal differentiation and morphology. Brain Res. 1067, 138–145 (2006).
Leung, K. C. et al. Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proc. Natl Acad. Sci. USA 100, 1016–1021 (2003).
Garcia-Segura, L. M., Arevalo, M. A. & Azcoitia, I. Interactions of estradiol and insulin-like growth factor-I signalling in the nervous system: new advances. Prog. Brain Res. 181, 251–272 (2010).
O'Kusky, J. & Ye, P. Neurodevelopmental effects of insulin-like growth factor signaling. Front. Neuroendocrinol. 33, 230–251 (2012).
Alberini, C. M. & Chen, D. Y. Memory enhancement: consolidation, reconsolidation and insulin-like growth factor 2. Trends Neurosci. 35, 274–283 (2012).
Chen, D. Y. et al. A critical role for IGF-II in memory consolidation and enhancement. Nature 469, 491–497 (2011).
Miltiadous, P., Stamatakis, A., Koutsoudaki, P. N., Tiniakos, D. G. & Stylianopoulou, F. IGF-I ameliorates hippocampal neurodegeneration and protects against cognitive deficits in an animal model of temporal lobe epilepsy. Exp. Neurol. 231, 223–235 (2011).
Torres Aleman, I. Insulin-like growth factor-1 and central neurodegenerative diseases. Endocrinol. Metab. Clin. North Am. 41, 395–408 (2012).
Graff, J. & Tsai, L. H. Cognitive enhancement: A molecular memory booster. Nature 469, 474–475 (2011).
Johannsson, G. Treatment of growth hormone deficiency in adults. Horm. Res. 71 (Suppl. 1), 116–122 (2009).
Lipworth, W. L., Ho, K., Kerridge, I. H. & Day, R. O. Drug policy at the margins: the case of growth hormone replacement for adults with severe growth hormone deficiency. Med. J. Aust. 197, 204–205 (2012).
Reimunde, P. et al. Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. Brain Inj. 25, 65–73 (2011).
Siemensma, E. P. et al. Beneficial effects of growth hormone treatment on cognition in children with Prader-Willi syndrome: a randomized controlled trial and longitudinal study. J. Clin. Endocrinol. Metab. 97, 2307–2314 (2012).
Baum, H. B. et al. Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency. J. Clin. Endocrinol. Metab. 83, 3184–3189 (1998).
Kokshoorn, N. E. et al. GH replacement therapy in elderly GH-deficient patients: a systematic review. Eur. J. Endocrinol. 164, 657–665 (2011).
Brummelman, P. et al. Effects of previous growth hormone excess and current medical treatment for acromegaly on cognition. Eur. J. Clin. Invest. 42, 1317–1324 (2012).
Maric, N. P. 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).
Baker, L. D. et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Arch. Neurol. 60, 1420–1429 (2012).
Bennett, R. M. Adult growth hormone deficiency in patients with fibromyalgia. Curr. Rheumatol. Rep. 4, 306–312 (2002).
Bennett, R. M., Clark, S. C. & Walczyk, J. A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia. Am. J. Med. 104, 227–231 (1998).
Cuatrecasas, G. et al. High prevalence of growth hormone deficiency in severe fibromyalgia syndromes. J. Clin. Endocrinol. Metab. 95, 4331–4337 (2010).
Glass, J. M. Review of cognitive dysfunction in fibromyalgia: a convergence on working memory and attentional control impairments. Rheum. Dis. Clin. North Am. 35, 299–311 (2009).
Kim, S. H. et al. Spatial versus verbal memory impairments in patients with fibromyalgia. Rheumatol. Int. 32, 1135–1142 (2012).
Donahue, C. P., Kosik, K. S. & Shors, T. J. Growth hormone is produced within the hippocampus where it responds to age, sex, and stress. Proc. Natl Acad. Sci. USA 103, 6031–6036 (2006).
This study was supported by grants from the Swedish Medical Research Council (Grant 9459) and from the Swedish Council for Working Life and Social Research.
The authors declare no competing financial interests.
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Nyberg, F., Hallberg, M. Growth hormone and cognitive function. Nat Rev Endocrinol 9, 357–365 (2013). https://doi.org/10.1038/nrendo.2013.78
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