Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional connectivity with other brain regions. Thus, the aim of this study was to examine the anatomical differences of the hypothalamus, mammillary bodies, and pituitary gland as well as resting state functional connectivity of the hypothalamus in children with PWS.
Twenty-seven children with PWS (13 DEL, 14 mUPD) and 28 typically developing children were included. Manual segmentations by a blinded investigator were performed to determine the volumes of the hypothalamus, mammillary bodies, and pituitary gland. In addition, brain-wide functional connectivity analysis was performed using the obtained masks of the hypothalamus.
Children with PWS showed altered resting state functional connectivity between hypothalamus and right and left lateral occipital complex, compared to healthy controls. In addition, children with PWS had on average a 50% smaller pituitary volume, an irregular shape of the pituitary, and a longer pituitary stalk. Pituitary volume did not increase in volume during puberty in PWS. No volumetric differences in the hypothalamus and mammillary bodies were found. In all subjects, the posterior pituitary bright spot was observed.
We report altered functional hypothalamic connectivity with lateral occipital complexes in both hemispheres, which are implicated in response to food and reward system, and absence of connectivity might therefore at least partially contribute to the preoccupation with food in PWS.
Siemensma EPC, de Lind van Wijngaarden RFA, Otten BJ, de Jong FH, Hokken-Koelega ACS. Testicular failure in boys with Prader-Willi syndrome: longitudinal studies of reproductive hormones. J Clin Endocrinol Metaboli. 2012;97(3):E452–E9. CrossRef
Siemensma EPC, van Alfen-van der Velden AAEM, Otten BJ, Laven JSE, Hokken-Koelega ACS. Ovarian function and reproductive hormone levels in girls with Prader-Willi syndrome: a longitudinal study. J Clin Endocrinol Metaboli. 2012;97(9):E1766–E73. CrossRef
Bakker NE, Kuppens RJ, Siemensma EPC, van Wijngaarden RFA T-de L, Festen DAM, Bindels-de Heus GCB, et al. Eight years of growth hormone treatment in children with Prader-Willi syndrome: maintaining the positive effects. Journal of Clinical Endocrinology & Metabolism. 2013;98(10):4013–22. CrossRef
de Lind van Wijngaarden RF, Otten BJ, Festen DA, Joosten KF, de Jong FH, Sweep FC, et al. High prevalence of central adrenal insufficiency in patients with Prader-Willi syndrome. J Clin Endocrinol Metab. 2008;93(5):1649–54. CrossRef
Vaiani E, Herzovich V, Chaler E, Chertkoff L, Rivarola MA, Torrado M, et al. Thyroid axis dysfunction in patients with Prader-Willi syndrome during the first 2 years of life. Clin Endocrinol. 2010;73(4):546–50.
Festen DA, Visser TJ, Otten BJ, Wit JM, Duivenvoorden HJ, Hokken-Koelega AC. Thyroid hormone levels in children with Prader-Willi syndrome before and during growth hormone treatment. Clin Endocrinol (Oxf). 2007;67(3):449–56. CrossRef
Tauber M, Barbeau C, Jouret B, Pienkowski C, Malzac P, Moncla A, et al. Auxological and endocrine evolution of 28 children with Prader-Willi syndrome: effect of GH therapy in 14 children. Horm Res Paediatr. 2000;53(6):279–87. CrossRef
Klomp A, Koolschijn PCMP, Hulshoff Pol HE, Kahn RS, Van Haren NEM. Hypothalamus and pituitary volume in schizophrenia: a structural MRI study. Int J Neuropsychopharmacol. 2012;15(02):281–8.
Lemaire J-J, Nezzar H, Sakka L, Boirie Y, Fontaine D, Coste A, et al. Maps of the adult human hypothalamus. Surg Neurol Int. 2013;4 Suppl 3:S156.
Festen DA, Wevers M, Lindgren AC, Bohm B, Otten BJ, Wit JM, et al. Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome. Clin Endocrinol (Oxf). 2008;68(6):919–25. CrossRef
- Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome
Suzanne E. van Dijk
Gerbrich E. van den Bosch
Aad van der Lugt
Anita C. Hokken-Koelega
- BioMed Central