Anomalous basal ganglia connectivity and obsessive–compulsive behaviour in patients with Prader Willi syndrome

Anomalous basal ganglia connectivity and obsessive–compulsive behaviour in patients with Prader Willi syndrome

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J Psychiatry Neurosci 2016;41(4):261-271

Jesus Pujol, MD; Laura Blanco-Hinojo, MSc; Susanna Esteba-Castillo, PhD; Assumpta Caixàs, MD; Ben J. Harrison, PhD; Marta Bueno, MSc; Joan Deus, PhD; Mercedes Rigla, MSc; Dídac Macià, MSc; Jone Llorente-Onaindia, MSc; Ramón Novell-Alsina, MD


Background: Prader Willi syndrome is a genetic disorder with a behavioural expression characterized by the presence of obsessive–compulsive phenomena ranging from elaborate obsessive eating behaviour to repetitive skin picking. Obsessive–compulsive disorder (OCD) has been recently associated with abnormal functional coupling between the frontal cortex and basal ganglia. We have tested the potential association of functional connectivity anomalies in basal ganglia circuits with obsessive–compulsive behaviour in patients with Prader Willi syndrome.

Methods: We analyzed resting-state functional MRI in adult patients and healthy controls. Whole-brain functional connectivity maps were generated for the dorsal and ventral aspects of the caudate nucleus and putamen. A selected obsessive–compulsive behaviour assessment included typical OCD compulsions, self picking and obsessive eating behaviour.

Results: We included 24 adults with Prader Willi syndrome and 29 controls in our study. Patients with Prader Willi syndrome showed abnormal functional connectivity between the prefrontal cortex and basal ganglia and within subcortical structures that correlated with the presence and severity of obsessive–compulsive behaviours. In addition, abnormally heightened functional connectivity was identified in the primary sensorimotor cortex–putamen loop, which was strongly associated with self picking. Finally, obsessive eating behaviour correlated with abnormal functional connectivity both within the basal ganglia loops and between the striatum and the hypothalamus and the amygdala.

Limitations: Limitations of the study include the difficulty in evaluating the nature of content of obsessions in patients with Prader Willi Syndrome and the risk of excessive head motion artifact on brain imaging.

Conclusion: Patients with Prader Willi syndrome showed broad functional connectivity anomalies combining prefrontal loop alterations characteristic of OCD with 1) enhanced coupling in the primary sensorimotor loop that correlated with the most impulsive aspects of the behaviour and 2) reduced coupling of the ventral striatum with limbic structures for basic internal homeostasis that correlated with the obsession to eat.

Submitted Nov. 14, 2014; Revised July 22, 2015; Accepted Sept. 2, 2015; Early-released Dec. 8, 2015

Acknowledgements: This study was supported in part by the Fondo de Investigación Santiaria del Instituto Carlos III (Grant PI-10/00940) and Fundació Parc Taulí (Grants CIR 2010/006 and CIR 2011/004). The Agency of University and Research Funding Management of the Catalonia Government participated in the context of Research Group SGR2014-1673. L. Blanco-Hinojo was supported by the PFIS grant FI10/00387 from the Fondo de Investigación Santiaria del Instituto Carlos III. Dr. B. Harrison was supported by a National Health and Medical Research Council (NHMRC, Australia) Clinical Career Development Fellowship (628509). We thank the Associació Catalana de Síndrome de Prader-Willi, Fundación Síndrome de Prader-Willi and all the patients and their families for agreeing to participate.

Affiliations: From the MRI Research Unit, CRC Mar, Hospital del Mar, Barcelona, Spain (Pujol, Blanco-Hinojo, Deus, Macià); the Centro Investigación Biomédica en Red de Salud Mental, CIBERSAM G21, Barcelona, Spain (Pujol); the Human Pharmacology and Clinical Neurosciences, Hospital del Mar Medical Research Institute, Barcelona, Spain (Blanco-Hinojo); the Parc Hospitalari Martí i Julià, Salt, Girona, Spain (Esteba-Castillo, Novell-Alsina); the Endocrinology and Nutrition Department. Sabadell University Hospital (UAB), Corporació Sanitària Parc Taulí, Sabadell, Spain (Caixàs, Rigla); the Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, Australia (Harrison); the Endocrinology and Nutrition Department, University Hospital Arnau de Vilanova, Lleida, Spain (Bueno); the Department of Clinical and Health Psychology, Autonomous University of Barcelona, Spain (Deus); and the Rheumatology Department, Hospital del Mar, Barcelona, Spain (Onaindia).

Competing interests: None declared.

Contributors: J. Pujol, S. Esteba-Castillo, A. Caixàs, J. Deus and R. Novell-Alsina designed the study. S. Esteba-Castillo, A. Caixàs, M. Bueno, M. Rigla and J. Llorente-Onaindia acquired the data, which J. Pujol, L. Blanco-Hinojo, B. Harrison, D. Macià and R. Novell-Alsina analyzed. J. Pujol, L. Blanco-Hinojo, A. Caixàs and B. Harrison wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140338

Correspondence to: J. Pujol, MRI Department, CRC-Mar, Hospital del Mar, Passeig Marítim 25-29. 08003, Barcelona;