J Psychiatry Neurosci 2013; 38(1):34-42
Trine Bjørg Hammer, MD, PhD; Bob Oranje, PhD; Arnold Skimminge, PhD; Bodil Aggernæs, MD, PhD; Bjørn H. Ebdrup, MD, PhD; Birte Glenthøj, MD, DMSc; William Baaré, PhD
Hammer, Orange, Aggernæs, Ebdrup, Glenthøj — Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Psychiatric Center Glostrup, Copenhagen University Hospital, Glostrup, Denmark; Skimminge, Baaré — Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
Background: Prepulse inhibition (PPI) of the startle reflex is modulated by a complex neural network. Prepulse inhibition impairments are found at all stages of schizophrenia. Previous magnetic resonance imaging (MRI) studies suggest that brain correlates of PPI differ between patients with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia.
Methods: We performed acoustic PPI assessment and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes.
Results: We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed in the left rostral dorsal premotor cortex, the right presupplementary motor area and the anterior medial superior frontal gyrus bilaterally. Follow-up analyses suggested that the rostral dorsal premotor cortex and presupplementary motor area correlations were driven predominantly by the controls.
Limitations: We used 2 different MRI scanners, which might have limited our ability to find subcortical associations since interscanner consistency is low for subcortical regions.
Conclusion: The superior parietal cortex seems to be involved in the regulation of PPI in controls and antipsychotic-naive men with first-episode schizophrenia. Our observation that PPI deficits in schizophrenia may be related to the rostral dorsal premotor cortex and presupplementary motor area, brain areas involved in maintaining relevant sensory information and voluntary inhibition, warrants further study.
Submitted Sept. 22, 2011; Revised Feb. 16, Mar. 31, 2012; Accepted Apr. 10, 2012.
Acknowledgements: This study was sponsored by The Danish Council for Independent Research | Medical Sciences, Gerhart Linds Foundation, Lundbeck Foundation, The Mental Health Service of the Capital Region of Denmark and Psykiatrisk Grundforskningsfond at Copenhagen University.
Competing interests: B. Glenthøj declares having received institutional grant support as listed above. None declared for T.B. Hammer, B. Oranje, A. Skimminge, B. AggernÃ¦s, B.H. Ebdrup and W. Baaré.
Contributors: T.B. Hammer, B. Oranje B. Aggernaes, B.H. Ebdrup, B Glenthøj and W. Barré designed the study. T.B. Hammer, B. Oranje, B. Aggernaes and W. Barré acquired and analysed the data. B.H. Ebdrup participated in data acquisition, and A. Skimminge and G. Glenthøj participated in data analysis. T.B. Hammer and B. Oranje wrote the article, which all authors reviewed and approved for publication.
Correspondence to: T.B. Hammer, Center for Neuropsychiatric Schizophrenia Research, University Psychiatric Center Glostrup, Ndr. Ringvej 29â€67, DKâ€2600 Glostrup, Denmark; firstname.lastname@example.org