Abstract
Background All perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear.
Methods We studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T structural magnetic resonance (MR) imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS) from MR images and constructed cortical folding covariance matrices organized by large-scale networks.
Results In both ethnic groups, we replicated a significantly shorter left PCS in patients with hallucinations compared to those without, and healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks.
Conclusion The discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins.
Competing Interest Statement
JS reports personal fees from GW Pharmaceuticals outside the submitted work. BD reports personal fees from Autifony outside the submitted work. All other authors declare no competing interests.
Funding Statement
The authors were supported by grants and scholarships from the following sources: Gates Cambridge (CPER), National Key Research and Development Program (2016YFC0906402) (RCKC), National Science Fund China (81571317) (RCKC), the CAS Key Laboratory of Mental Health, Institute of Psychology (RCKC). Neuroimaging data was processed and archived on the University of Cambridge High Performance Hub for Clinical Informatics (HPHI), which was funded by part of the MRC Clinical Research Infrastructure Award (MR/M009041/1). The funders had no input in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The current manuscript re-purposes two MRI datasets from independent studies of patients with recent-onset schizophrenia who underwent clinical assessment and 3T structural neuroimaging: (1) a predominantly White British sample assessed at multiple sites in the UK and; (2) a Han Chinese sample assessed in Shanghai, China. Studies were approved by the North West Manchester NHS Research Ethics Committee and Shanghai Mental Health Centre and the Institute of Psychology, respectively. Both studies have been published and include further details of ethical approval.
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
The datasets reported in this manuscript are not publicly available because of lack of informed consent and ethical approval. Requests for sharing the anonymised datasets should be addressed to BD for the UK sample and RCKC for the Shanghai sample. Data analysis scripts and result files are available upon request, which should be addressed to the lead author.