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Neurological Soft Signs Show Robust Heritability and Familiality in Healthy Twins, Patients with Schizophrenia and Non-psychotic First-degree Relatives

Sep 21, 2015     Email"> PrintText Size

Neurological soft signs (NSS) have long been considered as promising endophenotypes (a biomarker for mental disorder with genetic linkage) for schizophrenia. However, to qualify as an endophenotype, a marker must be associated with the illness, heritable, state-independent, demonstrates co-segregation and familial association, and be reliable and valid. While ample evidence suggested NSS fulfill many of these criteria of endophenotypes for schizophrenia, there are several unresolved problems to be further validated. One of these is the examination of heritability of NSS in both healthy populations and patients with schizophrenia.

Dr. CHAN Raymond’s team from the Institute of Psychology of Chinese Academy of Sciences and his international collaborators conducted a study to examine the heritability and familiality of NSS in the Han Chinese population. They adopted a healthy twin design and combined this method with clinical patients and their non-psychotic first-degree relatives.

In the study, the abridged version of the Cambridge Neurological Inventory was administered to 267 pairs of monozygotic twins, 124 pairs of dizygotic twins, and 75 pairs of patients with schizophrenia and their first-degree relatives in order to examine their NSS performances. The classical method and structure equation model analysis was used to examine the heritability and familiality of NSS in their participants.

The results showed that NSS were robustly heritable in the healthy twins sample, especially for the items relating to the motor coordination and sensory integration (with heritability of 0.5-0.6). Their findings also showed that patients with schizophrenia correlated significantly with their first-degree relatives on NSS.

It should be noted that the heritability of NSS they found in both healthy twins group and patient-relative pairs group were comparable to those reported by the Consortium on the Genetics of Schizophrenia (COGS), around 0.3-0.4. The COGS is an international consortium specifically established for the study of endophenotypes for schizophrenia. Unfortunately, the COGS did not include NSS in their assessment regime.

Substantial evidence suggested that clinical features and NSS share many similarities, or may even be equivalent in characterizing the different stages of the schizophrenic illness both behaviorally and morphologically. Given the brevity of NSS administration comparing to conventional neurocognitive assessment, NSS are informative endophenotype and have been incorporated into the assessment regime for schizophrenia in the early psychosis program jointly run by Dr. CHAN and Drs. CHEUNG Eric and LUI Simon from Castle Peak Hospital in Hong Kong.

NSS are also the key elements of the Consortium for the Human Information and Neurocognitive Endophenotype (CHINE) established by Dr. CHAN. The CHINE is intentionally established to pave the roadmap for neuropsychiatric disorders research. It not only identifies the biosignatures for neuropsychiatric disorders, but also serves as the central databank for examining the etiologies of major complex neuropsychiatric disorders and serving as the main basis for corresponding treatment development.

This study was supported by grants from the National Science Foundation of China Outstanding Investigator Award, the Beijing Training Project for the Leading Talents in S & T, and the CAS/SAFEA International Partnership Program for Creative Research Teams.

The paper is available on Psychological Medicine.


(Editor: CHEN Na)


CHAN Raymond

Institute of Psychology

E-mail: rckchan@psych.ac.cn

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