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Logo of bmcpsycBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Psychiatry
BMC Psychiatry. 2011; 11: 139.
Published online Aug 22, 2011. doi:  10.1186/1471-244X-11-139
PMCID: PMC3173301
A systematic review and meta-analysis of neurological soft signs in relatives of people with schizophrenia
Kishen Neelam,corresponding author1,2,3 Deepak Garg,4 and Max Marshall1,3
1Lantern centre, University of Manchester, Vicarage Lane, Preston, PR2 8DY, UK
2Greater Manchester West Mental Health NHS Foundation Trust, Bury New Road, Prestwich, Manchester, M25 3BL, UK
3Lancashire Care NHS Foundation Trust, Walton Summit, Preston, PR5 6AW, UK
4Humber NHS Foundation Trust, Clarendon Health Centre (Victoria House), Park Street, Hull, HU2 8TD, UK
corresponding authorCorresponding author.
Kishen Neelam: kishen.neelam/at/; Deepak Garg: deegarg/at/; Max Marshall: max.marshall/at/
Received June 2, 2010; Accepted August 22, 2011.
Neurological soft signs are subtle but observable impairments in motor and sensory functions that are not localized to a specific area of the brain. Neurological soft signs are common in schizophrenia. It has been established that soft signs meet two of five criteria for an endophenotype, namely: association with the illness, and state independence. This review investigated whether soft signs met a further criterion for an endophenotype, namely familial association. It was hypothesized that if familial association were present then neurological soft signs would be: (a) more common in first-degree relatives of people with schizophrenia than in controls; and (b) more common in people with schizophrenia than in their first-degree relatives.
A systematic search identified potentially eligible studies in the EMBASE (1980-2011), OVID - MEDLINE (1950-2011) and PsycINFO (1806-2011) databases. Studies were included if they carried out a three-way comparison of levels of soft signs between people with schizophrenia, their first-degree relatives, and normal controls. Data were extracted independently by two reviewers and cross-checked by double entry.
After screening 8678 abstracts, seven studies with 1553 participants were identified. Neurological soft signs were significantly more common in first-degree relatives of people with schizophrenia than in controls (pooled standardised mean difference (SMD) 1.24, 95% confidence interval (c.i) 0.59-1.89). Neurological soft signs were also significantly more common in people with schizophrenia than in their first-degree relatives (SMD 0.92, 95% c.i 0.64-1.20). Sensitivity analyses examining the effects of age and group blinding did not significantly alter the main findings.
Both hypotheses were confirmed, suggesting that the distribution of neurological soft signs in people with schizophrenia and their first-degree relatives is consistent with the endophenotype criterion of familial association.
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