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Dermatoglyphics and Schizophrenia: a meta-analysis and investigation of the impact of obstetric complications upon a-b ridge count

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Patients with schizophrenia show deviances in their dermatoglyphics, in particular reductions in palmar a-b ridge counts (ABRCs), which are evidence of an early developmental deviance. However, the severity or the origin of these ABRC changes has not
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  Dermatoglyphics and Schizophrenia: A meta-analysis andinvestigation of the impact of obstetric complicationsupon a–b ridge count  Elvira Bramon a, *, Muriel Walshe a  , Colm McDonald a  , Beatriz Martı´n  b ,Timothea Toulopoulou a  , Harvey Wickham a  , Jim van Os c , Paul Fearon a  ,Pak C. Sham a  , Lourdes Fan˜ana´s  b , Robin M. Murray a  a   Division of Psychological Medicine, Institute of Psychiatry, P.O. Box 63, De Crespigny Park, London SE5 8AF, United Kingdom  b  Laboratori d’Antropologia Animal, Universitat de Barcelona, Spain c Section of Social Psychiatry & Psychiatric Epidemiology, Maastricht University, The Netherlands Received 8 May 2004; received in revised form 26 August 2004; accepted 29 August 2004Available online 12 October 2004 Abstract  Background  : Patients with schizophrenia show deviances in their dermatoglyphics, in particular reductions in palmar a–b ridgecounts (ABRCs), which are evidence of an early developmental deviance. However, the severity or the srcin of these ABRCchanges has not been established.  Method  : (i) We examined the published literature on the ABRC in patients with schizophrenia against controls with a randomeffects meta-analysis. (ii) We used linear regression to study the ABRC in our sample of families including 125 patients withschizophrenia, 107 of their unaffected relatives and 98 controls. (iii) The effect of obstetric complications on the patient’sABRC was examined using the Lewis Murray scale.  Results : The pooled standardised effect size of ABRC differences between patients and controls obtained by our meta-analysiswas 0.39 (95% CI: 0.05–0.73;  p =0.03). In our sample, there were no significant differences in ABRCs between those withschizophrenia, their relatives and controls. Only those patients with obstetric complications had significantly reduced ABRCcompared to controls (  p =0.01). Conclusions : We confirmed the presence of significant yet mild ABRC reductions in schizophrenia. These represent a subtledeviance from the norm and could be present in certain subsets of patients, possibly those who suffered early developmentalinsults. D  2004 Elsevier B.V. All rights reserved.  Keywords:  Dermatoglyphics; a–b Ridge count; Obstetric complications; Family study; Schizophrenia; Meta-analysis0920-9964/$ - see front matter   D  2004 Elsevier B.V. All rights reserved.doi:10.1016/j.schres.2004.08.022* Corresponding author. Tel.: +44 (0) 207 848 5036; fax: +44 (0) 207 701 9044.  E-mail address:  e.bramon@iop.kcl.ac.uk (E. Bramon).Schizophrenia Research 75 (2005) 399–404www.elsevier.com/locate/schres  1. Introduction Epidermal ridges, also known as dermatoglyphics,appear on the hand between weeks 6 and 15 of life,and after this period, they remain unchanged (Davisand Bracha, 1996). Patients with schizophreniadisplay an increased prevalence of apparently inno-cent changes in the patterns and counts of their dermatoglyphics (Fan˜ana´s et al., 1990; Bracha et al.,1991; Saha et al., 2003). In par ticular, a number of  studies, summarised in Table 1, show that the a–b ridge count (ABRC), a quantitative dermatoglyphicmeasure of the palm, is reduced in patients withschizophrenia. However, several studies have not found such a–b ridge count reductions (Table 1) and the severity or the srcin of such deviances has not  been established.Dermatoglyphic alterations in schizophrenia aremarkers of disrupted early development and contrib-ute support to the neurodevelopmental model of schizophrenia (Murray and Lewis, 1987; Bramonand Murray, 2001). They show that an insult,whether genetic, environmental or both, occurredduring early–mid gestation (Green et al., 1994; Rosaet al., 2002).We set out to perform a meta-analysis of the published literature on ABRC in schizo- phrenia. We also examined the ABRC in our sample of families with members affected withschizophrenia. 2. Methods and materials 2.1. Meta-analysis A meta-analysis of peer-reviewed articles com- paring the a–b ridge count in patients withschizophrenia against controls was conducted in both Medline and in Science Citation Index fromJanuary 1983 to December 2003. For each primarystudy, the standardised effect size of the ABRC wasdefined as the difference between control and patient group means divided by the pooled standarddeviation. The standardised effect sizes were sub-sequently analysed using random effects meta-analysis, which provides a pooled effect size after weighting the effect size of each primary study bythe inverse of its variance. A test of heterogeneity between study results was also carried out. Wetested for publication bias using Begg and Mazum-dar’s (1994) adjusted rank correlation test. Further det ails on meta-analysis methods used can be foundin Bramon et al. (2004a,b). 2.2. Local study This included 125 probands, 107 of their unaf-fected first-degree relatives and 98 unrelated controlswith no personal or family history of psychosis.Further details on the nature of the sample have beendescribed previously (McDonald et al., 2002; Bramon Table 1The a–b ridge count in schizophrenia: studies published from 1983 to 2003Study Sample size (P/C) Population Patients mean(S.D.)Controls mean(S.D.)ES  P  -valueFan˜ana´s et al., 1990 125/72 Spanish 76.60 (9.78) 81.53 (9.81) 0.50 *Turek, 1990 310/400 Croatian 71.34 (9.88) 84.14 (12.03) 1.15 ***Fananas et al., 1996 92/69 (sample a) British 76.20 (11.10) 81.40 (11.40) 0.46 *339/59 (sample b) British 79.20 (9.40) 83.00 (5.10) 0.43 *Cantor-Graae et al., 1998 60/75 Swedish 79.94 (9.37) 80.24 (9.48) 0.03 n.s.Fearon et al., 2001 150/92 Irish 78.00 (16.1) 82.60 (14.70) 0.29 *Reilly et al., 2001 27/37 Irish 79.19 (14.94) 84.17 (11.22) 0.39 n.s.van Oel et al., 2001 19/70 Dutch 78.41 (12.19) 80.73 (10.53) 0.21 *Saha et al., 2003 181/228 Australian 84.31 (9.88) 83.83 (10.89)   0.05 n.s.Published studies included in the meta-analysis of the ABRC comparing patients with schizophrenia and controls. ES: effect size, calculated as(mean for controls  mean for patients)/pooled standard deviation. The  P  -values of the srcinal studies were either n.s.=non significant,*=significant at the 5% level or ***=significant at the 1% level.  E. Bramon et al. / Schizophrenia Research 75 (2005) 399–404 400  et al., 2004a,b). All participants were of Caucassianethnicity and underwent a detailed clinical assessment to obtain DSM 4 diagnoses. They all gave writteninformed consent to enter the study. This research wasapproved by the Institute of Psychiatry EthicalCommittee.Obstetric data was gathered via maternal inter-view using the Lewis–Murray scale (Lewis et al.,1989). Mothers were available and willing to participate for 96 patients only. Those patientswere classified in two subgroups having either  d definite T  complications or alternatively havingnone or   d equivocal T  complications. 2.3. Dermatoglyphic analysis The a–b ridge count is a quantitative dermato-glyphic metric of the second inter-digital area of the palm. BM and LF, who were blind todiagnosis and obstetric complication dat a, meas-ured the a–b ridge counts according to Cumminsand Midlo (1961). Further details are described inFig. 1. 2.4. Statistical analyses Comparisons of the total a–b ridge count across thethree groups were conducted using linear regressionwith robust standard errors, accounting for anycorrelations within families. Only where the effect of group was significant were post hoc comparisons andmultiple testing adjustments conducted. Finally, asubsidiary linear regression analysis was conductedto examine the impact of obstetric complications onABRC with two planned comparisons: (i) Patientswith equivocal or no obstetric complications against controls. (ii) Patients with definite obstetric complica-tions against controls. All analyses were carried out using STATA 7.0 (STATA, College Station, TX, USA). 3. Results 3.1. Meta-analysis of the previous literature We identified nine studies suitable for analysis,which are summarised in Table 1, and included 1303 Fig. 1. The a–b ridge count. Whenever three ridge systems meet at a point this is known as triradius. There are usually four triradii in each palm, placed at the base of digits 2 through 5. The triradii at the base of the index and middle fingers are known as A and B, respectively. The a–bridge count (ABRC) is the number of ridges between triradii A and B for both left and right hand added together (Cummins and Midlo, 1961).  E. Bramon et al. / Schizophrenia Research 75 (2005) 399–404  401   patients and 1102 controls. Using random effectsmeta-analysis, the pooled standardised effect size for the ABRC was 0.39 (95% CI: 0.05–0.73;  p =0.03).There was significant heterogeneity between studies(  p b 0.001). Begg’s test revealed that there was noevidence of a significant publication bias (coef-ficient=  5.01;  p =0.16). However, the number of studies (9) used for this test is small and thereforethe power to detect bias is limited (Begg and Mazumdar, 1994). Fig. 2 shows a forest plot with the main findings of the meta-analysis. 3.2. Local study3.2.1. Analysis of the a–b ridge count in our sample of   families The mean a–b ridge counts were found to besimilar for  the pat ients, relatives and controls as can be seen in Table 2. There was no significant effect of group on the a–b ridge count [  F  (2,219)=09.87;  p =0.42], so no further post hoc group comparisonswere conducted. 3.2.2. Is there a relationship between total a–b ridgecount and obstetric complications amongst our  patients? As can be seen in Table 2, the relationship between a–b ridge count and OCs was examined in a subsampleof 96 patients whose mother agreed to be interviewed.Patients without obstetric complications did not differ significantly from controls in ABRC. Compared tocontrols, those patients who suffered definite obstetriccomplications had significantly reduced ABRC[  p =0.01; regression coefficient=  4.91; 95% CI:  8.77 to  1.05]. 4. Discussion Our meta-analysis confirmed that patients withschizophrenia have reductions in their a–b ridge count that are statistically significant yet of mild severity(effect size of 0.39). As can be seen in Fig. 2, the study by Turek (1990) substantially deviates from theremaining primary studies. The meta-analysis exclud- Fig. 2. Forest plot for meta-analysis of published studies of the ABRC in schizophrenia. The above forest plot shows nine previously publishedstudies on the a–b ridge count comparing schizophrenia and controls. The horizontal lines represent 95% CI for each individual study. The sizeof the squares represents the weight given to each study in the meta-analysis. The diamond shows the pooled standardised effect sizes (PSES) of all nine studies using meta-analysis tools in STATA 7.0. The PSES was 0.39 (95% CI: 0.05–0.73;  p =0.03). Thus, this meta-analysis shows that  patients have a statistically significant yet modest reduction in ABRC compared to controls.  E. Bramon et al. / Schizophrenia Research 75 (2005) 399–404 402  ing this apparent outlier provides a smaller yet stillsignificant effect size of 0.27.Thus, we believe that the ABRC reductions inschizophrenia exist, but are just subtle deviations fromthe norm. It is also plausible that they are only present in certain subgroups of patients; possibly those wit hmore severe forms of the illness (Cannon et al., 1994). If so, it is not surprising that our predominantly stableand high-functioning outpatients had normal a–b ridgecounts. Similarly, and coinciding with findings byRosa et al. (2000), our larger sample of unaffectedrelatives also had normal ABRC.Twin studies consistently show that the ABRC isstrongly influenced by non-shared environmentalinfluences rather than being genetically determined(Bracha et al., 1991; 1992; Van Oel et al., 2001). Although, our design does not allow claims about causation of ABRC deviances, it seems interestingthat only those patients who suffered obstetriccomplications showed abnormally reduced ABRC,while patients without obstetric events and unaffectedrelatives did not differ from controls. This supportsthe idea that the subtle a–b ridge count reductionsdescribed in schizophrenia could be related to earlyenvironmental insults like obstetric complications;which, as highlighted in the meta-analysis by Cannonet al. (2002), are more likely to occur to the patientsthan to their relatives or controls. 4.1. Limitations Firstly, although our sample is large, it is not epidemiological. Secondly, our OC data were col-lected by maternal interview and recall bias cannot beruled out. Finally, because their mothers were not available for interview, we could not examine theassociation between ABRC and obstetric complica-tions in relatives or in controls. It is therefore possiblethat the correlation between obstetric complicationsand reduced AB ridge count found in our patients may be in fact unrelated to schizophrenia. Replication inunaffected groups is required. We used the broad termOCs including any complications during pregnancy or delivery. Clearly, the link between perinatal compli-cations and ABRC reductions (which must have taken place before the 16th week of pregnancy) seems less plausible (McNeil and Cantor-Graae, 1999). How- ever, evidence exists where perinatal obstetric com- plications have been associated with insults occurringearlier in pregnancy, for example, foetal hypoxia( Nelson and Ellenberg, 1986; O’Callaghan et al.,1992; McNeil et al., 2000; Cannon et al., 2002).In conclusion, we confirmed the presence of significant yet mild ABRC reductions in schizophre-nia. These represent a subtle deviance from the normand could be present in certain subsets of patients, particularly those who suffered early developmentalinsults. Acknowledgements This study was supported by the Wellcome Trust,the Schizophrenia Research Fund and the StanleyMedical Research Institute. E. Bramon, C. McDonaldand M. Walshe are sponsored by The Wellcome Trust  Table 2ABRC by groupComparison Mean ABRC (S.D.) by group Statistical comparisonsEffect of group on ABRC a  Controls,  n =98 81.1 (11.6) No significant effect of group on ABRC[  F  (2,219)=0.87;  p =0.42].Relatives,  n =107 79.6 (10.3)Patients,  n =125 79.1 (10.6)Effect of obstetric complicationson ABRC  b Patients without OCs,  n =48 81.06 (9.70) No significant ABRC difference between patientswithout OCs and controls (  p =0.98).Patients with OCs,  n =48 76.21 (11.44) ABRC significantly reduced in patients with OCscompared to controls [Dif.=  4.91; 95% CI:   8.77to   1.05;  p =0.01].Subsidiary analysis of obstetric complications in the patients.OCs: obstetric complications. a  Linear regression with robust and cluster options accounting for the family clusters in the data.  b Linear regression with two planned comparisons of each patient subgroup against controls.  E. Bramon et al. / Schizophrenia Research 75 (2005) 399–404  403
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