dermatoglyphic anomalies and neurocognitive deficits in sibling

www.elsevier.com/locate/psychres

Psychiatry Research 13

Dermatoglyphic anomalies and neurocognitive deficits in sibling

pairs discordant for schizophrenia spectrum disorders

Araceli Rosa a,*, Manuel J. Cuesta b, Vıctor Peralta b, Amalia Zarzuela b,

Fermın Serrano b, Alfredo Martınez-Larrea b, Lourdes Fananas a

a Unitat d’Antropologia, Facultat de Biologia, Universitat de Barcelona, Avinguda Diagonal 645, 08028 Barcelona, Spainb Psychiatric Unit, Virgen del Camino Hospital, Irunlarrea s/n, 31008 Pamplona, Spain

Received 23 January 2003; received in revised form 19 September 2004; accepted 20 July 2005

Abstract

The neurodevelopmental hypothesis of schizophrenia suggests that adverse genetic loading in conjunction with

environmental factors early in fetal life causes a disruption of neural development, decades before the symptomatic

manifestation of the disease. Neurocognitive deficits have been observed early on the course of schizophrenia, and their

association with an early developmental brain lesion has been postulated. Dermatoglyphics have been analyzed in

schizophrenia as markers of prenatal brain injury because of their early fetal ontogenesis and susceptibility to the same

environmental factors that can also affect cerebral development. The aim of our study was to conduct a comparative

examination of neurocognitive functions and dermatoglyphic variables in 89 sibling pairs discordant for schizophrenia

spectrum disorders. Therefore, we investigated the association between these two markers to explore the prenatal origin of

cognitive deficits in schizophrenia. The affected siblings were significantly impaired on all the cognitive variables assessed

(Wisconsin Card Sorting Test, Trail Making Test and Continuous Performance Test) and had a greater number of

dermatoglyphic anomalies. These results suggest the influence of intrauterine environmental factors in the siblings affected

with schizophrenia. However, we did not detect a significant association between these two vulnerability markers in the

schizophrenic patients, suggesting the role of genetic or late environmental factors in the origin of the neurocognitive

deficits found in these patients.

D 2005 Elsevier Ireland Ltd. All rights reserved.

Keywords: Dermatoglyphics; Neurocognition; Discordant sibling pairs; Psychosis; Prenatal markers; Neurodevelopment

0165-1781/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights re

doi:10.1016/j.psychres.2005.07.006

* Corresponding author. Tel.: +34 93 402 14 61.

E-mail address: [email protected] (A. Rosa).

1. Introduction

Kraepelin’s concept of schizophrenia as an early

dementia (dementia praecox) captured two core fea-

tures of the illness, namely cognitive dysfunction and

7 (2005) 215–221

served.

A. Rosa et al. / Psychiatry Research 137 (2005) 215–221216

a characteristic early age of onset. The neurodevelop-

mental hypothesis of schizophrenia was first formu-

lated by Clouston (1891), who noted a high-arched

palate in many of the patients he regarded as having

dadolescent insanityT. However, it was not until the

end of the 1980s that the hypothesis reemerged with

the detection of neuropathological and neuroimaging

findings that suggested that schizophrenia was char-

acterised by abnormal brain development (Murray and

Lewis, 1987; Weinberger, 1987).

Several studies have demonstrated that a signifi-

cant proportion of schizophrenic patients show neu-

ropsychological impairments from early in the course

of their illness (Goldberg et al., 1995; Cuesta et al.,

1998). Although the range of neurocognitive deficits

described is extremely broad, the cognitive functions

most frequently compromised are attention, executive

function, set shifting, and general and working mem-

ory (Goldberg et al., 1987; Weickert et al., 2000).

Despite the large number of studies exploring these

deficits, their nature and their association with an

early developmental brain lesion, genetic or environ-

mental in origin, are still controversial.

Family studies suggest that cognitive deficits in

schizophrenia may serve as a marker of the genetic

vulnerability to the disorder since relatives of patients

with schizophrenia exhibit subtle cognitive impair-

ments in attention, executive functioning, and sen-

sory-motor functions (Cannon et al., 1994; Saoud et

al., 2000; Staal et al., 2000). Nevertheless, prenatal

environmental factors such as viral or toxin exposure

or perinatal hypoxia are associated with both general

intellectual impairment and more specific cognitive

deficits, demonstrating the importance of the prenatal

and perinatal environment to the cognitive potential

of the human brain (Kremen et al., 1994; Rosa et al.,

2001). One marker of environmental influences acting

during prenatal brain development is dermato-

glyphics. Epidermal ridges share ectodermal origins

with the central nervous system. Their initial forma-

tion takes place about the 11th week; however, their

critical stage of differentiation occurs in fetal months

3–4, coinciding with a critical phase of brain devel-

opment (Rakic, 1988). Their morphology is geneti-

cally determined but is susceptible to the same

environmental factors that can also disrupt brain

development (Babler, 1991). Intriguingly, once der-

matoglyphic development is complete, by week 24,

they remain unchanged and can act as bfossilsQ of theprenatal environment. For that reason, they have been

used as markers of fetal malneurodevelopment with

reasonable success in the study of schizophrenia spec-

trum disorders. In these studies, three types of mea-

sure are typically used: quantitative counts of the

ridges on digits and hands, measures of asymmetry

between the left and right hands, and qualitative

dermatoglyphic abnormalities. Studies in schizophre-

nia spectrum disorders have shown lower ridge

counts (total finger ridge count and a–b ridge count)

(Turek, 1990; Fananas et al., 1990, 1996; Bracha et

al., 1991; Davis and Bracha, 1996; Fearon et al.,

2001), higher levels of fluctuating asymmetry (Mar-

kow and Wandler, 1986; van Oel et al., 2001) and

dermatoglyphic abnormalities including ridge disso-

ciations (RD) and abnormal palmar flexion creases

(APFC) in patients compared with healthy controls

and unaffected monozygotic twins (van Os et al.,

1997; Rosa et al., 2000, 2002).

Although the risk for schizophrenia appears to be

increased by problems in neurodevelopment, little is

known about the origin of its more subtle cognitive

sequelae. A possible approach to explore this relation-

ship is to study the association between markers of

prenatal insult [e.g. minor physical anomalies (MPAs)

and dermatoglyphics] and neurocognitive functioning

in patients with schizophrenia. Previous studies of

MPAs and information processing have led to contra-

dictory results (O’Callaghan et al., 1991; Green et al.,

1989). However, only one previous study has looked at

the relationship between dermatoglyphic anomalies

and neurocognitive deficits (Green et al., 1994). That

study failed to show an association between the neuro-

developmental markers studied (dermatoglyphic asym-

metry and total finger ridge count) and three measures

of information processing (Continuous Performance

Test, neuromotor speed and executive functioning).

To address these points, the aim of this study was

to explore the presence of neurocognitive and derma-

toglyphic abnormalities in sibling pairs discordant for

schizophrenia. We planned to explore the association

between neurodevelopmental markers, previously

reported altered in schizophrenia spectrum disorders

(dermatoglyphics) and selected neurocognitive func-

tions in order to establish if there is evidence to

support early prenatal origin of the cognitive deficits

found in these patients.

A. Rosa et al. / Psychiatry Research 137 (2005) 215–221 217

2. Methods

2.1. Subjects

The sample consisted of 89 patients with schizo-

phrenia spectrum disorders from the Psychiatric Unit,

Virgen del Camino Hospital, Pamplona. For each

patient, the healthy sibling nearest in age to the

patient was selected. We attempted whenever possi-

ble to identify the same-gender sibling pairs. The

gender composition of the pairs was: male patient–

male sibling: 31 (34.8%); female patient–male sib-

ling: 10 (11.2%); male patient–female sibling: 36

(40.5%); and female patient–female sibling: 12

(13.5%). Siblings were interviewed with the Interna-

tional Personality Disorders Examination scale

(IPDE) (Loranger et al., 1994) to exclude major

psychiatric illness in siblings.

The DSM-IV diagnostic breakdown of patients

was as follows: schizophrenia (n =48, 54%); schizo-

phreniform disorder (n =8, 9%); schizoaffective dis-

order (n =11, 12.4%); psychotic mood disorder

(n =14, 15.7%); delusional disorder (n =2, 2.2%);

brief psychotic disorder (n =5, 5.6%); and atypical

psychosis (n =1, 1.1%).

Demographic data, including age, educational

level, gender and other variables of interest for the

discordant sib pairs, are summarised in Table 1. Writ-

ten informed consent was obtained from all partici-

pants after they had received a complete description of

the study’s aims and procedures.

2.2. Cognitive assessment

The neuropsychological battery that was adminis-

tered to all individuals (patients and siblings) con-

sisted of the following three tests, selected because

Table 1

Demographic characteristics and duration of the illness, in years, in

the sample of 89 sib pairs discordant for schizophrenia and schizo-

phrenia spectrum disorders

Affected sibs Healthy sibs

MeanFS.D. MeanFS.D.

Age 26.8F5.8 27.7F6.8

Education 11.9F3.7 12.7F4.1

Age at onset 21.5F5.4 –

Duration of illness 5.2F5.9 –

they assess cognitive domains that have consistently

been implicated in schizophrenia spectrum disorders:

(1) The Wisconsin Card Sorting Test (WCST), a test

of executive function and set shifting. The number of

perseverative errors (WCST-PE) was used as an index

of test performance (Heaton, 1993). (2) Form B of the

Trail Making Test (TMTb) (Reitan, 1958), a test of

set-shifting ability that assesses frontal lobe function

and attention. The score used was the time taken to

complete the task. (3) The computerised version of the

Continuous Performance Test (CPT) (Cornblatt,

1996), a measure of sustained attention. The dV wasused as a measure of sensitivity for this test. All the

participants were assessed by an experienced psycho-

logist (AZ) and patients were at the discharge stage.

2.3. Dermatoglyphic variables

Palm and fingerprints were taken by FS using a

non-inky method (Prints-kit, Printscan Verification

SystemsLtd., Printscan Distributorship, UK). Derma-

toglyphic analysis was conducted by AR blind to

the diagnosis, sex and neurocognitive profile of the

individuals.

The dermatoglyphic variables analyzed were: (1)

the total a–b ridge count (TABRC) and (2) the pre-

sence of abnormal palmar flexion creases (APFC) and

ridge dissociation in fingers and palms (RD) (see Rosa

et al., 2001, for more details).

2.4. Statistical analysis

All statistical analyses were performed using

STATA software (StataCorp, 1999). As the data

were obtained, sibling-pairs differences between sib-

lings on the quantitative measures (i.e., cognitive

variables and total a–b ridge count) were analyzed

using two-tailed t-tests for paired samples. For dif-

ferences between siblings on the qualitative vari-

ables (i.e., abnormal palmar flexion creases and

presence of ridge dissociations), the McNemar test

was used.

Associations between the cognitive and dermato-

glyphic variables were calculated by using multiple

regression or logistic regression depending on the

nature of the dermatoglyphic variable used. Associa-

tions were expressed as regression coefficients (b) orodds ratios (OR). The association analyses were

Table 3

Associations between the dermatoglyphic variables analyzed


adjusted for sex, age, years of education and illness

duration as possible confounding factors.
(TABRC and presence APFC/RD) and the neurocognitive variables
(WCST-PE, TMTb and the dV), in the sample of patients affected by

schizophrenia spectrum disorders

Patients with schizophrenia spectrum disorders

TABRC APFC/RD

b P OR P

WCST-PE 0.02 0.8 0.9 0.5

TMTb 0.01 0.5 1 0.4

dV �1.1 0.4 0.7 0.2

b: multiple regression coefficient between the quantitative derma-

toglyphic variable TABRC and the neurocognitive variables ana-

lyzed (WCST-PE, TMTb and dV).OR: odds ratio from the logistic regression analysis between

qualitative dermatoglyphic abnormalities and neurocognitive tests

considered.

3. Results

As hypothesised, patients performed significantly

worse than their healthy siblings on all the neuropsy-

chological tasks assessed: executive function (WCST-

PE: t=2.9, df =77, P=0.005), set shifting (TMTb:

t=7.7, df =78, P=0.000), and attention (CPT: t = 3.3,

df =75, P=0.001) (Table 2). To explore a more homo-

genous patient group, we narrowed the definition of

patients to DSM-IV schizophrenia and schizophreni-

form disorder). This subgroup, which consisted of 49

pairs, demonstrated the same results (executive func-

tion: t =2.1, df =47, P=0.05; set shifting: t=6.4,

df =48, P=0.000; attention: t =�3.1, df =47,

P=0.004) (Table 2). Deficits were characterised by a

higher number of perseverative errors on the WCST,

more time taken to complete the TMT-B, and

decreased accuracy on the CPT dV index.Data on total a–b ridge count (TABRC) were avail-

able on 76 pairs. In the affected siblings, mean TABRC

was 80.1 (S.D.=11.6) and in the healthy siblings 80.2

(S.D.=12.1). For this variable, no large or significant

differences were found between the discordant sibs

(t=�0.1, df =75, P=0.9) (Table 2).

Abnormal palmar flexion creases were more fre-

quent in the patients (48.1%) compared with their

healthy sibs (36.7%). Ridge dissociation was present

in 29% of the patients and in 17% of the healthy sibs.

Table 2

Neurocognitive and dermatoglyphic scores in: (a) patients affected by schiz

and (b) patients with schizophrenia and schizophreniform disorder (SZ) (

Patients with SZSD Siblings of SZSD pa

MeanFS.D. MeanFS.D.

WCST-PE 19.1F10.5 14.5F10.5

TMTb 120.3F48.8 76.4F25.5

dV 0.6F0.9 1.0F0.9

TABRC 80.1F11.6 80.2F12.1

APFC/RD 72.8% 42%

WCST-PE: number of perseverative errors of the Wisconsin Card Sorting

TMTb: form b of the Trail Making Test.

dV: Continuous Performance Test measure of sensitivity dV.TABRC: total a–b ridge count.

APFC/RD: presence of either abnormal palmar flexion creases and/or der

In this regard, a statistically significant excess of

either APFC or RD was found in the affected sibs

compared with the unaffected sibs (McNemar test:

P b0.001) (Table 2).

The findings remained unchanged when we exam-

ined the narrow criteria subgroup (TABRC: t =0.7,

df =47, P=0.4; APFC/ RD, McNemar test: P=0.01).

Multiple regression analysis did not show a significant

association between lower TABRC and impaired

executive function, cognitive flexibility on TMTb or

sustained attention (dV) in patients (Table 3). Similarly,

logistic regression did not show that the presence of

APFC/RD was associated with the aforementioned

neurocognitive variables in the group of patients

(Table 3).

ophrenia spectrum disorders (SZSD) (n =79 pairs) and their siblings

n =49 pairs)

tients Patients with SZ Siblings of SZ patients

MeanFS.D. MeanFS.D.

18.3F10.4 14.6F10.8

119.3F49.1 73.5F25.1

0.6F0.9 1.1F0.9

80.6F12.3 79.62F10.0

69.4% 42%

Test.

matoglyphic ridge dissociation.


4. Discussion

In this study selected cognitive functions (executive

function, set shifting and sustained attention) and der-

matoglyphic variables (a–b ridge count and presence of

abnormal palmar flexion creases/dermatoglyphic ridge

dissociations) were analyzed in a young group of sib

pairs discordant for psychosis. The adult siblings

approach used offers advantages insofar as that for

some variables stratification bias is reduced.

The first finding from this study was that affected

sibs were significantly impaired in the cognitive func-

tions studied compared with their unaffected sibs.

This finding adds to the growing body of literature

suggesting that neurocognitive deficits may be gener-

ally characteristic of schizophrenia (e.g., Goldberg et

al., 1987). As we only assessed the well relatives of

patients and did not include a healthy control group,

we are not able to establish whether the neurocogni-

tive deficits found characterize both schizophrenic

patients and their well siblings, nor can we discuss

questions concerning a genetic origin of these deficits.

Regarding the markers of prenatal suffering ana-

lyzed, the total a–b ridge count (TABRC) did not

differ between the sib pairs. Our dermatoglyphic find-

ings for this variable contrasted with several previous

studies that found lower TABRCs in schizophrenic

patients compared with unrelated healthy controls

(e.g., Fananas et al., 1990). Regarding the other der-

matoglyphic variables analyzed, patients showed

higher frequencies of abnormal palmar flexion creases

and ridge dissociations. These dermatoglyphic

abnormalities have also been associated with psycho-

sis in previous studies carried out in twins (van Os et

al., 1997; Rosa et al., 2000, 2002). Our results support

the suggestion that intrauterine environmental factors

early in pregnancy are associated with the suscepti-

bility to schizophrenia.

Finally, we do not find any association between the

neurocognitive and the neurodevelopmental markers

assessed (TABRC and APFC/RD). Our results are

consistent with the two previous studies in which

the markers of neurodevelopment (minor physical

anomalies and/or dermatoglyphics) and the informa-

tion-processing measures were not found to be asso-

ciated (Green et al., 1989, 1994). However, the failure

to find an association between the dermatoglyphic and

cognitive variables assessed does not mean that such a

relationship does not exist. The cognitive disturbances

could be manifestations of prenatal disruptions in

brain formation that could lead to further neural dys-

maturation that can manifest in adolescence and adult-

hood as schizophrenia. Nevertheless, we have no

grounds to expect that the neurodevelopmental insult

hypothesised to intervene in the causation of neuro-

cognitive impairment necessarily occurs during the

short time window in which epidermal ridge develop-

ment takes place (i.e., between 11th and 24th weeks of

fetal life). Indeed, the link between early brain devel-

opmental disturbance and neurocognitive alteration

could still be plausible if we assume the interaction

of predisposing genes and hazardous intrauterine

environmental factors may actually happen after the

period of dermatoglyphic formation. Furthermore, it

should be contemplated that the neurocognitive

impairment found in schizophrenia is probably not

entirely caused by pure neurobiological abnormalities.

Educational factors, drug treatments, behavioural

peculiarities, and the effects of the illness itself, as

well as other environmental variables, probably have a

role in determining performance in these cognitive

tests.

Another possible explanation for the lack of asso-

ciation in this and the previous studies may be that the

cognitive deficits might be linked to the genetic liabi-

lity for schizophrenia, whereas these neurodevelop-

mental markers may reflect extragenic processes.

Nonetheless, studies of cognitive deficits in monozy-

gotic twin pairs discordant for schizophrenia contra-

dict a sole genetic effect. In addition, magnetic

resonance imaging studies, neuroanatomic, and neu-

rophysiological studies in discordant twins for schizo-

phrenia have demonstrated that the abnormalities

found in the affected twin compared with the healthy

co-twin were compatible with this hypothesis (Suddath

et al., 1990; Weinberger et al., 1992). With this in

mind, genetically sensitive designs such as the twin

method are appropriate to disentangle genetic factors

and shared environmental factors; unfortunately, these

effects cannot be determined from the current analyses.

Acknowledgments

This research was supported by a grant from the

Theodore and Vada Stanley Foundation. Araceli Rosa


was awarded a PhD grant from the University of Bar-

celona, and Amalia Zarzuela was awarded by the

Fondo de Investigacion Sanitaria (Spain, FIS 00/0132).

We thank the patients, families and staff from the

hospital whose generosity made this project possible.

Finally, we thank Dr. Marco Picchioni, Dr. Brendan

Kelly and Dr. Neus Barrantes-Vidal for constructive

criticism and suggestions in the last version of the

manuscript.

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