In Schizophrenia: Meta-Analysis Handedness, Language Lateralisation and Anatomical Asymmetry

10.1192/bjp.178.4.
344 Access the most recent version at DOI:

2001, 178:344-351. BJP
IRIS SOMMER, NICK RAMSEY, REN KAHN, ANDR ALEMAN and ANKE BOUMA
in schizophrenia: Meta-analysis
Handedness, language lateralisation and anatomical asymmetry
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Background Background Cerebral lateralisation Cerebral lateralisation
appears to be decreasedin schizophrenia. appears to be decreasedin schizophrenia.
Results of studiesinvestigating this, Results of studiesinvestigating this,
however, are equivocal. however, are equivocal.
Aims Aims Toreviewquantitatively the Toreviewquantitatively the
literature on decreasedlateralisation literature on decreasedlateralisation
in schizophrenia. in schizophrenia.
Method Method Meta-analyses were Meta-analyses were
conducted on19 studies onhandedness, conducted on19 studies onhandedness,
10 dichotic listening studies and 39 studies 10 dichoticlistening studies and 39 studies
investigatinganatomical asymmetry investigatinganatomical asymmetry
Results Results The prevalence of mixed- and The prevalence of mixed- and
left-handedness (`non-right-handedness') left-handedness (`non-right-handedness')
was significantlyhigherinpatients with was significantlyhigherinpatients with
schizophrenia as comparedto healthy schizophrenia as comparedto healthy
controls, and also as comparedto controls, and also as comparedto
psychiatric controls.The analysis of psychiatric controls.The analysis of
dichotic listening studies revealedno dichoticlistening studies revealedno
significant differenceinlateralisationin significant differenceinlateralisationin
schizophrenia. However, when analysis schizophrenia. However, when analysis
wasrestrictedtostudiesusingconsonant ^ wasrestrictedtostudies usingconsonant^
vowel or fusedwordtasks, significantly vowel or fusedwordtasks, significantly
decreasedlateralisationin schizophrenia decreasedlateralisationin schizophrenia
emerged. Asymmetryof the planum emerged. Asymmetryof the planum
temporale andthe Sylvianfissure was temporale andthe Sylvianfissure was
significantlydecreasedin schizophrenia, significantlydecreasedin schizophrenia,
while asymmetryof thetemporal horn while asymmetryof thetemporal horn
of thelateral ventricle was not. of thelateral ventricle was not.
Conclusion Conclusion Strongevidenceis Strongevidenceis
provided fordecreasedcerebral provided fordecreasedcerebral
lateralisationin schizophrenia. lateralisationin schizophrenia.
Declaration of interest Declaration of interest None None
Right-handedness, left cerebral dominance Right-handedness, left cerebral dominance
for language and normal cerebral asymme- for language and normal cerebral asymme-
try are considered to be secondary to a try are considered to be secondary to a
dominant allele, the `right-shift factor' dominant allele, the `right-shift factor'
(Annett, 1998). In schizophrenia, several (Annett, 1998). In schizophrenia, several
studies reported an excess of non-right- studies reported an excess of non-right-
handedness (Shan-Ming handedness (Shan-Ming et al et al, 1985), , 1985),
decreased language lateralisation on the decreased language lateralisation on the
dichotic listening paradigm (Bruder dichotic listening paradigm (Bruder et al et al, ,
1999) and decreased (Petty 1999) and decreased (Petty et al et al, 1995) or , 1995) or
reversed (Barta reversed (Barta et al et al, 1997) anatomical , 1997) anatomical
asymmetry. It has been postulated that the asymmetry. It has been postulated that the
genetic mechanism underlying normal left genetic mechanism underlying normal left
hemispheric dominance is altered in schizo- hemispheric dominance is altered in schizo-
phrenia (Crow phrenia (Crow et al et al, 1989). Were this to be , 1989). Were this to be
true, the discovery of the `right-shift factor' true, the discovery of the `right-shift factor'
may also identify a locus where genetic may also identify a locus where genetic
aberrations predispose for schizophrenia aberrations predispose for schizophrenia
(Crow, 1999). However, literature on de- (Crow, 1999). However, literature on de-
creased cerebral dominance in schizo- creased cerebral dominance in schizo-
phrenia is equivocal. The aim of the phrenia is equivocal. The aim of the
present study was therefore to review quan- present study was therefore to review quan-
titatively studies on handedness, language titatively studies on handedness, language
lateralisation on the dichotic listening para- lateralisation on the dichotic listening para-
digm and anatomical asymmetry in schizo- digm and anatomical asymmetry in schizo-
phrenia. phrenia.
METHOD METHOD
Literature search Literature search
Studies were retrieved that dealt with later- Studies were retrieved that dealt with later-
alisation in schizophrenia, published be- alisation in schizophrenia, published be-
tween January 1980 (introduction of tween January 1980 (introduction of
Diagnostic and Statistical Manual of Men- Diagnostic and Statistical Manual of Men-
tal Disorders tal Disorders (3rd edn), DSMIII) and (3rd edn), DSMIII) and
December 1999. Only English-language December 1999. Only English-language
publications from international journals publications from international journals
and book chapters were selected. and book chapters were selected.
Inclusion Inclusion
The included studies had to meet the fol- The included studies had to meet the fol-
lowing criteria. lowing criteria.
(a) (a) Patients had a diagnosis of schizo- Patients had a diagnosis of schizo-
phrenia, according to the criteria of phrenia, according to the criteria of
DSMIII, DSMIIIR, DSMIV, DSMIII, DSMIIIR, DSMIV,
Research Diagnostic Research Diagnostic Criteria (RDC), Criteria (RDC),
International Classification of Disease International Classification of Disease
ICD9 or ICD10. Studies on patients ICD9 or ICD10. Studies on patients
with schizophrenia- with schizophrenia-spectrum disorder spectrum disorder
(schizoaffective and schizophreniform (schizoaffective and schizophreniform
disorder or schizotypal personality disorder or schizotypal personality
disorder) were not included. disorder) were not included.
(b) (b) Studies had compared patients with Studies had compared patients with
schizophrenia to healthy controls who schizophrenia to healthy controls who
were not at increased risk for schizo- were not at increased risk for schizo-
phrenia or psychosis. For an additional phrenia or psychosis. For an additional
analysis on hand preference, we also analysis on hand preference, we also
included studies using non-schizo- included studies using non-schizo-
phrenia psychiatric and neurological phrenia psychiatric and neurological
patients as control groups. patients as control groups.
(c) (c) Studies reported data on handedness, Studies reported data on handedness,
language lateralisation as measured language lateralisation as measured
with the dichotic listening paradigm, with the dichotic listening paradigm,
or anatomical asymmetry of the or anatomical asymmetry of the
planum temporale, Sylvian fissure, planum temporale, Sylvian fissure,
temporal horn of the lateral ventricle temporal horn of the lateral ventricle
or superior temporal gyrus. or superior temporal gyrus.
(d) (d) Studies had reported sufficient statis- Studies had reported sufficient statis-
tical information, i.e. frequencies, tical information, i.e. frequencies,
means and standard deviations, exact means and standard deviations, exact
F F or or t t values, or exact values, or exact P P values. values.
Analyses Analyses
After computing effect sizes for each study After computing effect sizes for each study
(Hedges & Olkin, 1985), meta-analytic (Hedges & Olkin, 1985), meta-analytic
methods were applied in order to obtain a methods were applied in order to obtain a
combined effect size, which indicated the combined effect size, which indicated the
magnitude of the association across all stu- magnitude of the association across all stu-
dies (cf Aleman dies (cf Aleman et al et al, 1999). In addition, , 1999). In addition,
Stouffer's Stouffer's Z Z, weighted for sample size, pro- , weighted for sample size, pro-
vided an indication of the significance of vided an indication of the significance of
the difference between the patient and the the difference between the patient and the
comparison group. Finally, a homogeneity comparison group. Finally, a homogeneity
statistic ( statistic (Q Q) was calculated, to assess het- ) was calculated, to assess het-
erogeneity of results across studies (Shadish erogeneity of results across studies (Shadish
& Haddock, 1994). If heterogeneity & Haddock, 1994). If heterogeneity
reached significance, further analyses were reached significance, further analyses were
carried out to examine potential modera- carried out to examine potential modera-
tors on the effect size. In order to inves- tors on the effect size. In order to inves-
tigate such potential moderators, tigate such potential moderators,
correlations (Pearson coefficients, two- correlations (Pearson coefficients, two-
tailed) were calculated between the effect tailed) were calculated between the effect
size of the studies and available variables. size of the studies and available variables.
Handedness Handedness
Prevalences of mixed- and left-handedness Prevalences of mixed- and left-handedness
were grouped together as `non-right- were grouped together as `non-right-
handedness'. For each study, odds ratios handedness'. For each study, odds ratios
were calculated from the prevalence of were calculated from the prevalence of
non-right-handedness in schizophrenia or non-right-handedness in schizophrenia or
pre-schizophrenia subjects and in the pre-schizophrenia subjects and in the
comparison subjects. Odds ratios were comparison subjects. Odds ratios were
combined by applying the method of loga- combined by applying the method of loga-
rithmic odds ratio meta-analysis (Shadish rithmic odds ratio meta-analysis (Shadish
& Haddock, 1994). & Haddock, 1994).
3 4 4 3 4 4
BRI TI S H J OURNAL OF P SYCHI ATRY BRI TI S H J OURNAL OF P SYCHI ATRY ( 2 0 0 1) , 17 8 , 3 4 4 ^ 3 51 ( 2 0 0 1) , 17 8 , 3 4 4 ^ 3 51
Handedness, language lateralisation and Handedness, language lateralisation and
anatomical asymmetry in schizophrenia anatomical asymmetry in schizophrenia
Meta-analysis Meta-analysis
IRIS SOMMER, ANDRE ALEMAN, NICK RAMSEY, ANKE BOUMA IRIS SOMMER, ANDRE
ALEMAN, NICK RAMSEY, ANKE BOUMA

and RENE KAHN and RENE
KAHN
CEREBR AL L ATER ALI S ATION AND ANATOMI CAL ASYMME TRY IN S CHI ZOPHRENI A CEREBR AL L ATER ALI S ATION AND ANATOMI CAL ASYMME TRY IN S CHI ZOPHRENI A
Dichotic listening studies Dichotic listening studies
Effect sizes (Hedges & Olkin, 1985) were Effect sizes (Hedges & Olkin, 1985) were
calculated from the `right-ear advantages' calculated from the `right-ear advantages'
(score right ear minus score left ear) of (score right ear minus score left ear) of
patients and controls, from the `laterality patients and controls, from the `laterality
index' (score right ear minus score left index' (score right ear minus score left
ear, divided by ear, divided by score right ear plus score score right ear plus score
left ear) or from left ear) or from F F values. values.
Anatomical asymmetry Anatomical asymmetry
Brain torque Brain torque
Only two studies on brain torque (Luchins Only two studies on brain torque (Luchins
et al et al, 1981; Guerguerian & Lewine, 1998) , 1981; Guerguerian & Lewine, 1998)
reported means and standard deviations of reported means and standard deviations of
an asymmetry index for patients and an asymmetry index for patients and
controls, while others gave frequencies of controls, while others gave frequencies of
abnormal frontal and occipital asymmetry. abnormal frontal and occipital asymmetry.
On these studies, meta-analysis was per- On these studies, meta-analysis was per-
formed using the `difference rate', i.e. the formed using the `difference rate', i.e. the
difference between the proportion of indivi- difference between the proportion of indivi-
duals with absent or reversed asymmetry in duals with absent or reversed asymmetry in
the patient group and in the control group. the patient group and in the control group.
For the meta-analyses on asymmetry of the For the meta-analyses on asymmetry of the
planum temporale, Sylvian fissure, tempor- planum temporale, Sylvian fissure, tempor-
al horn of the lateral ventricle and superior al horn of the lateral ventricle and superior
temporal gyrus, effect sizes were computed temporal gyrus, effect sizes were computed
from the mean size (and standard devia- from the mean size (and standard devia-
tion) of left and right structures. The mea- tion) of left and right structures. The mea-
surements concerned absolute structure surements concerned absolute structure
sizes, not corrected for total brain volume, sizes, not corrected for total brain volume,
and total structure sizes (not only grey and total structure sizes (not only grey
matter volumes). When studies gave sepa- matter volumes). When studies gave sepa-
rate data for men and women, these were rate data for men and women, these were
included as two independent effect sizes, included as two independent effect sizes,
thereby increasing the total number of thereby increasing the total number of
effect sizes ( effect sizes (K K). ).
Each study was used for three meta- Each study was used for three meta-
analyses. In the first, asymmetry of the analyses. In the first, asymmetry of the
structure was calculated for the control structure was calculated for the control
subjects. In the second, asymmetry was subjects. In the second, asymmetry was
calculated for the patients. The third calculated for the patients. The third
meta-analysis was conducted on the differ- meta-analysis was conducted on the differ-
ence of the two ence of the two d d values of each group values of each group
and compared asymmetry in patients to and compared asymmetry in patients to
that in controls. In this way, differences in that in controls. In this way, differences in
overall brain size between patients and con- overall brain size between patients and con-
trols could not influence the outcome, as trols could not influence the outcome, as
every structure was compared to its contra- every structure was compared to its contra-
lateral homologue first, after which the re- lateral homologue first, after which the re-
sulting standardised asymmetry indices sulting standardised asymmetry indices
were compared between the groups. Differ- were compared between the groups. Differ-
ences in measurement technique between ences in measurement technique between
the studies were largely controlled for, as the studies were largely controlled for, as
well as the statistic results from within- well as the statistic results from within-
study comparisons. study comparisons.
When studies that measured the super- When studies that measured the super-
ior temporal gyrus provided separate data ior temporal gyrus provided separate data
on anterior, middle and posterior segments, on anterior, middle and posterior segments,
these were pooled. these were pooled.
All studies had included predominantly All studies had included predominantly
right-handed subjects, except for Holinger right-handed subjects, except for Holinger
et al et al (1999), who measured superior tem- (1999), who measured superior tem-
poral gyral volumes in left-handed patients poral gyral volumes in left-handed patients
with schizophrenia and left-handed con- with schizophrenia and left-handed con-
trols. To increase homogeneity among trols. To increase homogeneity among
studies, this study was excluded in the studies, this study was excluded in the
meta-analysis, but included for the calcula- meta-analysis, but included for the calcula-
tion of a possible correlation between tion of a possible correlation between
handedness distribution and asymmetry. handedness distribution and asymmetry.
RESULTS RESULTS
Sixteen cross-sectional studies that assessed Sixteen cross-sectional studies that assessed
handedness in patients with schizophrenia handedness in patients with schizophrenia
and healthy subjects were included (Taylor and healthy subjects were included (Taylor
et al et al, 1980; Chaugule & Master, 1981; , 1980; Chaugule & Master, 1981;
Piran Piran et al et al, 1982; Kameyama , 1982; Kameyama et al et al, 1983; , 1983;
Manschreck & Ames, 1984; Merrin, Manschreck & Ames, 1984; Merrin,
1985; Shan-Ming 1985; Shan-Ming et al et al, 1985; Green , 1985; Green et al et al, ,
1989; Nelson 1989; Nelson et al et al, 1993; Clementz , 1993; Clementz et al et al, ,
1994; Cannon 1994; Cannon et al et al, 1995; Green & Rieg, , 1995; Green & Rieg,
1995; O'Callaghan 1995; O'Callaghan et al et al, 1995; Taylor & , 1995; Taylor &
Amir, 1995; Malesu Amir, 1995; Malesu et al et al, 1996; Orr , 1996; Orr et al et al, ,
1999). 1999).
Meta-analysis on these studies showed Meta-analysis on these studies showed
that the prevalence of non-right-handed- that the prevalence of non-right-handed-
ness was significantly higher in patients ness was significantly higher in patients
with schizophrenia than in healthy subjects with schizophrenia than in healthy subjects
(Table 1). The magnitude of the odds ratios (Table 1). The magnitude of the odds ratios
of each study is shown in Fig. 1. of each study is shown in Fig. 1.
Three prospective follow-up studies Three prospective follow-up studies
measured hand preference in children of measured hand preference in children of
large birth cohorts, who were screened for large birth cohorts, who were screened for
schizophrenia in adult life (David schizophrenia in adult life (David et al et al, ,
1995; Crow 1995; Crow et al et al, 1996; Cannon , 1996; Cannon et al et al, ,
1997). From these, only one study (Crow 1997). From these, only one study (Crow
et al et al, 1996) provided quantitative indices , 1996) provided quantitative indices
on the degree of handedness. In the meta- on the degree of handedness. In the meta-
analysis of these studies, pre-schizophrenic analysis of these studies, pre-schizophrenic
subjects were significantly more often subjects were significantly more often
non-right-handed than were the general non-right-handed than were the general
population (Table 1). population (Table 1).
Additional analysis was performed on Additional analysis was performed on
nine studies where the comparison group nine studies where the comparison group
3 4 5 3 4 5
Table1 Table1 Summary of meta-analyses of difference in cerebral dominance between patients with schizophrenia and comparison subjects Summary of meta-analyses of difference in cerebral dominance between patients with schizophrenia and comparison subjects
Index Index K K N N D D OR OR DR DR 95% CI 95%CI Z Z ( (P P) ) O O ( (P P) )
Patients with schizophrenia Patients with schizophrenia v. v. healthy controls healthy controls
Patients with schizophrenia Patients with schizophrenia v. v. psychiatric controls psychiatric controls
Prospective Prospective
16 16
9 9
3 3
5467 5467
1492 1492
55 579 55 579
1.61 1.61
1.54 1.54
1.48 1.48
1.41^1.81 1.41^1.81
1.28^1.84 1.28^1.84
1.23^1.79 1.23^1.79
3.69 (0.0002) 3.69 (0.0002)
2.36 (0.009) 2.36 (0.009)
2.07 (0.02) 2.07 (0.02)
23.6 (0.13) 23.6 (0.13)
11.46 (0.2) 11.46 (0.2)
2.24 (0.31) 2.24 (0.31)
Dichotic listening Dichotic listening
All verbal tasks All verbal tasks
Only CVand fused-words Only CVand fused-words
10 10
6 6
434 434
267 267
7 70.19 0.19
7 70.48 0.48
7 70.6^0.2 0.6^0.2
7 70.83 to 0.83 to 7 70.14 0.14
7 70.92 (0.18) 0.92 (0.18)
12.74 (0.003) 12.74 (0.003)
29.2 (0.001) 29.2 (0.001)
8.9 (0.11) 8.9 (0.11)
Frontal torque Frontal torque
Occipital torque Occipital torque
Planum temporale Planum temporale
Sylvian fissure Sylvian fissure
Temporal horn lateral ventricle Temporal horn lateral ventricle
Superior temporal gyrus Superior temporal gyrus
Posterior segment STG Posterior segment STG
3 3
5 5
11 11
3 3
12 12
17 17
5 5
383 383
579 579
368 368
185 185
629 629
1020 1020
238 238
7 70.51 0.51
7 70.62 0.62
7 70.11 0.11
0.21 0.21
0.7 0.7
0.24 0.24
0.22 0.22
0.15^0.34 0.15^0.34
0.12^0.28 0.12^0.28
7 71.04^0.02 1.04^0.02
7 71.04^0.2 1.04^0.2
7 70.61^0.4 0.61^0.4
7 70.08^0.51 0.08^0.51
0.4^1 0.4^1
5.11 (0.05) 5.11 (0.05)
7.59 (0.01) 7.59 (0.01)
7 71.87 (0.03) 1.87 (0.03)
7 72.87 (0.002) 2.87 (0.002)
7 70.41 (0.34) 0.41 (0.34)
1.41 (0.08) 1.41 (0.08)
6.3 (0.0001) 6.3 (0.0001)
8.4 (0.05) 8.4 (0.05)
87.55 (0.003) 87.55 (0.003)
54.5 (0.0005) 54.5 (0.0005)
11.1 (0.03) 11.1 (0.03)
106.83 (0.0001) 106.83 (0.0001)
93.3 (0.0001) 93.3 (0.0001)
5.42 (0.37) 5.42 (0.37)
K K, number of effect sizes; , number of effect sizes; N N, number of subjects; , number of subjects; D D, mean weighted effect size; OR, mean weighted odds ratio; DR, mean weighted difference rate; CV, consonant^vowel; STG, , mean weighted effect size; OR, mean weighted odds ratio; DR, mean weighted difference rate; CV, consonant^vowel; STG,
superior temporal gyrus; Z, Stouffer's Z. superior temporal gyrus; Z, Stouffer's Z.
SOMMER ET AL SOMMER E T AL
consisted of non-schizophrenia psychiatric consisted of non-schizophrenia psychiatric
or neurological patients (Chaugule & Mas- or neurological patients (Chaugule & Mas-
ter, 1981; Piran ter, 1981; Piran et al et al, 1982; Manschreck & , 1982; Manschreck &
Ames, 1984; Merrin, 1985; Shan-Ming Ames, 1984; Merrin, 1985; Shan-Ming et et
al al, 1985; Clementz , 1985; Clementz et al et al, 1994; Taylor & , 1994; Taylor &
Amir, 1995; Malesu Amir, 1995; Malesu et al et al, 1996; Orr , 1996; Orr et al et al, ,
1999). The results indicated that the preva- 1999). The results indicated that the preva-
lence of non-right-handedness was signifi- lence of non-right-handedness was signifi-
cantly higher in schizophrenia subjects cantly higher in schizophrenia subjects
than in other psychiatric and neurological than in other psychiatric and neurological
patients (Table 1). patients (Table 1).
Meta-analysis was conducted on 10 dicho- Meta-analysis was conducted on 10 dicho-
tic listening studies that compared patients tic listening studies that compared patients
with schizophrenia to healthy controls with schizophrenia to healthy controls
(Hatta (Hatta et al et al, 1984; Wexler , 1984; Wexler et al et al, 1991; Carr , 1991; Carr
et al et al, 1992; Ragland , 1992; Ragland et al et al, 1992; Seidman , 1992; Seidman et et
al al, 1993; Grosh , 1993; Grosh et al et al, 1995; Sakuma , 1995; Sakuma et al et al, ,
1996; Oie 1996; Oie et al et al, 1998; Bruder , 1998; Bruder et al et al, 1999; , 1999;
Lberg Lberg et al et al, 1999). The right-ear advan- , 1999). The right-ear advan-
tage was not significantly decreased in tage was not significantly decreased in
schizophrenia, with significant hetero- schizophrenia, with significant hetero-
geneity among studies (Table 1). The geneity among studies (Table 1). The
magnitude of the effect size of each study magnitude of the effect size of each study
is represented in Fig. 2. is represented in Fig. 2.
A possible cause for the inhomogeneity A possible cause for the inhomogeneity
in these studies may be the difference in ver- in these studies may be the difference in ver-
bal tasks the studies used to elicit a right-ear bal tasks the studies used to elicit a right-ear
advantage. Four different tasks were used: advantage. Four different tasks were used:
the triad task, the fused-word task, the con- the triad task, the fused-word task, the con-
sonantvowel task and the sonantvowel task and the word-monitoring word-monitoring
task. The fused-word and the consonant task. The fused-word and the consonant
vowel tasks are considered to reflect vowel tasks are considered to reflect
cerebral cerebral dominance most accurately (see dominance most accurately (see
Discussion). When only studies that used Discussion). When only studies that used
the fused-word and the consonantvowel the fused-word and the consonantvowel
tasks were included, the right-ear advantage tasks were included, the right-ear advantage
was significantly lower in schizophrenia was significantly lower in schizophrenia
and studies were no longer heterogeneous and studies were no longer heterogeneous
(Table 1). (Table 1).
Brain torque Brain torque
Meta-analyses were conducted on the fre- Meta-analyses were conducted on the fre-
quency of abnormal asymmetry of the fron- quency of abnormal asymmetry of the fron-
tal lobe (Andreasen tal lobe (Andreasen et al et al, 1982; Jernigan , 1982; Jernigan et et
al al, 1982; Falkai , 1982; Falkai et al et al, 1995 , 1995b b) and the occi- ) and the occi-
pital lobe (Andreasen pital lobe (Andreasen et al et al, 1982; Jernigan , 1982; Jernigan
et al et al, 1982; Luchins & Meltzer, 1983, , 1982; Luchins & Meltzer, 1983,
1986; Falkai 1986; Falkai et al et al, 1995 , 1995b b). The results ). The results
showed that the frequency of abnormal showed that the frequency of abnormal
asymmetry was significantly higher in asymmetry was significantly higher in
schizophrenia for both the frontal and the schizophrenia for both the frontal and the
occipital lobe, but studies were hetero- occipital lobe, but studies were hetero-
geneous (Table 1). The small number of geneous (Table 1). The small number of
studies allowed no further investigation of studies allowed no further investigation of
potential moderators. potential moderators.
Planumtemporale Planum temporale
Meta-analysis was performed on 10 Meta-analysis was performed on 10
studies that measured the planum tempor- studies that measured the planum tempor-
ale in schizophrenia (Rossi ale in schizophrenia (Rossi et al et al, 1992, , 1992,
1994; Kleinschmidt 1994; Kleinschmidt et al et al, 1994; Falkai , 1994; Falkai et et
al al, 1995 , 1995a a; Kulynych ; Kulynych et al et al, 1995; Petty , 1995; Petty et al et al, ,
1995; Jacobsen 1995; Jacobsen et al et al, 1996; Barta , 1996; Barta et al et al, ,
1997; Frangou 1997; Frangou et al et al, 1997; Kwon , 1997; Kwon et et
al al, 1999). , 1999). In the meta-analysis, significant In the meta-analysis, significant
asymmetry favouring the left hemisphere asymmetry favouring the left hemisphere
was found for the healthy comparison was found for the healthy comparison
subjects, but not for the patients (Table subjects, but not for the patients (Table
2). Studies were homogeneous for the com- 2). Studies were homogeneous for the com-
parison subjects, but heterogeneous for the parison subjects, but heterogeneous for the
patients, indicating that difference in mea- patients, indicating that difference in mea-
surement technique is not a factor. Possible surement technique is not a factor. Possible
moderators may be found in characteristics moderators may be found in characteristics
of the patient samples. Only three variables of the patient samples. Only three variables
were reported frequently enough to calcu- were reported frequently enough to calcu-
late correlations, but no significant result late correlations, but no significant result
emerged: gender distribution emerged: gender distribution n n10, 10,
r r7 70.25, NS; handedness distribution 0.25, NS; handedness distribution
n n9, 9, r r0.38, NS; duration of illness 0.38, NS; duration of illness n n6, 6,
r r7 70.29, NS. 0.29, NS.
In the meta-analysis directly comparing In the meta-analysis directly comparing
patients and controls, asymmetry of the pla- patients and controls, asymmetry of the pla-
num temporale was significantly reduced in num temporale was significantly reduced in
patients (Table 1). The magnitude of the dif- patients (Table 1). The magnitude of the dif-
ference in effect sizes of asymmetry between ference in effect sizes of asymmetry between
patients and controls is shown in Fig. 3. patients and controls is shown in Fig. 3.
In the meta-analysis on studies on asymme- In the meta-analysis on studies on asymme-
try of the Sylvian fissure (Falkai try of the Sylvian fissure (Falkai et al et al, 1992; , 1992;
Hoff Hoff et al et al, 1992; Bartley , 1992; Bartley et al et al, 1993), both , 1993), both
controls and patients showed significant controls and patients showed significant
asymmetry favouring the left hemisphere asymmetry favouring the left hemisphere
(Table 2), but studies were heterogeneous (Table 2), but studies were heterogeneous
for both groups. The small number of stu- for both groups. The small number of stu-
dies allowed no further investigation of po- dies allowed no further investigation of po-
tential moderators. When asymmetry of the tential moderators. When asymmetry of the
Sylvian fissure was directly compared be- Sylvian fissure was directly compared be-
tween patients with schizophrenia and tween patients with schizophrenia and
healthy subjects, patients showed signifi- healthy subjects, patients showed signifi-
cantly decreased asymmetry (Table 1). cantly decreased asymmetry (Table 1).
3 4 6 3 4 6
Fig. 1 Fig. 1 Odds ratios of non-right-handedness in schizophrenia. Odds ratios of non-right-handedness in schizophrenia.
Fig. 2 Fig. 2 Effect sizes of dichotic listening studies in schizophrenia (patients^controls). Effect sizes of dichotic listening studies in schizophrenia (patients^controls).
Temporal horn of the lateral ventricle Temporal horn of the lateral ventricle
Eight studies on asymmetry of the temporal Eight studies on asymmetry of the temporal
horn of the lateral ventricle were included horn of the lateral ventricle were included
(Bogerts (Bogerts et al et al, 1990; Dauphinais , 1990; Dauphinais et al et al, ,
1990; DeLisi 1990; DeLisi et al et al, 1991; Zipursky , 1991; Zipursky et al et al, ,
1994; Flaum 1994; Flaum et al et al, 1995; Becker , 1995; Becker et al et al, ,
1996; Marsh 1996; Marsh et al et al, 1997; Pearlson , 1997; Pearlson et al et al, ,
1997). In healthy as well as in schizo- 1997). In healthy as well as in schizo-
phrenia subjects, rightward asymmetry phrenia subjects, rightward asymmetry
was found (Table 2). Studies were homo- was found (Table 2). Studies were homo-
geneous for the analysis of control subjects, geneous for the analysis of control subjects,
but heterogeneous in the patients' analysis but heterogeneous in the patients' analysis
(Table 2). Correlations between asymmetry (Table 2). Correlations between asymmetry
in patients and possible moderators were in patients and possible moderators were
not significant: gender distribution not significant: gender distribution n n8, 8,
n n5, 5, r r0.27, NS; duration of illness 0.27, NS; duration of illness n n6, 6,
r r7 70.7, NS. In the meta-analysis directly 0.7, NS. In the meta-analysis directly
comparing patients and controls, asymme- comparing patients and controls, asymme-
try of the temporal horn was not signifi- try of the temporal horn was not signifi-
cantly different between schizophrenia and cantly different between schizophrenia and
healthy subjects (Table 1). healthy subjects (Table 1).
Meta-analysis was performed on 15 studies Meta-analysis was performed on 15 studies
measuring superior temporal gyrus in measuring superior temporal gyrus in
schizophrenia subjects and healthy controls schizophrenia subjects and healthy controls
(Barta (Barta et al et al, 1990; Zipursky , 1990; Zipursky et al et al, 1994; , 1994;
Flaum Flaum et al et al, 1995; Menon , 1995; Menon et al et al, 1995; Vita , 1995; Vita
et al et al, 1995; Kulynych , 1995; Kulynych et al et al, 1996; Frangou , 1996; Frangou
et al et al, 1997; Marsh , 1997; Marsh et al et al, 1997; Pearlson , 1997; Pearlson et et
al al, 1997; Reite , 1997; Reite et al et al, 1997; Hirayasu , 1997; Hirayasu et al et al, ,
1998; Jacobsen 1998; Jacobsen et al et al, 1998; Bryant , 1998; Bryant et al et al, ,
1999; Havermans 1999; Havermans et al et al, 1999; Highley , 1999; Highley et et
al al, 1999). , 1999).
The results showed that the superior The results showed that the superior
temporal gyrus was larger in the right hemi- temporal gyrus was larger in the right hemi-
sphere in schizophrenia subjects, while con- sphere in schizophrenia subjects, while con-
trols showed a trend towards asymmetry in trols showed a trend towards asymmetry in
the same direction (Table 2). Studies were the same direction (Table 2). Studies were
heterogeneous for both groups and thus dif- heterogeneous for both groups and thus dif-
ferences in measurement technique may ferences in measurement technique may
have acted as moderators. The only study have acted as moderators. The only study
on post-mortem brains (Highley on post-mortem brains (Highley et al et al, ,
1999) found larger volumes of the superior 1999) found larger volumes of the superior
temporal gyrus in the left hemisphere in temporal gyrus in the left hemisphere in
controls, while 13 of 14 magnetic reso- controls, while 13 of 14 magnetic reso-
nance imaging (MRI) studies found larger nance imaging (MRI) studies found larger
volumes in the right hemisphere in controls. volumes in the right hemisphere in controls.
However, when the post-mortem study was However, when the post-mortem study was
excluded from analysis, heterogeneity excluded from analysis, heterogeneity
among studies remained high. Correlations among studies remained high. Correlations
between the effect size of asymmetry in between the effect size of asymmetry in
controls and other potential moderators controls and other potential moderators
were not significant (slice and gap thickness were not significant (slice and gap thickness
n n15, 15, r r7 70.039, NS; sample size 0.039, NS; sample size n n15, 15,
r r7 70.22, NS; gender distribution 0.22, NS; gender distribution n n15, 15,
n n15, 15, r r0.32, NS). Correlations between 0.32, NS). Correlations between
potential moderators and the effect size of potential moderators and the effect size of
asymmetry in patients were not significant asymmetry in patients were not significant
either (slice and gap thickness either (slice and gap thickness n n15, 15,
r r0.15, NS; sample size 0.15, NS; sample size n n15, 15, r r7 70.18, 0.18,
NS; gender distribution NS; gender distribution n n15, 15, r r7 70.27, 0.27,
NS; handedness distribution NS; handedness distribution n n15, 15,
r r7 70.29, NS; duration of illness 0.29, NS; duration of illness n n5, 5,
r r7 70.51, NS). 0.51, NS).
In the meta-analysis directly comparing In the meta-analysis directly comparing
patients and controls, the patients with patients and controls, the patients with
schizophrenia tended to have increased schizophrenia tended to have increased
asymmetry of the superior temporal gyrus asymmetry of the superior temporal gyrus
favouring the right hemisphere, but statisti- favouring the right hemisphere, but statisti-
cal significance was not reached (Table 1). cal significance was not reached (Table 1).
Posterior segment of the superior temporal Posterior segment of the superior temporal
gyrus gyrus
A separate analysis on five studies (Menon A separate analysis on five studies (Menon
et al et al, 1995; Kulynych , 1995; Kulynych et al et al, 1996; Pearlson , 1996; Pearlson
et al et al, 1997; Hirayasu , 1997; Hirayasu et al et al, 1998; Jacobsen , 1998; Jacobsen
et al et al, 1998) was performed to assess asym- , 1998) was performed to assess asym-
metry of the posterior segment of the super- metry of the posterior segment of the super-
ior temporal gyrus. Rightward asymmetry ior temporal gyrus. Rightward asymmetry
was found for the patients, while the con- was found for the patients, while the con-
trols showed a trend towards asymmetry trols showed a trend towards asymmetry
3 4 7 3 4 7
Table 2 Table 2 Summary of meta-analyses of difference in size between left and right hemispheric structures in controls and patients Summary of meta-analyses of difference in size between left and right hemispheric structures in controls and patients
Index Index K K N N D D 95%CI 95%CI Z Z ( (P P) ) Q Q ( (P P) )
Healthy controls Healthy controls
11 11
3 3
12 12
17 17
5 5
187 187
100 100
303 303
399 399
130 130
0.7 0.7
0.87 0.87
7 70.25 0.25
7 70.47 0.47
7 70.2 0.2
0.49^0.91 0.49^0.91
0.43^1.32 0.43^1.32
7 70.41 to 0.41 to 7 70.09 0.09
7 71.1^0.14 1.1^0.14
7 70.44^0.05 0.44^0.05
6.5 (0.00001) 6.5 (0.00001)
3.86 (0.00006) 3.86 (0.00006)
7 73.05 (0.001) 3.05 (0.001)
7 71.5 (0.07) 1.5 (0.07)
7 71.58 (0.06) 1.58 (0.06)
4.3 (0.89) 4.3 (0.89)
9.85 (0.04) 9.85 (0.04)
9.32 (0.59) 9.32 (0.59)
140.23 (0.0001) 140.23 (0.0001)
1.5 (0.9) 1.5 (0.9)
Patients with schizophrenia Patients with schizophrenia
11 11
3 3
12 12
17 17
5 5
181 181
97 97
324 324
469 469
108 108
0.18 0.18
0.31 0.31
7 70.42 0.42
7 70.73 0.73
7 70.9 0.9
7 70.33^0.69 0.33^0.69
7 71.04^0.2 1.04^0.2
7 70.88 to 0.88 to 7 70.04 0.04
7 71.2 to 1.2 to 7 70.25 0.25
7 70.17 to 0.17 to 7 70.62 0.62
0.7 (0.24) 0.7 (0.24)
2.87 (0.002) 2.87 (0.002)
7 71.81 (0.04) 1.81 (0.04)
7 72.95 (0.0016) 2.95 (0.0016)
7 76.23 (0.00001) 6.23 (0.00001)
48.7 (0.001) 48.7 (0.001)
4.72 (0.32) 4.72 (0.32)
92.5 (0.00001) 92.5 (0.00001)
151.7 (0.0001) 151.7 (0.0001)
4.85 (0.43) 4.85 (0.43)
K K, number of effect sizes; , number of effect sizes; N N, number of subjects; , number of subjects; D D, mean weighted effect size; , mean weighted effect size; Z Z, Stouffer's , Stouffer's Z Z; ; Q Q, within-category homogeneity statistic; STG, superior temporal gyrus. , within-category homogeneity statistic; STG, superior temporal gyrus.
Fig. 3 Fig. 3 Difference in asymmetry (patients^controls) of the planum temporale. Difference in asymmetry (patients^controls) of the planum temporale.
in the same direction (Table 2). In the meta- in the same direction (Table 2). In the meta-
analysis directly comparing patients and analysis directly comparing patients and
controls, rightward asymmetry of the pos- controls, rightward asymmetry of the pos-
terior segment of the superior temporal terior segment of the superior temporal
gyrus was significantly larger in patients gyrus was significantly larger in patients
(Table 1). (Table 1).
DISCUSSION DISCUSSION
The purpose of this study was to summarise The purpose of this study was to summarise
present literature on cerebral dominance in present literature on cerebral dominance in
schizophrenia quantitatively. The resulting schizophrenia quantitatively. The resulting
analyses showed that functional asymmetry analyses showed that functional asymmetry
is decreased in schizophrenia, which was is decreased in schizophrenia, which was
reflected in an increased prevalence of reflected in an increased prevalence of
non-right-handedness and decreased lan- non-right-handedness and decreased lan-
guage lateralisation in dichotic listening guage lateralisation in dichotic listening
studies that applied the fused-word or con- studies that applied the fused-word or con-
sonantvowel task. Decreased structural sonantvowel task. Decreased structural
asymmetry in schizophrenia was found for asymmetry in schizophrenia was found for
brain torque, the planum temporale and brain torque, the planum temporale and
Sylvian fissure, but not for the temporal Sylvian fissure, but not for the temporal
horn of the lateral ventricle. horn of the lateral ventricle.
Hand preference Hand preference
In the meta-analysis on handedness in In the meta-analysis on handedness in
cross-sectional studies, schizophrenia sub- cross-sectional studies, schizophrenia sub-
jects were more frequently non-right- jects were more frequently non-right-
handed than healthy persons. However, handed than healthy persons. However,
these studies mainly included hospitalised these studies mainly included hospitalised
patients with schizophrenia, thus tending patients with schizophrenia, thus tending
to overrepresent severe cases. Prospective to overrepresent severe cases. Prospective
cohort studies do not have this limitation, cohort studies do not have this limitation,
since they are population-based. In the since they are population-based. In the
meta-analysis on three prospective cohort meta-analysis on three prospective cohort
studies, the prevalence of non-right-handed- studies, the prevalence of non-right-handed-
ness in subjects that later developed ness in subjects that later developed
schizophrenia was significantly increased. schizophrenia was significantly increased.
However, many diseases that involve However, many diseases that involve
subtle brain damage may be accompanied subtle brain damage may be accompanied
by increased prevalence of non-right-hand- by increased prevalence of non-right-hand-
edness (Satz & Green, 1999). To investi- edness (Satz & Green, 1999). To investi-
gate the specificity of increased non-right- gate the specificity of increased non-right-
handedness in schizophrenia, an additional handedness in schizophrenia, an additional
analysis was conducted comparing schizo- analysis was conducted comparing schizo-
phrenia patients with non-schizophrenia phrenia patients with non-schizophrenia
psychiatric and neurological patients. In psychiatric and neurological patients. In
that analysis, non-right-handedness was that analysis, non-right-handedness was
still significantly increased in schizo- still significantly increased in schizo-
phrenia, suggesting that a specific cerebral phrenia, suggesting that a specific cerebral
lesion cannot explain the increased preva- lesion cannot explain the increased preva-
lence of non-right-handedness in schizo- lence of non-right-handedness in schizo-
phrenia. Thus, a more fundamental, phrenia. Thus, a more fundamental,
possibly genetic mechanism may be possibly genetic mechanism may be
involved. Interestingly, several studies involved. Interestingly, several studies
report increased non-right-handedness in report increased non-right-handedness in
healthy relatives of patients with schizo- healthy relatives of patients with schizo-
phrenia (Hallett phrenia (Hallett et al et al, 1986; Chapman & , 1986; Chapman &
Chapman, 1987; Orr Chapman, 1987; Orr et al et al, 1999), suggesting , 1999), suggesting
a genetic cause for decreased cerebral dom- a genetic cause for decreased cerebral dom-
inance in schizophrenia (Crow inance in schizophrenia (Crow et al et al, 1989). , 1989).
In the analysis of dichotic listening studies, In the analysis of dichotic listening studies,
the right-ear advantage was not the right-ear advantage was not significantly significantly
decreased in schizophrenia, while hetero- decreased in schizophrenia, while hetero-
geneity among studies was high. This may geneity among studies was high. This may
be attributable to the differences in verbal be attributable to the differences in verbal
tasks used to elicit a right-ear advantage. tasks used to elicit a right-ear advantage.
For the triad task and the word- For the triad task and the word-
monitoring task, subjects have to respond monitoring task, subjects have to respond
to all stimuli on either ear. Schizophrenia to all stimuli on either ear. Schizophrenia
subjects generally have a lower perfor- subjects generally have a lower perfor-
mance on these tasks than healthy subjects mance on these tasks than healthy subjects
(Hatta (Hatta et al et al, 1984; Carr , 1984; Carr et al et al, 1992; , 1992;
Seidman Seidman et al et al, 1993; Sakuma , 1993; Sakuma et al et al, 1996). , 1996).
On several items of these tasks, controls On several items of these tasks, controls
may have 100% correct response, in which may have 100% correct response, in which
case no perceptual asymmetry is measured. case no perceptual asymmetry is measured.
These ceiling effects in the control, but not These ceiling effects in the control, but not
in the schizophrenia group, may cause rela- in the schizophrenia group, may cause rela-
tively low ear asymmetry in the control tively low ear asymmetry in the control
group. For the consonantvowel and the group. For the consonantvowel and the
fused-word tasks, subjects were asked to re- fused-word tasks, subjects were asked to re-
spond only to the most clearly perceived spond only to the most clearly perceived
item, thereby avoiding the problem of ceil- item, thereby avoiding the problem of ceil-
ing effects. When only studies that applied ing effects. When only studies that applied
the consonantvowel or fused-word task the consonantvowel or fused-word task
were included, patients with schizophrenia were included, patients with schizophrenia
showed a significantly decreased right-ear showed a significantly decreased right-ear
advantage and heterogeneity disappeared. advantage and heterogeneity disappeared.
A decreased right-ear advantage was also A decreased right-ear advantage was also
reported in healthy parents (Grosh reported in healthy parents (Grosh et al et al, ,
1995) and children (Hallett 1995) and children (Hallett et al et al, 1986) of , 1986) of
patients with schizophrenia, supporting patients with schizophrenia, supporting
the hypothesised genetic origin of decreased the hypothesised genetic origin of decreased
lateralisation in schizophrenia. lateralisation in schizophrenia.
In the meta-analysis of anatomical studies, In the meta-analysis of anatomical studies,
the direction of brain torque was more fre- the direction of brain torque was more fre-
quently inverted, while the planum tempor- quently inverted, while the planum tempor-
ale and Sylvian fissure showed reduced ale and Sylvian fissure showed reduced
asymmetry in schizophrenia. The decreased asymmetry in schizophrenia. The decreased
temporo-parietal asymmetries probably re- temporo-parietal asymmetries probably re-
flect decreased language dominance, since flect decreased language dominance, since
planum temporale and Sylvian fissure planum temporale and Sylvian fissure
asymmetries are strongly related to cerebral asymmetries are strongly related to cerebral
dominance (Gerschlager dominance (Gerschlager et al et al, 1998). , 1998).
Shapleske Shapleske et al et al (1999) published an exten- (1999) published an exten-
sive review on the planum temporale that sive review on the planum temporale that
also contained a meta-analysis on the pla- also contained a meta-analysis on the pla-
num temporale in schizophrenia. The pre- num temporale in schizophrenia. The pre-
sent study, using more stringent inclusion sent study, using more stringent inclusion
criteria and including several recently pub- criteria and including several recently pub-
lished studies, confirms Shapleske lished studies, confirms Shapleske et al et al's 's
finding of decreased asymmetry of the finding of decreased asymmetry of the
planum temporale in schizophrenia. planum temporale in schizophrenia.
Crow Crow et al et al (1989) reported that the (1989) reported that the
temporal horn of the lateral ventricle was temporal horn of the lateral ventricle was
larger in the right hemisphere in the normal larger in the right hemisphere in the normal
control group of their post-mortem study, control group of their post-mortem study,
probably owing to the more extended probably owing to the more extended
language-related cortex at the dominant side. language-related cortex at the dominant side.
The present results fromthe meta-analysis The present results fromthe meta-analysis on on
healthy subjects confirm this finding. How- healthy subjects confirm this finding. How-
ever, while Crow reported reduced asym- ever, while Crow reported reduced asym-
metry of the temporal horn in metry of the temporal horn in
schizophrenia, the present meta-analysis schizophrenia, the present meta-analysis
found no significantly decreased asymmetry found no significantly decreased asymmetry
Asymmetry of the superior temporal Asymmetry of the superior temporal
gyrus is also frequently used as an indica- gyrus is also frequently used as an indica-
tion of language lateralisation (Pearlson tion of language lateralisation (Pearlson et et
al al, 1997; Highley , 1997; Highley et al et al, 1999; Holinger , 1999; Holinger et et
al al, 1999; Levitan , 1999; Levitan et al et al, 1999). However, di- , 1999). However, di-
rection and magnitude of asymmetry of this rection and magnitude of asymmetry of this
structure is not well established in healthy structure is not well established in healthy
subjects. In this meta-analysis, controls subjects. In this meta-analysis, controls
showed a trend towards asymmetry favour- showed a trend towards asymmetry favour-
ing the right hemisphere, while the superior ing the right hemisphere, while the superior
temporal gyrus was found to be greater on temporal gyrus was found to be greater on
the right in patients. The trend towards the right in patients. The trend towards
rightward asymmetry in healthy subjects is rightward asymmetry in healthy subjects is
surprising since it partly overlaps with Wer- surprising since it partly overlaps with Wer-
nicke's area. However, the superior tem- nicke's area. However, the superior tem-
poral gyrus also incorporates primary and poral gyrus also incorporates primary and
secondary auditory cortex that generally secondary auditory cortex that generally
shows rightward asymmetry, reflecting shows rightward asymmetry, reflecting
right hemispheric dominance for non- right hemispheric dominance for non-
verbal sounds (Zattore verbal sounds (Zattore et al et al, 1992). The , 1992). The
posterior segment of the superior temporal posterior segment of the superior temporal
gyrus might be a better candidate to reflect gyrus might be a better candidate to reflect
cerebral dominance for language, since it cerebral dominance for language, since it
mainly consists of language-related hetero- mainly consists of language-related hetero-
modal cortex (Pearlson, 1997). However, modal cortex (Pearlson, 1997). However,
in the current meta-analysis, this segment in the current meta-analysis, this segment
also showed a trend towards asymmetry also showed a trend towards asymmetry
favouring the right hemisphere in healthy favouring the right hemisphere in healthy
subjects. Therefore, neither the superior subjects. Therefore, neither the superior
temporal gyrus, nor its posterior segment temporal gyrus, nor its posterior segment
appears suited for the assessment of appears suited for the assessment of
cerebral dominance for language. cerebral dominance for language.
Limitations Limitations
The presented paper included only studies The presented paper included only studies
on language lateralisation that used the di- on language lateralisation that used the di-
chotic listening paradigm. We were unable chotic listening paradigm. We were unable
to retrieve enough visual half-field studies to retrieve enough visual half-field studies
using language stimuli to allow for meta- using language stimuli to allow for meta-
analysis. Data of functional imaging studies analysis. Data of functional imaging studies
are considered to be too diverse regarding are considered to be too diverse regarding
technical assessment and statistical analysis technical assessment and statistical analysis
to allow for direct comparison in a meta- to allow for direct comparison in a meta-
analysis (Lange, 1999). A second limitation analysis (Lange, 1999). A second limitation
of the study is our choice to include only of the study is our choice to include only
studies on patients with strict diagnosis of studies on patients with strict diagnosis of
3 4 8 3 4 8
schizophrenia, excluding studies that used schizophrenia, excluding studies that used
the broad DSMII criteria for schizo- the broad DSMII criteria for schizo-
phrenia and studies that used patients with phrenia and studies that used patients with
schizophrenia-spectrum disorders. Another schizophrenia-spectrum disorders. Another
reason that several studies could not be in- reason that several studies could not be in-
cluded was the absence of healthy control cluded was the absence of healthy control
groups. By applying these strict inclusion groups. By applying these strict inclusion
criteria, the total number of studies was criteria, the total number of studies was
lower, but the contrast between the experi- lower, but the contrast between the experi-
mental and the comparison group was mental and the comparison group was
maximal. maximal.
Clinical implications Clinical implications
The reported excess of non-right-handed- The reported excess of non-right-handed-
ness and decreased right-ear advantage in ness and decreased right-ear advantage in
healthy relatives of patients with schizo- healthy relatives of patients with schizo-
phrenia suggest a genetic cause underlying phrenia suggest a genetic cause underlying
the decreased cerebral lateralisation in the decreased cerebral lateralisation in
schizophrenia. If this were true, a deviation schizophrenia. If this were true, a deviation
of the genetic mechanism underlying cere- of the genetic mechanism underlying cere-
bral dominance, the hypothesised `right- bral dominance, the hypothesised `right-
shift factor' may cause a vulnerability to shift factor' may cause a vulnerability to
schizophrenia (Annett, 1999; Crow, schizophrenia (Annett, 1999; Crow,
1999). This implies that the search for 1999). This implies that the search for
genes predisposing for schizophrenia may genes predisposing for schizophrenia may
focus on loci that have a role in the estab- focus on loci that have a role in the estab-
lishment of cerebral dominance. In addi- lishment of cerebral dominance. In addi-
tion, indicators of decreased cerebral tion, indicators of decreased cerebral
dominance in individuals, such as non- dominance in individuals, such as non-
right-handedness, decreased right-ear ad- right-handedness, decreased right-ear ad-
vantage on the dichotic listening paradigm vantage on the dichotic listening paradigm
or decreased asymmetry of the planum tem- or decreased asymmetry of the planum tem-
porale may help to identify subjects at in- porale may help to identify subjects at in-
creased risk for schizophrenia. creased risk for schizophrenia.
In sum, when literature on handedness, In sum, when literature on handedness,
dichotic listening studies and asymmetry of dichotic listening studies and asymmetry of
language-related structures is reviewed language-related structures is reviewed
quantitatively, compelling evidence emer- quantitatively, compelling evidence emer-
ged for decreased cerebral dominance in ged for decreased cerebral dominance in
schizophrenia. schizophrenia.
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3 4 9 3 4 9
CLINICAL IMPLICATIONS CLINICAL IMPLICATIONS
& &
Finding the locus of the gene for cerebral dominance may unravel the genetic Finding the locus of the gene for cerebral dominance may unravel the genetic
predisposition for schizophrenia. predisposition for schizophrenia.
& & Mixed- and left-handed subjects may be at increased risk of schizophrenia. Mixed- and left-handed subjects may be at increased risk of schizophrenia.
& & The dichotic listening paradigm or measurement of planum temporale asymmetry The dichotic listening paradigm or measurement of planum temporale asymmetry
may help identify subjects at increased risk of schizophrenia. may help identify subjects at increased risk of schizophrenia.
LIMITATIONS LIMITATIONS
& &
Visual half-field studies using language stimuli were not included. Visual half-field studies using language stimuli were not included.
& & Functional imaging studies with language activation were not included. Functional imaging studies with language activation were not included.
& & Narrowdefinitions were used for inclusion in the schizophrenia and healthy Narrowdefinitions were used for inclusion in the schizophrenia and healthy
groups. groups.
IRIS SOMMER, MD, NICKRAMSEY, PhD, RENE KAHN, PhD, Department of Psychiatry, University Medical IRIS SOMMER, MD, NICKRAMSEY, PhD, RENE
KAHN, PhD, Department of Psychiatry, University Medical

Centre Utrecht, The Netherlands; ANDRE ALEMAN, MA, Department of Psychonomics, University of Centre Utrecht, The Netherlands; ANDRE
ALEMAN, MA, Department of Psychonomics, University of

Utrecht; ANKE BOUMA, PhD, Department of Neuropsychology, University of Groningen, The Netherlands Utrecht; ANKE BOUMA, PhD, Department of Neuropsychology, University of Groningen, The Netherlands
Correspondence: Iris Sommer, Department of Psychiatry,University Medical Centre Utrecht, Correspondence: Iris Sommer, Department of Psychiatry,University Medical Centre Utrecht,
Heidelberglaan100, 3584CXUtrecht, The Netherlands. Tel: ++3130 2508352; fax: ++3130 2505443; Heidelberglaan100, 3584CXUtrecht, The Netherlands. Tel: ++3130 2508352; fax: ++3130 2505443;
e-mail: I.Sommer e-mail: I.Sommer@ @AZU.nl AZU.nl
(First received 27 April 2000, final revision 11September 2000, accepted13 September 2000) (First received 27 April 2000, final revision11September 2000, accepted 13 September 2000)
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ALEMAN, NICK RAMSEY, ANKE BOUMA

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