Atypical Handedness in Schizophrenia:
Some Methodological and Theoretical Issues
by Paul Satz and Michael Foster Qreen
in the etiology of schizophrenia (Weinberger 1987;
Murray et al. 1992a, 1992*). One behavioral index has
gradually emerged as a potential marker of a neurodevelopmental insult in a subgroup of schizophrenia patients,
namely, atypical handedness.
The purpose of this article is threefold. First, we
review the current status of atypical handedness in schizophrenia to determine whether a leftward shift in the distribution of handedness exists. Second, we examine the current status of neurodevelopmental factors and
mechanisms in schizophrenia that might, in part, explain
this pathological shift, including both left-handedness and
mixed handedness (MH). Finally, we determine whether
this lateral shift is associated with or predicts certain key
symptoms and neural substrates in the disorder (e.g.,
thought disorder, negative symptoms, neuropsychological
impairment, family history, and brain anatomy).
Abstract
An updated review of the literature strongly supports
the view that in schizophrenia there is an atypical leftward shift in the handedness distribution that, while
comprising different subtypes, is characterized by a
more variable and less completely lateralized pattern
of manual preference, referred to as mixed handedness
(MH) or ambiguous handedness (AH). Only two studies revealed an increased prevalence of left-handedness
suggestive of pathological left-handedness (PLH). This
article also examines the current status of neurodevelopmental factors and mechanisms in schizophrenia
that purport to explain these pathological shifts in
handedness (PLH, MH, AH). Different theoretical
positions were evaluated, each involving some aspect
of left hemisphere insult (unilateral or bilateral).
Finally, it was shown that these shifts predict certain
key symptoms and neural substrates in schizophrenia
including thought disorder, negative symptoms, neuropsychological impairment, family history, and brain
anatomy. These subtypes may represent neurodevelopmental markers of insult during intrauterine life that
are nongenetic in origin.
Key words: Handedness, laterality, neuropsychological impairment
Schizophrenia Bulletin, 25(l):63-78,1999.
Atypical Handedness: Is There a Shift
in the Distribution?
The last and most comprehensive review of this literature
was reported by Green et al. (19896). Although the studies varied widely in terms of methodology, procedures,
and results, the predominant finding was a shift in the distribution away from right-handedness. This finding was
based on a majority of the studies (9 positive, 5 null, 2
paradoxical), which included some of the methodologically stronger and more recent studies. Interestingly, this
leftward shift in the distribution, which deviated from the
typical J-shaped distribution long reported in die normal
population (Annett 1972), was composed of two rather
distinct subtypes, one left-handed and the other mixedhanded. The assessment methods used to measure and
classify tiiese two subtypes will be described below.
A well established fact about schizophrenia is that
first-degree relatives have an increased risk of the disorder. Few now doubt that schizophrenia has a
genetic basis, yet its mode has to be explained. Even
the identical twin [of an individual with schizophrenia] stands a better than 50% chance of escaping the
illness. Genetic factors are not the whole story.
[Murray and Lewis 1987, p. 681]
In the past decade, interest has increasingly focused on
the role of neurodevelopmental factors as independent or
aggregated effects of genetic and environmental burdens
Reprint requests should be sent to Dr. P. Satz, Neuropsychiatric
Institute, 760 Westwood Plaza, University of California, Los Angeles,
CA 90024-1759.
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Schizophrmia Bulletin, Vol. 25, No. 1, 1999
P. Satz and M.F. Green
Since our last review (Green et al. 19896), 19 additional studies have addressed the association between
handedness and schizophrenia. Seven of the studies
examined the prevalence of different handedness subtypes
(left or mixed) to determine whether a shift in handedness
distribution exists in a subgroup of schizophrenia patients
(Nelson et al. 1993; Clementz et al. 1994; Manoach 1994;
Cannon et al. 1995; O'Callaghan et al. 1995; Taylor and
Amir 1995; Malesu et al. 1996). The studies used a variety of methods to assess and classify handedness, ranging
from self-reports and multiple-item questionnaires to
demonstration methods. Four of the seven studies showed
a leftward shift in the handedness distribution (all except
for O'Callaghan et al. 1995; Taylor and Amir 1995; and
Malesu et al. 1996). However, in the Malesu et al. study
(1996) a trend toward increased MH was in the hypothesized direction. The remaining studies addressed the association between non-right-handedness (left or mixed) and
other behavioral, cognitive, neurological and brain imaging abnormalities in schizophrenia that will be discussed
later in this review.
Because a similar shift in the distribution of nonright-handedness was found in the majority of the earlier
and current reviews, we decided to pool data across studies and tally the overall box score outcomes. The results
(14 positive, 7 null, 2 paradoxical) provide some support
for a leftward or atypical shift in the handedness distribution. We then examined each study to determine the
nature of the leftward bias in terms of subtype frequency
(i.e., left or mixed). In the vast majority of studies reporting prevalence data, the leftward shift was due to an
increase of MH compared with normal or patient controls.
Only two studies reported an increase in left-handedness
(Gur 1977; Manoach et al. 1988). To interpret these subtype findings, it is important to describe some of the key
methodological issues related to the assessment and classification of handedness in these studies.
First, two studies (Gur 1977; Manoach et al. 1988)
used observed writing hand or self-report as the sole basis
for assessment and classification, which permits only a
dichotomous outcome (left-handed or right-handed). In
such cases, reports of an increased prevalence of lefthandedness could be misleading if some subjects turned
out to be mixed-handed. The latter determination would
require a questionnaire or observed demonstration procedure. A similar issue arises when right-handedness is classified by self-report or observed writing hand, because the
majority of mixed-handers, when assessed by multipleitem questionnaires, use the right hand for writing (Annett
1972). Also, if one attempts to determine the prevalence
of left-handedness in schizophrenia patients, one would
need to conduct a large-scale or epidemiologic survey
because of the low base rate frequency of left-handedness
in the normal population (writing hand 10%-12%, questionnaire 5%). These problems will be discussed later in
this review.
Second, while most of the studies on prevalence used
a variety of questionnaire formats, they differed markedly
in terms of items and number. This is important because
the larger the number of items used, the greater the chance
of finding some mixed-handed preferences (Harris and
Carlson 1988). In other words, an inverse relationship
exists between the number of items and MH- or lefthandedness.
Third, the criterion used to classify handedness varied across studies. Studies using a more conservative criterion (100%) were more likely to find an increase in MH,
especially if many items were employed in the questionnaire (Annett 1972). For example, while the prevalence
of right-handedness is approximately 90 percent in the
normal population (based on self-report or writing hand),
this prevalence drops to approximately 65 percent when a
multiple-item preference questionnaire is used (Annett
1972). Using a 12-item questionnaire, one typically finds
the following distribution of handedness subtypes in the
normal population: left 5 percent, mixed 30 percent, right
65 percent (Annett 1972).
Fourth, although the number of potential items
(tasks) used to assess handedness is endless, given man's
complex motor programming and output functions, only a
few tasks are differentially sensitive to hemispheric dominance. Steenhuis and Bryden (1989) have shown that
those manual tasks that require chaining of complex
motor sequences (proximal and distal) are represented on
a general laterality factor whose neural substrate is hemispherically specialized. In contrast, discrete lateral movements (e.g., picking up a pin) may be less lateralized.
Fifth, the assessment used to classify handedness can
be based on a multiple-item preference questionnaire
(self-report) or a multiple-item demonstration test. The
demonstration approach allows a more direct measure
(observation) of hand preference than the preference
approach, and it determines the status of within-task consistency on individual items. The demonstration approach
has revealed that a subgroup of mixed-handed institutionalized patients have no consistent directional asymmetry
on a given task and should be differentiated from the
larger population of mixed-handers who, while variable in
hand preference between tasks, are not inconsistent within
tasks. We have labeled the former subgroup as having
ambiguous handedness (AH) because of the near-randomness of their manual preference.
Although the presence of these atypical handedness
subtypes in schizophrenia, as well as in other brain disorders, signals some type of pathological shift in the distribution of handedness, the neural substrates or mechanisms
64
Atypical Handedness
Schizophrenia Bulletin, Vol. 25, No. 1, 1999
that underlie these subtypes have been less clear, especially in psychiatric studies of schizophrenia. For this
reason, the next section has a brief review of some neurodevelopmental factors in the etiology of some schizophrenia subgroups, with particular focus on specific brain
substrates or mechanisms that are hypothesized to account
for these atypical handedness subtypes.
problems arose during cell migration, because these cells
cannot change their orientation after this phase. Although
the studies initially involved only the left hemisphere, a
subsequent study also found comparable cell disorganization in the right hemisphere (Conrad et al. 1991).
Akbarian and colleagues (1993a, 19936) stained cells
for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase in the prefrontal and temporal regions of
schizophrenia patients and matched controls. In both of
these regions, the cells of the patients were located in
deeper layers compared with controls. The interpretation
is that the abnormal cell placement reflects abnormalities
in cell migration. Interestingly, cell migration occurs during the second trimester, a time period that was implicated
by the epidemiological studies.
An "archival-observational" approach has been used
by Walker and colleagues (Walker and Lewine 1990;
Walker et al. 1993) to study the neurodevelopment of
schizophrenia. They obtained childhood home movies
from families in which at least one child subsequently
developed schizophrenia and at least one did not. In the
initial study, raters were able to identify the pre-schizophrenic child significantly above chance. Although the
raters in this initial study were not given any specific
instructions on how to select the pre-schizophrenia child,
subsequent studies have found that the pre-schizophrenia
siblings showed greater negative emotions (Walker et al.
1993) and a higher rate of neuromotor dysfunction
(Walker et al. 1994).
The approach most relevant for the current discussion
has been the search for markers of abnormal neurodevelopment in adult schizophrenia patients. These markers
are usually measurable characteristics in adults that reflect
abnormal neurodevelopmental processes which occurred
before or shortly after birth. Markers of abnormal development have included dermatoglyphic signs (Bracha et al.
1991, 1992; Mellor 1992) and minor physical anomalies
(Gualtieri et al. 1982; Guy et al, 1983; Green et al. 1989a,
1994a, 19946; O'Callaghan et al. 1991a; Lohr and Flynn
1993).
Dermatoglyphic procedures with schizophrenia
patients have suggested two types of abnormalities:
changes in total finger ridge counts (TFRC) and increased
dermatoglyphic asymmetry. Recent studies of TFRC
have used a powerful design involving monozygotic
twins, only one of whom is diagnosed with schizophrenia.
Results revealed that one subgroup of schizophrenia
patients had lower ridge counts (perhaps due to ischemia
during the second trimester) than their twins, whereas a
second subgroup showed higher ridge counts than their
twins (perhaps indicating edema during the second
trimester) (Bracha et al. 1992).
Neurodevelopmental Factors in the Etiology of Schizophrenia. The neurodevelopmental model of schizophrenia has received considerable support from both empirical
and conceptual sources (Weinberger 1987; Murray et al.
1992a, 19926). Empirical support for the neurodevelopmental model is difficult to obtain because of a thorny
methodological obstacle: The onset of symptoms in schizophrenia typically occurs in early adulthood, so the time
period of interest (usually prenatal or perinatal) occurs
decades before the data collection. Several creative
approaches have been applied to circumvent this problem.
Epidemiologic studies have evaluated whether naturally occurring influenza epidemics increase the risk that a
fetus will develop schizophrenia as an adult. In a wellconducted and frequently cited study, Mednick et al.
(1988) considered the effects of a relatively brief and
fairly widespread A2 influenza epidemic in the Helsinki
area in 1957. This study examined the rates of schizophrenia in adulthood for individuals who were presumably exposed to the A2 influenza virus while in utero
compared with controls who were born in the same hospitals during the same months in previous years. The individuals who were exposed to the influenza virus while in
the second trimester of fetal development (but not the first
or third trimester) had higher rates of schizophrenia than
control subjects. Hence, a virus may have disrupted some
aspect of fetal neurodevelopment, which in turn increased
the risk for schizophrenia. This finding, while not entirely
consistent across studies (Kendell and Kemp 1989;
Bowler and Torrey 1990; Crow et al. 1992) has generally
been replicated (Barr et al. 1990; O'Callaghan et al.
19916). Part of the difficulty in replicating the finding is
the somewhat unexpected possibility that the increased
risk may be largely limited to females (Takei et al. 1994).
Another approach to the neurodevelopmental model
has used neurohistology. These studies, while using substantially different methods, have generally supported the
epidemiological studies by finding abnormalities in cell
orientation and cell placement that likely reflect disruption
during the second trimester. For example, Scheibel and
colleagues (Kovelman and Scheibel 1984; Conrad and
Scheibel 1987) found that in the brains of schizophrenia
patients the pyramidal cells of the hippocampus showed
directional disorientation compared with those of controls.
The finding of disorientation strongly suggests that the
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Schizophrenia Bulletin, Vol. 25, No. 1, 1999
P. Satz and M.F. Green
It is typically stated that schizophrenics are more frequently left-handed than other groups. Although this
is probably true, the more general finding is that
schizophrenics are less frequently unambiguously
dextral. In order to maintain consistency with previous literature and to improve this article's readability,
we frequently use the term 'left-handed' to refer to
nondextral subjects. [Clementz et al. 1994, p. 400]
A second dermatoglyphic finding in schizophrenia is
increased dermatoglyphic asymmetry (also called fluctuating asymmetry; see Markow and Wandler 1986;
Markow and Gottesman 1989; Mellor 1992), which is
considered a sign of possible disturbances in fetal neurodevelopment or a lower neurodevelopmental stability
(Mellor 1992).
Minor physical anomalies (MPAs) are minor abnormalities of the head, face, hands, and feet (e.g., highsteepled palate, epicanthal folds, gaps between toes). The
studies that have compared MPAs in patients with schizophrenia with normal controls have all found an excess of
MPAs in schizophrenia (Gualtieri et al. 1982; Guy et al.
1983; O'Callaghan 1991a; Lohr and Flynn 1993; Green et
al. 1994a), which does not seem to be an artifact of socioeconomic status (Green et al. 1994a). More recently,
O'Callaghan et al. (1995) failed to find a relationship
between MPAs and ventricular brain volumes in schizophrenia patients using magnetic resonance imaging
(MRI). Although MPAs were previously thought to
reflect processes from the first trimester, data suggest that
second trimester events are relevant to the development of
MPAs (Green et al. 1994a, 19946).
It is our view that atypical handedness, like abnormal
dermatoglyphics and MPAs, is a marker of problems in
neurodevelopment. As such, we expect elevated rates of
atypical handedness in schizophrenia. In fact, it would be
a problem for a neurodevelopmental model of schizophrenia to incorporate the absence of a shift in the handedness
distribution.
The neurohistological studies suggest that early problems in cell migration are not restricted to a particular
lobe or to one hemisphere. Why then does a neurodevelopmental abnormality that is most likely diffuse or multifocal yield a shift in handedness that is unidirectional?
The next section will address some of the mechanisms
and neural substrates known or hypothesized to underlie
different pathological shifts in the handedness distribution.
An increased incidence of PLH has long been reported in
other clinical disorders with known early focal brain
insult (e.g., epilepsy, stroke, hemiplegia, hemispherectomy; see Harris and Carlson 1988 for a review). PLH
refers to a subset of natural right-handers who, because of
early brain injury to the left hemisphere (before age 6),
suffer a hypofunction of the right hand (often transient),
which in turn causes a shift to preference for the left hand.
The model advanced by Satz (1972, 1973) computes the
proportion of natural right-handers with left-sided brain
insult who would have to shift handedness to account for a
raised incidence (above the population base rate) in any
clinical disorder. According to Harris and Carlson (1988),
there are two basic assumptions in the model. The first is
that the location of the brain lesion is random, just as
likely to strike the left hemisphere as the right. Thus, in
statistical terms, the brain lesion is a binomial function.
The second assumption is that left hemisphere lesions lead
to a greater incidence of switched-handedness because of
the predominance of right-handers in the general population (approximately 90%). Consequently, when early focal
brain injury causes a shift in handedness, the result will
almost always be PLH rather than pathological right-handedness (PRH). The PRH subtype, the result of right brain
insult in a natural left-hander, is seldom discussed because
of its relative infrequency compared with PLH (approximately 11:1; Satz 1972). The Satz model also postulates
two types of manifest left-handedness in the general population: (1) a natural group whose hand preference springs
from genetic and/or environmental factors and (2) an epigenetic pathological group whose hand preference springs
from early brain injury primarily to the left hemisphere.
This model contrasts with other positions that view all
forms of manifest left-handedness as pathological—both
prenatal and postnatal (Bakan 1971; Geschwind and
Galaburda 1985). These latter views, however, have not
received much empirical support in recent years (Harris
and Carlson 1988; Bishop 1990).
If PLH represents a smaller subset of the general population of manifest left-handers, then how can the two
handedness subtypes be differentiated? It has recently
been shown that the lesion that produces the shift in manual preference may also produce other alterations in lateral development, including hemispheric speech (right or
Neurodevelopmental Mechanisms in Subtypes of
Atypical Handedness.
Pathological left-handedness (PLH). Although an
increased prevalence of this subtype would lend additional credence to those who postulate a left hemisphere
substrate in schizophrenia (Posner et al. 1988; Crow et al.
1989; Posner and Early 1990; Bracha 1991), only two
studies have reported such an association (Gur 1977;
Manoach et al. 1988). As noted earlier, even these results
could have been biased by the absence of an assessment
for MH. Despite these problems, the tendency in psychiatric studies has been to associate all forms of atypical
handedness with left-handedness:
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Atypical Handedness
Schizophrenia Bulletin, Vol. 25, No. 1, 1999
not possible if the brain insult is early but diffuse, as in
closed head injury (Ewing-Cobbs et al. 1987; Levin et al.
1987). In such cases, the symptoms are more general and
symmetrical with no alteration in handedness, even when
the injuries occurred before age 6 (Levin et al. 1987).
What implications do these findings on PLH have for
schizophrenia, in which evidence of diffuse ectopic
changes in cell migration are known to occur in some subgroups during prenatal development? The initial conclusion is none. The neurodevelopmental factors in schizophrenia are most probably diffuse and nonfocal and,
therefore, unlikely to produce marked asymmetries in lateral preference such as PLH. This conclusion is further
buttressed by the infrequency of empirical reports of lefthandedness in schizophrenia, as noted above. At the same
time, alternative views that postulate a left hemisphere
substrate in schizophrenia (Posner et al. 1988; Crow et al.
1989; Posner and Early 1990; Bracha 1991) could challenge the preceding conclusions. For this reason, the PLH
construct may still have relevance to schizophrenia.
These views will be addressed below.
Mixed-handedness (MH) and ambiguous handedness (AH). In contrast with PLH, studies lend support
for a raised incidence of MH in some schizophrenia
groups. We suggest that the term "mixed-handedness"
refers to a more heterogeneous population of subjects who
are less lateralized and who, by definition, vary in their
manual preference for different tasks (e.g., ambidexters).
However, it has traditionally been assumed that this variation in manual preference among tasks is at least consistent wiuiin tasks. This assumption proved false when put
to empirical test. By varying die method typically used in
the assessment of human handedness, we developed the
Hand Preference Demonstration Test (HPDT), in which
subjects were asked to demonstrate their manual preference for eight simple items requiring skilled movement of
predominantly distal musculature (e.g., picking up a
spoon and a dime, using a crayon or a hammer). The
items were administered three times in quasi-random
order within one session or within two sessions spaced a
week apart to determine within-task consistency.
In a series of studies with autistic patients (Satz et al.
1985; Soper et al. 1986) and nonautistic, mentally
retarded institutionalized patients (Soper et al. 1987), we
found an increased incidence of MH (approximately 50%)
in these patients. However, when consistency of withintask responses was examined, we found that the vast
majority of these mixed-handers had no consistent directional preference for most tasks. In fact, many of their
responses seemed almost random. We referred to this
subgroup as AH.
Although this assessment procedure has not been
used with the developmentally disabled before, other
bilateral), cognition (relatively preserved language, but
impaired visual-spatial ability [i.e., crowding effect]), and
limb length (right hemihypoplasia), that constitute elements of a clinical syndrome (Satz et al. 1985; Strauss et
al. 1990). Although hemihypoplasia (hand and/or foot
length) was first observed by Penfield and Robertson
(1943), its correlation with other elements of the syndrome was recognized only recently. The potential use of
this index as a biological marker of PLH (and early left
hemisphere insult) was replicated on a sample of children
with unilateral vascular injuries related to cardiac catherization (Aram et al. 1986). All but one of the children
with right hemihypoplasia (and left-brain injury) were
left-handed, whereas none of those with left hemihypoplasia (and right-brain injury) were left-handed.
A second biological marker of PLH was reported by
Bishop (1980, 1984), who hypothesized that marked inferiority in hand skill for the nonpreferred hand would constitute a unilateral "soft" neurological sign in otherwise
nonsymptomatic samples. Her reasoning was that PLH
could also be the result of a brain abnormality too mild to
produce clinical symptoms (e.g., epilepsy, mental retardation, or hemiplegia) but sufficient to make the genotypically preferred hand clumsy, thus forcing a preference for
the other hand. In three separate studies (Bishop 1980,
1984; Gillberg 1983), children showing the poorest nonpreferred hand performance (left or right) were significantly more likely to be left-handed and to have speech
problems. However, these subjects showed no impairment in their preferred hand. These findings are provocative because they suggest that "even so mild a dysfunction
as clinically asymptomatic clumsiness of the right hand
may be sufficient to induce preference for the left hand"
(Harris and Carlson 1988, p. 356). The results also
strengthen other reports of PLH in patients with very mild
left focal injury without any clinical signs of hemiplegia
or motor impairment (Varga-Khadem et al. 1985). In fact,
Varga-Khadem et al. noted that very early and consistent
preference for the left hand (before age 6) was often associated with PLH and early left brain insult, because normal hand preference is typically unstable during this
developmental period (Satz 1988).
The preceding findings strongly suggest that the
neural substrate in PLH is associated primarily with a leftsided focal brain insult during the prenatal or postnatal
period up to age 6. Further, this insult may vary from a
mild injury involving no clinical symptoms (other than
PLH) to a more severe injury involving changes in brain
organization and cognition (PLH syndrome). In the latter
case, die symptom pattern is marked by differential sparing
as well as impairment due to functional reorganization during this early period of brain plasticity. An important point
to note, however, is that this functional reorganization is
67
Schizophrenia Bulletin, Vol. 25, No. 1, 1999
P. Satz and M.F. Green
investigators have also reported a subgroup of autistic
patients (approximately 40%) whose hand preference has
been labeled incomplete, not established, or mixed (Colby
and Parkison 1977; Barry and James 1978; Tsai 1982;
Fein et al. 1984). In more recent studies using the HPDT
procedure, results have confirmed the more frequent presence of an AH subtype in two cohorts of mentally
retarded patients (Morris and Romski 1993; L. Vermue
and H. Van der Vlugt, personal communication 1989).
More recently, the AH subtype has been found in a
subset of hospitalized schizophrenia patients in two separate studies using the HPDT procedure (Green et al.
1989*; Nelson et al. 1993). These findings were somewhat unexpected in patients without severe mental retardation or autism. Although there was also an increased
prevalence of MH in both schizophrenia groups (40%
compared with 15% in controls), approximately half of
the mixed-handers met the criteria for AH (i.e., inconsistent on at least two tasks).
What mechanism might account for this atypical
form of manual preference or dominance? We had earlier
suggested (Soper and Satz 1984) that the AH subtype represents a third pathological phenotype that, unlike PLH or
PRH, arises from early brain damage of such severity that
neither side of the brain is sufficiently intact for the
expression of manual (or cerebral) dominance.
Interestingly, in our autism study (Soper et al. 1986) we
found that this subtype achieved significantly lower IQ
scores than did the two lateralized groups (left and right).
Similar results have also been observed for the MH subtype by other autism investigators (Tsai 1982; Fein et al.
1984).
Although a bilateral hemispheric insult represents a
likely substrate for AH because of the well-documented
diffuse and multifocal neurodevelopmental abnormalities
in a subset of schizophrenia subjects, this hypothesis fails
to explain why the shift is unidirectional and leftward in
cases of AH as well as MH including AH. In some
respects, the distinction between AH and MH is arbitrary
except for the distinction between within-task and
between-task consistency. Otherwise, AH represents a
specific subgroup of MH. As such, the mechanisms likely
to induce a leftward shift in handedness, given an underlying bilateral or diffuse prenatal insult, are most probably
the same in both cases, except perhaps in their severity.
By the end of the second trimester, the right hemisphere has achieved almost full-term; thus secondtrimester injuries affecting, that is, anoxic, ischemic,
toxic, or infectious insults that are systemic and bilateral, will affect the left hemisphere more than the
right hemisphere, [p. 551]
This hypothesis is based on earlier postmortem studies of
nonschizophrenia subjects that suggested that the left
hemisphere matures more slowly than the right hemisphere during the early and mid-prenatal periods, which
increases the window of vulnerability to epigenetic events
(Fontes 1944; Chi et al. 1977). Also, because the left temporal region is hypothesized to be the last cortical area to
complete neuronal migration, it is especially vulnerable to
injury.
If this delay hypothesis were true, it would fit nicely
with developmental positions that state that the immaturity
of a system (prenatal or early postnatal) is a predictor of its
vulnerability to birth stress (Bradley and Mistretta 1975).
Similar outcomes have also been reported in head injury, in
which those developmental skills in ascendancy are more
vulnerable to trauma than those skills already established
(i.e., later in development; Ewing-Cobbs et al. 1987).
Interestingly, the lag hypothesis represents one of the
main postulates of Geschwind and Galaburda's (1985)
theory of dyslexia, which attempts to link left hemisphere
insult, left-handedness, and immune disorder in dyslexia.
Unfortunately, the left hemisphere lag hypothesis has
received little empirical support and some serious challenges (see Best 1988 and Bishop 1990 for reviews). In
fact, Bishop (1990) states that this hypothesis is one of the
most confusing parts of the Geschwind and Galaburda
(1985) theory and should be abandoned. For example, if
the left hemisphere delay leads to shifts in language
(right) and handedness (left) (i.e., because of right hemisphere acceleration, which they regard as the norm), then
according to Bishop (1990), "this would seem to entail
that left-handedness and right hemisphere language representation should be the normal state of affairs, which
clearly is not the case" (p. 151). Another major problem
for the hypothesis is that, while there is some evidence to
suggest that the right planum temporale develops about
the 30th week of gestation, just a week to 10 days before
the left (Chi et al. 1977), they also note that a larger
Sylvian fissure is present on the left side as early as 16
weeks' gestation. This latter structure includes
Wernicke's association area, which is the critical substrate
for receptive language. A time window differential of 10
days hardly warrants the status of a vulnerability lag.
Finally, the lag hypothesis, as noted by Bishop (1990), is
diametrically opposed to reviews by Annett (1985) and
Morgan and Corbalhs (1978).
Left Hemisphere Lag Hypothesis. This hypothesis
states that during normal development of the fetal brain,
the left hemisphere lags behind the right in intrauterine
growth, causing the left hemisphere to be smaller than the
right hemisphere throughout the early and mid-prenatal
period (Bracha 1991):
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Schizophrenia Bulletin, Vol. 25, No. 1, 1999
conflicts with considerable other CT and postmortem
anatomic evidence of bilateral (symmetric) ventricle-brain
ratio (VBR) enlargement in schizophrenia (see Pearlson et
al. 1989 for a review). A final problem in this otherwise
provocative hypothesis is that, like Bracha (1991), it
makes no clear predictions about cognitive (i.e., linguistic) or motor (hand preference) sequelae that would result
from a defect in cerebral dominance involving the left
temporal cortex.
In summary, both views of the lag hypothesis, while
innovative, have problems, and neither position has yet
collected data on handedness or language function that, if
altered, could provide some additional support for both
views. Such support remains unlikely at the present time,
based on the scarcity of studies showing an increased
incidence of left-handedness in schizophrenia. A final
comment concerns the lag hypothesis. If Bracha (1991)
dropped this assumption, which may contain unnecessary
surplus meaning anyway, then his position acknowledging
a bilateral or multifocal insult due to epigenetic factors
would be compatible with the two hypotheses that follow.
Bracha's (1991) use of the lag hypothesis provides an
interesting attempt to explain reports of structural brain
asymmetry in the presence of bilateral prenatal insults. In
fact, he suggests that "the asymmetry may be merely an
artifact of the timing of the insult and may be most useful
as a marker of the timing of the insult (i.e., second
trimester)" (p. 551). Unfortunately, this position rests on
the somewhat tenuous claim of a differential lag in left
hemisphere growth. Also, the hypothesis makes no clear
predictions on cognitive (i.e., linguistic) or motor (hand
preference) sequellae that would result from a left temporal lobe abnormality.
Another variant of the left hemisphere lag hypothesis
has been proposed by Crow et al. (1989). However, in
contrast with Bracha's (1991) position, Crow et al. (1989)
hypothesize that this lag is primarily due to a unilateral
mechanism that is genetic and that is responsible for both
schizophrenia and cerebral dominance. Crow et al. (1989)
suggest three possible explanations for the structural brain
changes in schizophrenia:
(1) normal brain development proceeds in a sequence
in which growth in temporal and occipital structures
is completed relatively late; (2) growth continues
later on the left than on the right side; and (3) if there
is arrest of the sequence, this is seen most clearly in
left temporo-occipital structures and is more easily
detected as a change in ventricular size than brain
substance. [Crow et al. 1989, p. 1149]
Left Hemisphere Vulnerability Hypothesis. The left
hemisphere vulnerability hypothesis, which has not been
addressed in schizophrenia to date, suggests that the left
hemisphere may be more vulnerable to prenatal or perinatal insults because of inherent differences in its vascular
or metabolic properties, not because of its rate of maturation. The primary evidence in support of this hypothesis
is based on studies of severely premature infants with
very low birth weights (Guzzetta et al. 1986; Raz et al.
1994). The most common cerebral lesion in these premature neonates is the intracranial hemorrhage of subependymal origin (Volpe 1989). Using ultrasound scans,
the investigators found that cerebral insults caused by
intracranial bleeds affected the cerebral hemispheres
unevenly. In a majority of cases the bleeds were unilateral (3:1 on the left), but in cases of bilateral hemorrhage
the pattern was also asymmetric, with a similar ratio of
left hemisphere involvement (3:1) (Raz et al. 1994).
More difficult to explain are the possible mechanisms
that might underlie this vulnerability. Although it has
been suggested that the germinal matrix in the left hemisphere (a richly vascularized region overlying the head of
the caudate nucleus) is exhausted at a slower rate, thereby
requiring relative augmentation of vascular support
(Taylor 1969), other explanations have suggested that
developmental asynchronies in hemispheric vascularization may be involved or that a relative increase of germinal cells in the left hemisphere may require relative
amplification in blood supply to this region (see Raz et al.
1994 for a review). Cannon et al. (1972) have also suggested that the right hemisphere might enjoy greater vas-
Crow et al.'s (1989) reformulation of the lag hypothesis
makes a clear and compelling argument for a unilateral
defect in the left hemisphere, and they report postmortem
anatomical and computed tomography (CT) data to support their claim that the left temporal horn enlargement in
schizophrenia reflects an arrest in intrauterine brain
growth that is under genetic control. This position, along
with Bracha's (1991), provides a heuristic framework for
other positions that advocate a left hemisphere substrate
in schizophrenia (Flor-Henry 1976; Posner et al. 1988;
Posner and Early 1990).
Unfortunately, this reformulation again rests, in part,
on the controversial assumption of a lag in left hemisphere neuronal migration. Furthermore, Crow et al.
(1989) make some additional claims that could prove
troublesome. First, they eschew any role for exogenous
trauma factors (epigenetic) that are known to occur in
some patients with schizophrenia during the prenatal or
perinatal periods and may result in more diffuse or multifocal insult As such, the theory implies that schizophrenia is etiologically a homogeneous disorder (under
unspecified genetic control) without different subgroups
of "sporadic" cases induced by trauma. Also, the assumption that the defect in cerebral dominance is unilateral
69
Schizophrenia Bulletin, Vol. 25, No. 1, 1999
P. Satz and M.F. Green
cular supply than the left hemisphere, which would provide more protection from adverse metabolic events.
Although these explanations are speculative, the fact
remains that the left hemisphere is more vulnerable to
adverse hypoxic events in very low birthweight infants.
However, only a minority of premature births are in this
category of bleeds, and the association between birth
complications and schizophrenia, while present, confers
only a small relative risk (Goodman 1988). Also, the
hemispheric vulnerability hypothesis faces the same basic
problem as the lag hypothesis, namely, accounting for the
increased incidence of MH in schizophrenia.
One possible clue to this phenomenon would be to
assume that in a subset of patients with schizophrenia,
certain sporadic exogenous events (e.g., infections or
bleeds) traumatized the genetically predisposed fetus at
some critical time, leading to diffuse and multifocal brain
insult. In such cases, the insult would further increase the
left hemisphere's predisposed vulnerability, thereby shifting manual preference leftward. However, the presence
of a diffuse insult including the right brain would inhibit a
more extreme shift to the left (PLH), as with a focal leftsided lesion. This explanation would be strengthened if
one could link the co-occurrence of atypical handedness
with diffuse structural brain insult in schizophrenia.
Five studies provide support for this key association,
although in four of them the term "left-handedness" was
based either on writing hand (Katsanis and Iacono 1989),
convenience (Clementz et al. 1994), or not defined
(Pearlson et al. 1989; O'Callaghan et al. 1995). Pearlson
et al. (1989) showed that a history of abnormal birth stress
and the presence of left-handedness were significant predictors of an enlarged VBR on multiple regression analysis. Katsanis and Iacono (1989) found enlargement of the
lateral ventricles (based on CT) in a subgroup of lefthanders with schizophrenia, but not right-handers. Also,
the former group had more neuropsychological test
impairment. Clementz et al. (1994) also found a similar
VBR enlargement in left-handed versus right-handed
patients with schizophrenia, but no VBR enlargement or
excess of left-handedness was found in a group of patients
with affective disorders. O'Callaghan et al. (1995) investigated the association between handedness and ventricular brain volume (using MRI) in a small sample of
patients with schizophrenia, nine of whom (20%) were
left-handed based on an unspecified dichotomous classification using the Edinburgh inventory (1971). Results
showed a bilateral increase in ventricular volume in the
non-right-handed male patients. However, among female
patients, non-right-handedness was associated with lower
premorbid intelligence.
ized (n = 10) chronic schizophrenia patients using the
HPDT, in which the lateralized group was classified based
on consistent preference in the same direction (right in all
but one patient) for all tasks across repeated presentations.
The MRI scans were also compared with those from a
normal control group (n = 25). This is the only study to
date to show an association between VBR asymmetry and
atypical handedness. Nine of the 10 nonlateralized schizophrenia patients had larger left versus right VBRs compared with none of the lateralized schizophrenia patients
or controls. Interesting, though unclear, was the finding
of a structural asymmetry on the left, which would be
compatible with the views of Bracha (1991) and especially Crow et al. (1989), except for the unnecessary and
probably false assumption of a lag in left hemisphere maturation. However, the enlarged left VBR was associated
with an increase in MH, not left-handedness. In fact,
while 2 of the 10 subjects wrote with the left hand, they
were clearly MH or AH.
Hemispheric Specialization Hypothesis. The final
hypothesis on the putative mechanism underlying MH in
schizophrenia, the hemispheric specialization hypothesis,
makes no implicit assumption regarding a predisposed left
hemisphere vulnerability in either maturation rate or
metabolic constraints. However, it again introduces the
concept of a left hemisphere factor—but as a necessary,
though insufficient, explanation of PLH and MH.
The hypothesis states that in the vast majority of
humans there is a biological substrate for hemispheric
specialization in which the left hemisphere plays a dominant role in the mediation of speech, language, and related
analytic functions (Molfese and Segalowitz 1988). This
asymmetry, regardless of acceleration rate, is structurally
evident early in intrauterine life, as well as electrophysiologically and behaviorally during early postnatal life.
The primary anatomical evidence for this substrate
concerns asymmetries in the planum temporale. The horizontal bank of this structure underlies auditory association
cortex and is posterior to the Heschl's gyrus, which is primary auditory cortex. Geschwind and Levitsky (1968)
reported the first documentation based on measurements
of planum length in 100 postmortem brains: 65 percent of
the plana were longer on the left, 24 percent were symmetrical, and only 11 percent were longer on the right.
This leftward asymmetry was later confirmed in newborn
(Witelson and Pallie 1973), infant (Wada et al. 1975), and
fetal brains (Chi et al. 1977). Additional anatomic evidence for this hypothesis is based on the role of the left
inferior frontal convolution in language production and
the left posterior temporal cortex in language comprehension (Geschwind and Galaburda 1985).
The fifth study (Satz et al. 1990), reported MRI data
on a small sample of lateralized (n = 25) and nonlateral-
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Schizophrenia Bulletin, Vol. 25, No. 1, 1999
Pearlson et al. 1989; Barr et al. 1990; Joseph 1990; Satz et
al. 1990; Faustman et al. 1991; Kern et al. 1991; Brown et
al. 1992; Tyler et al. 1995; Manschreck et al. 1996;
Morgenstern et al. 1996; Hayden et al. 1997. Most of
these studies were not addressed in the original review by
Green et al. (1989i>) because of its focus on assessment
methodology and prevalence.
In terms of clinical correlates, some studies have considered the relationship between handedness and formal
thought disorder in schizophrenia (Taylor et al. 1982;
Manoach et al. 1988; Manoach 1994; Taylor and Amir
1995; Manschreck et al. 1996). Taylor et al. (1982) evaluated the relationship between handedness and a range of
psychiatric symptoms in a large sample (n = 232) of
schizophrenia patients. A series of 15 contrasts were performed by dividing patients into groups by symptom and
then comparing the handedness distributions of the
groups. Only one symptom—the presence of formal
thought disorder—was associated with left-handedness
and MH. This finding came from the male patients: of the
88 male patients with thought disorder, 47 percent were
mixed- and left-handers. In contrast, of the 44 patients
without thought disorder, 23 percent were mixed- or lefthanders. In a curious interpretive twist, the authors concluded that the group without thought disorder formed the
most pathological group. The reason for this unexpected
interpretation is that the authors were viewing the results
within a perspective of abnormal dextrality in schizophrenia because they had previously found a paradoxical shift
toward dextrality in schizophrenia (Taylor et al. 1980).
Naturally, we view the results as supporting a relationship
between thought disorder and atypical shift away from
dextrality.
Subsequent interest in the relationship between formal thought disorder and handedness stemmed from the
notion that atypical handedness may reflect an underlying
disruption in the dominant hemisphere and that this disruption may also result in reduced hemispheric specialization for linguistic processes. Manoach et al. (1988) evaluated handedness and formal thought disorder in 58 male
schizophrenia patients. They determined handedness only
by writing hand. As noted earlier, a more comprehensive
handedness assessment likely would have revealed that a
number of the left-handed subjects actually had MH. In
this initial study, the left-handers had higher rates of formal thought disorder.
A later study (Manoach 1994) with both normal and
psychiatric controls and using a dimensional handedness
assessment yielded similar results. Sinistrality was associated with increased thought disorder for male schizophrenia patients (there were too few females to analyze
separately). This relationship between sinistrality and
thought disorder may have been linked to either left-
Other investigators have suggested that this hemispheric asymmetry (i.e., cerebral dominance), while probably under genetic control, induces a contralateral bias for
both motor (handedness) and attentional processes (e.g.,
the rightward shift bias; Annett 1972). It has also been
suggested that the left cerebral hemisphere may play a
dominant role in the innervation of dopaminergic activity
(Tucker and Williamson 1984), which may provide a neurochemical substrate for both manual laterality and contralateral hemiattentional orientation (Glick and Russ
1981; Kinsboume 1988; Posner et al. 1988).
To date, this hypothesis has provided a reasonable
explanation for alterations in manual laterality when the
left hemisphere is injured focally during prenatal or early
childhood life (as noted earlier). The critical issue, however, concerns the conditions under which this construct
could account for an increased incidence of MH. The
explanation is rather straightforward and parsimonious if
one assumes that a proportion of schizophrenia patients
have bilateral brain damage, whether genetically or
exogenously induced. Rather than postulating a left
hemisphere vulnerability predisposition (even if true), one
would merely have to state that the presence of a diffuse
insult (including the right hemisphere) would shift one's
manual preference in a leftward, though incomplete,
direction, resulting in MH or AH. This explanation
avoids the assumption necessary in the preceding two
hypotheses without challenging either of them.
It should be clear from the preceding comments that
atypical handedness, whether expressed as PLH, MH, or
AH, represents a potential biological marker of an underlying neurodevelopmental insult that occurred much earlier during prenatal development. If so, these markers
could represent potential signs of nongenetic cases of
schizophrenia. However, this latter interpretation could
be challenged if it were shown that alterations in handedness were also under genetic control. Such a finding
would not change the role of atypical handedness as a
neurodevelopmental marker, only its reference to genetic
versus epigenetic events.
Are There Clinical and Cognitive
Correlates of Atypical Handedness?
Recent studies have addressed the association between
non-right-handedness (left or mixed) and other behavioral, cognitive, neurological, and brain-imaging abnormalities in schizophrenia. Five of these studies also
reported data on prevalence, as noted earlier in this review
(Clementz et al. 1994; Manoach 1994; Cannon et al.
1995; O'Callaghan et al. 1995; Taylor and Amir 1995).
The remaining studies were Katsanis and Iacono 1989;
71
Schizophrenia Bulletin, Vol. 25, No. 1, 1999
P. Satz and M.F. Green
handedness or MH; the results in this regard were unclear.
In addition, a variability index of hand proficiency (based
on the standard deviation of various proficiency tests) was
related to both thought disorder and language functioning
for the combined male and female schizophrenia sample,
but not for the normal or psychiatric controls. The results
from the two Manoach studies were interpreted as evidence for a disruption in the establishment of hemispheric
dominance that resulted in both impaired language functioning and increased sinistrality.
Similar findings were reported in a study by
Manschreck et al. (1996) that also investigated the association between left-handedness and memory and thought
disorder in schizophrenia. Using a single item from
Annett's (1972) handedness inventory, 21 right-handed
and 21 left-handed patients selected from a larger patient
pool were assessed on an experimental memory task and
for the presence and severity of thought disorder (e.g.,
derailment, illogicality, and poverty of speech content).
The two groups of patients were individually matched on
word recall ability, age, sex, and education. Results
showed that the left-handed patients were less able to take
advantage of increasing context to assist in word recall
and had more symptoms of disorder.
Tyler et al. (1995) also showed an increased prevalence of persistent auditory hallucinations in a sample of
94 left-handed versus 595 right-handed schizophrenia
patients whose relatives were members of the United
Kingdom National Schizophrenia Fellowship. Handedness was dichotomized on a single variable from an unspecified handedness questionnaire. This study also
found that the left-handed patients had more cognitive and
behavioral abnormalities in childhood than did the righthanded patients.
In contrast with the preceding findings, Taylor and
Amir (1995) failed to find an association between lefthandedness or MH and thought disorder, mania, depression, or emotional blunting. Results also failed to show
an increase of non-right-handedness in the schizophrenia
group. This study used Oldfield's (1971) assessment battery to classify handedness groups in a large sample of
patients with DSM-III (American Psychiatric Association
1980) schizophrenia (n = 163), affective patients (n =
103), and normal controls (n = 112). However, as in most
of the other studies, the criteria for subtype classification
was not specified.
Moving from symptomatic to demographic and
familial correlates, Cannon et al. (1995) evaluated 96
patients with schizophrenia for an association between
handedness and clinical features such as age at onset,
chronicity, family history, and gender. They reported a
prevalence of mixed handedness of 36.4 percent, which is
almost identical to the 38.7 percent rate reported by Green
et al. (19896) using a different handedness assessment.
Cannon et al. (1995) found that MH was significantly
associated with greater chronicity of illness, and there
were trends (p < 0.1) associating it with a negative family
history for schizophrenia and with being male. Handedness was not associated with age at onset in this study.
These qualities (i.e., chronic, male, early onset, and negative family history) have been suggested as characteristics
of a "neurodevelopment" type of schizophrenia (Murray
et al. 1992a, 1992*). The patients with MH in this study
shared most of these characteristics, suggesting that atypical handedness may be a reflection of this proposed subtype of schizophrenia.
The connection between MH and negative family history for schizophrenia (p = 0.06) is noteworthy because it
suggests that MH is associated with factors that are independent of the genetic diathesis for schizophrenia. Family
history is a rather imprecise method; however, the notion
that atypical handedness is related to nongenetic factors
received more direct support in a study by Clementz et al.
(1994) that failed to find any increased non-right-handedness in the relatives of schizophrenia patients.
As mentioned earlier, several studies have found an
association between handedness and increased VBRs in
schizophrenia (Katsanis and Iacono 1989; Pearlson et al.
1989; Satz et al. 1990; Clementz et al. 1994). It would be
reasonable to expect that the relationships between atypical handedness and neuroanatomy would be mirrored by
associations between handedness and neurocognition. In
fact, they appear to be.
Some studies have found evidence of neuropsychological impairment in left-handed schizophrenia patients.
Katsanis and Iacono (1989) compared 51 right-handed
subjects with 12 left-handed subjects in a fairly comprehensive neuropsychological battery. The left-handed
patients performed worse than right-handed patients
across most tests of the neuropsychological battery,
regardless of the particular cognitive process assessed by
the test. The differences between handedness groups
reached significance for the Wisconsin Card Sorting Test
(Heaton 1981) and the performance IQ on the Wechsler
Adult Intelligence Scale—Revised (Wechsler 1981).
In a similar study, Faustman et al. (1991) compared
left- and right-handed schizophrenia patients (n = 24 per
group), and left- and right-handed controls (n = 15 per
group) on selected measures from the Luria Nebraska
Neuropsychological Battery (Moses et al. 1983). Instead
of examining a range of abilities, the authors selected
measures that they considered to be sensitive to cognitive
dysfunction in schizophrenia based on their previous
research. The measures included rhythm, memory, intellectual processes, and global score. While the left- and
right-handed controls did not differ in these measures, the
72
Atypical Handedness
Schizophrenia Bulletin, Vol. 25, No. 1, 1999
sized that the seemingly paradoxical protective effect was
due to early diffuse insult, which not only induced a leftward shift in manual laterality, but also probably rendered
primary dopaminergic receptors in the left hemisphere
(Tucker and Williamson 1984) less sensitive to the
chronic antidopaminergic effects of neuroleptics.
left-handed schizophrenia patients performed worse than
right-handed patients in rhythm and memory.
These studies suggest greater cognitive compromise
in left-handed patients. A limitation of both studies is that
handedness was determined only by writing hand. As
mentioned earlier, when handedness is defined only by
writing hand, the left-handed group probably includes a
subgroup of individuals who would have been considered
mixed-handed if a dimensional handedness assessment
had been used. This inherent heterogeneity in comparing
left- with right-handers creates more difficulty in interpreting study results. It is conceptually more direct to
compare subjects who have atypical handedness to those
who are lateralized.
In a recent study from our laboratory (Hayden et al.
1997), we specifically evaluated differences in memory
between two groups of patients: those with AH (i.e.,
within-item inconsistency; n = 19) and those who were
lateralized (n = 39). The patients had various forms of
chronic mental illness, with schizophrenia being the most
common diagnosis. The patients received a battery of
tests that included measures of verbal memory, executive
functioning, and motor performance. The AH group performed significantly worse on measures of verbal memory
and manual dexterity. The groups, however, did not differ
on a measure of motor learning.
Taken together, these studies argue diat the abnormalities in neurodevelopment may also be associated with
certain symptoms (especially those that are heavily
dependent on language functioning) as well as with other
neurocognitive sequelae.
A final correlate of particular interest concerns the
relationship between non-right-handedness and tardive
dyskinesia (TD). Two early studies (McCreadie et al.
1982; Joseph 1990) reported an association between lefthandedness and TD. These early studies, which
employed dichotomous measures of handedness, have
been challenged in more recent studies (Barr et al. 1990;
Kern et al. 1991; Brown et al. 1992; Morgenstern et al.
1996). In fact, the latter studies have shown just the
opposite effect—that non-right-handedness is a protective
factor against TD, regardless of whether patients were
inpatients or outpatients. The most compelling support
for this view is based on the recent Yale University TD
study, a prospective cohort investigation of 362 psychiatric outpatients in New Haven, Connecticut
(Morgenstem et al. 1996). Hand preference was assessed
with a 17-item laterality questionnaire. Pure left-handers
and mixed-handers were pooled and showed lower rates
of TD compared with predominantly right-handed
patients (42% with schizophrenia). The University of
California Los Angeles study (Kern et al. 1991) hypothe-
Conclusions
The results reviewed in the preceding sections provide
some reasonable support for the view that, in schizophrenia, there is an atypical leftward shift in the handedness
distribution. This shift is largely characterized by a more
variable and less completely lateralized pattern of manual
preference, namely, MH or AH. While one typically uses
the term "left-handed," to refer to these nondextral subtypes (Clementz et al. 1994), it was shown that this term
is potentially misleading and probably incorrect. The two
studies reporting an increased incidence of left-handedness used writing hand as the sole basis for classification.
This approach unfortunately prevents a determination of
the proportion of MH and consequently lowers the overall
rate of non-right-handedness in a sample. Another point
to note is that while a majority of the studies reported a
leftward shift in the distribution (2:1), there was sufficient
variability to warrant more large-scale epidemiological
research on this topic. One likely explanation for this
variability is the marked differences in the assessment and
classification of handedness across studies.
It was also suggested that the different types of atypical handedness (MH, PLH, and AH) represent neurodevelopmental markers of an early brain insult, probably
diffuse or multifocal, during prenatal life; they also predict other key symptoms and neural substrates in the disorder. Studies reporting these pathological links to nonright-handedness in schizophrenia have marshaled
compelling evidence for this hypothesis, which should be
viewed as complementary to the prevalence findings
noted earlier. While prevalence estimates have varied,
probably as a function of differences in study procedures
and methodology, results have been consistent in linking
deviations in manual laterality to other clinical and neurobiological aspects of the disorder.
Finally, it was suggested that these deviations in lateral preference be viewed as epigenetic events that, when
aggregated with genetic factors, may result in more severe
forms of schizophrenia (Murray et al. 1992a, \992b).
However, this interpretation rests on the assumption that
deviations in hand preference are induced only by exogenous, not genetic, events, which may not be true.
Although current evidence favors the former view, more
research should focus on whether atypical deviations in
73
Schizophrenia Bulletin, Vol. 25, No. 1, 1999
P. Satz and M.F. Green
hand preference may occur in schizophrenia in the
absence of any known prenatal exogenous insult.
Different hypotheses were reviewed that purport to
explain different subtypes of atypical handedness (PLH,
MH, AH) in schizophrenia, with particular attention to
MH. Although each hypothesis addressed some aspect
pertaining to the left hemisphere (lag, vulnerability, hemispheric specialization), it was shown that a more parsimonious explanation could result by avoiding surplus meaning associated with concepts of unilateral insult or
vulnerability of the left hemisphere and postulating that
an early bilateral or multifocal brain insult would be necessary and sufficient to alter the left hemisphere's control
over cognitive (language) and contralateral motor (handedness) functions leading to a less complete and more
variable form of MH. However, alternative explanations
favoring a focal left hemisphere insult in utero, while still
of potential merit and appeal, still lack sufficient support
that shows a more extreme leftward shift in the handedness distribution. We hope this review will encourage
future studies of this issue.
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The Authors
Paul Satz, Ph.D., is Professor of Medical Psychology and
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Announcement
The 13th International Symposium for the
Psychotherapy of Schizophrenia (ISPS) will be held in
Stavanger, Norway, June 4—9, 2000. A call for papers will
be ready in the autumn of 1998. The theme of the symposium is "Schizophrenia and Other Psychoses: Different
Stages-Different Treatment?" Registration will be on
Sunday, June 4th, and the official opening will begin
Monday, June 5th. Some of the topics to be discussed are:
Monday—"The Nature of Psychosis" and "History of
Psychotherapy"; Tuesday—"What Kind of Psychotherapy
for Which Patient? Phase-Specific Treatment," "Cognition
and Psychotherapy," and "Therapeutic Alliance and
Psychotherapy"; Wednesday—"Early Intervention in
Psychosis" and "Personality and Psychosis"; Thursday—
"Integrated Treatment" and "Guidelines: New AntiPsychotics and the Combination With Other Therapies";
and Friday—"Research in Psychotherapy" and "Models
for Training and Competence Building."
For further information, please contact:
ISPS 2000
Stavanger Forum
P.O. Box 410
N-4001 Stavanger, Norway
Tele: 47 51 59 81 00
Fax: 47 51 55 10 15
E-mail: [email protected]
78