"Schizotaxia": Clinical Implications and
New Directions for Research
by Stephen V. Faraone, Alan I. Qreen, Larry J. Seidman,
and Ming T. Tsuang
The At Issue section of the Schizophrenia Bulletin con-
tains viewpoints and arguments on controversial issues.
Articles published in this section may not meet the strict
editorial and scientific standards that are applied to
major articles in the Bulletin. In addition, the viewpoints
expressed in the following article do not necessarily rep-
resent those of the staff or the Editorial Advisory Board of
the Bulletin— The Editors.
Abstract
We sought to show that (1) schizotaxia (Meehl's term
for the predisposition to schizophrenia) is a clinically
consequential condition, and (2) distinguishing it from
schizotypal personality disorder may be useful from
both clinical and scientific perspectives. We review the
features of schizotaxia that may be relevant in clinical
settings and discuss their implications for the diagno-
sis, psychosocial functioning, family intervention and
treatment of people in schizophrenia families. Our
review indicates that prior work finds some of the
nonpsychotic and nonschizotypal relatives of schizo-
phrenia patients to have a psychiatric syndrome char-
acterized by negative symptoms, neuropsychological
impairment, and psychosocial dysfunction. Following
Meehl, we call this constellation of clinical and neuro-
biological features schizotaxia. The studies we review
suggest it may be worthwhile to consider schizotaxia
as a separate diagnostic class. Doing so would alert
clinicians to a neurobehavioral syndrome not ade-
quately covered by current diagnostic criteria and
would motivate researchers to develop diagnostic and
therapeutic approaches aimed at helping schizotaxic
individuals and, perhaps, preventing the onset of
schizophrenia.
Keywords: Schizophrenia, schizotaxia, genetics,
prevention, spectrum
Schizophrenia Bulletin, 27(1):1-18,2001.
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In 1962, Paul Meehl used the term "schizotaxia" to
describe the genetic predisposition to schizophrenia
(Meehl 1962). Schizotaxic individuals, he surmised,
would develop either schizotypy or schizophrenia,
depending on environmental circumstances. Eventually,
schizotypy (in the form of schizotypal personality disor-
der) entered the diagnostic nomenclature. Schizotaxia did
not. It was used in research to indicate the premorbid neu-
rological substrate of schizophrenia, but it was not exam-
ined as a clinically meaningful syndrome.
Now, almost 4 decades later, research suggests that
schizotaxia may be a clinically consequential condition.
This work describing abnormalities in affect, cognition,
and social functioning among the nonschizotypal and
nonpsychotic relatives of schizophrenia patients shows
that schizotaxia is not merely a theoretical construct; it
has psychiatric and neurobiological features that may jus-
tify further research about its nosologic validity.
Although our use of the term schizotaxia is consistent
with Meehl's view of it as the underlying defect among
people genetically predisposed to schizophrenia, we do
not endorse other aspects of his theory if we have not
explicitly done so in this article. For example, having
written his theory before molecular genetic data was
available, Meehl favored a single major gene theory of
schizophrenia, which has since been proven false by
genetic linkage studies. Also, Meehl viewed schizotypy as
the only clinical phenotype of schizotaxia. This article
suggests that, when not expressed as schizotypy, schizo-
taxia results in neuropsychological deficits and negative
symptoms.
There have already been comprehensive reviews of
these schizotaxic features (see, e.g., the issue of
Schizophrenia Bulletin (20(1), 1994) edited by Moldin
and Erlenmeyer-Kimling). In this article, we seek not to
reproduce that information but to inform clinicians about
Send reprint requests to Dr. M. Tsuang, Harvard Dept. of Psychiatry,
Massachusetts Mental Health Center, 74 Fenwood Road, Boston, MA
02115; e-mail: ming_tsuang@hms.harvard.edu.
 Schizophrenia Bulletin, Vol. 27, No. 1, 2001
the clinical features of schizotaxia and to motivate
researchers to develop diagnostic and therapeutic
approaches aimed at helping those with schizotaxia.
Clinical Features of Schizotaxia
The clinical descriptions of most psychiatric conditions
originally derived from reports of patients who presented
with a specified cluster of signs and symptoms. In con-
trast, clinical descriptions of schizotaxia come from stud-
ies of people genetically predisposed to schizophrenia: the
relatives of schizophrenia patients. Such studies infer a
clinical or neurobiological abnormality to be a potential
feature of schizotaxia if it is elevated among these rela-
tives and among schizophrenia patients. In this section we
consider three clinically relevant areas of research: psy-
chiatric signs and symptoms, neuropsychological per-
formance, and psychosocial functioning.
Psychiatric Signs and Symptoms. Because family,
adoption, and twin studies firmly support the idea that
relatives of schizophrenia patients are at high risk for
schizotypal personality disorder (Torgersen 1985;
McGuffin and Thapar 1992; Battaglia and Torgersen
1996), several studies have attempted to determine
which schizotypal symptoms are most common among
the relatives of patients with schizophrenia. For exam-
ple, Gunderson, et al. (1983) found that relatives of
schizophrenia patients were at high risk for social isola-
tion, interpersonal dysfunction, and impoverished affec-
tive experiences. In that study, mild psychotic like symp-
toms such as recurrent illusions and magical thinking
were more common in relatives who were themselves
diagnosed with borderline personality disorder. Tsuang
et al. (1991) reported that negative symptoms (especially
flat affect and avolition) were significantly elevated in
the schizophrenia families, while positive symptoms
were not. In the Roscommon family study, odd speech,
social dysfunction, and negative symptoms strongly dis-
criminated relatives of schizophrenia patients from con-
trols. In contrast, positive symptoms, suspicious behav-
ior, and avoidant symptoms were less discriminating
(Kendler et al. 1995).
Consistent with these studies, psychometric assess-
ments of schizotypal symptoms among relatives of
patients with schizophrenia have found a predominance of
negative rather than positive symptoms. For example,
Grove et al. (1991) showed that relatives of schizophrenia
patients have greater deficits on the Physical Anhedonia
Scale (which measures negative schizotypal features) than
on the Perceptual Aberration Scale (which measures posi-
tive schizotypal features). Although we must consider the
possibility that artifacts of self-report scales such as
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S.V. Faraone et al.
defensiveness might have led to these results, their consis-
tency with direct interview studies is compelling.
In summary, the literature to date provides firm sup-
port for the idea that nonpsychotic relatives of schizophre-
nia patients are at risk for schizotypal personality traits.
The literature also shows that the relatives in schizophre-
nia families are more likely to express negative symptoms
than positive symptoms, although, as the Roscommon
study showed, positive schizotypal symptoms are also
found among nonpsychotic relatives of schizophrenia
patients.
These studies have focused on positive and negative
schizotypal traits because several studies suggested that
schizotypal symptoms fell along two dimensions: cogni-
tive-perceptual and interpersonal, or positive and negative
(Raine and Allbutt 1989; Kendler et al. 1991). But three-
and even four-dimensional solutions have also been
reported by others (Muntaner et al. 1988; Bentall et al.
1989; Hewitt and Claridge 1989; Raine et al. 1994; Chen
et al. in press). These studies suggest that, as is the case
for schizophrenia, we may need a third dimension, disor-
ganization, to adequately describe schizotypal signs and
symptoms. Thus, a more complex view of clinical schizo-
typal traits should be examined in future studies of
schizotaxia.
Given that negative schizotypal symptoms are promi-
nent among relatives of schizophrenia patients, we would
expect these relatives to also show an excess of schizoid
personality disorder. But relevant data are mixed. In a
Danish adoption study, the biological relatives of schizo-
phrenia patients did not show an excess of schizoid per-
sonality (Kety et al. 1994). Similar results were reported
in a family study by Maier et al. (1994a; 19946) and a
twin study by Torgersen et al. (1993). In contrast, two
family studies found higher rates of schizoid personality
among relatives of schizophrenia patients compared with
relatives of controls (Dorfman et al. 1993; Kendler et al.
1993). Because there are no systematic differences
between studies that do and do not find schizoid personal-
ity in schizophrenia families, further work is needed to
clarify the nature of the negative symptoms of schizotaxia
and to determine why these are expressed in negative
schizotypal, but not schizoid traits.
Neuropsychological Performance. When the genes for
schizophrenia do not lead to frank psychosis, will they
nonetheless affect the brain and lead to neurobiological
abnormalities and neuropsychological deficits? Several
decades of research suggest that the answer is "yes"
(Seidman 1997). Abnormalities found among relatives of
schizophrenia patients include eye tracking dysfunction
(Levy et al. 1994), allusive thinking (Catts et al. 1993),
neurologic signs (Erlenmeyer-Kimling et al. 1982), char-
acteristic auditory evoked potentials (Friedman and
 At Issue
Squires-Wheeler 1994), neuropsychological impairment
(Kremen et al. 1994), and structural brain abnormalities
assessed by magnetic resonance imaging (Seidman et al.
1997). Although each of these domains of research has
provided valuable data about the neurobiological features
of schizotaxia, we focus here on the neuropsychological
findings because they describe deficits that have clinically
meaningful implications for members of schizophrenia
families.
Two research paradigms—studies of children of
schizophrenia patients and studies of adult relatives of
schizophrenia patients—have provided data about the
neuropsychological features of schizotaxia. It is useful to
distinguish studies of child and adult relatives because,
unlike children, adults have lived through some, or all, of
the risk period for schizophrenia. Thus, both types of rela-
tive groups will include some schizotaxic individuals but
studies of children are more likely to include cases that
will eventually develop schizophrenia.
One neuropsychological function that differentiates
child relatives is motor ability. Impaired motor ability pre-
sents in children as soft neurological signs such as dis-
turbed gait, poor balance, uncoordination, motor impersis-
tence and impaired mirror drawing (Lifshitz et al. 1985;
Asarnow and Goldstein 1986). In contrast, motor func-
tioning has been less consistently impaired among adult
relatives of schizophrenia patients (Kinney et al. 1986;
Cannon et al. 1994; Faraone et al. 19956; Kinney et al.
1991; Rosen etal. 1991).
Perceptual-motor speed tests assess the ability to per-
ceive stimuli and react to them quickly in an appropriate
manner. Among the children of schizophrenia patients,
there is consistent evidence for deficits on such tests
(Erlenmeyer-Kimling et al. 1982; Nuechterlein and
Dawson 1984). Similar results have also been found
among adult relatives. For example, in studies from two
different research groups, nonpsychotic relatives were sig-
nificantly slower on the Trail Making Test (Pogue-Geile et
al. 1991; Keefe et al. 1992; Keefe et al. 1994). Similar
trends were reported by others (Goldberg et al. 1990;
Condray and Steinhauer 1992).
Tests of short-term memory assess the ability to retain
information in memory for a brief duration (e.g., recalling
a phone number after finding it in the directory). In most
(Mednick and Schulsinger 1968; Sohlberg 1985; Landau
et al. 1989) but not all (Worland and Hesselbrock 1980)
studies, children of schizophrenia patients showed poor
short-term memory as measured by oral arithmetic scores
(which require short-term memory to manipulate mathe-
matical concepts). They are not consistently impaired
when asked to recall a string of digits (Mednick and
Schulsinger 1968; Worland and Hesselbrock 1980;
Cornblatt and Erlenmeyer-Kimling 1985; Lifshitz et al.
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Schizophrenia Bulletin, Vol. 27, No. 1, 2001
1985), but they do show deficits if distracted during digit
recall (Harvey et al. 1981; Winters et al. 1981; Cornblatt
and Erlenmeyer-Kimling 1985; Spring 1985). Short-term
digit recall has not been impaired in studies of adult rela-
tives (Roxborough et al. 1993; Faraone et al. 19956),
probably because of the lack of a distraction component
in those studies.
Impaired vigilance (often referred to as sustained
attention) is usually measured with a continuous perform-
ance test (CPT), which presents a long series of stimuli
and asks the subject to respond whenever a rare target
stimulus appears. Cornblatt and Keilp's (1994) review of
40 studies using the CPT shows that vigilance deficits are
evident among both the adult and child relatives of schiz-
ophrenia patients.
There has been little neuropsychological evaluation
of verbal ability and language among children of schizo-
phrenia patients. Most studies of adult relatives have not
found differences in general verbal ability, although there
was some evidence for poorer vocabulary scores in one
sample (Faraone et al. 19956). Notably, three studies
found significant impairments in speed and ease of verbal
production (Pogue-Geile et al. 1991; Keefe et al. 1992;
Roxborough et al. 1993; Keefe et al. 1994) and Cannon et
al. (1994) found deficits in language abilities.
Difficulties with language have also been docu-
mented in studies of communication deviance, which have
found unclear, amorphous, disruptive, or fragmented com-
munication among the parents of schizophrenia patients
(Wynne and Singer 19636; Singer and Wynne 1965;
Doane et al. 1981; Rund 1986; Velligan et al. 1990;
Docherty 1993; Docherty 1994; Miklowitz 1994; Rund
1994; Velligan et al. 1995; Docherty et al. 1996; Velligan
et al. 1996). Given these communication problems, it is
not surprising that relatives of schizophrenia patients also
show signs of thought disorder (Lidz et al. 1962; Wynne
and Singer 1963a; Wynne and Singer 19636; Rosman et
al. 1964; Singer and Wynne 1965; Schopler and Loftin
1969; Arboleda and Holzman 1985; Saccuzzo et al. 1988;
McConaghy 1989; Shenton et al. 1989; Romney 1990).
Indeed, communication deviance and thought disorder are
usually associated with one another (Docherty 1994). The
thought disorder observed among relatives is never as
severe as that seen among schizophrenia patients, but it
does share qualitatively similar characteristics such as
looseness of associations, autistic logic, word finding dif-
ficulties, perseveration, and conceptual disorganization.
Studies of children of schizophrenia patients have
provided scant information about the ability to learn and
recall verbal material. Adult relatives, however, have dif-
ficulties recalling the details of a short story (Roxborough
et al. 1993; Cannon et al. 1994; Faraone et al. 19956;
Faraone et al. in press;) or using the semantic similarities
 Schizophrenia Bulletin, Vol. 27, No. 1, 2001
of words to aid in their recall (Lyons et al. 1995). In con-
trast, deficits in simple visual-spatial learning and mem-
ory tasks are not usually found in schizotaxic adults
(Orvaschel et al. 1979; Driscoll 1984; Neuchterlein and
Dawson 1984; Cannon et al. 1994), although some posi-
tive findings have been reported (Faraone et al. 19956;
Faraone et al., in press).
Executive functions are essential for planning, for
processing abstract concepts and for using retained infor-
mation in other cognitive tasks. Children of people with
schizophrenia do poorly on measures of concept forma-
tion (Asarnow et al. 1978) but not on object sorting tests
that require them to abstract a rule from a series of stimu-
lus presentations (Winters et al. 1981). Adult relatives also
do poorly on concept formation tests (Pogue-Geile et al.
1989; Condray and Steinhauer 1992) and, although there
is some contrary evidence (Condray and Steinhauer 1992;
Keefe et al. 1992; Roxborough et al. 1993; Keefe et al.
1994), most studies have found adult relatives to be
impaired on sorting tests (Pogue-Geile et al. 1991; Franke
et al. 1992; Mirsky et al. 1992; Faraone et al. 19956).
Consistent with these findings of executive dysfunction,
adult relatives are impaired on tests of working memory
that assess the ability to remember information over a
short period of time so that it can be used in a subsequent
task (Park et al. 1995; Faraone et al. in press).
Table 1 summarizes the neuropsychological studies
of child and adult relatives. It renders a clear conclusion:
in schizophrenia families, some relatives have neuropsy-
chological deficits in multiple domains. The domains
impaired in these relatives are consistent with the cogni-
tive dysfunctions thought to be central to schizophrenia
patients themselves. This consistency supports the idea
that some relatives in schizophrenia families have a famil-
Table 1. Neuropsychological functions impaired in child and adult relatives
Neuropsychological domain Children/adolescents
Motor ability
Perceptual-motor speed
Short-term memory
Sustained attention
Verbal ability and language
Verbal learning and memory
Visual-spatial learning and memory
Executive functions
Note.—+ = impaired; - = not impaired; +/- = variable results; ? = not sufficiently studied.
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S.V. Faraone et al.
ially transmitted syndrome—schizotaxia, which manifests
as abnormalities in neuropsychological performance.
Psychosocial Functioning. If schizotaxia is a clinically
significant condition, it should be associated with disabil-
ity at work, in school, or with interpersonal relationships.
For adult relatives, one might infer such disability from
their profile of neuropsychological impairments. For
example, at work and in school, impaired executive func-
tions will jeopardize successful achievement, which
requires planning and organizational skills and the ability
to process abstract concepts. Moreover, impairments in
vigilance will make it difficult for schizotaxic people to
succeed in settings that require concentration over long
periods. One might infer interpersonal dysfunction from
the subtle thought disorder and communication associated
with schizotaxia.
Although these neuropsychological inferences are
compelling, few studies of adult relatives have directly
examined psychosocial functioning. One exception is the
work of Toomey et al. (1997), who reported adult rela-
tives to have deficits in the social perception of nonverbal
cues; these deficits were associated with poor vigilance.
We also know that schizotaxia leads to negative symp-
toms, which include indexes of psychosocial failure such
as impersistence at school or work, recreational interests
and activities, sexual activity, and relationships with
friends and peers.
In contrast to the dearth of psychosocial information
about adult relatives, psychosocial dysfunction has been
documented among the children of schizophrenia patients
("child relatives" for short). For example, data from the
New York High-Risk Project found child relatives to have
poorer social functioning and more restricted interests
Type of Relative
Adults
 At Issue Schizophrenia Bulletin, Vol. 27, No. 1, 2001

than psychiatric or normal controls (Small 1990). The ropsychological deficits might improve the psychosocial
social competence of child relatives decreased between functioning of schizotaxic people.
childhood and early adolescence but remained stable from
early to late adolescence (Dworkin et al. 1994).
In the Israeli high risk study, Auerbach et al. (1993) Clinical Implications of Schizotaxia
found boys of schizophrenia parents to be more with-
To recap, schizotaxia is a subtle syndrome of brain dys-
drawn than boys of nonschizophrenia parents. The boys
function expressed, in part, as negative symptoms and
who developed schizophrenia-related disorders had been
neuropsychological deficits, but not as psychosis. This
shy and withdrawn or aggressive and antisocial (Hans et
syndrome is qualitatively similar—yet less severe—than
al. 1992). In the Danish high risk study, child relatives
that observed among schizophrenia patients. In this sec-
were described by teachers as passive and socially iso-
tion we address questions that these findings pose for clin-
lated, and by mothers as both passive and aggressive.
ical practice: How does one diagnose schizotaxia and dif-
When compared with controls, teachers described child
ferentiate it from schizotypal personality? Does
relatives as less socially competent and more aggressive;
schizotaxia have implications for family interventions for
peers described them as more aggressive, withdrawn,
schizophrenia? What are the treatment options for schizo-
and unlikable (Ledingham 1990). Notably, Asarnow's
taxic people?
review (1988) determined that all studies of adolescent
relatives have found them to have significant social dys-
function. How Does One Diagnose Schizotaxia and Differentiate
It From Schizotypal Personality? For schizotaxia to be a
Thus, like neuropsychological impairment, there is
useful diagnostic class, requires the formulation of specific
consistent evidence for psychosocial dysfunction among
diagnostic criteria is required. But specifying diagnostic
children at risk for schizophrenia. Moreover, studies of
criteria is not currently possible given that this issue has not
children link these two domains of dysfunction. For
been directly examined in prior research. We expect such
example, in Auerbach et al.'s (1993) study, the socially
criteria to evolve as future research assesses the concurrent
withdrawn children also had motor abnormalities.
and predictive validity of schizotaxia criterion sets.
Walker and Lewine (1990) rated videotapes of children
Moreover, such research will need to document the diver-
who subsequently developed schizophrenia. These chil-
gent validity of schizotaxia: Is the syndrome sufficiently
dren had neuropsychological impairments (poor fine and
different from other disorders to warrant a separate cate-
gross motor coordination) and evidence of social dys-
gory? Here we address the most difficult differential diag-
function (poor eye contact, more negative affect and low
nostic hurdle for schizotaxia: is it sufficiently different from
social responsiveness). In the New York High-Risk
schizotypal personality to warrant a separate category?
Project, attentional problems in childhood predicted
social dysfunction in adolescence and social isolation in Notably, in a reformulation of his theory, Meehl
adulthood (Dworkin et al. 1993). Notably, an association (1989) conceded the possibility that some schizotaxic per-
between neuropsychological performance and functional sons might not develop schizotypal personality. Although
impairment is also seen for schizophrenia patients he thought this outcome would require "a sufficiently
(Green 1996). well-managed prophylaxis" (p. 938), subsequent data
Because neuropsychological impairment is evident have shown that—even without intervention—many
at an early age (e.g., Fish and Hagin 1973) and typi- schizotaxic persons will neither become schizotypal nor
cally emerges prior to social dysfunction (Dworkin et develop schizophrenia. The core features of schizotaxia
al. 1993), it is intriguing to speculate about a causal (negative symptoms and neuropsychological impair-
link between these two features of schizotaxia. As sug- ments) occur in 20 percent to 50 percent of such relatives
gested by Cornblatt and Keilp (1994), an early atten- (Faraone et al. 1995a, 1995fc), but less than 10 percent of
tional deficit could impair the processing of interper- adult family members of schizophrenia patients will be
sonal information and lead to failure in social diagnosed with schizotypal personality disorder. Thus,
interactions. unlike schizotypal personality, schizotaxia appears to be
common among relatives of schizophrenia patients.
Cornblatt and Keilp's model predicts that interper-
Because schizotypal personality should be evident by
sonal interactions will frequently fail, leading to increased
adulthood, finding that many schizotaxic adults are not
stress and a repeated cycle of increased psychosocial dif-
schizotypal shows that the former condition does not
ficulties and stress. We would extend this model to
always evolve into the latter.
include other neuropsychological deficits as potential
causes of psychosocial dysfunction. Future confirmation There is another reason to demarcate schizotaxia
of these causal links would suggest that treatment of neu- from schizotypal personality: The latter is a heteroge-

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 Schizophrenia Bulletin, Vol. 27, No. 1, 2001
neous disorder. This heterogeneity stems from the two
methods used to study it: The "clinical method" has iden-
tified personality disordered patients who seem to exhibit
a mild form of schizophrenia symptoms; the "family
research method" has identified relatives of patients with
schizophrenia who exhibited subtle schizophrenia like
psychopathology (Kendler 1985). Although the people
recruited by these two methods show some clinical simi-
larities, several studies suggest that "clinical" and "famil-
ial" schizotypal personality may be different disorders
(Kendler 1985).
For example, among subjects diagnosed with
schizotypal personality, Torgersen (1985) reported that
the negative symptoms of social withdrawal and impair-
ment were genetically related to schizophrenia while
positive, psychotic-like symptoms were not. Thaker et
al. (1993&) found clinical schizotypal subjects to show
more evidence of magical ideation and perceptual
ideation than familial schizotypal subjects. The two
groups, however, did not differ in either physical or
social anhedonia.
A family study reported elevated rates of schizotypal
personality among relatives of patients with mood disor-
der (Squires-Wheeler et al. 1989), but compared with
schizotypal relatives in schizophrenia families, the schizo-
typal relatives in mood-disordered families were more
likely to show symptoms of anxiety and depression at a
follow up assessment (Squires-Wheeler et al. 1992).
Similarly, Lyons et al. (1994) compared schizotypal rela-
tives of schizophrenia probands with schizotypal relatives
of mood disordered probands. The former group had more
inadequate rapport and anxiety whereas the latter had
higher rates of impulsive-dramatic personality disorders.
Biological studies also find evidence for two types of
schizotypal personality. An early review by Siever (1985)
concluded that a subgroup of schizotypal subjects exhib-
ited biological abnormalities that were similar to those
seen in schizophrenia patients. This subgroup manifested
negative symptoms and neuropsychological impairment
(two features of schizotaxia), but rarely exhibited positive
symptoms. Moreover, Condray and Steinhauer (1992)
found impaired language comprehension among schizo-
typal subjects with a family history of schizophrenia, but
not among those without such a history and Kendler et al.
(1991) showed that among schizotypal subjects, negative
symptoms predicted attentional and eye-tracking dysfunc-
tion (likely features of schizotaxia) but the positive syn-
drome did not. Results consistent with these were
reported by Thaker et al. (1996), who assessed eye track-
ing among subjects with paranoid, schizoid, and schizo-
typal personality. Eye-tracking abnormalities were associ-
ated with these disorders, but only for subjects with a
family history of schizophrenia.
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S.V. Faraone et al.
The view that schizotypal personality is heteroge-
neous finds further support from family studies. For
example, Thaker et al.'s review (1993a), shows that most
studies of clinically derived schizotypal probands did not
find elevated rates of schizophrenia among the proband
relatives. Subsequent reports have also supported that
assertion (Battaglia et al. 1995). These findings suggest
that many clinically ascertained schizotypal patients do
not carry the genetic predisposition to schizophrenia (i.e.,
they do not have schizotaxia).
In figure 1, schizotaxia (the left circle) and schizo-
typal personality (the right circle) are shown as conditions
that sometime co-occur. The lack of complete overlap
between the two circles illustrates the notion that schizo-
taxia is a broader construct than the subset of schizotypal
persons who have predominantly negative symptoms. The
area of overlap between the circles corresponds to people
showing both schizotaxic and schizotypal symptoms.
These people have been described as having "familial"
schizotypal personality in the research literature. The por-
tion of the schizotypal personality circle not overlapping
with the schizotaxia circle contains those patients
described as having "clinical" schizotypal personality.
We leave to future research the goal of parsing the
comorbidity between schizotypal personality and schizo-
taxia. Because comorbidity is a common feature of psy-
chiatric illness, recognizing both conditions and their
comorbidity might be a reasonable solution. In contrast, it
may be preferable to sharpen diagnostic criteria with the
goal of separating schizotaxia from schizotypal personal-
Figure 1. Overlap between schizotaxia and
schizotypal personality
— Schizotaxia
=
Schizotypal Personality
Familial Schizotypal Personality
Clinical Schizotypal Personality
 At Issue
ity. This would require psychometric studies that would
find diagnostic criterion sets that eliminate the extensive
comorbidity between the two conditions.
If successful, such studies would designate schizo-
taxia as the syndrome of negative symptoms and neu-
ropsychological dysfunction observed among relatives of
schizophrenia patients (all of figure 1 's schizotaxia circle)
and schizotypal personality disorder as the schizophrenia-
like syndrome in which positive symptoms dominate the
clinical picture (the portion of figure 1 's schizotypal per-
sonality circle that does not overlap with the schizotaxia
circle). Reformulating the diagnoses in this manner would
increase the homogeneity of schizotypal personality and
free researchers to define schizotaxia in a manner that
might further validate it as a syndrome.
If future work refines definitions of schizotaxia and
schizotypal personality, it will also need to clarify how
these conditions are related to schizophrenia, which is
itself clinically and genetically heterogeneous (Tsuang
and Faraone 1995). Such work would need to consider
alternative theoretical models. For example, there may be
several dimensions of schizotaxia and schizotypal person-
ality. Predisposing a person to each of these may be dif-
ferent sets of genes that, in combination, predispose a per-
son to schizophrenia. It is also possible that the genes
predisposing people to schizotaxia and schizotypal per-
sonality may be related to different forms of schizophre-
nia. Moreover, it is not clear if schizotaxia is a discrete
entity or a quantitative trait that varies in severity from
subclinical to clinically meaningful manifestations.
Addressing such issues could facilitate genetic studies,
and might clarify the treatment implications of schizo-
taxia for people in schizophrenia families.
Does Schizotaxia Have Implications for Family
Interventions for Schizophrenia? Because families are
often involved in treatment programs for patients with
schizophrenia, it is likely that many schizotaxic persons
participate in the treatment of their relative with schizo-
phrenia. Psychoeducational family therapies ask family
members to learn facts about the disorder and methods of
coping with their relative's illness (Falloon et al. 1986).
Moreover, response acquisition methods are often used to
teach communication skills to family members (Falloon et
al. 1986). Because family members need to learn, recall,
and generalize the use of these skills, therapists engage
family members in a variety of tasks requiring intact neu-
ropsychological functioning.
Although the nonschizotaxic relatives should benefit
from family interventions, it is likely that the neuropsy-
chological impairments of other family members would
hinder the course of treatment (Seidman 1994). The dis-
tractibility of schizotaxic relatives may make it difficult
for them to follow lessons and absorb information.
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Memory deficits will likely compromise their ability to
learn skills and use them outside the treatment session.
Relatives with abstraction deficits will not be able to inte-
grate course material and plan for its use in the home
environment. Considering that family interventions also
tax the capacity of family members to tolerate difficult
emotions and face family conflict, the added burden of
neuropsychological deficits may make it hard for family
members to learn skills or to generalize them from treat-
ment sessions to real-world settings.
Thus, full participation in family interventions will
likely be compromised by the neuropsychological impair-
ments of schizotaxia. Moreover, it is possible that thera-
pist observations of inattentiveness, slow learning, or poor
memory for lessons may be misinterpreted as indicating
resistance on the part of the family member. That could
lead to counterproductive therapeutic strategies.
What Are the Treatment Options for Schizotaxia? The
features of schizotaxia raise two distinct questions for
treatment. First, can we alleviate the negative symptoms,
neuropsychological impairment, and social dysfunction of
adult schizotaxia? Second, can we prevent schizophrenia
in schizotaxic adolescents?
Treating adult schizotaxia. Age-at-onset data show
that the risk for schizophrenia becomes very small in the
third decade of life (Pulver et al. 1990; Faraone et al.
1994; Sham et al. 1994). Moreover, most patients with
schizotypal personality disorder do not go on to develop
schizophrenia. Thus, most adults with schizotaxia are not
at high risk for schizophrenia and any proposed treatment
of such adults cannot be predicated on the notion that it
will prevent that disorder. Instead, proposed treatments
should be aimed at alleviating the negative symptoms,
neuropsychological impairment, and social dysfunction of
schizotaxia.
Clinicians who work with schizophrenia families fre-
quently deal with psychologically distressed or psychoso-
cially impaired relatives. When clinicians interpret dis-
tress as a reasonable reaction to the schizophrenia in the
family, they will try to help family members cope with the
relative's illness. Such interventions can be very effective,
but they do not address an alternative clinical hypothesis:
that some of the distress and social disability of family
members might be a direct effect of schizotaxia.
Moreover, the psychological vulnerabilities of
schizotaxic people may be exacerbated by stress, which
would include the emotional burdens and practical com-
plexities of dealing with a relative with schizophrenia
along with the background level of life events and psy-
chosocial conflict that would occur in a nonschizophrenia
family. These considerations suggest that the direct treat-
ment of schizotaxia might be useful in the therapeutic
approach to schizophrenia families. But, how would one
 Schizophrenia Bulletin, Vol. 27, No. 1, 2001
treat schizotaxia? Although there is no specific therapy for
the condition, here we speculate on potential psychologi-
cal and pharmacological approaches, which may not be
mutually exclusive.
The treatment of schizotaxia may benefit from meth-
ods effective in the psychotherapy of other neurodevelop-
mental conditions (e.g., adult attention deficit hyperactiv-
ity disorder), which share some clinical features with
schizotaxia. As discussed by Seidman (1994), therapists
who treat patients with subtle neuropsychological impair-
ments should attend to several issues.
First, the therapist should have an objective under-
standing of the patient's neuropsychological strengths and
weaknesses. This knowledge helps patients and the signif-
icant people in their lives to reformulate their view of the
behavioral consequences of cognitive dysfunction. For
example, schizotaxic people with deficits in attention and
verbal memory may view themselves as "stupid" because
they cannot learn in the many educational settings that
require these skills. Therapy can help them reinterpret
these difficulties and develop coping strategies. Moreover,
teaching schizotaxic people about their neuropsychologi-
cal profile might help them develop realistic expectations
and better plan their occupational and educational pur-
suits.
Clinicians could also help schizotaxic people develop
cognitive-behavioral strategies to cope with specific
deficits. For example, relatives with memory deficits
would benefit from learning mnemonic strategies; those
with abstraction deficits could be taught systematic meth-
ods of planning and organizing their activities. Thus, stan-
dard tools used to aid recall (e.g., appointment books, cal-
endars) could be part of the therapeutic toolbox.
Therapists can also use neuropsychological informa-
tion to facilitate an empathic approach to the issues of
shame, inferiority and performance anxiety that often
arise in patients with neurocognitive disorders (Seidman
1994). Such maladaptive emotions may stem directly
from the experiences of failure caused by the schizotaxic,
neuropsychological syndrome. They may be reactions to
the stress and stigma of having a relative with schizophre-
nia. Or, they may derive from the relative's fear of devel-
oping schizophrenia. Furthermore, the language and self-
regulation deficits of schizotaxic people may make it
difficult for them to articulate their awareness of these
feelings. Without therapeutic attention, these emotional
consequences might worsen cognitive performance and
lead to a downward spiral toward further dysfunction.
Although psychological interventions, as noted
above, would appear to be appropriate, research is needed
to clarify which psychotherapeutic approaches are most
effective and whether pharmacotherapy would also be
useful. Of course, there are no known medications for
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S.V. Faraone et al.
schizotaxia, and no clinical guidelines can be suggested at
this time. It is worthwhile, however, to examine the impli-
cations for future pharmacotherapeutic research suggested
by the data reviewed in this article. These data suggest
that schizotaxia shares causal and pathophysiological
components with schizophrenia. Thus, the data raise a
provocative question: Would schizotaxic traits respond to
medications used in the treatment of schizophrenia?
Answering this question is not straightforward. The
answer must assume that antipsychotic medications are of
value in treating negative symptoms and improving neu-
ropsychological functions. Although treatment with low
doses of typical neuroleptic drugs has shown some effi-
cacy for schizotypal personality (e.g., Hymowitz et al.
1986), these drugs may not effectively treat the schizo-
taxic syndrome of negative symptoms and neuropsycho-
logical impairment. Moreover, studies of schizotypal
patients suggest that neuroleptic side effects lead to med-
ication discontinuation rates as high as 50 percent
(Hymowitz et al. 1986).
The atypical or novel antipsychotic drugs may be
more promising for the treatment of schizotaxia. Although
not all studies agree, and the relative effects of these
agents on "primary" and "secondary" symptoms is under
debate (Carpenter et al. 1995; Meltzer 1995), several
reports suggest that the first of the atypical agents, cloza-
pine, improves at least some negative symptoms
(Carpenter et al. 1995; Meltzer 1995) and some neurocog-
nitive deficits (Mortimer and Dye 1997; Potkin et al.
1997; Stone et al. 1997) in severely ill, treatment-refrac-
tory patients. Although the toxicity of clozapine pro-
scribes its use in the absence of clear psychotic symp-
toms, the post-clozapine agents—risperidone, olanzapine,
and quetiapine—may all improve negative symptoms in
patients (Marder and Meibach 1994; Beasley et al. 1996;
Small et al. 1997), and risperidone appears to improve
some neurocognitive deficits (Green et al. 1997;
Lindenmayer et al. 1997).
Clearly, knowledge about the effects of these novel
agents in patients is nascent, but the intriguing hints about
their effects on negative symptoms and neurocognitive
deficits, coupled with their acceptable safety profile, sug-
gests that they might be reasonable candidates for a thera-
peutic trial in schizotaxic relatives. Moreover, other
experimental agents may also be appropriate after more is
learned about their properties.
Currently, however, there are several obstacles to the
treatment of schizotaxia with atypical antipsychotic med-
ications. In prior studies of schizophrenia patients,
improvements in neuropsychological functioning were
modest. Moreover, the response of negative symptoms
relative to that observed for conventional neuroleptics
could have been due to the milder side effects of the atyp-
 At Issue
ical drugs, which lead to fewer secondary negative symp-
toms. Thus, because of the limitations of extant work,
strong conclusions about the value of atypical antipsy-
chotics for the treatment of schizotaxic traits must await
future studies using more sensitive measures.
If pharmacological treatment studies of schizotaxia
proceed, careful pilot investigations would need to assess
the potential occurrence of side effects and clarify the
dose and titration schedules suitable for schizotaxic peo-
ple. A very cautious approach to this potential use of
antipsychotics is especially warranted given reports of
spontaneous dyskinesias in schizotypal subjects (Cassady
et al. 1998), and widespread neurological abnormalities in
nonpsychotic relatives of patients with schizophrenia
(Kinney et al. 1986; Kinney et al. 1991; Ismail et al.
1998). Assuredly, proposed studies of antipsychotic treat-
ment would need to weigh the potential benefits of reduc-
ing schizotaxic symptoms against the risks for drug-
induced side effects.
Developing treatments for schizotaxia could have
several implications. Effective therapies, be they psycho-
logical or psychopharmacologic, might improve the neu-
ropsychological deficits and negative symptoms typically
found in relatives. If Cornblatt and Keilp's (1994) model
is correct, improvements in these domains should lessen
the distress of the individuals themselves and allow them
to function better in family, occupational, and societal
roles. Moreover, improving the welfare of schizotaxic
family members would indirectly benefit their relatives
with schizophrenia by decreasing stress in the home and
facilitating the progress of family interventions.
Our discussion of the treatment of schizotaxia raises
an additional question: Do schizotaxic persons seek treat-
ment for themselves other than around dealing with a rel-
ative with overt schizophrenia? Because of the dearth of
data on this issue, a definitive answer awaits future
research. Such research should consider several possibili-
ties. Many relatives of schizophrenia patients will deny
pathology in themselves, either to avoid identifying with
their schizophrenia relative or because they do not experi-
ence disability or distress from schizotaxic phenomena.
When viewed in contrast to the intense adverse outcomes
of schizophrenia, the experience of schizotaxia may not
feel much different from normal. We will not know if
these people want or need treatment until appropriate
research is completed.
We must also consider that many schizotaxic people
do not have a relative with schizophrenia. This occurs
because of the play of chance: If a family transmits schiz-
ophrenia genes, members are at increased risk for schizo-
phrenia, but not all such families will have a member with
schizophrenia. Although, such schizotaxic people should
theoretically exist, they have never been studied. Thus, we
await future research to answer a variety of intriguing
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Schizophrenia Bulletin, Vol. 27, No. 1, 2001
questions: Do schizotaxic people show up in mental
health clinics? If so, are they diagnosed with schizotypal
personality disorder? Or do their attentional difficulties
lead to a diagnosis of attention deficit hyperactivity disor-
der? Do life failures associated with schizotaxic deficits
lead to depression?
The treatment of schizotaxic adolescents: Can
schizophrenia be prevented? It is intriguing to wonder
whether our clinical reformulation of schizotaxia has
implications for the primary prevention of schizophre-
nia, although speculative. To move from speculation to a
preventive trial, we would need to establish at least two
facts: (1) that it is possible to accurately define the popu-
lation at risk for schizophrenia, and (2) that there is a
compelling rationale for the proposed preventive treat-
ment.
Can the onset of schizophrenia be predicted?
Because a primary prevention trial would target persons
at high risk for schizophrenia, its success presupposes a
method of defining that risk. A simple method would be
to choose adolescent children or siblings of schizophre-
nia patients. This group has a ten-fold elevated risk for
the disorder and is entering the age period of greatest
risk for the onset of psychosis. But even though the ele-
vation in risk for this group is substantial, only 10 per-
cent would be expected to develop schizophrenia or a
related psychotic disorder. This magnitude of risk is not
sufficient for defining the at risk population for preven-
tive trials (unless there was a low-risk treatment that was
inexpensive to administer).
Fortunately, research suggests that measures of
schizotaxia may improve risk prediction to the level
where it would be useful in defining populations at very
high risk for schizophrenia. For example, in two inde-
pendent studies of children of schizophrenia patients,
Fish (1992), described a syndrome of motor abnormali-
ties that predicted subsequent schizophrenia or related
disorders. Similarly, in both the Copenhagen and New
York high risk projects, neuromotor impairment pre-
dicted the onset of schizophrenia (Olin and Mednick
1996; Erlenmeyer-Kimling 1997). These findings are
consistent with Walker and Lewine's (1990) finding of
poorer fine and gross motor coordination in videotapes
of children who subsequently developed schizophrenia.
In addition to neuromotor impairment, attentional
deficits also have been found to predict subsequent
schizophrenia and related disorders (e.g., L. Erlenmeyer-
Kimling, personal communication, 1997).
Given the established link between neuropsychologi-
cal and social impairment in child relatives, it is not sur-
prising that psychosocial dysfunction also predicts subse-
quent schizophrenia and related disorders. In the Israeli
high risk study, subjects who eventually developed schiz-
ophrenia-related disorders had been shy and withdrawn or
 Schizophrenia Bulletin, Vol. 27, No. 1, 2001
aggressive and antisocial as children (Hans et al. 1992).
Walker and Lewine's (1990) videotape study described
the children who developed schizophrenia as having had
poorer eye contact, more negative affect, and diminished
social responsiveness. Similarly, in the Copenhagen high
risk study, teacher-rated social behaviors were predictive
of subsequent schizophrenia (Olin and Mednick 1996).
Thus, among children of schizophrenia patients,
schizotaxic traits may predict subsequent psychosis. Yet,
more needs to be known about the diagnostic accuracy of
schizotaxic traits—that is, their sensitivity and specificity
as predictors of psychosis (Faraone and Tsuang 1994)—
before they can be used in prevention trials. Many of the
studies reviewed above are difficult to interpret because
the outcome they predict is rather broad (i.e., schizophre-
nia and related disorders). Because trials with antipsy-
chotics would not be warranted for preventing some
related disorders (e.g., schizotypal personality), future
work needs to precisely estimate the degree to which
schizotaxia can predict schizophrenia. Moreover, because
no diagnostic criteria are available for schizotaxia, it is
not possible to compare the diagnostic accuracy of schizo-
taxia and schizotypal personality as predictors of psy-
chosis. Future work will need to address this issue.
Theoretically, risk prediction should dramatically
improve after molecular genetic studies discover genes
for schizophrenia. Notably, linkage studies have discov-
ered regions of the genome that may harbor schizophrenia
genes. Four promising chromosomal regions are: 22qll-
ql3, 6p23, 8p22-21, 15ql3-ql4, and 10pl4-pl2 (Pulver
et al. 1994; Straub et al. 1995, 1998; Wang et al. 1995;
Schizophrenia Collaborative Linkage Group
(Chromosome 22) 1996; Schizophrenia Linkage
Collaborative Group for Chromosomes 3 6 and 8 1996;
Freedman et al. 1997; Faraone et al. 1998; Leonard et al.
1998; Schwab et al. 1998). Although these findings are
promising, no schizophrenia gene has yet been found.
After geneticists identify the mutations leading to schizo-
phrenia, these results can be used in combination with
schizotaxic signs to delineate a group at very high risk for
the disorder.
Is there a compelling rationale for a preventive inter-
vention? Although a reasonably accurate ability to predict
who will develop schizophrenia is a necessary precondi-
tion for prevention trials, it is far from sufficient. There
also needs to be a compelling rationale to support an
attempt at preventive treatment. In this section we exam-
ine possible rationales for psychosocial and psychophar-
macologic interventions but emphasize that more research
is needed to clarify the potential efficacy of either
approach.
Theoretically, psychosocial interventions could
choose two foci for intervention: the at-risk individual and
the individual's environment. On one hand, such interven-
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S.V. Faraone et al.
tions might help the at-risk person withstand the stressful
situations that are inherent in life but may be toxic to peo-
ple predisposed to schizophrenia. On the other hand, since
some data, albeit controversial, suggest that the nature of
family relationships may be a risk factor for symptoms of
schizophrenia (e.g., Goldstein 1987), family interventions
might reduce stressors that affect vulnerable family mem-
bers.
But studies of family interaction must be interpreted
cautiously. Rather than being causes of subsequent schiz-
ophrenia, family relationships may be influenced by the
negative symptoms, neurocognitive dysfunction or psy-
chosocial impairments of the at-risk schizotaxic individ-
ual or by the effects that these features produce among
other family members who may never themselves develop
schizophrenia. If a higher genetic risk for schizophrenia
leads to a greater expression of schizotaxic traits, then
measures of stress in the family might well be correlated
with the level of genetic vulnerability in the family. If so,
then any apparent causal link between the nature of fam-
ily relationships and subsequent schizophrenia in family
members might be spurious.
Clearly, further research is needed to create a scien-
tific foundation for potentially preventive psychosocial
interventions. In addition, the possibility that psychophar-
macologic approaches might improve the stress tolerance
of at-risk persons should also be considered. As
researchers begin to address this lacuna in the literature,
they will likely develop several research strategies. One
idea would be to consider the possibility that treatment
studies of schizotaxic adults might inform prevention tri-
als for schizotaxic adolescents.
This research strategy assumes that (1) adult schizo-
taxia provides a suitable model of the pathophysiology of
premorbid schizophrenia, and (2) treatments that amelio-
rate adult schizotaxia do so through neural mechanisms
involved in the onset of psychosis in schizotaxic adoles-
cents. If neurobiological studies can verify this hypothe-
sis, then an effective medication for adult schizotaxia
might be the logical choice for a primary prevention trial
of schizophrenia.
That psychopharmacologic treatment might prevent
the onset of schizophrenia is a logical extension of
Wyatt's (1995) idea that early intervention for schizophre-
nia might alter the course of the illness. His review of 21
controlled studies found that patients who had been
treated with antipsychotic medication during their first or
second hospitalization had a better outcome than patients
who had not been treated early in the course of the illness.
Others have suggested that early treatment, especially
with newer agents, might preserve brain plasticity and
reduce the clinical deterioration of chronic schizophrenia
(Green and Schildkraut 1995; Lieberman 1996;
McGlashan and Johannessen 1996). It is also possible
 At Issue
that, rather than having a neuroprotective effect, early
treatment mitigates the social consequences of schizo-
phrenia psychopathology, which may result in better out-
come by allowing for the easier re-integration of patients
into their social networks. This line of reasoning has moti-
vated the creation of early detection and intervention pro-
jects seeking to treat schizophrenia patients during their
prodrome or first episode (Green and Schildkraut 1995;
Falloon et al. 1996; McGlashan 1996; McGlashan and
Johannessen 1996; McGorry et al. 1996; Olin and
Mednick 1996; Vaglum 1996; Yung et al. 1996).
More work is needed to determine if early treatment
with novel antipsychotics exerts a neuroprotective effect or
if its success is mediated through social factors. If neuropro-
tective effects can be shown for first episode schizophrenia
patients, is it possible that pharmacological treatment would
have neuroprotective effects for schizotaxic adolescents. If
so, would the medications protect them from the first onset
of psychosis? Although this possibility is intriguing, it is
hypothetical and faces several obstacles. Although the bene-
fits of preventing psychosis are clear, a case must be made
that they outweigh the risks of treating schizotaxic adoles-
cents with antipsychotic medication. These medications
have some side effects in adults, and their effects on adoles-
cent development are unknown. For these reasons, any pro-
posed preventive intervention for schizotaxic adolescents
would demand a high level of ethical scrutiny and would
presuppose a compelling rationale for any proposed treat-
ment along with the ability to accurately predict who will
and who will not develop schizophrenia.
Conclusion
Our inquiry into schizotaxia yields clear conclusions from
prior work and intriguing hypotheses for future study.
Schizotaxia, we conclude, is not merely a theoretical con-
struct describing the unknown neural substrate of schizo-
phrenia. Almost 4 decades after Meehl first coined the
term, an accumulation of research reveals schizotaxia to
be a clinically consequential condition. Indeed, the nega-
tive symptoms, neuropsychological deficits and psychoso-
cial disabilities of the schizotaxic person constitute a
chronic syndrome that may compromise quality of life
and goal attainment.
Because some schizotaxic people meet criteria for
schizotypal personality disorder, one might argue for
incorporating the former into the latter. But that would
blur the meaning of schizotypal personality, which is
already a heterogeneous diagnosis. Moreover, cleaving
schizotypal personality into groups with and without a
family history of schizophrenia creates subgroups that dif-
fer on etiologic, neurobiological, and clinical features.
Thus, we propose to join schizophrenia-related
schizotypal personality disorder with other cases of
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Schizophrenia Bulletin, Vol. 27, No. 1, 2001
schizotaxia. This leaves future research the goal of refin-
ing diagnostic criteria to accent the distinction between
schizotaxia and schizotypal personality disorder. In partic-
ular, although negative symptoms and neuropsychological
impairments appear to be hallmarks of schizotaxia, some
positive symptoms such as mild thought disorder might
also be considered as diagnostic criteria. The validity of
proposed diagnostic criteria could be examined in family
studies of schizophrenia, but family studies of schizotaxia
would also be needed to fully clarify the familial relation-
ship between the two conditions.
Our reformulation of schizotaxia has several clinical
implications. In family interventions for schizophrenia,
knowledge of schizotaxic deficits should help clinicians
refine their clinical approach to relatives of schizophrenia
patients. Likewise, the psychotherapy of schizotaxia would
benefit from the clinical insights of those who work with
other neuropsychological disorders. There are, of course,
no protocols for the psychosocial therapy of schizotaxia.
Their invention is another goal for future research.
Our conclusions are limited in several ways. Because
there are no agreed upon diagnostic criteria for schizo-
taxia, studies that have examined this construct among
relatives of schizophrenia patients have not used compa-
rable samples. Many of these studies have examined puta-
tive indicators of schizotaxia in samples that include sub-
jects with personality disorders, thus obscuring the
relative contributions of schizotaxia and known clinical
conditions to the expression of schizotaxic traits.
Moreover, we have also drawn inferences from studies of
schizotypal personality disorder which, as we have dis-
cussed in this paper, is itself heterogeneous.
Assuredly, our comments regarding the pharma-
cotherapy of schizotaxic adults and the prevention of
schizophrenia are speculative. We view these as clinical
hypotheses rooted in a nascent scientific literature. They
call for studies of schizotaxia: to describe its genetic
roots, to delineate its risk factors, to detail its pathophysi-
ology, and to determine why its outcome is not solely
schizophrenia.
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Acknowledgments
Preparation of this article was supported in part by
the National Institute of Mental Health Grants
1 R01MH41874-01, 5 UO1MH46318, and
1 R37MH43518 to Dr. Ming T. Tsuang as well as
R01MH49891 and R01MH52376 to Dr. Alan I. Green; by
grants from the Stanley Foundation to Dr. Larry J.
Seidman; and by the Commonwealth Research Center of
the Massachusetts Department of Mental Health.
 Schizophrenia Bulletin, Vol. 27, No. 1, 2001 S.V. Faraone et al.

The Authors
Stephen V. Faraone, Ph.D., is Associate Professor at the
Harvard Medical School, Boston, MA. Alan I. Green,
M.D., is Associate Professor at the Harvard Medical,
Boston, MA. Larry J. Seidman, Ph.D., is Associate
Professor at the Harvard Medical School, Boston, MA.
Ming T. Tsuang, M.D., Ph.D., is the Stanley Cobb
Professor of Psychiatry at the Harvard Medical School,
Boston, MA.

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