Neuroscience and Biobehavioral Reviews 30 (2006) 651–665

www.elsevier.com/locate/neubiorev

Review

ADHD and schizophrenia phenomenology: Visual scanpaths to emotional

faces as a potential psychophysiological marker?
Pamela J. Marsh a,b,c,*, Leanne M. Williams a,b
a
Western Clinical School, The Brain Dynamics Centre, University of Sydney, Sydney, NSW, Australia
b
Westmead Millennium Institute, Westmead Hospital, Westmead, NSW, Australia
c
School of Psychology, University of Sydney, Sydney, NSW 2000, Australia
Received 14 November 2005; accepted 28 November 2005

Abstract
Commonalities in the clinical phenomenology and psychopharmacology of ADHD and schizophrenia are reviewed. The potential of
psychostimulants to produce psychotic symptoms emphasizes the need for objective psychophysiological distinctions between these disorders.
Impaired emotion perception in both disorders is discussed. It is proposed that visual scanpaths to facial expressions of emotion might prove a
potentially useful psychophysiological distinction between ADHD and schizophrenia. There is consistent evidence that both facial affect
recognition and scanpaths to facial expressions are impaired in schizophrenia, with emerging empirical evidence showing that facial affect
recognition is impaired in ADHD also. Brain imaging studies show reduced activity in the medial prefrontal and limbic (amygdala) brain regions
required to process emotional faces in schizophrenia, but suggest more localized loss of activity in these regions in ADHD. As amygdala activity
in particular has been linked to effective visual scanning of face stimuli, it is postulated that condition-specific breakdowns in these brain regions
that subserve emotional behavior might manifest as distinct scanpath aberrations to facial expressions of emotion in schizophrenia and ADHD.
q 2006 Published by Elsevier Ltd.

Keywords: Adolescence; Schizophrenia; ADHD; Facial expressions of emotion; Visual scanpath; Fixations; Amygdala; Medial prefrontal cortex; Anterior cingulate
cortex; Psychostimulants and psychotic symptoms

Contents

1. Phenomenology of ADHD and premorbid schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 652

2. Dopamine and case studies of co-occurring ADHD with psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 653
3. Emotion perception and social functioning in schizophrenia and ADHD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655
4. Facial affect recognition in schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 655
5. Visual scanpaths to facial expressions of emotion in schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 656
6. Facial affect recognition in ADHD (compared to schizophrenia) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 657
7. Studies of inattention: ADHD versus schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 658
8. Brain-imaging studies and emotion perception impairments in ADHD and schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 659
9. Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 660
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661

ADHD and schizophrenia are both heterogeneous disorders
(Biederman and Faraone, 2002; El-Sayed, 2003; Goldstein,
* Corresponding author. Address: BDC, Acacia House, Westmead Hospital,
Westmead, NSW 2145, Australia. Tel.: C61 2 9845 6688; fax: C61 2 9845
8190.
E-mail address: pamelam@psych.usyd.edu.au (P.J. Marsh).
0149-7634/$ - see front matter q 2006 Published by Elsevier Ltd.
doi:10.1016/j.neubiorev.2005.11.004
2002) characterized by a profile of attention deficits (Barr,
2001; Karatekin and Asarnow, 1998a,b, 1999; Øie et al., 1999),
early neurodevelopmental disturbances (Barr, 2001; Bilder,
2001; Cornblatt et al., 2003; Niemi et al., 2003), and difficulties
with social interactions (Aghevli et al., 2003; Cadesky et al.,
2000; Levine, 2003; Mueser et al., 1996). Each of these
disorders has a profound impact on individuals and families
presenting significant social and economic burdens.
Schizophrenia, for example, accounts for approximately
2.3% of combined social and economic expenditure in
652 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
developed countries (Mueser and McGurk, 2004). Likewise,
ADHD is known to disproportionately burden health, criminal,
educational, and social service resources (Biederman, 2005)
with 5–66% of children showing persistent symptoms into
adulthood (Biederman, 2005). Thus, accurate diagnosis and
treatment is essential to enhance early intervention and
potentially reduce the social, individual, and economic
consequences of these disorders (Barr, 2001; Parnas, 1999;
Winters et al., 1991).
Neurodevelopmental or trait features of schizophrenia are
evident in infancy and early childhood, encompassing
cognitive, affective, and perceptuomotor domains, in addition
to poor social competency. These impairments are thought to
predict overt disorder (Niemi et al., 2003; Parnas, 1999).
However, ADHD symptomatology also manifests in inatten-
tion, impulsivity, and hyperactivity (Biederman, 2005;
Seidman et al., 2005), showing perceptuomotor deficits
(Jonkman et al., 2004; Karatekin and Asarnow, 1998b), and
higher rates of depression (LeBlanc and Morin, 2004),
compared to children without ADHD. Hence, inattention is a
core symptom of both schizophrenia and ADHD (see review in
Barr, 2001), and retrospective studies show that ‘preschizo-
phrenia’ children who later develop schizophrenia, and
children at high risk for schizophrenia (i.e. have a relative
with schizophrenia) sometimes manifest behaviors including
inattention, impulsivity, reduced frustration tolerance, and
diminished social competency that parallel ADHD presen-
tation (Alaghband-Rad et al., 1995; Asarnow et al., 1995;
Elman et al., 1998; Goodman, 1991; Green et al., 1992; Russell
et al., 1989). Thus, the early detection of schizophrenia might
be confounded by phenomenological similarities with ADHD-
defined behaviors.
Nevertheless, there are also important differences between
these two disorders of attention (Ross et al., 2000a,b) and it is
essential that these differences be distinguished to allow proper
diagnosis and the best possible outcome (Barr, 2001). The most
apparent distinction between these two disorders is the clinical
manifestation of delusions and hallucinations in schizophrenia
compared to ADHD (Ross et al., 2000a,b), and the implications
of psychotic symptoms on prognosis and functioning (Kelly
and Gamble, 2005). In fact, ADHD and schizophrenia are
categorized as distinct diagnostic entities in The Diagnostic
and Statistical Manual of Mental Disorders (4th ed., American
Psychiatric Association, 1994), wherein ADHD is defined as a
pattern of persistent and developmentally inappropriate
inattention and/or hyperactivity–impulsivity that cannot be
diagnosed within the context of schizophrenia. Additionally,
the age of onset for ADHD must occur before seven (American
Psychiatric Association, 1994). Conversely, the onset of
schizophrenia, is variable, typically occurring during late
adolescence or early adulthood (Asarnow Rosenbaum et al.,
1994; Benes, 2003; Mueser and McGurk, 2004; Rosenbaum
Asarnow and Tompson, 1999), however, cases have been
reported in children as young as 5 years (Gordon et al., 1994).
The DSM-IV diagnostic criteria for schizophrenia comprise
delusions, hallucinations, disorganized speech, grossly dis-
organized or catatonic behavior, and negative symptoms such
as affective flattening, alogia, or avolition (American
Psychiatric Association, 1994).
While neither the etiology nor the pathophysiology of
ADHD or schizophrenia are well understood, there is evidence
that both disorders involve an interaction of genetic,
neurophysiological, neuropharmacological, and environmental
factors (Durston, 2003; Parnas, 1999). In this review, we focus
on commonalities in the clinical phenomenology and pharma-
cology of ADHD and schizophrenia and specifically, ADHD-
defined symptoms in the premorbid presentation of schizo-
phrenia. This is followed by a review of emotion perception
studies in both disorders with a discussion of how visual
scanpaths to facial expressions of emotion might provide a
useful first step in clarifying the nature of emotion perception
impairments in ADHD and schizophrenia.
1. Phenomenology of ADHD and premorbid
schizophrenia
Longitudinal studies have produced conflicting results
regarding the percentage of children with ADHD who later
become psychotic (Weiss and Hechtman, 1986). However,
such studies frequently exclude children who have a parent
with schizophrenia or children with signs of major psycho-
pathology potentially reducing the chance of finding a
schizophrenia outcome (Bellak et al., 1987; Pine et al.,
1993). However, retrospective studies of individuals with
schizophrenia have shown a history of ADHD premorbidly, or
concomitantly, with schizophrenia. Interestingly, it has been
suggested that behavioral problems might be diagnostically
non-specific indicators of the onset of major psychopathology
such as fever is in physical illness (Asarnow et al., 1991). We
postulate that the degree of phenomenological overlap between
ADHD symptoms and childhood-onset schizophrenia (COS)
might, in some cases, contribute to a distinct neurodevelop-
mental progression of schizophrenia. Moreover, the overlap in
the phenomenological presentation of ADHD and schizo-
phrenia, together with the potential of stimulant drugs to
precipitate or exacerbate psychotic symptoms in schizophrenia
(Cherland and Fitzpatrick, 1999; Schaeffer and Ross, 2002),
emphasizes the need to differentiate these disorders on the basis
of objective neurophysiological and neurobiological features.
Phenomenological studies of premorbid or concomitant
ADHD-like symptoms in schizophrenia are reviewed below.
Studies of COS have shown behavioral precursors to
psychotic onset that are consistent with ADHD, indicating an
overlap in the phenomenology of these disorders. For instance,
Russell et al. (1989) found that 40% of 35 children with
schizophrenia had premorbid histories of attention deficits and
hyperactivity suggestive of ADHD. Likewise, Kolvin et al.
(1971) reported that 24% of 33 children with a psychotic onset
between 5 and 15 years displayed behaviors that are central to
an ADHD diagnosis; including restlessness and impulsivity.
This pattern was paralleled in the same study by 24% of 47
children with onset of psychosis before 3 years. In a sample of
38 children with COS, Green et al. (1992) also observed non-
psychotic precursors consistent with ADHD, comprising
 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
school behavioral problems, hyperactivity, distractibility,
increased anxiety, over sensitivity to discipline, temper
tantrums, aggressiveness, and poor peer relationships.
More specifically, several studies have revealed explicit
premorbid diagnoses of ADHD for a substantial percentage of
children with schizophrenia. Spencer and Campbell (1994), for
instance, found that 31% of 16 children with schizophrenia had
a previous diagnosis of ADHD. Likewise, Alaghband-Rad
et al. (1995) showed that 30% of 23 children with
schizophrenia onset before age 12, exhibited clear evidence
of premorbid ADHD, while Asarnow et al. (1991) found that an
even larger 46.6% of 15 schizophrenia children were
prescribed stimulant medications to treat symptoms consistent
with ADHD. As early as 1967, Menkes et al. (1967) reported
that 22.2% of 18 children with hyperactivity subsequently
developed a psychosis. Similarly, Gomez et al. (1981) reported
that 19% of 26 psychotic individuals had a history of both
childhood and adulthood ADHD, with a further 15% of adults
with psychosis demonstrating a history of ADHD in childhood
but not in adulthood. In a recent study, Schaeffer and Ross
(2002) found that nearly half of 17 (z47%) children with COS
had received a prior diagnosis of ADHD, and 13 (77%) of those
were treated with psychostimulants. Thus, these authors
speculated that high levels of attentional psychopathology
preceding the onset of psychosis resulted in treatment for
attention deficits, and exposure to psychostimulants may have
contributed to the childhood-onset psychotic break.
The above studies found a history of ADHD symptoms in
individuals with overt schizophrenia illness. However, studies
of individuals at high risk for schizophrenia have also revealed
a history of ADHD in individuals with schizotypal traits.
Schizotypal traits are generally accepted as attenuated forms of
schizophrenia symptoms (Venables and Bailes, 1994) and form
similar clusters to overt schizophrenia symptoms (Williams,
1994, 1995). For example, Asarnow and BenMeir (1988) found
that 30% of 14 children with schizotypal personality disorder
had a comorbid, or premorbid diagnosis of ADHD, while
another study (McDaid et al., 1999) found a strong correlation
between positive schizotypy traits, comprising unusual
experiences, cognitive disorganization and impulsive non-
conformity, and ADHD scores. Similarly, in a study of
psychosis proneness and ADHD in young relatives of
individuals with schizophrenia, Keshavan et al. (2003) found
that 31% of the 29 young relatives presented symptoms
resembling ADHD.
Elman et al. (1998) examined more specific patterns in the
overlap of schizophrenia and ADHD symptoms, including sex
differences and psychological function. They found an over-
representation of males in schizophrenia patients with
premorbid ADHD compared to schizophrenia controls without
a history of ADHD, which is consistent with the generally
higher prevalence of males with ADHD (Silver, 1992).
Additionally, 40.5% of the (schizophrenia) patients with
premorbid ADHD, compared to only 7.5% in a non-ADHD
schizophrenia control group, showed a pattern of a relatively
late diagnosis of ADHD with a relatively young first
hospitalization for psychosis (age 12–14 years). Moreover,
653
the schizophrenia with ADHD group in this study showed
a relatively poorer response to neuroleptics in addition to a
significantly poorer outcome defined by the ability to function
at work or school (13.5% compared to 52.5%). Thus, Elman
et al. concluded that a history of ADHD might represent a
marker for a relatively poor prognosis in subsequent
schizophrenia psychosis.
The evidence reviewed above suggests that ADHD-like
behaviors sometimes manifest before the first onset of
schizophrenia symptoms, suggesting phenomenological simi-
larities between ADHD and prodromal schizophrenia. Given
the degree of phenomenological overlap, ADHD symptoms, in
some cases, might contribute to a distinct neurodevelopmental
progression of schizophrenia. Thus, it is important to
distinguish these disorders to provide correct treatment to
alleviate symptoms as it is well known that stimulant drugs can
potentially precipitate or exacerbate psychotic symptoms in
schizophrenia (Cherland and Fitzpatrick, 1999; Opler et al.,
2001; Schaeffer and Ross, 2002).
2. Dopamine and case studies of co-occurring ADHD
with psychosis
Despite the potential of psychostimulants to precipitate
psychosis, there is evidence that shows stimulants have also
been used successfully to treat some psychotic disorders.
Studies of the clinical efficacy of pharmacological treatment
might provide insights into the neurochemical dysfunctions in
both ADHD and schizophrenia. For instance, case studies of
treatment efficacy have suggested a link between ADHD and
psychosis that might support ADHD symptomatology as either
a neurodevelopmental feature of schizophrenia or a distinct
ADHD psychosis (Bellak, 1985, 1994; Bellak et al., 1987; Pine
et al., 1993). These case studies of ADHD and psychotic
disorders in relation to pharmacological interventions are
discussed below.
It is outside the scope of this review to provide a detailed
account of the psychopharmacology of ADHD and schizo-
phrenia, however, dopamine dysfunction in the limbic-frontal
networks is implicated in both of these disorders (Carrière
et al., 2000; Pani, 2002; Solanto, 2002; Sonuga-Barke, 2002,
2003). Over-activity in the meso-limbic dopamine pathway has
been associated with positive symptoms of schizophrenia, and
under-activity in the meso-cortical pathway has been linked
with cognitive dysfunction and negative symptoms (Carrière
et al., 2000; Pani, 2002). Similarly, hyperactivity and
impulsivity in ADHD have been associated with hyperdopa-
minergia of the meso-limbic system in response to reward
stimuli (Durston, 2003; Solanto, 2002; Volkow et al., 2001,
2002), whereas under-activity of the meso-cortical dopamine
system might contribute to cognitive symptoms (Durston,
2003; Sergeant et al., 2003; Solanto, 2002; Sonuga-Barke,
2002, 2003).
Case studies of treatment efficacy have suggested a link
between ADHD and psychosis that might support ADHD
symptomatology as a distinct ADHD psychosis. For instance,
Pine et al. (1993) described two patients, a 39-year-old female,
654 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
and a 31-year-old male, both of whom presented with
concurrent ADHD and psychotic features. Both individuals
showed an initial amelioration of psychotic symptoms with a
combination of psychostimulants and neuroleptics, followed
by successful treatment with stimulants alone. Therefore, Pine
et al. concluded that these patients represented a distinct
diagnostic group of ADHD and atypical psychosis. Similarly,
Huey et al. (1978) successfully treated a 23-year-old male, who
presented with an ongoing history of ADHD behaviors and
adult onset of delusions of reference, auditory hallucinations
and confusion, with psychostimulant medication.
Indeed, Bellak et al. (1987) specifically proposed a
diagnostic category of ‘ADD psychosis’ (hereafter referred to
as ADHD psychosis to reflect the most recent DSM-IV
[American Psychiatric Association, 1994] nomenclature) that
represents an extreme manifestation on a continuum of ADHD
symptomatology and is distinguishable from schizophrenia in
terms of development, family history, therapeutic response,
psychometric indicators, and symptomatology (Bellack and
Opler, 1994; see also Opler et al., 2001). Bellak et al. (1987)
provided a comprehensive profile of features that differentiate
ADHD psychosis from schizophrenia including medication
response. Whereas, schizophrenia will respond well to
dopamine antagonists and poorly to dopamine agonists,
ADHD psychosis will show the reverse pattern with a positive
response to stimulants and negative response to neuroleptics.
Opler et al. (2001) further speculated that stimulants
ameliorate both attentional and psychotic symptoms in
ADHD psychosis by enhancing dopamine in the frontal
lobes, which studies show are dysfunctional in both schizo-
phrenia and ADHD. Nonetheless, recent research shows that
the newer atypical antipsychotic, amisulpride, is made unique
by its dual action that enhances dopamine activity in the
prefrontal cortex via blockade of D2 and D3 autoreceptors
while decreasing dopamine in subcortical areas through
postsynaptic blockade (Carrière et al., 2000; Lecrubier, 2002;
Pani, 2002). Similarly, aripiprazole is a partial agonist at
dopaminergic neurons, which causes a decrease or an increase
in dopamine transmission in areas of hyperdopaminergic or
hypodopaminergic activity, respectively (DeLeon et al., 2004).
However, unlike amisulpride (Pani, 2002), aripiprazole also
has affinity for serotonin receptors (DeLeon et al., 2004). Both
psychostimulants and neuroleptics, used in the treatment of
ADHD and schizophrenia, respectively, act by complex dual
actions that enhance prefrontal dopamine and reduce dopamine
transmission in the limbic system (Pani, 2002; Seeman and
Madras, 2002; Solanto, 2002). Thus, it has been postulated that
the neuropathology of both these disorders might involve
dysfunctional interconnectivity between prefrontal, subcortical
and cortical structures resulting in various emotional,
behavioral, and cognitive impairments (Fallon et al., 2003;
Fuster, 1999).
Tossell et al. (2004) examined the efficacy of psychostimu-
lants to treat ADHD symptoms in COS from the perspective of
comorbidity and found that four of five subjects showed an
improvement in ADHD symptoms, without a worsening of
psychotic symptoms when treated with psychostimulants in
addition to an antipsychotic (clozapine). Although one child
showed a worsening of both psychotic and ADHD symptoms
following treatment with a stimulant, the authors postulated
that this response might have been precipitated by the
administration of stimulant medication before the stabilization
of psychosis. Thus, Tossell et al. speculated that stimulants
might be useful for treating individuals whose D2 receptors are
under-stimulated as psychostimulants increase dopamine via
blockade of dopamine transporters. Nonetheless, as noted
above the atypical antipsychotic, amisulpride also enhances
prefrontal dopamine via blockade of D2 and D3 autoreceptors
and thus may be a useful alternative to the potentially riskier
use of psychostimulants for the treatment of ADHD symptoms
in psychosis.
Other case studies have suggested a developmental
progression from predominantly behavioral symptoms to
acute psychosis. Schmidt and Freidson (1990) reported the
case of a 6-year-old male with an initial presentation of
hyperactivity, distractibility, disruptive behavior, and flat affect
but no diagnosable psychosis. While the child’s symptoms
responded positively to stimulant medication initially, they
escalated at 11 years of age and were not further ameliorated by
increased methylphenidate but were, instead, stabilized on
phenothiazine. The development of overt psychotic symptoms
at 13 years was followed by diagnosable schizophrenia at 17
years. Notably, the patient retrospectively reported auditory
hallucinations from several years before the onset of overt
psychotic symptoms, indicating that psychosis was present
substantially earlier than the presentation of observable
psychosis.
Similarly, Gartner et al. (1997) discussed the case of a 12-
year-old male with ADHD and subsequent psychosis.
Although the authors had not made a decisive diagnosis of
either schizophrenia or mania at the time this case was
published, some amelioration of symptoms had been achieved
with perphenazine and lithium carbonate. However, clarifica-
tion of the nature of the patient’s psychotic disorder was
reportedly hindered by the predominance of attention deficits
and disruptive behavior. Both this case study, (Gartner et al.,
1997) and that of Schimdt and Freidson (1990), show patterns
of psychotic development analogous to that reported in a study
of COS (Russell, 1994). Russell found a common prepsychotic
pattern of symptoms in COS that paralleled the symptom
presentation of ADHD, and occurred insidiously over several
years. Thus, Russell suggested that children might not
distinguish psychotic experiences from reality, and therefore,
psychotic symptoms might not be apparent to observers such as
parents and clinicians, which highlights the need for direct and
structured questioning of both parents and child to ascertain the
presence of psychosis (Gartner et al., 1997; Russell, 1994;
Zuddas et al., 2000).
Undoubtedly, further empirical evidence is needed to clarify
the relationship between schizophrenia and ADHD, both
phenomenologically and pharmacologically. ADHD symp-
toms may represent a common pathway resulting in two
disorders; namely, schizophrenia and ADHD, and ADHD
might manifest in psychosis in extreme forms. Schaeffer and
 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
Ross (2002) suggested a condensed pathway to COS,
consistent with the developmental pathway to adult onset
schizophrenia; a preschool phase of non-specific concerns that
something is wrong, an early school-age period of non-specific
impairments in attention and behavior that affects school
functioning, followed by overt psychosis. Similar to Russell
(1994), Schaeffer and Ross found that diagnosis was on
average delayed by 2 years following the onset of psychotic
symptoms, therefore, ADHD-like symptoms could represent an
overt manifestation of a psychosis that has been present for
some time but is not overtly apparent to observers. Thus, the
overlap of symptoms in ADHD and schizophrenia, with the
potential of stimulant drugs to precipitate or exacerbate
psychotic symptoms in schizophrenia (Cherland and Fitzpa-
trick, 1999; Opler et al., 2001; Schaeffer and Ross, 2002),
emphasizes the need to differentiate these disorders at an
objective neurophysiological level. Moreover, there is an
increasing recognition that earlier detection of, and interven-
tion in, first-episode psychosis can potentially lead to a better
outcome (McGorry et al., 2001; Schaeffer and Ross, 2002;
Woods et al., 2001).
While this review focuses on phenomenological similarities
between ADHD and schizophrenia, there are important
differences between these disorders. ADHD is one of the
most common disorders of childhood (McGough and
McCracken, 2000), which frequently has a poor adult outcome
in terms of a greater likelihood of developing adult mental
disorders including depression, anxiety, substance abuse, and
antisocial personality (Biederman, 2005). However, schizo-
phrenia is the most severe psychiatric illness (McGlashan,
1998) impacting multiple aspects of functioning (Kelly and
Gamble, 2005), and frequently presenting chronic functional
deficits, which represents a disproportionate social and
economic cost (McGlashan, 1998). We recognize that despite
phenomenological similarities, overlapping cognitive and
neural impairments in schizophrenia and ADHD (without
psychosis) might be expressed in distinct clinical profiles such
as hallucinations, delusions, and thought disorder in overt
schizophrenia (Ross et al., 2000a,b). For instance, although
thought disorder may be apparent in ADHD as a secondary
consequence of attentional problems (Caplan et al., 2001),
thought disorder in schizophrenia is significantly more
pervasive and severe (Caplan et al., 2001). The differences
between ADHD and schizophrenia, serve to further highlight
the need to objectively distinguish between these two disorders
of attention.
3. Emotion perception and social functioning
in schizophrenia and ADHD
Impaired social functioning and interpersonal interactions
are central to both ADHD and schizophrenia (Cadesky et al.,
2000; Edwards et al., 2002; Frommann et al., 2003; Hoza et al.,
2000; Wheeler and Carlson, 1994; Wheeler Maedgen and
Carlson, 2000) and impaired emotion perception may be a
factor in this dysfunction. Indeed, evidence suggests that
impaired social functioning might represent vulnerability
655
factors for schizophrenia that are present in the prodromal
phase (Cornblatt et al., 2003; Davidson et al., 1999; Häfner
et al., 1999; Schaeffer and Ross, 2002), and in non-psychotic
children of parents with schizophrenia (Hans et al., 2000).
Moreover, Davidson et al. (1999) found that poor social
adjustment was the most significant premorbid predictor for
schizophrenia in male adolescents, while another study (Häfner
et al., 1999) showed that social disability preceded first
hospitalisation by 2–4 years in over half of schizophrenia
patients studied.
Studies of facial affect recognition in schizophrenia have
shown specific associations with impaired social functioning
(Penn et al., 1996), impoverished interpersonal relations (Poole
et al., 2000), as well as impaired communication, occupational,
and self-presentation functioning (Hooker and Park, 2002),
thus, suggesting that face affect recognition might be a
significant predictor of social dysfunction (Hooker and Park,
2002). Nevertheless, a longitudinal study by Kee et al. (2003)
did not find a relationship between social functioning/family
relations and perception of emotion. However, this study
showed a significant association between emotion perception
and work functioning/independent living that was stable over
12 months. Kee et al. suggested that emotion perception is an
important factor in the interpersonal interactions required for
vocational performance thus, difficulty in interpreting others’
emotional states could contribute to poorer work functioning.
Emotion perception studies might therefore, increase knowl-
edge of the social and interpersonal difficulties experienced by
individuals with both ADHD and schizophrenia.
4. Facial affect recognition in schizophrenia
Deficits in affect recognition have been shown in adult
schizophrenia (see reviews in Edwards et al., 2002; Mandal
et al., 1998), childhood and adolescent schizophrenia
(Walker et al., 1980), first-episode psychosis (Edwards et al.,
2001), schizotypal personality disorder (Mikhailova et al.,
1996), delusion-prone individuals (Green et al., 2003a),
unaffected siblings of individuals with schizophrenia (Kee
et al., 2004), and first-degree relatives of schizophrenia
individuals (Loughland et al., 2004). Conversely, one study
of children of parents with schizophrenia did not show
impaired emotion perception (Davalos et al., 2004; Loughland
et al., 2004) in this high-risk group. However, the forced, four-
option task used in this study might not have been difficult
enough to show potential deficits. Research has shown that
both first-degree relatives of individuals with schizophrenia
(Loughland et al., 2004) and individuals with schizophrenia
themselves (Loughland et al., 2002b) did not show deficits
under a relatively simple three-option, forced choice condition
but performed more poorly than normal controls under a higher
difficulty seven-option task. Thus, taken together the evidence
largely supports the hypothesis that affect recognition deficits
might represent a vulnerability or trait feature of schizophrenia
(Edwards et al., 2001; Green et al., 2003a; Kee et al., 2004;
Loughland et al., 2004; Streit et al., 1997).
656 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
Evidence further suggests that face affect recognition in
schizophrenia is a stable deficit (Addington and Addington,
1998; Streit et al., 1997; Wölwer et al., 1996) that is more
impaired in acute phases of illness compared to remitted
patients (Edwards et al., 2002; Penn et al., 2000), and is
attenuated in first-episode psychosis (Edwards et al., 2001) and
psychosis-prone individuals (Green et al., 2003a; Mikhailova
et al., 1996). Moreover, these deficits in schizophrenia cannot
be explained by medication effects (Kerr and Neale, 1993;
Poole et al., 2000; Salem et al., 1996; Streit et al., 1997) and
have also been found relative to other psychiatric control
groups such as depression (Loughland et al., 2002a) and
bipolar disorder (Addington and Addington, 1998). However,
other studies have shown that other psychiatric conditions
show the same emotion recognition impairment to schizo-
phrenia but to a lesser degree (see review in Johnston et al.,
2001), and results in comparison to other psychotic disorders,
such as bipolar disorder, have been inconsistent (Pinkham
et al., 2003). Nonetheless studies that statistically controlled for
the variance contributed by generalised cognitive variables,
suggest that impaired face affect recognition in schizophrenia
represents a specific emotion perception deficit, which occurs
within the context of more general cognitive deficits (Borod
et al., 1993; Bryson et al., 1997; Feinberg et al., 1986; Mandal
et al., 1998; Penn et al., 2000).
5. Visual scanpaths to facial expressions of emotion
in schizophrenia
Several studies have focussed on visual scanning to facial
expressions to examine the nature of the emotion perception
deficit in schizophrenia. Visual scanpaths show the direction
and extent of eye movements during the viewing of complex
visual stimuli and provide a psychophysiological measure of
attention (Noton and Stark, 1971; Phillips and David, 1994,
1997, 1998). Specifically, eye movement recordings provide an
overt, real-time, high temporal resolution indicator of visual
processing and deployment of visual attention (Manor and
Gordon, 2003). The visual scanpath comprises fixations or
‘points of attention’ wherein the fovea is directed toward and
held stationary at a particular point of a visual scene whereas,
saccades represent rapid voluntary shifts between fixations,
which direct the fovea to a particular point of attention or
interest (Manor and Gordon, 2003; Phillips and David, 1997;
Phillips et al., 2000; Yang et al., 2002). It has been noted that an
eye movement always elicits attention, and is influenced by an
interaction between stimulus- and data-driven information
processes (Groner and Groner, 1989; Phillips and David, 1997),
thus providing a useful measure of the later stages of visual
information processing, as attention is focused and refocused
on various components of the stimulus (Phillips et al., 2000).
Compared to healthy participants, who generally show a
triangular pattern of scanning with fixations focused on the
nose, mouth, and eyes (Groner and Groner, 1989; Groner et al.,
1984; Phillips and David, 1997; Walker-Smith et al., 1977),
individuals with schizophrenia consistently show relatively
more ‘restricted’ scanpaths to faces, comprising fewer fixations
of a longer duration, and a shorter distance between fixations
when viewing neutral faces (Gordon et al., 1992; Loughland
et al., 2002a; Manor et al., 1999; Phillips and David, 1997,
1998) and to specific facial expressions (Green et al., 2003b;
Loughland et al., 2002b; Streit et al., 1997). As well as in
general schizophrenia samples (Green et al., 2003b; Loughland
et al., 2002b; Manor et al., 1999; Williams et al., 1999),
restricted scanpaths have been demonstrated in negative
schizophrenia (Streit et al., 1997) and deluded schizophrenia
(Green et al., 2003b; Phillips and David, 1997, 1998) thus
attesting to the pervasive nature of this impairment in
schizophrenia. Several studies have also analyzed the
distribution of fixations to facial expressions and found that
individuals with schizophrenia made significantly fewer
fixations to facial features than controls (Green et al., 2003b;
Phillips and David, 1998; Williams et al., 1999).
However, our scanpath studies suggest that the allocation of
fixations to the facial features of specific expressions may vary
due to illness chronicity in schizophrenia (Green et al., 2003b;
Loughland et al., 2002b). Loughland et al. (2002b) found that,
within the context of restricted scanpaths, individuals with
chronic schizophrenia showed an enhanced distribution of
fixations to the features of sad faces (cf. a ‘baseline’ neutral
face) that did not differ from controls. Loughland et al. further
found that the schizophrenia group did not differ from controls
on recognition accuracy for sad faces, which was associated
with less restricted scanpaths and a greater focus on features
(Loughland et al., 2002b). In contrast to Loughland et al.
(2002b), Green et al. (2003b) found an attentional bias away
from negative expressions (sad and anger) in delusional
schizophrenia, which was attributed to the acute nature (vs.
chronic in Loughland et al.) of their sample. Therefore,
evidence from scanpath studies suggest that while chronic
schizophrenia might involve a bias towards negative faces,
which manifests in enhanced attention to features (Loughland
et al., 2002b), acute delusional schizophrenia involves a
‘vigilance–avoidance’ (Green et al., 2003b) with a conscious
avoidance of facial features in later directed stages of
processing, to avoid perceived threatening stimuli (Green
et al., 2000; Green and Phillips, 2004). Thus, vigilance to the
facial features of specific affect in schizophrenia might vary as
a function of illness phase; if it is hypovigilance or
hypervigilance might be determined by whether an individual
is experiencing an acute (delusional) psychotic episode or not,
respectively.
Abnormal visual scanpaths to facial expressions in
schizophrenia have also been found in comparison to affective
disorder (Loughland et al., 2002a) attesting to the diagnostic
specificity of scanpath dysfunction in schizophrenia. More-
over, attenuated restricted scanpaths and an extreme avoidance
of facial features have also been demonstrated in first-degree
relatives of individuals with schizophrenia (siblings, offspring,
and parents) thus supporting the hypothesis that impaired
visual scanpaths to faces might represent a trait marker for
schizophrenia (Loughland et al., 2004). Conversely, Green et
al. (2003a) found that delusion-prone individuals showed
generally ‘extended’ scanpaths characterized by increased
 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
distances between fixations for angry, fearful, and happy faces
with fewer fixations for angry and fearful faces, which the
authors suggested might be indicative of hypervigilance toward
threatening stimuli in delusion-prone individuals. These
divergent scanpath patterns shown by individuals at high-risk
for schizophrenia (Green et al., 2003a; Loughland et al., 2004)
might be a result of symptom specificity. Loughland et al.
examined general familial transmission, whereas Green et al.
focused on specific delusion-proneness. Moreover, Loughland
et al. speculated that the extreme avoidance of salient features
found in first-degree relatives might represent a learnt
avoidance to circumvent potentially negative interactions that
may trigger symptoms in their schizophrenia relative (e.g.
paranoia).
Medication effects have not been found to account for
dysfunctional scanpaths in schizophrenia (Loughland et al.,
2002b; Streit et al., 1997). Rather evidence suggests that
atypical antipsychotics, such as risperidone, enhance some
aspects of scanpaths in schizophrenia (Williams et al., 2003).
An important question is whether aberrant scanpaths to
faces in schizophrenia represent specific face perception
impairment or are attributable to general cognitive impair-
ments. There is evidence that individuals with schizophrenia
show impaired eye movements to various non-face stimuli (e.g.
Kojima et al., 2001; Minassian et al., 2005; Obayashi et al.,
2003). In addition, an early study of visual scanning by Gaebel
et al. (1987) showed that while patients with positive symptom
schizophrenia produced extended scanpaths to complex scenes
those with negative symptoms demonstrated the opposite
pattern of restricted scanpaths. However, recent evidence
directly comparing face and non-face stimuli suggests that the
more biologically salient a stimulus is, the more specific and
severe the impairment shown by individuals with schizo-
phrenia becomes. For instance, Williams et al. (1999) found
that schizophrenia participants showed relatively restricted
scanpaths to both recognizable (non-degraded images) and
non-recognizable (degraded) faces, but scanpath disturbances
were most pronounced for non-degraded faces. Whereas
controls enhanced their attention to the features of non-
degraded faces (cf. degraded faces), focusing more on salient
features, the schizophrenia group divided their attention evenly
between feature and non-feature areas of both face types. In
addition, Manor et al. (1999) found that while schizophrenia
participants displayed restricted scanpaths (cf. controls) to a
neutral face, they did not differ from controls in how they
scanned a complex geometric figure (Rey figure, Rey, 1942).
Likewise, another study (Schwartz et al., 1999) found that
visual scanning in schizophrenia is unaffected by inverting face
stimuli, which normally disrupts rapid early scanning because
the familiar schema of the face is disturbed. Taken together,
these results suggest that aberrant scanpaths to faces in
schizophrenia reflect a specific deficit in the gestalt processes
required to extract sufficient feature detail from biologically
relevant faces.
Further evidence that emotional/social perception is
specifically impaired in schizophrenia comes from research
showing that specific brain regions are involved in facial and
657
emotional processing and that these regions show abnormal-
ities in schizophrenia (see reviews in Phillips et al., 2003;
Pinkham et al., 2003 and discussion below). In addition, there
is evidence of a dissociation of perceptual judgment of emotion
intensity from eye movements (Ferber and Murray, 2005).
Ferber and Murray found that when they used prismatic lenses
to shift eye movements rightwards, there was no concurrent
shift in perceptual judgment (leftward bias for faces) in normal
controls. Likewise, David (1993) used a brief exposure time
that did not allow exploratory eye movements and found a left-
hemi facial bias in normal controls, which suggests that
perceptual judgement occurs before eye movements occur
(Ferber and Murray, 2005). However, a leftward bias was not
found in schizophrenia and together these results indicate that
schizophrenia involves impaired emotion perception, rather
than abnormal eye movements per se.
6. Facial affect recognition in ADHD (compared to
schizophrenia)
Notwithstanding the pervasiveness and central nature of
social dysfunction in ADHD (Hoza et al., 2000; Maedgen and
Carlson, 2000; Wheeler and Carlson, 1994), few studies have
examined affect perception in this disorder. Singh et al. (1998)
found that children with ADHD correctly identified facial
affect 74% of the time compared with 89% for normal children.
However, the descriptive nature of this study precluded a direct
statistical comparison between ADHD and non-ADHD
children. Nevertheless, an earlier study by Shapiro et al.
(1993) found a generalized facial affect recognition deficit in
younger (under 8 years), but not older children (over 8 years),
with ADHD, which the authors suggested might show a
developmental improvement in attentional allocation, or that
ADHD children develop compensatory strategies to cope with
their deficit in emotion perception as they mature. Nonetheless,
a more difficult emotion perception task than the matching
facial expressions task employed in this study might show
potential deficits in older children with ADHD.
Two more recent studies (Cadesky et al., 2000; Corbett and
Glidden, 2000) supported the notion that children with ADHD
were relatively impaired in their ability to perceive facial
expressions. Corbett and Glidden (2000) found that when
children with ADHD were asked to identify a facial expression
from a choice of seven (anger, disgust, fear, happiness, sadness,
surprise, and neutral) they were less accurate than controls.
However, this study did not analyze individual expressions of
emotion and thus demonstrated only general emotion recog-
nition impairment in ADHD.
Cadesky et al. (2000), however, showed that children with
ADHD were less accurate than normal controls when
identifying happy, sad, and fearful faces but not angry.
Cadesky et al. also examined the qualitative nature of ADHD
children’s erroneous responses relative to Conduct Disorder.
Unlike conduct disordered children, who revealed a propensity
to misinterpret faces as angry, ADHD did not show bias for a
particular type of error but instead made a greater number of
random errors similar to normal controls. Thus, Cadesky et al.
658 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
postulated that ADHD deficits in encoding emotional faces
were due to inattention and other general regulatory processes
rather than a distortion in interpreting emotional valence.
Cadesky et al. (2000) distinguished between attentional
deficits and distortions using Pont’s (1995) empirical extra-
polation of Kendall’s (1985, 1993) cognitive behavioral model.
Kendall (1993) delineated cognitive deficiencies as an absence
of thinking or a lack of careful information processing (e.g.
impulsivity) whereas a cognitive distortion represents dysfunc-
tional or biased information processing. Thus, Pont argued that
a cognitive deficiency would manifest in quantitative differ-
ences whereas a cognitive distortion will show as a qualitative
bias in a cognitive activity such as consistently misinterpreting
sadness as anger (Cadesky et al., 2000; Pont, 1995). Hence,
Cadesky et al. argued that random errors in emotion perception
in ADHD suggested an encoding deficit that differed from
controls only quantitatively.
Under this model of cognitive processing, studies of affect
recognition might suggest biased or distorted emotion
perception impairment in schizophrenia, particularly to
negative facial expressions of emotion. As noted above,
scanpath studies support an attentional bias or vigilance toward
sad faces in chronic schizophrenia (Loughland et al., 2002b;
Williams et al., 1999) and a vigilance–avoidance of fearful and
sad faces in delusional schizophrenia (Green et al., 2003b).
Thus, the direction of emotional bias to negative affect in
schizophrenia might manifest as either an initial orienting or a
vigilance toward negative affect in chronic schizophrenia
(Loughland et al., 2002b), or a vigilance–avoidance in acute
schizophrenia (Green et al., 2003b), particularly of threat-
related affect (fear and anger). In aggregate, emotion
recognition and scanpath studies might suggest both cognitive
distortions and cognitive deficiencies in schizophrenia com-
prising generally more affect recognition errors and concomi-
tant impaired scanpaths to all facial affect, with a cognitive bias
to negative affect in particular.
7. Studies of inattention: ADHD versus schizophrenia
An important consideration is whether this postulated
cognitive distortion/bias versus deficiency distinction between
schizophrenia and ADHD, respectively, holds up when these
groups are compared on other neuropsychological tests.
Although studies that have directly compared these two
disorders on tests of inattention have been comprehensively
reviewed elsewhere (Barr, 2001), a brief overview is pertinent
to provide a context for divergent attentional dysfunction in
these two disorders.
Studies of smooth pursuit eye movement (SPEM) have
consistently shown greater anticipatory saccades in children of
schizophrenic parents (Ross et al., 1996), adult schizophrenia
(Ross et al., 2000a,b), and children and adolescents with
schizophrenia (Jacobsen et al., 1996). Increased anticipatory
saccades are thought to represent an inability to select task
appropriate behavior, which leads to increased task-inappropri-
ate attentional shifts (Ross et al., 1996). Ross et al. (2000a,b)
and Jacobsen et al. directly compared SPEM in schizophrenia
to ADHD and did not find increased anticipatory saccades in
this disorder. However, Ross et al. (1994) examined eye
movements during an oculomotor delayed response task in
ADHD, and found that children with ADHD exhibited more
premature saccades than healthy controls consistent with an
impaired ability to inhibit responses. However, a later study by
this group (Ross et al., 2000a,b) found that both ADHD and
schizophrenia participants showed inhibitory impairments
(increased premature saccades) on an oculomotor delayed
response task. Taken together, these results suggest schizo-
phrenia might involve pervasive impairments in both the
ability to select task appropriate targets and to inhibit responses
to task irrelevant information, whereas ADHD may be
impaired on only the latter.
Studies using the continuous performance test (CPT) have
consistently found that ADHD children show an increase in
errors of commission on this test compared to healthy control
children while individuals with schizophrenia demonstrate a
poor sensitivity to detection of targets (see review in Barr,
2001). In particular, Nuechterlein (1983, 1984) directly
compared a group of children born to mothers with
schizophrenia to hyperactive children using a degraded CPT.
The high-risk schizophrenia children were characterized by a
reduced ability to discriminate relevant from irrelevant stimuli.
In contrast, the hyperactive children were distinguished by a
lack of response caution, reflective of a willingness to respond
as if stimuli are relevant even when there is little evidence of
relevance.
In the first study, to compare visual scanning of a complex
picture in ADHD with schizophrenia Karatekin and Asarnow
(1999) found a trend toward shorter fixations than normal
controls in ADHD when attention was directed to specific areas
of the stimulus by a focal question. Conversely, compared to
both healthy controls and ADHD, schizophrenia children
showed a decreased allocation of attention to relevant versus
irrelevant areas in response to global (what is happening) and
focal questions. In addition, children with schizophrenia
produced restricted scanpaths in response to the global
question, but not when they were directed toward specific
areas of the pictures. Karatekin and Asarnow postulated that
the restricted scanpaths produced by children with schizo-
phrenia was attributable to the later stages of scene perception
comprising actively testing, confirming and modifying initial
hypotheses, rather than an impairment in the earlier stages of
information processing.
The children with ADHD in the Karatekin and Asarnow
(1999) study did not show the predicted extensive scanning
behavior that would suggest an inability to inhibit eye
movements to irrelevant details when viewing thematic
pictures. However, Karatekin and Asarnow suggested that
conditions requiring systematic problem solving, delay
responses, or fast-accurate or slow-careful responding on
effortful tasks might have been more likely to show this
behavior.
Our group directly compared the specificity of target and
non-target ERP deficits in first-episode psychosis (FEP) and
ADHD on an auditory oddball task (Brown et al., 2003). While
 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
both clinical groups demonstrated a reduced P300, FEP
participants were distinguished by a lack of non-target before
targetOnon-target after target N100 amplitude found in both
control and ADHD participants. In addition, the FEP group was
distinguished from the ADHD and control groups by a
diminished discrimination between target and non-target
stimuli, suggesting an impaired ability to discriminate and
process salient targets and inhibit non-salient (non-target)
information (see also in Brown et al., 2002).
Rubia (2002) speculated that executive dysfunctions in
externalizing disorders (i.e. ADHD) could be explained by
deficient inhibitory mechanisms compared to deficient initia-
tory/executive mechanisms in internalizing disorders such as
schizophrenia. This is consistent with studies that show
individuals with schizophrenia (reviewed in Braff et al.,
2001; see also Kumari, 2002; Mackeprang et al., 2002), first-
episode psychosis (Ludewig et al., 2003), and first-degree
relatives of schizophrenia individuals (Cadenhead et al., 2000)
have an impaired prepulse inhibition of the startle reflex, an
operational measure of preattentive sensorimotor gating.
Moreover, a positive correlation has been found between
impaired sensorimotor gating in schizophrenia and social
cognition, indicating that early information processing deficits
impact negatively on higher level processes required for
adequate social perception (Wynn et al., 2005). In contrast to
schizophrenia, ADHD (without comorbidity) has not been
shown to be marked by deficiencies in prepulse inhibition (see
review in Braff et al., 2001). Rather, studies of prepulse
inhibition in children (Hawk et al., 2003) and adults (Hollings-
worth et al., 2001) with ADHD provide evidence of reduced
controlled attentional processing in ADHD children, which is
believed to represent the stage of controlled attentional
allocation when distinctions between relevant and irrelevant
information are made (Hawk et al., 2003). However, similar
deficits in directed attention have also been found in other
neurodevelopmental disorders including schizophrenia (Hawk
et al., 2003).
Taken together these studies comparing ADHD and
schizophrenia on various measures of cognitive functioning
suggest that schizophrenia might be distinguished from ADHD
by an impaired ability to discriminate salient (target) from non-
salient (non-target) information. Conversely, ADHD appears to
primarily involve deficient inhibition, responding to all stimuli
as relevant even in the absence of evidence that a target is
relevant, however, individuals with schizophrenia might show
similar deficiencies.
8. Brain-imaging studies and emotion perception
impairments in ADHD and schizophrenia
Evidence from brain imaging studies of emotion perception
indicate that different neural substrates might mediate these
two types of cognitive impairments and these substrates might
be differentially impaired in ADHD and schizophrenia.
Limbic system involvement in emotion perception
(Damasio, 1996; LeDoux, 1996) has been substantiated by
neuroimaging studies of facial emotion processing (Gur et al.,
659
2002; Killgore and Yurgelun-Todd, 2004; Phan et al., 2002;
Pinkham et al., 2003), which show that facial expressions of
emotion activate brain areas distinct from those activated by
neutral facial expressions (Gur et al., 2002; Kesler/West et al.,
2001; Williams et al., 2001). The most robust responses have
been observed for negative expressions of emotion, particu-
larly in the amygdala, insula and subgenual cingulate, while
positive emotions have been associated with basal ganglia
involvement, albeit less consistently (Phan et al., 2002;
Williams et al., 2005). Cortical regions, particularly the medial
prefrontal and anterior cingulate regions, have been associated
with the top-down modulation of emotional response in the
amygdala during cognitive evaluation or labeling of emotion
(Hariri et al., 2000, 2003; Nomura et al., 2004). In
schizophrenia, brain imaging studies have shown decreased
responses in both the amygdala and medial prefrontal cortex
during the perception of negative emotion in particular,
consistent with a dysregulation in these circuits (Schneider
et al., 1998; Takahashi et al., 2004; Williams et al., 2004). The
amygdala also triggers autonomic arousal and the visceral
signs of emotion, and amygdala–arousal interactions provide
reciprocal feedback to the medial prefrontal regions (Williams
et al., 2001). Further evidence for a dysregulation in the
subcortical–cortical circuits underlying emotion processing in
schizophrenia have been shown by a disjunction between the
loss of amygdala-medial prefrontal activity and excessive
arousal responses (Williams et al., 2004). Although Gur et al.
found that a lack of subcortical activity was not associated with
impaired performance for simple emotion recognition accu-
racy, they suggested it is possible that such a relationship
would only be revealed in a more demanding emotional
discrimination task, or that parallel neural and behavioral
deficits are involved.
Barr (2001) reviewed the literature on attentional dysfunc-
tions in both schizophrenia and ADHD and concluded that
schizophrenia might be characterized by a relatively more
pervasive pattern of cerebral dysfunction involving predomi-
nantly left hemispheric dysfunction with disturbances pre-
dominantly in frontal and temporo-limbic (cortical and
subcortical) regions. In contrast, ADHD appears to involve
predominantly right hemispheric dysfunction with a more
specific disturbance of frontostriatal regions (Barr, 2001).
Likewise, Bush et al. (2005) provided a comprehensive review
of data from neuroimaging, neuropsychological, genetics, and
neurochemical studies and concluded that dysfunction of
frontostriatal structures are likely to underlie the pathophysiol-
ogy of ADHD. No studies to date have examined the neural
substrates that underlie emotion perception impairments in
ADHD. However, a recent fMRI study (Hare et al., 2005)
found differential involvement of the amygdala and striatal
systems in response to an emotional go/nogo task. The
amygdala was activated in evaluating negative emotional
content, and showed slower response latencies when approach-
ing negative targets, whereas the caudate nucleus was recruited
when avoiding positive non-targets and was associated with
decreased false alarms, consistent with the role of this region in
behavioral inhibition and impulse control (Hare et al.). Thus,
660 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
emotion perception impairments in ADHD and schizophrenia
might represent relatively distinct breakdowns in the regulation
of prefrontal and subcortical circuits, which are central to the
effective functioning of emotional and motivational behavior.
Adolphs and colleagues (Adolphs, 2004; Adolphs et al.,
2005) argued that the amygdala both modulates early visual
information processing via feedback to the visual cortex, in
addition to directing the visual information sought by the eyes
to fixate and attend to. Moreover, Adolphs et al. (2005) found
that normal control subjects explored facial expressions of
emotion by fixating predominantly on the eyes, using this
information to correctly discriminate emotion context. In
contrast, a woman with bilateral amygdala damage consistently
failed to fixate on the eye region of facial expressions of
emotion and was subsequently unable to use information from
the eyes to identify fearful faces in particular. While happy
facial expressions can be distinguished using information from
the smile alone, information from the eyes has particular
salience in the recognition of fear, sadness, and anger (Adolphs
et al., 2005). Thus, amygdala dysfunction in relation to the
perception of negative emotion in schizophrenia (Schneider
et al., 1998; Williams et al., 2004, 2005) might represent an
abnormal perception of emotional face content, rather than a
relatively simpler misinterpretation of affect.
In aggregate, the decreased amygdala activity, with
concomitant disjunction between the loss of amygdala-medial
prefrontal activity and enhanced arousal, shown in schizo-
phrenia individuals while viewing negative facial expressions
(Williams et al., 2004), may underlie the biased viewing styles
reported in visual scanning studies (Green et al., 2003b;
Loughland et al., 2002b). Increased levels of arousal and
subsequent anxiety might lead to an initial bias toward negative
affect, which is subjectively perceived as threatening, followed
by a tendency to avoid salient features (i.e. eyes) due to the
failure of the amygdala to direct the visual system to fixate the
eyes of facial stimuli. In fact, Adolph et al. (2005) found that
impaired fear recognition in their subject with bilateral
amygdala damage was not due to impaired visuoperceptual
Fig. 1.
capacity to process information from the eyes, but was rather a
failure of the amygdala to direct and make use of salient
information from the region of the eyes in facial expressions of
emotion. In contrast to schizophrenia, and in light of the
general absence of limbic involvement in ADHD attention
deficits (Barr, 2001), emotion recognition impairments in this
group might represent a relatively more simple failure to
correctly interpret affect due to inattention and/or impulsivity.
That is, emotion perception impairment in schizophrenia might
be distinguished by distorted or biased information processing
while ADHD may result from a deficit in information
processing of the emotional content of facial expressions.
9. Future directions
It would be useful for future research to directly compare
emotion perception, and specifically scanpaths to facial
expressions of emotion, in ADHD and schizophrenia as a
first step to further clarify the nature of emotional aberrations in
these disorders. To our knowledge scanpaths to facial
expressions of emotion have not been examined in first-
episode schizophrenia (FES), which would lend additional
support to the hypothesis that impaired emotion perception is a
trait marker for schizophrenia and would further show the role
of illness phase in biased emotion perception in schizophrenia.
We are also not aware of any studies of visual scanpaths in
ADHD during a face-viewing task, which might further clarify
the nature of the emotion perception impairment in ADHD. If
impaired emotion perception in ADHD is a result of their
attentional deficits and impulsive responding they would be
expected to show visual scanpaths to faces that are not biased
to any particular affect (indexed by fixations toward or away
from features). We are currently analysing data from a study of
scanpaths to facial expressions of emotion in FES and ADHD.
As it is difficult to concisely diagnose schizophrenia in the first
episode of psychosis (Harris et al., 2005) we adopted a broader
definition of schizophrenia similar to the World Health
Organisation’s 10-country study of schizophrenia (Jablensky
 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
et al., 1992). Thus, the FES group in our study included
schizophrenia, schizophreniform, psychosis not otherwise
specified, and schizoaffective disorder and excluded affective
and drug induced psychoses. In this study, we hypothesized
that participants with FES would show a biased emotion
perception deficit characterized by generally ‘restricted’
scanpaths and a concomitant bias to negative affect. In
contrast, we expected that ADHD would show a deficient
and extensive pattern of scanpaths without specific biases,
indexed by a decreased number and duration of fixations and
more extensive or random scanning. Preliminary analyzes from
this study support our hypotheses of restricted scanpaths in
FES and relatively more extensive scanning in ADHD (Marsh
et al., 2000). The FES group showed relatively ‘restricted’
scanpaths to all faces indexed by fewer fixations of a longer
duration, a shorter scanpath length, and a shorter distance
between fixations. In contrast, compared to FES only, ADHD
participants revealed an opposing pattern of scanning
producing longer scanpath lengths. Typical scanpaths to a
sad face are depicted in Fig. 1. Both young people with FES
and adolescents with ADHD were less accurate than controls in
recognizing facial expressions of emotion.
In conclusion, evidence shows that the defining symptoms
of ADHD sometimes present premorbidly in schizophrenia and
psychostimulants, used to treat ADHD, can precipitate
psychotic symptoms (Schaeffer and Ross, 2002). Thus, these
factors highlight the importance of establishing objective
differences between these two disorders early in their clinical
presentation to allow an optimal clinical outcome. Given that
both disorders comprise attentional and social dysfunction, we
postulated that distinct impairments in the perception of facial
expressions of emotion might distinguish these disorders in
childhood and adolescence. Given the inherent risks of treating
prodromal schizophrenia with psychostimulants, scanpath
analysis could provide an important first step in distinguishing
emotion-processing aberrations in both ADHD and schizo-
phrenia. This has potential clinical implications as the
cognitive remediation of social functioning in both disorders
might involve different strategies. Frommann et al. (2003) have
developed a Training of Affect Recognition (TAR) program to
specifically target restitution and compensation strategies
underlying face perception, which has shown promising results
in schizophrenia. In contrast, social functioning in ADHD
children might be better served by cognitive-behavioral
therapy teaching these children to stop, look and anticipate
consequences (Kendall, 1993).
References
Addington, J., Addington, D., 1998. Facial affect recognition and information
processing in schizophrenia and bipolar disorder. Schizophrenia Research
32, 171–181.
Adolphs, R., 2004. Emotional vision. Nature Neuroscience 7, 1167–1168.
Adolphs, R., Gosselin, F., Buchanan, T.W., Tranel, D., Schyns, P.,
Damasio, A.R., 2005. A mechanism for impaired fear recognition after
amygdala damage. Nature 433, 68–72.
661
Aghevli, M., Blanchard, J.J., Horan, W., 2003. The expression and experience
of emotion in schizophrenia: a study of social interactions. Psychiatry
Research 119, 261–270.
Alaghband-Rad, J., McKenna, K., Gordon, C.T., Albus, K.E., Hamburger, S.D.,
Rumsey, J.M., et al., 1995. Childhood-onset schizophrenia: the severity of
premorbid course. Journal of the American Academy of Child and
Adolescent Psychiatry 34, 1273–1283.
Anon., 1994. Diagnostic and Statistical Manual of Mental Disorders, fourth ed.
American Psychiatric Association, Washington, DC.
Asarnow, J.R., BenMeir, S., 1988. Children with schizophrenia spectrum and
depressive disorders: a comparative study of onset patterns, premorbid
adjustment, and severity of dysfunction. Journal of Child Psychology and
Psychiatry and Allied Disciplines 29, 477–488.
Asarnow, J.R., Asarnow, R.F., Hornstein, N., Russell, A., 1991. Childhood-
onset schizophrenia: developmental perspectives on schizophrenic dis-
orders. In: Walker, E.F. (Ed.), Schizophrenia: A Life-Course Develop-
mental Perspective. Academic Press, San Diego, CA, pp. 95–121.
Asarnow, E.D., Caplan, R., Asarnow, J.R., 1995. Neurobehavioral studies of
schizophrenic children: a developmental perspective on schizophrenic
disorders. In: Häfner, H., Gattaz, W.F. (Eds.), Search for the Causes of
Schizophrenia, vol. III. Springer, Berlin, pp. 87–113.
Asarnow Rosenbaum, J., Tompsen, M.C., Goldstein, M.J., 1994. Childhood-
onset schizophrenia: a follow-up study. Schizophrenia Bulletin 20,
599–617.
Barr, W., 2001. Schizophrenia and attention deficit disorder two complex
disorders of attention. Annals of the New York Academy of Sciences 931,
239–250.
Bellack, A.S., Opler, L.A., 1994. Conceptualizing ADHD. Journal of Clinical
Psychiatry 55, 312–313.
Bellak, L., 1985. ADD psychosis as a separate entity. Schizophrenia Bulletin
11, 523–527.
Bellak, L., 1994. The schizophrenic syndrome and attention deficit disorder
thesis, antithesis, and synthesis? American Psychologist 49, 25–29.
Bellak, L., Kay, S.R., Opler, L.A., 1987. Attention deficit disorder psychosis as
a diagnostic category. Psychiatric Developments 3, 239–263.
Benes, F.M., 2003. Why does psychosis develop during adolescence and early
adulthood? Current Opinions in Psychiatry 16, 317–319.
Biederman, J., 2005. Attention-deficit/hyperactivity disorder: a selective
overview. Biological Psychiatry 57, 1215–1220.
Biederman, J., Faraone, S.V., 2002. Current concepts on the neurobiology of
attention-deficit/hyperactivity disorder. Journal of Attention Disorders 6,
S7–S16.
Bilder, R.M., 2001. Schizophrenia as a neurodevelopmental disorder. Current
Opinions in Psychiatry 14, 9–15.
Borod, J.C., Martin, C.C., Alpert, M., Brozgold, A., Welkowitz, J., 1993.
Perception of facial emotion in schizophrenic and right brain-damaged
patients. The Journal of Nervous and Mental Disease 181, 494–502.
Braff, D.L., Geyer, M.A., Swerdlow, N.R., 2001. Human studies of prepulse
inhibition of startle: normal subjects, patient groups, and pharmacological
studies. Psychopharmacology 156, 234–258.
Brown, K.J., Gonsalvez, C.J., Harris, A.W., Williams, L.M., Gordon, E., 2002.
Target and non-target ERP disturbances in first episode vs. chronic
schizophrenia. Clinical Neurophysiology 113, 1754–1763.
Brown, K.J., Gonsalvez, C.J., Harris, A.W., Lazzaro, I., Williams, L.M.,
Gordon, E., 2003. Specificity of target: non-target ERP disturbance in
schizophrenia: a comparison of first episode schizophrenia and attention
deficit hyperactivity disorder. Australian Journal of Psychology 55,
p.13, Supplement.
Bryson, G., Bell, M., Lysaker, P., 1997. Affect recognition in schizophrenia: a
function of global impairment or a specific cognitive deficit. Psychiatry
Research 71, 105–113.
Bush, G., Valera, E.M., Seidman, L.J., 2005. Functional neuroimaging of
attention-deficit/hyperactivity disorder: a review and suggested future
directions. Biological Psychiatry 57, 1273–1284.
Cadenhead, K.S., Swerdlow, N.R., Shafer, K.M., Diaz, M., Braff, D.L., 2000.
Modulation of the startle response and startle laterality in relatives of
662 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
schizophrenic patients and in subjects with such personality disorder:
evidence of inhibitory deficits. American Journal of Psychiatry 157, 1660–
1668.
Cadesky, E.B., Mota, V.L., Schachar, R.J., 2000. Beyond words: how do
children with ADHD and/or conduct problems process nonverbal
information about affect? Journal of the American Academy of Child and
Adolescent Psychiatry 39, 1160–1167.
Caplan, R., Guthrie, D., Tang, B., Nuechterlein, K.H., Asarnow, R.E., 2001.
Thought disorder in attention-deficit disorder. Journal of the American
Academy of Child and Adolescent Psychiatry 40, 965–972.
Carrière, P., Bonhomme, D., Lempérière, T., 2000. Amisulpride has a superior
benefit/risk profile to haloperidol in schizophrenia: results of a multicentre,
double-blind study (the Amisulpride Study Group). European Psychiatry
15, 321–329.
Cherland, E., Fitzpatrick, R., 1999. Psychotic side effects of psychostimulants:
a 5-year review. Canadian Journal of Psychiatry 44, 811–813.
Corbett, B., Glidden, H., 2000. Processing affective stimuli in children with
attention-deficit hyperactivity disorder. Child Neuropsychology 6,
144–155.
Cornblatt, B.A., Lenez, T., Smith, C.W., Correll, C.U., Auther, A.M.,
Nakayama, E., 2003. The schizophrenia prodrome revisited: a neurodeve-
lopmental perspective. Schizophrenia Bulletin 29.
Damasio, A.R., 1996. Descartes’ Error: Emotion, Reason and the Human Brain.
Papermac, London.
Davalos, D.B., Compagnon, N., Heinlein, S., Ross, R.G., 2004. Neuropsycho-
logical deficits in children associated with increased familial risk for
schizophrenia. Schizophrenia Research 67, 123–130.
David, A.S., 1993. Spatial and selective attention in the cerebral hemispheres in
depression, mania, and schizophrenia. Brain and Cognition 23, 166–180.
Davidson, M., Reichenberg, M.S., Rabinowitz, D.S.W., Wieiser, M.,
Kaplan, Z., Mordehai, M., 1999. Behavioral and intellectual markers for
schizophrenia in apparently healthy male adolescents. The American
Journal of Psychiatry 156, 1328–1335.
DeLeon, A., Patel, N.C., Lynn Crismon, M., 2004. Aripiprazole: a
comprehensive review of its pharmacology, clinical efficacy, and
tolerability. Clinical Therapeutics 26, 649–666.
Durston, S., 2003. A review of the biological bases of ADHD: what have we
learned from imaging studies? Mental Retardation and Developmental
Disabilities Research Reviews 9, 184–195.
Edwards, J., Pattison, P.E., Jackson, H.J., Wales, R.J., 2001. Facial affect and
affective prosody recognition in first-episode schizophrenia. Schizophrenia
Research 48, 235–253.
Edwards, J., Jackson, H.J., Pattison, P.E., 2002. Emotion recognition via facial
expression and affective prosody in schizophrenia: a methodological
review. Clinical Psychology Review 22, 789–832.
Elman, I., Sigler, M., Kronenber, J., Lindenmayer, J., Doron, A., Melovic, S.,
et al., 1998. Characteristics of patients with schizophrenia successive to
childhood attention deficit hyperactivity disorder (ADHD). Israel Journal of
Psychiatry and Relative Science 35, 280–286.
El-Sayed, E., 2003. ‘Maturational lag’ hypothesis of attention deficit
hyperactivity disorder: an update. Acta Paediatrica 92, 776–784.
Fallon, J.H., Opole, I.O., Potkin, S.G., 2003. The neuroanatomy of
schizophrenia: circuitry and neurotransmitter systems. Clinical Neuro-
science Research 3, 77–107.
Feinberg, T.E., Fifkin, A., Schaffer, C., Walker, E., 1986. Facial discrimination
and emotional recognition in schizophrenia and affective disorders.
Archives of General Psychiatry 43, 276–279.
Ferber, S., Murray, L.J., 2005. Are perceptual judgments dissociated from
motor processes? A prism adaptation study. Cognitive Brain Research 23,
453–456.
Frommann, N., Streit, M., Wölwer, W., 2003. Remediation of facial affect
recognition impairments in patients with schizophrenia: a new training
program. Psychiatry Research 117, 281–284.
Fuster, J.M., 1999. Synopsis of function and dysfunction of the frontal lobe.
Acta Psychiatrica Scandinavica 99, 51–57.
Gaebel, W., Ulrich, G., Frick, A., 1987. Visuomotor performance of
schizophrenic patients and normal controls in a picture viewing task.
Biological Psychiatry 22, 1227–1237.
Gartner, J., Weintraub, S., Carlson, G.A., 1997. Childhood-onset psychosis:
evaluation and comorbidity. American Journal of Psychiatry 154, 256–261.
Goldstein, G., 2002. Neurobehavioral heterogeneity in schizophrenia. Archives
of Clinical Neuropsychology 9, 265–276.
Gomez, R.L., Janowsky, D., Zetin, M., Huey, L., Clopton, P.L., 1981. Adult
psychiatric diagnosis and symptoms compatible with the hyperactive child
syndrome: a retrospective study. Journal of Clinical Psychiatry 42,
389–394.
Goodman, S.H., 1991. Early social and affective development in schizophrenic
offspring. In: Walker, E.F. (Ed.), Schizophrenia: A Life-Course Develop-
mental Perspective. Academic Press, San Diego, pp. 59–91.
Gordon, E., Coyle, S., Anderson, J., Healey, P., Cordaro, J., Latimer, C., et al.,
1992. Eye movement response to a facial stimulus in schizophrenia.
Biological Psychiatry 31, 626–629.
Gordon, C.T., Frazier, J.A., McKenna, K., Giedd, J., Zametkin, A., Zahn, T.,
et al., 1994. Childhood-onset schizophrenia: an NIMH study in progress.
Schizophrenia Bulletin 20, 697–712.
Green, M.J., Phillips, M.L., 2004. Social threat perception and the evolution of
paranoia. Neuroscience and Biobehavioral Reviews 28, 333–342.
Green, W.H., Padron-Gayol, M., Hardesty, A.S., Bassiri, M., 1992.
Schizophrenia with childhood onset: a phenomenological study of 38
cases. Journal of the American Academy of Child and Adolescent
Psychiatry 31, 968–976.
Green, M.J., Williams, L.M., Hemsley, D.R., 2000. Cognitive theories of
delusion formation: the contribution of visual scanpath research. Cognitive
Neuropsychiatry 5, 63–74.
Green, M.J., Williams, L.M., Davidson, D., 2003a. Visual scanpaths and facial
affect recognition in delusion-prone individuals: increased sensitivity to
threat? Cognitive Neuropsychiatry 8, 19–41.
Green, M.J., Williams, L.M., Davidson, D., 2003b. Visual scanpaths to threat-
related faces in deluded schizophrenia. Psychiatry Research 119, 271–285.
Groner, R., Groner, M.T., 1989. Attention and eye movement control: an
overview. European Archives of Psychiatry and Neurological Science 239,
9–16.
Groner, R., Walder, F., Groner, M., 1984. Looking at faces: local and global
aspects of scanpaths. In: Gale, A.G., Johnson, F. (Eds.), Theoretical and
Applied Aspects of Eye Movement Research. Elsevier North-Holland.
Gur, R.C., Schroeder, L., Turner, T., McGrath, C., Chan, R.M., Turetsky, B.I.,
et al., 2002. Brain Activation during facial emotion processing. Neuro-
image 16, 651–662.
Häfner, H., Löffler, W., Maurer, K., Hambrecht, M., der Heiden, W., 1999.
Depression, negative symptoms, social stagnation and social decline in the
early course of schizophrenia. Acta Psychiatra Scandinavica 100, 105–118.
Hans, S.I., Auerbach, J.G., Asarnow, J.R., Styr, B., Marcus, J., 2000. Social
adjustment of adolescents at risk for schizophrenia: the Jerusalem infant
development study. Journal of the American Academy of Child Psychiatry
39, 1406–1414.
Hare, T.A., Tottenham, N., Davidson, M.C., Glover, G.H., Casey, B.J., 2005.
Contributions of amygdala and striatal activity in emotion regulation.
Biological Psychiatry 57, 624–632.
Hariri, A.R., Bookheimer, S.Y., Mazziotta, J.C., 2000. Modulating emotional
responses: effects of a neocortical network on the limbic system.
Neuroreport 11, 43–48.
Hariri, A.R., Mattay, V.S., Tessitore, A., Fera, F., Weinberger, D.R., 2003.
Neocortical modulation of the amygdala response to fearful stimuli.
Biological Psychiatry 53, 494–501.
Harris, A.W., Brennan, J., Anderson, A.T., Sanbrook, M., Fitzgerald, D.,
Lucas, S., et al., 2005. Clinical profiles, scope and general findings of the
Western Sydney first episode psychosis project. Australian and
New Zealand Journal of Psychiatry 39, 36–43.
Hawk, L.W., Yartz, A.R., Pelham, W.E., Lock, T.M., 2003. The effects of
methylphenidate on prepulse inhibition during attended and ignored
prestimuli among boys with attention-deficit hyperactivity disorder.
Psychopharmacology 165, 118–127.
Hollingsworth, D.E., McAuliffe, S.P., Knowlton, B.J., 2001. Temporal
allocation of visual attention in adult attention deficit hyperactivity
disorder. Journal of Cognitive Neuroscience 13, 298–305.
 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
Hooker, C., Park, S., 2002. Emotion processing and its relationship to social
functioning in schizophrenic patients. Psychiatry Research 112, 41–50.
Hoza, B., Waschbusch, D.A., Pelham, W.E., Molina, B.S., Milich, R., 2000.
Attention-deficit/hyperactivity disordered and control boys’ responses to
social success and failure. Child Development 71 (2), 432–446.
Huey, L.Y., Zetin, M., Janowsky, D.S., Judd, L.L., 1978. Adult minimal brain
dysfunction and schizophrenia: a case report. American Journal of
Psychiatry 135, 1563–1565.
Jablensky, A., Sartorius, N., Ernberg, G., Anker, M., Korten, A., Cooper, J.E.,
et al., 1992. Schizophrenia: Manifestations, incidence and course in
different cultures. A World Health Organization ten-country study.
Psychological Medical Monograph 20.
Jacobsen, L.K., Hong, W.L., Hommer, D.W., Hamburger, S.D.,
Castellanos, F.X., Frazier, J.A., et al., 1996. Smooth pursuit eye movements
in childhood onset schizophrenia: comparison with ADHD and normal
controls. Biological Psychiatry 40, 1144–1154.
Johnston, P.J., Katsikitis, M., Carr, V.C., 2001. A generalised deficit can
account for problems in facial emotion recognition in schizophrenia.
Biological Psychology 58, 203–227.
Jonkman, L.M., Kenemans, J.L., Kemner, C., Verbaten, M.N., van
Engeland, H., 2004. Dipole source localization of event-related brain
activity indicative of an early visual selective attention deficit in ADHD
children. Clinical Neurophysiology 115, 1537–1549.
Karatekin, C., Asarnow, R.F., 1998a. Working memory in childhood-onset
schizophrenia and attention-deficit/hyperactivity disorder. Psychiatry
Research 80, 165–176.
Karatekin, C., Asarnow, J.R., 1998b. Components of visual search in
childhood-onset schizophrenia and attention-deficit/hyperactivity disorder.
Journal of Abnormal Child Psychology 26, 357–380.
Karatekin, C., Asarnow, J.R., 1999. Exploratory eye movements to pictures in
childhood-onset schizophrenia and attention-deficit hyperactivity disorder.
Journal of Abnormal Child Psychology 27, 35–49.
Kee, K.S., Green, M.F., Mintz, J., Brekke, J.S., 2003. Is emotion processing a
predictor of functional outcome in schizophrenia? Schizophrenia Bulletin
29, 487–497.
Kee, K.S., Horan, W., Mintz, J., Green, M.F., 2004. Do the siblings of
schizophrenia patients demonstrate affect perception deficits? Schizo-
phrenia Research 67, 87–94.
Kelly, M., Gamble, C., 2005. Exploring the concept of recovery in
schizophrenia. Journal of Psychiatric and Mental Health Nursing 12,
245–251.
Kendall, P.C., 1985. Towards a cognitive-behavioural model of child
psychopathology; and a critique of related interventions. Journal of
Abnormal Child Psychology 13, 357–372.
Kendall, P.C., 1993. Cognitive-behavioral therapies with youth: guiding
theory, current status, and emerging developments. Journal of Consulting
and Clinical Psychology 61, 235–247.
Kerr, S.L., Neale, J.M., 1993. Emotion perception in schizophrenia: specific
deficit or further evidence of generalized poor performance? Journal of
Abnormal Psychology 102, 312–318.
Keshavan, M.S., Sujata, M., Mehra, A., Montrose, D.M., Sweeney, J.A., 2003.
Psychosis proneness and ADHD in young relatives of schizophrenia
patients. Schizophrenia Research 59, 85–92.
Kesler/West, M.L., Andersen, A.H., Smith, C.D., Avison, M.J., Davis, C.E.,
Kryscio, R.J., et al., 2001. Neural substrates of facial emotion processing
using fMRI. Cognitive Brain Research 11, 213–226.
Killgore, W.D.S., Yurgelun-Todd, D.A., 2004. Activation of the amygdala and
anterior cingulate during nonconscious processing of sad versus happy
faces. Neuroimage 21, 1215–1223.
Kojima, T., Matsushima, E., Ohta, K., Toru, M., Han, Y.-H., Shen, Y.-C., et al.,
2001. Stability of exploratory eye movements as a marker of schizo-
phrenia—a WHO multi-center study. Schizophrenia Research 52, 203–213.
Kolvin, I., Ounsted, C., Humphrey, M., McNay, A., 1971. The phenomenology
of childhood psychoses. British Journal of Psychiatry 118, 385–395.
Kumari, V., 2002. Effects of typical and atypical antipsychotics on prepulse
inhibition in schizophrenia: a critical evaluation of current evidence and
directions for future research. Psychopharmacology 162, 97–101.
663
LeBlanc, N., Morin, D., 2004. Depressive symptoms and associated factors in
children with attention deficit hyperactivity disorder. Journal of Child and
Adolescent Psychiatric Nursing 17, 49–55.
Lecrubier, Y., 2002. Amisulpride: progress and outcomes. Current Medical
Research and Opinions 18, 18–22.
LeDoux, J.E., 1996. The Emotional Brain. Phoenix, New York.
Levine, P., 2003. Presentation, diagnosis, and treatment of ADHD. Drug
Benefit Trends 15, 3–16.
Loughland, C.M., Williams, L.M., Gordon, E., 2002a. Schizophrenia and
affective disorder show different visual scanning behaviour for faces: a trait
versus state-based distinction? Biological Psychiatry 52, 338–348.
Loughland, C.M., Williams, L.M., Gordon, E., 2002b. Visual scanpaths to
positive and negative facial emotions in an outpatient schizophrenia
sample. Schizophrenia Research 55, 159–170.
Loughland, C.M., Williams, L.M., Harris, A.W., 2004. Visual scanpath
dysfunction in first-degree relatives of schizophrenia probands: evidence
for a vulnerability marker? Schizophrenia Research 67, 11–21.
Ludewig, K., Geyer, M.A., Vollenweider, F.X., 2003. Deficits in prepulse
inhibition and habituation in never-medicated, first-episode schizophrenia.
Biological Psychiatry 54, 121–128.
Mackeprang, T., Kristiansen, K.T., Glenthoj, B.Y., 2002. Effects of
antipsychotics on prepulse inhibition of the startle response in drug-naive
schizophrenic patients. Biological Psychiatry 52, 863–873.
Maedgen, J.W., Carlson, C.L., 2000. Social functioning and emotional
regulation in the attention deficit hyperactivity disorder subtypes. Journal
of Clinical Child Psychology 29, 30–42.
Mandal, M.K., Pandey, R., Prasad, A.B., 1998. Facial expressions of emotions
and schizophrenia: a review. Schizophrenia Bulletin 24, 399–412.
Manor, B.R., Gordon, E., 2003. Defining the temporal threshold for ocular
fixation in free-viewing visuocognitive tasks. Journal of Neuroscience
Methods 128, 85–93.
Manor, B.R., Gordon, E., Williams, L.M., Rennie, C.J., Bahramali, H.,
Latimer, C.R., et al., 1999. Eye movements reflect impaired face
processing in patients with schizophrenia. Biological Psychiatry 46,
963–969.
Marsh, P.J., Lazzaro, I., Manor, B.R., Harris, A.W.F., Williams, L.M.,
Gordon, E., et al., 2000. Facial expressions of emotion and visual scanpaths
in attention-deficit hyperactivity disorder (ADHD) and first-episode
psychosis (FEP). Schizophrenia Research 41, 288.
McDaid, A.M., Easton, T., Higgins, C.J., Kidane, L., Calvin, C.M.,
Corrie, A.C., et al., 1999. Schizotypal traits and attention deficit/-
hyperactivity. Schizophrenia Bulletin 36, 25.
McGlashan, T.H., 1998. Early detection and intervention with schizophrenia
rationale: and research. British Journal of Psychiatry 172, 3–6.
McGorry, P.D., Yung, A., Phillips, L., 2001. Ethics and early intervention in
psychosis: keeping up the pace and staying in step. Schizophrenia Research
51, 17–29.
McGough, J.J., McCracken, J.T., 2000. Assessment of attention deficit
hyperactivity disorder: a review of recent literature. Current Opinion in
Pediatrics 12, 319–324.
Menkes, M.M., Rowe, J.S., Menkes, J.H., 1967. A twenty-five year follow-up
study on the hyperkinetic child with minimal brain dysfunction. Pediatrics
39, 393–399.
Mikhailova, E.S., Vladimirova, T.V., Iznak, A.F., Tsusulkovskaya, E.J.,
Sushko, N.V., 1996. Abnormal recognition of facial expression of emotions
in depressed patients with major depression disorder and schizotypal
personality disorder. Biological Psychiatry 40, 697–705.
Minassian, A., Granholm, E., Verney, S., Perry, W., 2005. Visual scanning
deficits in schizophrenia and their relationship to executive functioning
impairment. Schizophrenia Research 74, 69–79.
Mueser, K.T., McGurk, S.R., 2004. Schizophrenia. The Lancet 363, 2063–
2072.
Mueser, K.T., Doonan, R., Penn, D.L., Blanchard, J.J., Bellack, A.S.,
Nishith, P., et al., 1996. Emotional recognition and social competence in
chronic schizophrenia. Journal of Abnormal Psychology 105, 271–275.
Niemi, L.T., Suvisaari, J.M., Tuulio-Henriksson, A., Lonnqvist, J.K., 2003.
Childhood developmental abnormalities in schizophrenia: evidence from
high-risk studies. Schizophrenia Research 60, 239–258.
664 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
Nomura, M., Ohira, H., Haneda, K., Iidaka, T., Sadato, N., Okada, T., et al.,
2004. Functional association of the amygdala and ventral prefrontal cortex
during cognitive evaluation of facial expressions primed by masked angry
faces: an event-related fMRI study. Neuroimage 21, 352–363.
Noton, D., Stark, L., 1971. Eye movements and visual perception. Scientific
American 224, 34–43.
Nuechterlein, K.H., 1983. Signal detection in vigilance tasks and behavioral
attributes among offspring of schizophrenic mothers and among hyper-
active children. Journal of Abnormal Child Psychology 92, 4–28.
Nuechterlein, K.H., 1984. Sustained attention among children vulnerable to
adult schizophrenia and among hyperactive children. In: Watt, N.F.,
Anthony, E.J., Wynne, L.C., Rolf, J.E. (Eds.), Children at Risk for
Schizophrenia: A Longitudinal Perspective. Cambridge University Press,
London.
Obayashi, S., Msatsushima, E., Ando, H., Ando, K., Kojima, T., 2003.
Exploratory eye movements during the benton visual retention test:
characteristics of visual behavior in schizophrenia. Psychiatry and Clinical
Neurosciences 57, 409–415.
Øie, M., Sundet, K., Rund, B.R., 1999. Contrasts in memory functions between
adolescents with schizophrenia or ADHD. Neuropsychologia 37,
1351–1358.
Opler, L.A., Frank, D.M., Ramirez, P.M., 2001. Psychostimulants in the
treatment of adults with psychosis and attention deficit disorder. Annals of
the New York Academy of Sciences 931, 297–301.
Pani, L., 2002. Clinical implications of dopamine research in schizophrenia.
Current Medical Research and Opinions 18, 3–7.
Parnas, J., 1999. From predisposition to psychosis: progression of symptoms in
schizophrenia. Acta Psychiatra Scandinavica 99, 20–29.
Penn, D.L., Spaulding, W., Reed, D., Sullivan, M., 1996. The relationship of
social cognition to ward behavior in chronic schizophrenia. Schizophrenia
Research 20, 327–335.
Penn, D.L., Combs, D.R., Ritchie, M., Francis, J., Cassisi, J., Morris, S., et al.,
2000. Emotion recognition in schizophrenia: further investigation of
generalized versus specific deficit models. Journal of Abnormal Psychology
109, 512–516.
Phan, K.L., Wager, T., Taylor, S.F., Liberzon, I., 2002. Functional
neuroanatomy of emotion: a meta-analysis of emotion activation studies
in PET and fMRI. Neuroimage 16, 331–348.
Phillips, M.L., David, A.S., 1994. Understanding the symptoms of schizo-
phrenia using visual scan paths. British Journal of Psychiatry 165, 673–675.
Phillips, M.L., David, A.S., 1997. Visual scan paths are abnormal in deluded
schizophrenics. Neuropsychologia 35, 99–105.
Phillips, M.L., David, A.S., 1998. Abnormal visual scan paths: a psychophy-
siological marker of delusion in schizophrenia. Schizophrenia Research 29,
235–245.
Phillips, M.L., Senior, C., David, A.S., 2000. Perception of threat in
schizophrenics with persecutory delusions: an investigation using visual
scan paths. Psychological Medicine 30, 157–167.
Phillips, M.L., Drevets, W.C., Rauch, S.L., Lane, R., 2003. Neurobiology of
emotion perception II: implications for major psychiatric disorders.
Biological Psychiatry 54, 515–528.
Pine, D.S., Klien, R.G., Lindy, D.C., Marshall, R.D., 1993. Attention-deficit
hyperactivity disorder and comorbid psychosis: a review and two clinical
presentations. Journal of Clinical Psychiatry 54, 140–144.
Pinkham, A.E., Penn, D.L., Perkins, D.O., Lieberman, J., 2003. Implications
for the neural basis of social cognition for the study of schizophrenia. The
American Journal of Psychiatry 160, 815–824.
Pont, H.B., 1995. Maladjustment and socio-cognitive problem solving: the
validity of quantitative and qualitative assessment. British Journal of
Clinical Psychology 34, 53–65.
Poole, J.H., Tobias, F.C., Vinogradov, S., 2000. The functional relevance of
affect recognition errors in schizophrenia. Journal of the International
Neuropsychological Society 6, 649–658.
Rey, A., 1942. L’examen psychologique dans les cas d’encéphalopathie
traumatique. Archives of Psychology 28, 286–340.
Rosenbaum Asarnow, J., Tompson, M.C., 1999. Childhood-onset schizo-
phrenia: a follow-up study. European Child & Adolescent Psychiatry 8,
pp. 1/9–1/12 in Supplement 1.
Ross, R.G., Hommer, D., Breiger, D., Varley, C., Radant, A., 1994. Eye
movement task related to frontal lobe functioning in children with attention
deficit disorder. Journal of the American Academy of Child and Adolescent
Psychiatry 33, 869–875.
Ross, R.G., Hommer, D., Radant, A., Roath, M., Freedman, R., 1996. Early
expression of smooth-pursuit eye movement abnormalities in children of
schizophrenic parents. Journal of the American Academy of Child and
Adolescent Psychiatry 35, 941–949.
Ross, R.G., Harris, J.G., Olincy, A., Radant, A., 2000a. Eye movement task
measures inhibition and spatial working memory in adults with
schizophrenia, ADHD, and a normal comparison group. Psychiatry
Research 95, 35–42.
Ross, R.G., Olincy, A., Harris, J.G., Sullivan, B., Radant, A., 2000b. Smooth
pursuit eye movements in schizophrenia and attentional dysfunction: adults
with schizophrenia, ADHD, and a normal comparison group. Biological
Psychiatry 48, 197–203.
Rubia, K., 2002. The dynamic approach to neurodevelopment psychiatric
disorders: use of fMRI combined with neuropsychology to elucidate the
dynamics of psychiatric disorders, exemplified in ADHD and schizo-
phrenio. Behavioural Brain Research 130, 47–56.
Russell, A.T., 1994. The clinical presentation of childhood-onset schizo-
phrenia. Schizophrenia Bulletin 20, 631–645.
Russell, A.T., Bott, L., Sammons, C., 1989. The phenomenology of
schizophrenia occurring in childhood. Journal of the American Academy
of Child and Adolescent Psychiatry 3, 399–407.
Salem, J.E., Kring, A.M., Kerr, S.L., 1996. More evidence for generalized poor
performance in facial emotion perception in schizophrenia. Journal of
Abnormal Psychology 105, 480–483.
Schaeffer, J.L., Ross, R.G., 2002. Childhood-onset schizophrenia: premorbid
and prodromal diagnostic and treatment histories. Journal of the American
Academy of Child and Adolescent Psychiatry 41, 538–545.
Schimdt, K., Freidson, S., 1990. Atypical outcome in attention deficit
hyperactivity disorder. Journal of the American Academy of Child and
Adolescent Psychiatry 29, 566–570.
Schneider, F., Weiss, U., Kessler, C., Salloum, J.B., Posse, S., Grodd, W., et al.,
1998. Differential amygdala activation in schizophrenia during sadness.
Schizophrenia Research 34, 133–142.
Schwartz, B.L., Rosse, R.B., Johri, S., Deutsch, S.I., 1999. Visual scanning of
facial expressions in schizophrenia. The Journal of Neuropsychiatry and
Clinical Neurosciences 11, 103.
Seeman, P., Madras, B., 2002. Methylphenidate elevates resting dopamine
which lowers the impulse-triggered release of dopamine: a hypothesis.
Behavioural Brain Research 130, 79–83.
Seidman, L.J., Valera, E.M., Makris, N., 2005. Structural brain imaging of
attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 1263–
1272.
Sergeant, J.A., Geurts, H., Huijbregts, S., Scheres, A., Oosterlaan, J., 2003. The
top and the bottom of ADHD: a neuropsychological perspective.
Neuroscience and Biobehavioral Reviews 27, 583–592.
Shapiro, E.G., Hughes, S.J., August, G.J., Bloomquist, M.L., 1993. Processing
of emotional information in children with attention-deficit hyperactivity
disorder. Developmental Neuropsychology 9, 207–224.
Silver, L.B., 1992. Attention-deficit Hyperactivity Disorder: A Clinical Guide
to Diagnosis and Treatment. American Psychiatric Press, Washington, DC.
Singh, S.D., Ellis, C.R., Winton, A.W., Singh, N.N., Leung, J.P., Oswald, D.P.,
1998. Recognition of facial expressions of emotion by children with
attention-deficit hyperactivity disorder. Behavior Modification 22,
128–142.
Solanto, M.V., 2002. Dopamine dysfunction in AD/HD: integrating clinical
and basic neuroscience research. Behavioural Brain Research 130, 65–71.
Sonuga-Barke, E.J.S., 2002. Psychological heterogeneity in AD/HD–a dual
pathway model of behaviour and cognition. Behavioural Brain Research
130, 29–36.
Sonuga-Barke, D.J.S., 2003. The dual pathway model of AD/HD: an
elaboration of neuro-developmental characteristics. Neuroscience and
Biobehavioral Reviews 27, 593–604.
 P.J. Marsh, L.M. Williams / Neuroscience and Biobehavioral Reviews 30 (2006) 651–665
Spencer, E.K., Campbell, M., 1994. Children with schizophrenia: diagnosis,
phenomenology, and pharmacotherapy. Schizophrenia Bulletin 20,
713–725.
Streit, M., Wölwer, W., Gaebel, W., 1997. Facial-affect recognition and visual
scanning behaviour in the course of schizophrenia. Schizophrenia Research
24, 311–317.
Takahashi, T., Koeda, M., Oda, K., Matsuda, T., Matsushima, E., Matsuura, M.,
et al., 2004. An fMRI study of differential neural response to affective
pictures in schizophrenia. NeuroImage 22, 1247–1254.
Tossell, J.W., Greenstein, D.K., Davidson, A.L., Job, S.B., Gochman, P.,
Lenane, M.C., et al., 2004. Stimulant drug treatment in childhood-onset
schizophrenia with comorbid ADHD: an open-label case series. Journal of
Child and Adolescent Psychopharmacology 14, 448–454.
Venables, P., Bailes, K., 1994. The structure of schizotypy, its relation to
subdiagnoses of schizophrenia and to sex and age. British Journal of
Clinical Psychology 33, 277–294.
Volkow, N.D., Wang, G.-J., Fowler, J.S., Logan, J., Gerasimov, M.,
Maynard, L., et al., 2001. Therapeutic doses of oral methylphenidate
significantly increase extracellular dopamine in the human brain. The
Journal of Neuroscience 21, 1–5.
Volkow, N.D., Fowler, J.S., Wang, G.-J., Ding, Y.-S., Gatley, S.J., 2002. Role
of dopamine in the therapeutic and reinforcing effects of methylphenidate
in humans: results from imaging studies. European Neuropsychopharma-
cology 12, 557–566.
Walker, E., Marwit, S.J., Emory, E., 1980. A cross-sectional study of
emotion recognition in schizophrenics. Journal of Abnormal Psychology
89, 428–436.
Walker-Smith, G.J., Gale, A.G., Findlay, J.M., 1977. Eye movement strategies
involved in face perception. Perception 6, 313–326.
Weiss, G., Hechtman, L., 1986. Hyperactive Children Grown Up. Guilford,
New York.
Wheeler, J., Carlson, C.L., 1994. The social functioning of children with ADD
with hyperactivity and ADD without hyperactivity: a comparison of their
peer relations and social deficits. Journal of Emotional and Behavioral
Disorders 2, 2–12.
Wheeler Maedgen, J., Carlson, C.L., 2000. Social functioning and emotional
regulation in the attention deficit hyperactivity disorder subtypes. Journal of
Clinical Child Psychology 29, 30–42.
Williams, L.M., 1994. The multidimensional nature of schizotypal traits: a
cluster analytic study. Personality and Individual Differences 16, 103–112.
665
Williams, L.M., 1995. Further evidence for a multidimensional personality
disposition to schizophrenia in terms of cognitive inhibition. British Journal
of Clinical Psychology 34, 193–213.
Williams, L.M., Loughland, C.M., Gordon, E., Davidson, D., 1999. Visual
scanpaths in schizophrenia: is there a deficit in face recognition.
Schizophrenia Research 40, 189–199.
Williams, L.M., Philips, M.L., Brammer, M.J., Skerrett, D., Lagopoulos, J.,
Rennie, C., et al., 2001. Arousal dissociates amygdala and hippocampal
fear responses: evidence from simultaneous fMRI and skin conductance
recording. Neuroimage 14, 1070–1079.
Williams, L.M., Loughland, C.M., Green, M.J., Harris, A.W., Gordon, E.,
2003. Emotion perception in schizophrenia: an eye movement study
comparing the effectiveness of risperidone vs. haloperidol. Psychiatry
Research 120, 13–27.
Williams, L.M., Das, P., Harris, A.W., Liddell, B.B., Brammer, M.J.,
Olivieri, G., et al., 2004. Dysregulation of arousal and amygdala-prefrontal
systems in paranoid schizophrenia. American Journal of Psychiatry 161,
1–10.
Williams, L.M., Das, P., Liddell, B., Olivieri, G., Peduto, A., Brammer, M.J.,
et al., 2005. BOLD, sweat and fears: fMRI and skin conductance
distinguish facial fear signals. Neuroreport 16, 49–52.
Winters, L., Cornblatt, B.A., Erlenmeyer-Kimling, L., 1991. The prediction of
psychiatric disorders in late adolescence. In: Walker, E.F. (Ed.),
Schizophrenia: A life-Course Developmental Perspective. Academic
Press, San Diego.
Wölwer, W., Streit, M., Polzer, U., Gaebel, W., 1996. Facial affect recognition
in the course of schizophrenia. European Archives of Psychiatry and
Clinical Neuroscience 246, 165–170.
Woods, S.W., Miller, T.J., Davidson, L., Hawkins, K.A., Sernyak, M.J.,
McGlashan, T.H., 2001. Estimated yield of early detection of prodromal or
first episode patients by screening first degree relatives of schizophrenic
patients. Schizophrenia Research 52, 21–27.
Wynn, J.K., Sergi, M.J., Dawson, M.E., Schell, A.M., Green, M.F., 2005.
Sensorimotor gating orienting and social perception. Schizophrenia
Research 73, 319–325.
Yang, G.-Z., Dempere-Marco, L., Hu, X.-P., Rowe, A., 2002. Visual search:
psychophysical models and practical applications. Image and Vision
Computing 20, 291–305.
Zuddas, A., Ancilletta, B., Muglia, P., Cianchetti, C., 2000. Attention-
deficit/hyperactivity disorder: a neuropsychiatric disorder with childhood
onset. European Journal of Paediatric Neurology 4, 53–62.