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JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY

2010, 32 (7), 737–751

Neurocognitive function in schizophrenia with comorbid


NCEN

posttraumatic stress disorder

Lisa A. Duke,1 Daniel N. Allen,1 Sylvia A. Ross,1 Gregory P. Strauss,1


Schizophrenia PTSD Comorbidity

and Jason Schwartz2


1
University of Nevada Las Vegas, Las Vegas, NV, USA
2
Mojave Adult, Child and Family Services, Las Vegas, NV, USA

Individuals with schizophrenia are at a greater risk for experiencing trauma and developing posttraumatic stress
disorder (PTSD) than the general population. Despite an increased incidence of neurocognitive dysfunction in both
schizophrenia and PTSD, there are few studies that have examined the potential compounding effects of these diag-
noses when they co-occur. The current study examined this issue by administering comprehensive diagnostic, symp-
tom, and neurocognitive evaluations to four groups including normal controls (C), as well as individuals with
PTSD (PTSD), schizophrenia (SZ), or both schizophrenia and PTSD (SZP). Results indicated that when compared to
the SZ group, the SZP group exhibited higher rates of positive symptoms, general psychopathology, and PTSD symp-
toms, as well as lower rates of negative symptoms. Regarding neurocognitive test performance, both schizophrenia
groups performed significantly worse than the C and PTSD groups across all neurocognitive domains. However,
differences were not significant between the SZP and SZ groups, although a differential pattern of performance
between the groups was indicated. Results of this study do not support the idea that the presence of comorbid
PTSD in SZ results in a substantial increase in cognitive impairment.

Keywords: Schizophrenia; Posttraumatic stress disorder; Learning and memory; Negative symptoms; Positive
symptoms; Depression; Comorbidity.

Individuals with schizophrenia and other severe mental abuse, greater risk of homelessness, increased hospitaliza-
illnesses are exposed to traumatic events at a much tions, earlier age of first psychiatric admission, increased
higher rate than the general population (Cascardi, Mueser, use of medication, and increased levels of positive
DeGiralomo, & Murrin, 1996; Goodman, Rosenberg, symptoms, depression, anxiety, somatization, and
Mueser, & Drake, 1997b; Goodman et al., 2001; Hutchings dissociation (Beck & van der Kolk, 1984; Craine et al.,
& Dutton, 1993; Jacobson, 1989; Lipschitz et al., 1996) 1988; Goodman et al., 1997b; Goodman et al., 2007;
such that prevalence rates of posttraumatic stress disor- Goodman et al., 2001; Holowka, King, Saheb, Pukall, &
der (PTSD) range between 29% and 66% in those with Brunet, 2003; Lysaker, Meyer, Evans, & Marks, 2001b;
severe mental illness, compared to 8% in the general popu- Morgan & Fisher, 2007; Mueser et al., 1998; Read, van
lation (Craine, Henson, Coliver, & MacLean, 1988; Os, Morrison, & Ross, 2005; Ross, Anderson, & Clark,
Mueser et al., 2001). Many times the traumatic event has 1994; Strauss et al., 2006.). Those with severe mental
occurred in the recent past. For example, up to 79% of illness who have been sexually abused also exhibit signifi-
individuals with severe mental illness have been victimized cantly more symptoms commonly linked to sexual abuse
within the last year (Cascardi et al., 1996) with 33% of (e.g. compulsive sexual behavior, crying, low energy)
mentally ill homeless women having been sexually or suggesting that trauma causes additional symptoms that
physically assaulted within the last 30 days (Goodman, are distinct from the symptoms associated with schizo-
Dutton, & Harris, 1997a). phrenia alone (Craine et al., 1988; Resnick, Bond, &
A history of trauma exposure is associated with Mueser, 2003).
poorer functional and treatment outcomes in individuals There is also substantial documentation of neurobio-
with schizophrenia including higher rates of substance logical and neurocognitive impairment associated with

Address correspondence to Daniel N. Allen, Neuropsychology Research Program, Department of Psychology, Box 455030, University
of Nevada Las Vegas, Las Vegas, NV 89154–5030, USA (E-mail: daniel.allen@unlv.edu).

© 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business
http://www.psypress.com/jcen DOI: 10.1080/13803390903512660
738 DUKE ET AL.

schizophrenia and to a lesser degree in PTSD, with some (Bremner, 2002; Shin et al., 2004). Consistent with neu-
overlap in affected brain regions. In particular, research roimaging findings, neuropsychological evaluation has
has documented abnormalities in temporal and frontal documented deficits in attention and executive
lobe regions in both PTSD and schizophrenia, as well as functions in those with PTSD (Felmingham, Bryant,
on neurocognitive measures associated with these Kendall, & Gordon, 2002; Gilbertson, Gurvits, Lasko,
regions. Temporal lobe abnormalities have been implicated Orr, & Pitman, 2001; Semple et al., 1996; Stein et al.,
in key schizophrenia symptoms, such as auditory halluci- 2002), although these results are not entirely consistent
nations, negative symptoms, and thought disorder (Barta, across studies (Vasterling, Brailey, Constans, & Sutker,
Pearlson, Powers, Richards, & Tune, 1990; Liddle & 1998). Evidence from neuropsychological studies of
Pantelis, 2003; Petty et al., 1995; Shenton et al. 1992; PTSD document impairment on neurocognitive tests
Vignal, Maillard, McGonigal, & Chauvel, 2007; associated with frontal and temporal regions, which
Weinstein, Woodward, & Ngan, 2007). Both structural may be the result of HPA abnormalities arising from an
and functional abnormalities have been identified (Heckers extreme stressor, or reflects premorbid neurological
et al., 1998; Hirayasu et al., 1999; Liddle & Pantelis, abnormalities that predispose an individual to the
2003; Nelson, Saykin, Flashman, & Riordan, 1998; development of PTSD. Regardless of etiology, neuro-
Roth, Pfefferbaum, Kelly, Berger, & Kopell, 1981; Stein, cognitive impairment is expected to be present in those
Koverola, Hanna, Torchia, & McClarty, 1997; Velakoulis with both current and lifetime diagnoses of PTSD.
et al., 1999; Zedkova, Woodward, Harding, Tibbo, & A trauma history in individuals with schizophrenia con-
Purdon, 2006). Consistent with these structural and tributes to increased psychiatric symptoms and poorer
functional abnormalities, individuals with schizophrenia functional outcomes. Similarly, one could expect that the
exhibit deficits in learning, memory, and auditory process- cognitive impairment associated with PTSD would further
ing (Aleman, Hijman, de Haan, & Kahn, 1999; Pelletier, impact the cognitive impairment associated with schizo-
Achim, Montoya, Lal, & Lepage, 2005). phrenia, in that there is a limited cognitive reserve in indi-
With regard to PTSD, the hippocampus is a region of viduals with schizophrenia to compensate for the HPA
interest because noradrenergic activity during the stress stress response associated with PTSD. However, despite the
response directly affects the hypothalamic-pituitary- high prevalence of trauma in schizophrenia, evidence sup-
adrenal (HPA) axis disrupting the normal activities of porting neuropathology in PTSD, evidence for neurobio-
the limbic structures (Everly & Horton, 1989). Magnetic logical and neurocognitive dysfunction in both
resonance imaging (MRI) studies have demonstrated schizophrenia and PTSD, and the observation of increased
that trauma survivors with PTSD have bilateral symptoms and poorer outcomes in those with schizophre-
hippocampal volume reductions (Bremner et al., 1997; nia who have a PTSD diagnosis, little information is avail-
Gurvits et al., 1996; Smith, 2005; Stein, Kennedy, & able regarding structural and functional brain
Twamley, 2002), although it is unclear whether abnormalities in those individuals with comorbid diagnoses
decreased hippocampal volume is the result of PTSD, of schizophrenia and PTSD. In fact, only three studies have
or whether it is a risk factor that exists prior to the examined the impact of trauma on neurocognitive function
development of PTSD (Gilbertson et al., 2002; Gurvitz in schizophrenia. Lysaker et al. (2001b) found that males
et al., 1996; Stein et al., 1997). When examining neuro- with schizophrenia spectrum disorders who self-reported
cognitive deficits in PTSD, studies have found explicit childhood sexual abuse (n = 15) exhibited more severe
memory deficits on an array of explicit memory scales positive symptoms and worse performance on tests of
including the Wechsler Memory Scale and the California executive functions and working memory than did those
Verbal Learning Test (Aleman et al., 1999; Jenkins, who did not report childhood sexual abuse. C. Good-
Langlais, Delis, & Cohen, 1998; Johnsen & Asbjornsen, man et al. (2007) also reported that survivors of the
2008; McNally, 1998; Yehuda, Golier, Halligan, & holocaust who had schizophrenia and comorbid PTSD
Harvey, 2004). (n = 14) performed significantly worse than patients with
In schizophrenia, frontal lobe structural and func- schizophrenia who were not exposed to the holocaust on
tional abnormalities have been identified including tests assessing verbal memory, processing speed, and
decreased frontal lobe volume (Andreasen et al., 1994; visual scanning. Fan et al. (2008) also recently reported
Breier, Buchanan, Elkashef, Munson, Kirkpatrick, & that patients with schizophrenia and PTSD (n = 15)
Gellad, 1992; Nopoulos et al., 1995) and hypoactivity exhibited poorer performance on tests of attention,
in the dorsolateral prefrontal cortex (Carter et al., working memory, and executive functions than did
1998), among others. Neurocognitive deficits consistent patients with schizophrenia alone. Although having a
with these frontal lobe abnormalities have been exten- number of limitations including small numbers of par-
sively documented in schizophrenia, including impair- ticipants, limited evaluation of neurocognitive abili-
ments in attention, executive function, and working ties, reliance on clinical diagnoses of PTSD and
memory (H. A. Allen, Frith, & Liddle, 1993; Carter et al., schizophrenia, and examination of individuals exposed
1998; Fleming, Goldberg, Gold, & Weinberger, 1995; to trauma who may or may not have developed PTSD,
Heinrichs & Zakzanis, 1998; Knight & Silverstein, results of these studies (C. Goodman et al., 2007;
1998; Nuechterlein et al., 1992; Spindler, Sullivan, Lysaker et al., 2001b) are generally consistent with a
Menon, Lim, & Pfefferbaum, 1997). Frontal lobe abnor- compounding effect of PTSD on the symptom and
malities are also reported in PTSD, including hypoactivity neurocognitive abnormalities already present in indi-
of the mediolateral and dorsolateral prefrontal cortex viduals with schizophrenia.
SCHIZOPHRENIA PTSD COMORBIDITY 739

Based on these considerations, the primary objective METHOD


of the current study was to determine whether there
was indeed a neurocognitive profile unique to schizo- Participants
phrenia with comorbid PTSD that would differentiate
it from schizophrenia or PTSD alone and to further The sample consisted of 94 participants who were
examine the symptom profile of the comorbid patients. recruited from the community, a southwestern university,
To examine these issues, an extensive battery of diagnostic, and a community mental health center. Participants
symptom, and neurocognitive measures was administered were divided into four groups that included a healthy
to a healthy comparison group (C), individuals with comparison group (n = 26), individuals diagnosed with
PTSD (PTSD), individuals with schizophrenia (SZ), PTSD (n = 21), individuals with schizophrenia (n = 26) and
and individuals with schizophrenia and a comorbid individuals with both schizophrenia and PTSD (n = 21).
diagnosis of PTSD (SZP). As mentioned above, it was The average age of onset of schizophrenia was 19.0
hypothesized that the comorbid SZP group would years, with a mean of 8.44 hospitalizations, and the SZ
exhibit more severe generalized impairment than the SZ and SZP group did not differ in this regard. Chi-square
group on neuropsychological measures because of the analysis indicated significant differences in the subtypes
neuropathological changes associated with PTSD, with of schizophrenia between the two groups. Most notably
specific deficits in domains of neurocognitive function that there were 9 participants with schizoaffective dis-
impaired in PTSD including learning and memory, order in the SZP group while there were not any in the
attention, working memory, and executive functions. It SZ group. Alternatively, there were no individuals clas-
was also hypothesized that both the SZ and SZP groups sified as disorganized in the SZP group, whereas 3 people
would exhibit greater neuropsychological deficits than in the SZ group were classified with the disorganized
the PTSD group. With regard to symptoms, it was subtype. Demographic data for these groups are pre-
hypothesized that the SZP group would exhibit higher sented in Table 1. Types of traumatic event experi-
levels of positive symptoms and lower levels of negative enced by the participants are shown in Table 2.
symptoms than the SZ group. Furthermore, it was Individuals were excluded from participation in any of
hypothesized that the two groups with PTSD would the groups if they had a history of head injury, neurological
score higher than the SZ group on measures of depression disorder, mental retardation, or a current substance
and PTSD symptoms. abuse or dependence diagnosis, if they were using

TABLE 1
Demographic characteristics for the healthy comparison, PTSD, schizophrenia, and schizophrenia with PTSD groups

Group

C PTSD SZ SZP

Variable Mean (SD) Mean (SD) Mean (SD) Mean (SD) F(3, 88) p Post hoc Scheffé

Age (years) 36.3 (13.2) 26.6 (13.2) 39.5 (10.4) 40.7 (8.6) 6.60 .00 P<SZ,SZP
Education (years) 13.2 (1.3) 13.1 (1.0) 12.8 (1.5) 12.1 (1.0) 3.15 .03 None
Age of onset (years) 20.2 (4.9) 18.2 (7.2) 0.90 .35
No. of hospitalizations 5.7 (4.4) 13.4 (22.9) 2.74 .10

Variable N (%) N (%) N (%) N (%) c2(21) p

Subtype of SZ — —
Undifferentiated — — 18 (75) 6 (32)
Paranoid — — 3 (13) 5 (26)
Disorganized — — 3 (13) 0 (0)
Schizoaffective — — 0 (0) 8 (42)
Ethnicity 28.55 ns
Asian American 1 (4) 1 (5) 1 (4) 1 (5)
African American 1 (4) 3 (14) 12 (46) 3 (14)
European American 16 (66) 10 (48) 11 (42) 12 (57)
Hispanic American 2 (8) 1 (5) 1 (4) 1 (5)
Native American 0 (0) 2 (10) 0 (0) 1 (5)
Pacific Islander 0 (0) 1 (5) 0 (0) 0 (0)
Other 4 (16.5) 3 (14) 1 (4) 4 (19.5)
Sex 10.24 .02
Male 7 7 18 7
Female 17 12 8 14

Note. C = healthy comparison group; PTSD = posttraumatic stress disorder group; SZ = schizophrenia group; SZP = schizophrenia
with PTSD group. In right-hand column, P = PTSD group.
740 DUKE ET AL.

TABLE 2 diagnosis, and 11 had a lifetime diagnosis of PTSD.


Types of traumatic event experienced by the healthy Individuals in the SZ and SZP groups were recruited
comparison, PTSD, schizophrenia, and schizophrenia with through a community mental health center and had a
PTSD groups clinical diagnosis of schizophrenia when they were
contacted to participate in the study. The clinical
Group
diagnosis of schizophrenia was confirmed using the
C PTSD SZ SZP Total SCID, as was the diagnosis of PTSD in the SZP group.
In the SZP group there were 12 participants with a cur-
Type of trauma N N N N Mean rent diagnosis of PTSD and 9 with a lifetime diagnosis
of PTSD.
Natural disaster 6 2 7 6 5.25
Fire or explosion 3 1 2 7 3.25
MVA 10 5 11 12 9.50 Measures
Serious accident 3 1 1 5 2.50
Exposure to toxins 0 1 0 2 0.75
A comprehensive battery of tests was administered in
Physical assault 4 4 11 14 8.25
order to establish diagnosis, to assess for symptoms of
Assault w/a deadly weapon 3 2 6 11 5.50
Sexual assault 0 3 2 10 3.75 schizophrenia and PTSD, and to examine neurocognitive
Unwanted sexual experience 0 2 2 8 3.00 function. A brief description of each measure follows
Exposure to a war zone 0 1 0 2 0.75 with more extensive descriptions available from the cited
Captivity 0 2 0 3 1.25 references and from standard neuropsychological texts
Life-threatening illness 2 0 2 4 2.00 (Lezak, Howieson, & Loring, 2004; Reitan & Wolfson,
Severe human suffering 1 0 0 3 1.00 1993).
Sudden violent death 3 5 0 3 2.75
Sudden unexpected death 12 8 8 6 8.50
Diagnostic and symptom measures
Serious injury 0 3 2 2 1.75
Other traumatic event 2 5 2 6 3.75 The Structured Clinical Interview for DSM-IV was
used to diagnose Axis I disorders in all groups. The
Note. Participants may be included in more than one column.
Life Events Checklist from the Clinician Administered
C = healthy comparison group; PTSD = posttraumatic stress
disorder group; SZ = schizophrenia control group; SZP =
PTSD Scale (CAPS; Weathers, Litz, Herman, Huska,
schizophrenia with PTSD group. MVA = motor vehicle accident. & Keane, 1993) was used to assess types of trauma
and the Post-Traumatic Stress Disorder Checklist
(PCL; Blake et al., 1990) was used to assess the pres-
ence and severity of PTSD symptoms. This measure is
a self-report questionnaire commonly used to evalu-
medications that had potential central nervous system ate symptoms of PTSD and consists of 17 items repre-
(CNS) effects other than those used to treat the symptoms senting the DSM–IV (Diagnostic and Statistical
associated with schizophrenia or PTSD, or if English Manual of Mental Disorders–Fourth Edition; Ameri-
was not their first language. Individuals in the healthy can Psychiatric Association, 1994) criteria for PTSD
comparison group (C) had no lifetime diagnosis of schizo- and has been found to have excellent psychometric
phrenia, bipolar affective disorder, or PTSD, and they properties and diagnostic utility (Blake et al., 1990).
had no other Axis I psychiatric disorder within the past Information from the CAPS was used to supplement
year, including attention deficit hyperactivity disorder, information obtained from the SCID in order to
learning disabilities, or any other neurodevelopmental diagnose PTSD.
disorders. While some control participants had been The Brief Psychiatric Rating Scale (BPRS; Overall &
exposed to a traumatic event, those who experienced any Gorham, 1962) was utilized to rate overall severity of
significant PTSD symptoms as a result of the trauma psychiatric symptoms, and the Calgary Depression Rating
were excluded. Control participants could not be currently Scale (CDS; Addington, Addington, & Schissel, 1990)
taking any prescribed or over-the-counter medications was used to measure severity of depression and suicidality.
with CNS effects, or have a first- or second-degree relative The Scale for the Assessment of Positive Symptoms
diagnosed with or suspected to have a psychotic disorder. (SAPS; Andreasen, 1984) assessed positive symptoms
Individuals in the PTSD group were diagnosed with and provides a total positive symptom severity score, as
PTSD based on the Structured Clinical Interview for well as individual scores for the domains of hallucina-
DSM–IV Disorders (SCID-IV; First, Spitzer, Gibbon, tions, delusions, bizarre behavior, and thought disorder.
& Williams, 2002), and participants were not ruled out The Scale for the Assessment of Negative Symptoms
because of comorbid anxiety or depressive disorders. A (SANS; Andreasen, 1984) was used to evaluate negative
total of 5 individuals in the SZP group had comorbid symptoms and provides a total negative symptom severity
diagnoses of generalized anxiety disorder; 1 of those score as well as individual scores for the domains of
individuals also was also diagnosed with a current panic affective flattening, alogia, avolition-apathy, anhedonia-
disorder. In the PTSD group, 3 individuals met criteria asociality, and attention. These measures were completed
for a current panic disorder, 1 met criteria for social pho- based on information obtained in a semistructured clinical
bia, and 1 met criteria for a major depressive disorder. interview for symptoms present during the two weeks
In the PTSD group 10 participants had a current prior to the evaluation.
SCHIZOPHRENIA PTSD COMORBIDITY 741

Neuropsychological measures were extensively trained to complete the procedures in a


reliable and valid manner conducted all of the testing.
Neuropsychological functioning was measured using a
Clinical and control participants recruited from the
battery of tests selected to evaluate seven domains of
community received monetary compensation for
functioning, including intellectual ability, executive
participation.
functions, attention, motor function, working memory,
verbal learning/memory, and visual learning/ memory.
Multiple tests were utilized to assess each neuropsycho- Data analysis
logical domain in order to improve reliability of measure-
ment. Tests were grouped into neuropsychological Dependent variables used in the analyses are listed in
domains based on prior studies supporting that they Table 3 (symptom measures) and Table 4 (neuropsycho-
assess similar constructs as determined by factor analysis, logical measures). The general approach to data analysis
literature review, or expert consensus (Aleman, Agrawal, was to compare the four groups on the symptom and
Morgan, & David, 2006; Allen et al., 1997; Genderson neuropsychological variables. For the symptom variables,
et al., 2006; Jaeger, Czobor, & Berns, 2003; Nuechterlein separate analyses of variance (ANOVAs) were used to
et al., 2004; Park, Allen, Barney, Ringdahl, & Mayfield, compare the groups on the BPRS and Calgary Depression
2009). The Information, Vocabulary and Block Design Scale (CDS) total scores. The subscales of the SANS and
subtests from the Wechsler Adult Intelligence Scale Third then the SAPS were included in separate multivariate
edition (WAIS–III; Wechsler, 1997a) were used to estim- analyses of variance (MANOVAs) to compare profile of
ate global intellectual function. Executive functions were negative and positive symptoms among the groups. For
measured by the Trail Making Test Part B (Reitan & the neuropsychological variables, separate MANOVAs
Wolfson, 1993), Wisconsin Card Sorting Test (WCST; were conducted for each neurocognitive domain with the
Heaton, Chelune, Talley, Kay, & Curtis, 1993), and individual test scores used as dependent variables in the
Controlled Oral Word Association Test (Lezak et al., analyses. In this study, raw scores were used rather than
2004). Measures of attention/psychomotor speed age-corrected scores. Type I error was controlled for by
included the Trail Making Test Part A (Reitan & interpreting individual tests when the MANOVA was
Wolfson, 1993) and a computerized version of the Stroop significant. When the overall MANOVA was significant
task, color–word condition (Strauss, Allen, Jorgensen, & for a particular domain, planned comparisons were then
Cramer, 2005). Auditory and spatial working memory per- used to examine differences among groups on the individ-
formance was assessed using the Digit Span Forward ual test scores, followed by post hoc analyses (Scheffé) to
and Backward subtests from the WAIS–III (Wechsler, examine difference among the individual groups. Finally,
1997a) and the Visual Span Forward and Backward sub- in order to further compare the groups on the neuropsy-
tests from the Wechsler Memory Scale–III (Wechsler, chological domain scores, composite scores were calcu-
1997b), respectively. The California Verbal Learning lated for each domain. To calculate composites, the
Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) was individual test scores were first converted to standard
used as a measure of auditory verbal learning and mem- scores (z-scores) based on the performance of the
ory. Learning and memory for visual information was healthy control group. Within each neurocognitive
assessed using the Biber Figure Learning Test–Extended domain, the mean of the standard scores for the tests
(BFLT–E; Glosser, Cole, French, Saykin, & Sperling, assessing the respective domain was then calculated, and
1997), which was designed to be a visual analog of the these means served as the composite scores for each
CVLT (Glosser, Cole, Khatri, DellaPietra, & Kaplan, domain.
2002). Like the CVLT, the BFLT–E involves a series of
five learning trials and an interference task, as well as
immediate recall, delayed recall, and recognition trials.
RESULTS
Motor function was assessed with the Finger Oscillation
Test (Halstead, 1947) and the Purdue Pegboard Test
As can be seen from Table 1, ANOVA indicated that the
(Tiffin & Asher, 1948).
groups were significantly different with regard to age,
with post hoc analyses indicating that the PTSD group
Procedure was significantly younger than the controls and schizo-
phrenia groups, while the control, SZ, and SZP groups
After informed consent had been provided, demographic did not significantly differ from one another. ANOVA
and medical information was collected, and the SCID also indicated a significant difference for education,
was administered to establish diagnosis, following which although post hoc analyses did not reveal any significant
a semistructured clinical interview was conducted to further differences between any of the groups. The groups did
assess psychiatric symptoms in the clinical groups. The not differ with regard to ethnicity, c2(21) = 29.07, p =
neurocognitive tests were administered following the .10, although there was a significant difference for sex,
screening and symptom rating scales. Evaluations c2(3) = 10.24, p = .02. This difference appeared to be
occurred in a quiet and private setting and were typically accounted for by an overrepresentation of females in the
conducted over two or three sessions. Breaks from testing C, PTSD, and SZP groups.
were provided as needed in order to diminish fatigue and Consistent with prior studies investigating the percent-
maintain motivation. Doctoral-level technicians who age of trauma in individuals with schizophrenia, 76% of
742 DUKE ET AL.

TABLE 3
Symptom ratings for the PTSD, schizophrenia, and schizophrenia with PTSD groups

Group PTSD SZ SZP

Variable Mean SD Mean SD Mean SD F(2, 67) p Post hoc Scheffé

BPRS Total 29.00 10.17 40.12 6.54 45.43 16.00 11.69 .001 P<SZ,SZP
SANS
Affective flattening 0.52 0.81 3.00 1.36 1.85 1.31 24.84 .001 P<SZP<SZ
Alogia 0.14 0.48 1.96 1.51 1.45 1.43 12.64 .001 P<SZP,SZ
Avolition-apathy 0.48 0.87 2.15 1.71 1.85 1.35 9.22 .001 P<SZP,SZ
Anhedonia-asociality 0.52 0.75 2.50 1.48 1.80 1.67 12.33 .001 P<SZP,SZ
Attention 0.38 0.50 2.70 1.33 2.55 1.05 32.87 .001 P<SZP,SZ
Total score 3.10 4.60 12.27 6.10 9.50 4.69
SAPS
Hallucinations 0.24 0.63 1.96 1.69 2.95 1.50 20.48 .001 P<SZ,SZP
Delusions 0.14 0.16 2.50 0.91 3.70 0.80 123.18 .001 P<SZ<SZP
Bizarre behavior 0.48 0.98 1.73 1.12 1.05 1.36 6.94 .01 P< SZ
Thought disorder 0.24 0.54 1.62 1.42 0.95 1.15 8.73 .001 P< SZ
Total score 1.48 2.50 7.81 3.14 8.65 2.30
CDS Total Score 4.10 4.05 1.31 1.67 7.71 7.08 16.76 .001 SZ,P<SZP
PCL Total Score 34.10 17.08 6.69 13.05 51.86 20.56 42.85 .001 SZ<P<SZP

Note. BPRS = Brief Psychiatric Rating Scale; SANS = Schedule for the Assessment of Negative Symptoms; SAPS = Scale for the Assess-
ment of Positive Symptoms; CDS = Calgary Depression Scale; PCL = Posttraumatic Stress Disorder Checklist. PTSD = posttraumatic
stress disorder group; SZ = schizophrenia group; SZP = schizophrenia with PTSD group. In right-hand column, P = PTSD group.

the individuals with schizophrenia had been exposed to although not significant. Conversely, on the bizarre
at least one traumatic event (see Table 2). A total of 17 behavior and thought disorder subscales the SZP group
types of trauma were assessed, and the sample was heter- attained lower scores than the SZ group, and the SZP
ogeneous with regard to the type of trauma experienced. and PTSD groups did not significantly differ from each
Rates of specific types of trauma were similar in the control other on these two ratings.
groups and PTSD groups with the exception of sexual ANOVAs also revealed significant differences on the
assault and captivity, which were not endorsed by either CDS, BPRS, and Posttraumatic Stress Disorder
the controls or the SZ only group. A total of 11 of the Checklist (PCL) among the groups. On the CDS, the
participants in the SZ group and 16 in the SZP had a SZ group scored significantly lower than the PTSD
lifetime substance use disorder. and SZP groups, indicating more depressive symptoms
in the PTSD and SZP groups. For the PCL, the SZ
group obtained the lowest score, followed by the
Symptom pattern and severity
PTSD group and then the SZP group, which had the
highest score. For the BPRS, the SZP group exhibited
Descriptive statistics for the symptom ratings are pre-
increased levels of overall psychiatric symptoms,
sented in Table 3. MANOVA comparing the groups on
although the differences between the SZ and SZP
the SANS subscales was significant, F(10, 122) = 6.54,
groups were not significant.
p < .001. Subsequent ANOVAs and Scheffé post hoc
comparisons of the subscales indicated that the PTSD
group scored significantly lower than the schizophrenia Neuropsychological functioning
groups on all of the subscale scores. On the affective
flattening subscale, the SZ group had the highest score Table 4 presents results of the MANOVAs that were
followed by the SZP group and then the PTSD group, used to examine differences among the groups on the
which had the lowest score. On the alogia, avolition- neuropsychological domains, as well as descriptive data
apathy, anhedonia-asociality, and attention subscales, and post hoc comparisons. Composite scores for each
the SZ and SZP groups did not differ from one another, neuropsychological domain are presented in Figure 1.
but obtained significantly higher scores than the PTSD MANOVAs revealed significant overall differences (p <
group. .05) among the groups for the intellectual function,
The MANOVA for the SAPS subscales was also signi- motor function, verbal learning/memory, visuospatial
ficant, F(8, 124) = 15.46, p < .001. However, unlike the learning/memory, working memory, executive func-
SANS, the SZP group scored higher than the SZ group tioning, and attention domains. The pattern of differ-
on a number of the SAPS subscales. Specifically, the ences among the groups indicated that the control and
SZP group had significantly higher scores than the SZ PTSD groups performed significantly better than the
group on the delusions subscale. The score on the SZ and SZP groups. The PTSD group did not signifi-
hallucination subscale was also higher in the SZP group, cantly differ from the control group, and, similarly, the
SCHIZOPHRENIA PTSD COMORBIDITY 743

TABLE 4
Neurocognitive domain performance for healthy comparisons, PTSD, schizophrenia controls, and comorbid schizophrenia with
PTSD groups

Groups

C PTSD SZ SZP Univariate Post hoc


Neuropsychological tests tests:
domains and tests Mean SD Mean SD Mean SD Mean SD F Scheffé

Intellectual function
Vocabulary 42.35 12.02 36.90 8.63 26.38 12.72 25.62 12.16 11.43** C,P>SZ,SZP
Information 16.00 4.84 15.76 4.17 11.08 4.67 10.57 4.58 9.19** C,P>SZ,SZP
Block Design 37.43 9.52 38.24 14.51 23.50 9.19 23.33 9.42 13.56** P,C>SZ,SZP
Motor
Finger Tapping Dom. 49.46 6.13 48.20 14.82 36.81 14.38 32.24 14.85 10.03** C,P>SZ,SZP
Finger Tapping Ndom. 44.71 6.79 46.19 13.48 35.04 11.63 30.86 15.06 8.53** P,C>SZ,SZP
Peg Board Dom. 12.96 5.45 13.14 4.00 8.38 2.06 9.86 3.62 7.89** C,P>SZ
Peg Board Ndom. 12.38 5.00 12.29 3.50 8.23 3.02 9.14 3.44 7.40** P,C>SZ
Peg Board Both 19.46 8.86 20.33 5.89 11.65 5.24 12.43 7.30 9.92** P,C>SZP,SZ
Verbal learning/memory
CVLT: Trials 1–5 55.25 9.06 54.24 9.58 29.77 10.88 33.19 15.36 32.99** C,P>SZP,SZ
Distractor List 7.25 1.92 7.67 2.03 3.92 1.65 4.10 2.45 22.74** P,C>SZP,SZ
Short Delay Free Recall 11.21 2.95 11.62 2.91 5.50 3.53 6.71 4.17 19.38** C,P>SZP,SZ
Long Delay Free Recall 11.67 2.76 11.86 2.37 5.12 3.52 6.24 4.38 26.32** P,C>SZP,SZ
Recognition 15.29 1.85 14.81 1.86 16.73 6.64 15.76 7.91 0.59 SZ,SZP,C,P
Visual learning/memory
Biber: Trials 1–5 140.43 40.08 137.05 48.80 60.27 40.63 71.90 32.14 24.25** C,P>SZP,SZ
Distractor List 13.04 7.18 12.16 5.64 4.08 4.39 4.60 2.35 18.77** C,P>SZP,SZ
Short Delay Free Recall 34.26 8.32 31.00 11.16 14.27 11.34 16.65 9.85 21.85** C,P>SZP,SZ
Long Delay Free Recall 35.39 7.17 32.95 11.00 14.77 10.42 17.80 9.64 26.74** C,P>SZP,SZ
Recognition 14.57 0.73 13.79 3.49 10.92 4.05 12.55 2.50 6.74** C,P>SZ
Working memory
Digit Span Forward 10.67 1.81 10.52 2.52 7.85 2.19 7.90 2.17 12.09** C,P>SZP,SZ
Digit Span Backward 7.04 1.65 6.52 1.60 4.42 1.84 4.10 1.61 17.65** C,P>SZ,SZP
Spatial Span Forward 8.75 2.03 8.19 1.75 6.27 2.49 5.67 1.71 11.92** C,P>SZP,SZ
Spatial Span Backward 7.54 2.28 7.14 2.54 4.46 2.25 5.29 1.74 10.54** C>SZ,SZP; P>SZ
Executive function
WCST % perseverative 10.92 5.63 17.24 15.01 33.62 22.09 27.05 24.29 7.47** C<SZP,SZ;P<SZ
WCST cat. complete 5.29 1.57 4.62 1.80 1.88 2.03 3.20 2.44 14.19** SZP,SZ<C;SZ<P
Letter Fluency (FAS) 37.75 9.53 39.10 10.15 28.92 12.77 26.60 9.53 6.12** C>SZP;P>SZ,SZP
Category Fluency 19.88 4.10 20.43 3.43 13.62 5.11 13.80 4.00 15.14** P,C>SZP, SZ
Trails B 65.71 19.11 62.52 20.24 183.88 85.93 179.15 97.18 23.31** P,C>SZP,SZ
Attention
Stroop (color word) 79.29 1.43 78.57 3.22 76.65 4.40 73.15 10.06 5.20* C,P>SZP
Trails A 33.08 11.41 28.57 7.18 56.12 30.28 46.85 19.40 9.64** P<SZP,SZ;C<SZ

Note. Scores on the intellectual function domain are raw scores. Finger Tapping scores are the mean number of taps in 10 seconds. Peg
Board scores represent the number of pegs placed in 30 seconds. Dom. = dominant hand. Ndom. = Nondominant hand. CVLT (Cali-
fornia Verbal Learning Test) scores are the number of words recalled (or recognized on recognition trial). Biber scores represent the
total number of points earned where each shape is worth a possible of 3 points. The recognition score is the number of correctly iden-
tified shapes. WCST (Wisconsin Card Sorting Test) scores are the percentage of perseverative errors and number of categories com-
pleted. Letter Fluency and Category Fluency scores are the number of words generated. Trails A and B scores are the number of
seconds. Trails A score is the time in seconds required to complete the task. Stroop scores are percentage correct. C = healthy compar-
ison group; PTSD = posttraumatic stress disorder group; SZ = schizophrenia control group; SZP = comorbid schizophrenia with
PTSD group. In right-hand column, P = PTSD group.
*p < .01. **p < .001.

SZ and SZP groups did not significantly differ from Covariance analyses to examine influence of age,
each other; however, some exceptions to this were education, and symptoms on neuropsychological
noted. For example, in some cases, the C and PTSD domains
groups did not differ from the SZP group (Peg Board
Dominant and Nondominant hands, Biber Recogni- Given the associations between age, education, and
tion trial), and in one case no group differences were symptoms with neuropsychological functioning, two
found (CVLT Recognition). multivariate analyses of covariance (MANCOVAs) were
744 DUKE ET AL.

Figure 1. Neuropsychological composite scores of each of the Figure 2. Neuropsychological composite scores for each group
groups. ATT = attention; EXEC = executive function; WM = corrected for age and education differences among the groups.
working memory; VERM = verbal memory; VISM = visual ATT = attention; EXEC = executive function; WM = working
memory; MOT = motor function; WAIS = Wechsler Adult memory; VERM = verbal memory; VISM = visual memory;
Intelligence Scale IQ Score. MOT = motor function; WAIS = Wechsler Adult Intelligence
Scale IQ score.

accomplished for each neuropsychological domain. The


first MANCOVA included age and education as covari-
ates, and the second included positive, negative, and
PTSD symptoms as covariates. Group membership
served as the between-subjects variable, and the neu-
ropsychological test scores were used as the dependent
variables. Additionally comparisons were made between
individuals in the SZP group who had lifetime or current
diagnosis of PTSD to determine whether diagnosis was
associated with differences in neurocognitive perform-
ance.

Effects of age and education on


neuropsychological domains
When age and education were included as covariates Figure 3. Neuropsychological composite scores of each of the
in MANCOVAs, results indicated that age and educa- groups corrected for symptom differences (Scale for the Assess-
tion were not significant covariates for the motor, verbal ment of Positive Symptoms, SAPS; Scale for the Assessment of
learning and memory, visual learning and memory, or Negative Symptoms, SANS; and Posttraumatic Stress Disorder
executive function domains. For the working memory Checklist, PCL) among the clinical groups. ATT = attention;
domain, education was a significant covariate, F(4, 82) = EXEC = executive function; WM = working memory; VERM =
2.78, p < .05; however, the overall effect for group verbal memory; VISM = visual memory; MOT = motor func-
remained significant, F(12, 252) = 3.97, p < .001. For tion; WAIS = Wechsler Adult Intelligence Scale IQ score.
PTSD = posttraumatic stress disorder group; SZ = schizophre-
attention, age was a significant covariate, F(2, 84) =
nia control group; SZP = comorbid schizophrenia with PTSD
3.65, p < .05, and education approached significance, group. Control group scores are not corrected for symptoms.
F(2, 84) = 2.94, p = .06. The overall effect for group
remained significant, F(6, 170) = 4.80, p < .001. Figure 2
presents the composite scores after partialing out the
(SAPS and SANS total scores) and PTSD symptoms
effects of age and education. As can be seen by compar-
(PCL total score) on neuropsychological differences
ing Figures 1 and 2, the pattern of results is generally the
among the groups. None of the symptom measures were
same after the influence of age and education were con-
significant covariates for the motor and visual learning
trolled, although there were slight increases in the differ-
and memory domains. However, the SANS total score
ences between the control and PTSD groups as well as
was a significant covariate for verbal learning and memory,
between the SZ and SZP groups.
F(4, 81) = 3.02, p < .05, working memory, F(4, 81) =
3.41, p < .05, executive function, F(4, 81) = 2.56, p < .05,
Effects of symptoms on neuropsychological
and attention domains, F(2, 82) = 5.75, p < .01. Figure 3
domains
presents the composite scores for each group with the
MANCOVAs were performed to evaluate the influence effects of the positive, negative, and PTSD symptoms
of positive and negative symptoms of schizophrenia partialed out. Comparison of Figures 1 and 3 indicate
SCHIZOPHRENIA PTSD COMORBIDITY 745

that symptoms did, in fact, alter the pattern of performance were present between the SZ and SZP groups, which were
across the groups. In general, after controlling for associated with demographic and symptom variables.
symptoms, the PTSD group’s performance declined, as
did the performance of the SZP group. With regard to
Symptom pattern and severity
the SZP group, after covarying out the influence of
symptoms, the SZP group’s performance actually fell
When global psychiatric symptoms were examined using
below that of the SZ group on the attention, executive
BPRS total scores, results indicated that the PTSD
function, working memory, verbal learning and memory,
group had the least symptoms, and the SZP group had
motor, and intellectual function domains, essentially
the highest level of total symptoms. Importantly, however,
reversing the pattern of performance of the SZ and SZP
differences in BPRS total scores found between the SZ
groups.
and SZP groups were only at the trend level and did not
reach statistical significance. The finding of heightened
Effects of lifetime versus current diagnosis of levels of psychiatric symptoms in our SZP patients is
PTSD on neurocognitive function consistent with the findings of Kim, Kaspar, Noh, and
Nam (2006) who also reported elevated levels of psychiatric
Analyses were also conducted to investigate whether symptoms in individuals with schizophrenia who had a
there were differences in neurocognitive function and history of physical or sexual abuse.
symptoms based on current versus lifetime diagnosis of Differences were also apparent among patient groups
PTSD in the SZP and PTSD groups. For the PTSD with regard to depression, PTSD, and positive and negative
group, a MANOVA was used to compare participants symptoms of psychosis. When symptoms of depression
with lifetime diagnoses, current diagnoses, and controls were examined using the CDS, results indicated that the
on each of the cognitive domains. For the cognitive SZ group had the lowest overall severity of depressive
domains MANOVAs indicated that there were no differ- symptoms, followed by the PTSD only group and the
ences among the groups. When MANCOVAs were comorbid SZP group who exhibited the greatest severity
conducted using symptom measures as covariates, the of depressive symptoms. A greater severity of depressive
working memory domain, F(5, 39) = 3.09, p < .05, visual symptoms for the PTSD than the SZ group is surprising
learning/memory, F(5, 39) = 3.53, p < .01, and executive when one considers that individuals with schizophrenia
function domains, F(5, 39) = 4.12, p < .01, were all signi- are at increased risk for depression. Such differences
ficant. Inspection of the adjusted means on these three may indicate that the affective disturbance associated
domains do not follow a consistent pattern of impairment, with PTSD is greater than that of SZ and more strongly
such that the lifetime PTSD group exhibited the poorest related to clinically significant mood disturbance.
performance on the working memory domain, the control Furthermore, this affective disturbance appears to be
group performed most poorly on the visual learning/ compounded in individuals with schizophrenia and
memory, and the current PTSD group performed the comorbid PTSD who displayed the highest level of
most poorly on the executive function domain. depressive symptoms. These findings are consistent with
When comparable MANOVAs and MANCOVAs previous studies and may explain why a history of
were performed to examine differences among those in trauma and comorbid PTSD diagnosis has been found
the SZP group who had lifetime or current diagnoses of to be associated with suicidality in individuals with
PTSD, all of the differences between the current and lifetime schizophrenia (Read & Ross, 2003).
diagnosis groups were not significant (all ps > .05). Findings regarding the severity of PTSD symptoms
were also consistent with the hypothesis. Specifically,
when PTSD symptoms on the PCL were compared
DISCUSSION among groups, results indicated that the SZ group had
the lowest severity of PTSD symptoms, followed by the
The purpose of the current study was to evaluate the PTSD only patients, and then the SZP patients. Analyses
impact of PTSD in individuals with schizophrenia on examining differences in SAPS total positive symptom
both psychiatric and neurocognitive symptoms. It was scores were also consistent with prior studies in that the
expected that comorbid PTSD in individuals with schiz- SZP group exhibited a greater severity of psychotic
ophrenia would be associated with increased positive symptoms than patients with SZ alone (Read et al.,
and general psychiatric symptoms, decreased negative 2005; Ross et al., 1994). When individual SAPS sub-
symptoms, and increased neurocognitive impairment. domains were examined, results indicated that the SZP
Results of the current study suggest that: (a) The two patients had a greater severity of delusional symptoms
patient groups with a diagnosis of PTSD (i.e., SZP and than SZ or PTSD patients, which is consistent with
PTSD alone) evidenced higher symptoms of PTSD and previous studies that have identified delusions as
depression than the SZ and C groups; (b) patients in the uniquely elevated in schizophrenia–PTSD comorbidity
SZP group displayed greater severity of positive symp- (Read et al., 2005). However, SZ and SZP patients did
toms and lower severity of negative symptoms than did not differ in the severity of other psychotic symptoms, as
the SZ group; (c) both groups of SZ patients exhibited there were no significant differences in SAPS hallucina-
impaired neurocognitive function relative to the PTSD tions, thought disorder, or bizarre behavior domains. It
and C groups; and (d) subtle neurocognitive differences should be noted, however, that SZP patients did show a
746 DUKE ET AL.

trend toward having greater severity of hallucinations and primary negative symptoms protects against the devel-
lower ratings of thought disorder and disorganization than opment of PTSD by blunting the emotional impact of
the SZ patients. trauma. Such a mechanism would explain the higher
To date, few studies have examined the association incidence of negative symptoms in our SZ group.
between negative symptoms and trauma/PTSD. Prior When results of symptom data are viewed together, a
results have been mixed in this regard, with some studies comorbid diagnosis of PTSD does not uniformly
reporting no differences in negative symptoms associated increase core positive and negative symptoms of schizo-
with abuse history in schizophrenia (Goodman et al., phrenia. Rather, comorbid PTSD appears to be associated
2007; Lysaker, Meyer, Evans, Clements, & Marks, with a distinct symptom presentation that is characterized
2001a; Read, Agar, Argyle, & Aderhold, 2003; Resnick by slightly elevated positive symptoms, particularly
et al., 2003) and others reporting decreased levels of delusions, a decrease in negative symptoms, and greater
negative symptoms in those with trauma histories (Goff, severity of PTSD symptoms and depression. The similarities
Brotman, Kindlon, Waites, & Amico, 2003; Ross et al., between these findings and those previously reported for
1994). In the current study, results indicated that SZ studies of schizophrenia with comorbid PTSD support
patients displayed the greatest severity of negative the generalizability of the current results.
symptoms as reflected by the SANS total score, followed
by SZP and PTSD groups. When individual SANS
domains were analyzed, significant differences were Neuropsychological impairment
present between the SZ and SZP groups on affective
flattening alone, with SZ patients exhibiting more Previous studies examining neurocognition in individuals
pronounced flat affect than SZP patients. These differences with PTSD and healthy comparisons indicate that PTSD
suggest that it is of considerable importance to determine is most commonly associated with deficits in learning
which aspects of PTSD and trauma are and are not and memory and in attention, with some support for
associated with negative symptoms. Two potential impairment in working memory and executive function
explanations for this association are that the negative as well (Brewin, Kleiner, Vasterling, & Field, 2007;
symptoms associated with the comorbid PTSD presenta- Jenkins et al., 1998; Johnsen & Asbjornsen, 2008;
tion in schizophrenia are secondary in nature, resulting Yehuda et al., 2004). Effect sizes for memory alterations
from core features of PTSD such as emotional numbing associated with PTSD are small to moderate (Brewin et al.,
and avoidance. A second, but equally tenable, hypothesis 2007; Johnsen & Asbjornsen, 2008), and a number of
would be that decreased emotional responsiveness studies fail to find differences between healthy control
characteristic of primary negative symptoms acts as a and PTSD samples (Crowell, Kieffer, Siders, & Vander-
buffer against the development of PTSD following ploeg, 2002; Johnsen & Asbjornsen, 2008; Neylan et al.,
trauma, so patients with primary negative symptoms are 2004). Additionally, these effects appear to be at least
less likely to develop PTSD when exposed to trauma. partly dependent on the tests themselves, with the
Recent preliminary findings suggest that secondary Wechsler Memory Scale and Rey Auditory Verbal
negative symptoms but not primary negative symptoms Learning Test producing stronger effects than the CVLT
are elevated in SZP, whereas primary negative symptoms (Johnsen & Asbjornsen, 2008). Consistent with some of
appear to buffer against the onset of PTSD in those with these previous studies, we found that participants with
schizophrenia who have experienced trauma (Strauss, PTSD performed somewhat worse than controls on most
Duke, Ross, & Allen, in press). In this study, we did not tests, although these differences did not reach statistical
examine whether the negative symptoms experienced significance. Differences became more apparent when
by our patients were primary or secondary (Kelley, van symptoms were controlled through covariance analyses
Kammen, & Allen, 1999), although two common (see Figure 3). However, the absence of statistically
sources of secondary negative symptoms—depression significant differences between our PTSD and C groups
and medication effects—do not appear to account for may reflect the relatively small effect sizes reported for
the group differences. In this regard, even though nega- even the most consistently reported neurocognitive deficits
tive symptoms were higher in the SZ group than in the in PTSD, learning, and memory. It may also be that only
SZP group, depression was lower than in the SZP group, specific subsets of individuals with PTSD experience
and medication profiles did not appreciably differ. severe cognitive deficits (Sutker, Vasterling, Brailey, &
Whether the negative symptoms are primary in nature Allain, 1995; Twamley, Hami, & Stein, 2004) or that
and tend to be higher in the schizophrenia group prior to cognitive deficits may vary based on the age at which the
the experience of a traumatic event or diminish after traumatic event occurred (Bremner & Vermetten, 2001).
such an event has been experienced was not directly Based on a recent meta-analysis of memory function in
addressed. However, the former suggestion seems more PTSD that was based on 28 studies that contained a
consistent with reports indicating that negative symptoms total of 667 participants with PTSD and 822 controls,
are not significantly associated with trauma-related Johnsen and Asbjornsen (2008) found medium effect
variables (Resnick et al., 2003) and are minimally affected sizes overall when comparing PTSD to control samples.
by stressful life events and emotional reactivity However, they failed to find any effect for comparisons
(Docherty, St-Hilaire, Aakre, & Seghers, 2009). Based between sexually abused PTSD groups and exposed
on these considerations, it may be that the diminished controls. Since the PTSD group in our study was
emotional experience associated with the presence of heterogeneous with regard to these factors we could not
SCHIZOPHRENIA PTSD COMORBIDITY 747

directly examine these issues. But in any case, the current with findings generally indicating that neurocognitive
results suggest that when neurocognitive deficits are impairment is more highly associated with negative than
present in PTSD, they are relatively subtle in nature and with positive symptoms (D. N. Allen et al., 2000; Bowie
do not typically reach the severity that is observed in & Harvey, 2005).
psychiatric disorders such as schizophrenia (Reichenberg In our sample, the effects of negative symptoms are
& Harvey, 2007) or neurological disorders such as clearly illustrated by the reversal in the pattern of
dementia. performance between the SZ and SZP groups that can
To our knowledge, this is the first extensive comparison be seen in Figures 1 and 3. Prior studies of SZP have not
of neurocognitive function between comorbid SZ and specifically examined associations between negative
PTSD, although PTSD is known to impact psychiatric symptoms and neurocognitive test performance (Fan
symptoms in individuals with SZ. It would further be et al., 2008; Goodman et al., 2008; Lysaker et al., 2001b),
expected that the neurocognitive impairment associated which may partially explain why our results were apparently
with PTSD would impact the already impaired neuro- discrepant with past findings, prior to covarying
cognitive function in individuals with SZ. As previously negative symptoms. This suggestion may be particularly
mentioned, neurocognitive deficits associated with relevant to understanding apparent differences among
PTSD are generally small to moderate in magnitude, but studies, given that in schizophrenia negative symptoms
for schizophrenia, large effects are typically observed demonstrate stronger association with neurocognitive
across a number of neurocognitive domains. Meta-analyses function than do positive symptoms, and varying
of episodic memory and executive functions reveal that patterns of symptoms between schizophrenia and schizo-
these deficits persist even in the absence of florid psychotic phrenia–trauma groups were reported in prior studies (Fan
symptoms (Reichenberg & Harvey, 2007). et al., 2008; C. Goodman et al., 2007; Lysaker et al., 2001b).
Prior research provided some indication that the pres- In support of the current results, this study provides
ence of childhood sexual abuse (Lysaker et al., 2001b) and the most extensive evaluation of neurocognitive function
PTSD (Fan et al., 2008; Goodman et al., 2007) are associ- in the largest SZP sample studied to date, and it uses rig-
ated with greater neurocognitive impairment in SZ. How- orous diagnostic procedures including the SCID to
ever, contrary to our hypotheses, results indicated that establish DSM–IV–TR (Diagnostic and Statistical Man-
there were no significant differences between the SZ and ual of Mental Disorders–Fourth Edition, Text Revision;
SZP groups on any of the seven core neuropsychological American Psychiatric Association, 2000) diagnoses of
domains. When group differences in overall psychiatric schizophrenia and PTSD, which has not previously been
symptoms were controlled, the SZP group performed in accomplished in neurocognitive studies of SZP. However,
the expected direction by displaying greater impairment with regard to sample size, our groups containing 26
than the SZ group on all domains (with the exception of participants with SZ and 21 with SZP may still have
visual learning/memory). These differences were not sta- lacked adequate power to detect between-group differences
tistically significant although there was a trend toward sig- on some tests (e.g., WCST perseverative errors). Also,
nificance in the working memory domain. the limitations of self-report or symptom checklists to
Thus, since most of the neurocognitive differences diagnose PTSD have been previously indicated (Mueser
between the SZ and the SZP groups were not significant, et al., 1998), and it is clear that depending on the specific
the compounding effects of PTSD on the neurocognitive diagnostic criteria used, substantial differences can result
deficits of schizophrenia in our sample appear to be in the number of individuals who are diagnosed with
minimal. This is not unlike findings reported for other PTSD. A recent example comparing DSM–IV and ICD–10
comorbid conditions that commonly occur in schizo- (International Classification of Diseases–10th Revision)
phrenia, such as alcoholism, where the neurocognitive PTSD criteria found that the two criteria produced consid-
deficits associated with schizophrenia are sufficiently erable differences in the prevalence of PTSD diagnoses
severe to overshadow those that result from alcoholism, (O’Connor, Lasgaard, Spindler, & Elklit, 2007). While
particularly in younger patients (Allen, Goldstein, & the impact of diagnostic methods and criteria on apparent
Aldarondo, 1999; Goldstein, Allen, & Sanders, 2002; differences in neurocognitive studies of SZP is unknown,
Thoma, Wiebel, & Daum, 2007). It may also be that the the current study has employed a widely accepted and
clinical neuropsychological tests were not sensitive empirically validated diagnostic system (DSM–IV–TR)
enough to detect differences between the SZ and SZP and used standardized procedures (SCID-IV and CAPS)
groups in the more severe range of impairment. However, to establish Axis I diagnoses.
examination of the raw test scores suggested that floor It is also unclear whether differences in neurocognitive
effects were not accounting for the absence of differences performance that emerge after symptoms are controlled for
between these groups. Furthermore, whatever differ- in SZP represent preexisting conditions that predispose to
ences did exist appeared to be largely accounted for by the development of PTSD, or alternatively if they are
differences in negative symptoms that are present between more strongly associated with neuropathophysiological
the groups. When positive symptoms, negative symp- changes that develop during and after the traumatic
toms, and PTSD symptoms were entered as covari- event and that are dependent on the type of trauma
ates in the analyses, it was negative symptoms that were experienced. The literature on the developmental effects of
the only significant predictor of neurocognitive function- trauma on neurocognition is somewhat mixed and pro-
ing. Associations among symptoms of schizophrenia and vides little indication as to which of these two possibilities is
cognitive functioning have been extensively investigated, more likely. There is, however, some evidence suggesting
748 DUKE ET AL.

that childhood sexual abuse adversely effects brain been detected with increased numbers of participants.
development (Perry & Pate, 1994; Teicher, Ito, Glod, Relevant to the current study, whether neurocognitive
Surrey, & Sweet, 1997), that children who have limited deficits represent premorbid abnormalities or are caused
cognitive capacities are more likely to be the victims of sex- by the trauma itself, they should be apparent in individuals
ual abuse, and that subtle premorbid cognitive deficits with both lifetime and current diagnoses of PTSD.
increase the risk of developing PTSD after exposure to a In conclusion, the current study found that increased
traumatic event (Horner & Hamner, 2002). On the other delusions, PTSD symptoms, and depressive symptoms,
hand, there is evidence pointing to reductions in hippoc- along with a decrease in affective flattening, characterized
ampal volume in PTSD that occur after trauma exposure individuals with schizophrenia and comorbid PTSD. A
(Bremmer & Marmar, 1998; Yehuda, 1999) and are diagnosis of PTSD was not associated with a substantial
potentially due to dysregulation of the hypothalamic– impairment in neurocognitive function, although there
pituitary axis that results in an exaggerated cortisol were differences in the attention, executive function, and
response to stress in PTSD, but also produces abnor- visual memory domains. Overall, the comorbid group
mally low levels of cortisol under basal conditions (de Kloet performed better than the SZ group on all of the
et al., 2006; but also see Meewisse, Reitsma, De Vries, domains with the exception of attention, until psychiatric
Gersons, & Olff, 2007). This study was not longitudinal, symptoms were partialed out, and then that pattern of
and so we were unable to evaluate these developmental impairment reversed, favoring the SZP group. Further
factors. It is likely that a combination of premorbid and investigation is needed in order to clarify alterations in
trauma-related variables accounts for differences in neurocognitive function that result from PTSD comorbidity
neurocognition seen in the SZ and SZP groups once in schizophrenia, as well as the role that neurocognitive
symptoms have been controlled for. The present results deficits play in the increased levels of distress, poorer
are therefore consistent with the notion that the subjective quality of life, and poorer treatment outcomes
neurocognitive deficits affecting individuals with schizo- experienced by these patients.
phrenia who have a comorbid diagnosis of PTSD arise
from a complex interaction between premorbid, trauma- Original manuscript received 16 August 2009
related, demographic, and symptom-related variables. Revised manuscript accepted 23 November 2009
Additionally, there was heterogeneity within the First published online 2 March 2010
trauma groups with regard to the type of traumatic event
they experienced, as PTSD could have resulted from any
type of trauma. There is some evidence to suggest that REFERENCES
certain types of trauma differentially contribute to
neurocognitive impairment and similarly that the age at Addington, D., Addington, J., & Schissel, B. (1990). A depres-
which the traumatic event takes place may influence the sion rating scale for schizophrenics. Schizophrenia Research,
impact of trauma on neurocognitive function (Johnsen 3, 247–251.
& Asbjornsen, 2008). Also, consistent with prior studies Aleman, A., Agrawal, N., Morgan, K. D., & David, A. S. (2006).
in this area, individuals were included in the SZ and C Insight in psychosis and neuropsychological function: Meta-
analysis. British Journal of Psychiatry, 189, 204–212.
groups even if they had experienced a traumatic event at Aleman, A., Hijman, R., de Haan, E. H., & Kahn, R. S. (1999).
some time in their lives, although they were excluded if Memory impairment in schizophrenia: A meta-analysis.
any significant PTSD symptoms resulted from the American Journal of Psychiatry, 156, 1358–1366.
trauma. Because other studies of SZP have not ruled out Allen, D. N., Anastasiou, A., Goldstein, G., Gurklis, J. A.,
Gilbertson, M. W., & van Kammen, D. P. (2000). Influ-
trauma in normal or schizophrenia comparison groups, ence of haloperidol on the relationship of frontal lobe
differences between the results found here and those function to psychomotor poverty and disorganization
previously reported are probably not due to our inclusion syndromes. Psychiatry Research, 93, 33–36.
and exclusion criteria. Finally, studies examining differ- Allen, D. N., Gilbertson, M. W., van Kammen, D. P., Kelley,
ences in severity of neurocognitive impairment based on a M. E., Gurklis, J. A., Jr., & Barry, E. J. (1997). Chronic
haloperidol treatment does not affect structure of attention
current versus lifetime diagnosis of PTSD have produced in schizophrenia. Schizophrenia Research, 25, 53–61.
inconsistent results. For example, Tischler et al. (2006) Allen, D. N., Goldstein, G., & Aldarondo, F. (1999). Neurocogni-
found that verbal learning and memory deficits were tive dysfunction in patients diagnosed with schizophrenia and
correlated with a lifetime but not a current diagnosis of alcoholism. Neuropsychology, 13, 62–68.
Allen, H. A., Frith, C. D., & Liddle, P. F. (1993). Negative fea-
PTSD and reflected changes in hippocampal volume. tures, retrieval processes and verbal fluency in schizophrenia.
However, contradictory results are reported by Eren- British Journal of Psychiatry, 163, 769–776.
Kocak, Kilic, Aydin, and Hizli (2009) who found that American Psychiatric Association. (1994). Diagnostic and stat-
current PTSD was associated with poorer verbal istical manual of mental disorders (4th ed.). Washington,
memory and prefrontal function. Our study was not DC: Author.
American Psychiatric Association. (2000). Diagnostic and
designed to address this issue, but preliminarily analyses statistical manual of mental disorders (4th ed., text rev.).
do not provide any support for systematic alterations in Washington, DC: Author.
neurocognitive abilities based on a current versus lifetime Andreasen, N. C. (1984). Scale for the Assessment of Negative
diagnosis of PTSD, either in our PTSD group or in our Symptoms/Scale for the Assessment of Positive Symptoms
(manual). Iowa City, IA: University of Iowa Press.
SZP group. However, because in each of these analyses Andreasen, N. C., Flashman, L., Flaum, M., Arndt, S., Swayze,
the lifetime diagnosis samples were small, ranging V. W., & O’Leary, D. S. (1994). Regional brain abnormali-
between 9 and 12 participants, differences may have ties in schizophrenia measured with magnetic resonance
SCHIZOPHRENIA PTSD COMORBIDITY 749

imaging. Journal of the American Medical Association, 272, disorder, cognitive function and quality of life in patients
1763–1769. with schizophrenia. Psychiatry Research, 159, 140–146.
Barta, P. E., Pearlson, G. D., Powers, R. E., & Tune, L. E. Felmingham, K. L., Bryant, R. A., Kendall, C., & Gordon, E.
(1990). Auditory hallucinations and smaller superior (2002). Event-related potential dysfunction in posttraumatic
temporal gyral volume in schizophrenia. American Journal stress disorder: The role of numbing. Psychiatry Research,
of Psychiatry, 147, 1457–1462. 109, 171–179.
Beck, J. C., & van der Kolk, C. (1984). Reports of childhood incest First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W.
and current behavior of chronically hospitalized psychotic (2002). Structured Clinical Interview for DSM-IV-TR Axis I
women. American Journal of Psychiatry, 144, 1474–1476. Disorders, Research Version, Patient Edition (SCID-I/P).
Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., New York: Biometrics Research, New York State Psychiat-
Klauminzer, G., Charney, D. S., et al. (1990). A clinician ric Institute.
rating scale for assessing current and lifetime PTSD CAPS-1. Fleming, K., Goldberg, T. E., Gold, J. M., & Weinberger, D. R.
Behavior Therapist, 13, 187-188 (1995). Verbal working memory dysfunction in schizophre-
Bowie, C. R., & Harvey, P. D. (2005). Cognition in schizophre- nia: Use of a Brown–Peterson paradigm. Psychiatry
nia: Impairments, determinants, and functional importance. Research, 56, 155–161.
Psychiatric Clinics of North America, 28, 613–633. Genderson, M. R., Dickinson, D., Diaz-Asper, C. M., Egan,
Breier, A., Buchanan, R. W., Elkashef, A., Munson, R. C., M. F., Weinberger, D. R., & Goldberg, T. E. (2006). Factor
Kirkpatrick, B., & Gellad, F. (1992). Brain morphology and analysis of neurocognitive tests in a large sample of schizo-
schizophrenia. A magnetic resonance imaging study of lim- phrenic probands, their siblings, and healthy controls.
bic, prefrontal cortex, and caudate structures. Archives of Schizophrenia Research, 94, 231–239.
General Psychiatry, 49, 921–926. Gilbertson, M. W., Gurvits, T. V., Lasko, N. B., Orr, S. P., &
Bremmer, J., & Marmar, C. (1998). Trauma, memory and disso- Pitman, R. K. (2001). Multivariate assessment of explicit
ciation. Washington, DC: American Psychiatric Press. memory function in combat veterans with posttraumatic
Bremner, J. D. (2002). Structural changes in the brain in depres- stress disorder. Journal of Traumatic Stress, 14, 413–432.
sion and relationship to symptom recurrence. CNS Spec- Gilbertson, M. W., Shenton, M. E., Ciszweski, A., Kasai, K.,
trums, 7, 129–130. Lasko, N. B., Orr, S. P., et al. (2002). Smaller hippocampal
Bremner, J. D., Randall, P., Vermetten, E., Staib, L., Bronen, R. volume predicts pathologic vulnerability to psychological
A., Mazure, C., et al. (1997). Magnetic resonance imaging- trauma. Nature Neuroscience, 5, 1242–1247.
based measurement of hippocampal volume in posttraumatic Glosser, G., Cole, L. C., French, J. A., Saykin, A. J., & Sper-
stress disorder related to childhood physical and sexual ling, M. R. (1997). Predictors of intellectual performance in
abuse—a preliminary report. Biological Psychiatry, 41, 23–32. adults with intractable temporal lobe epilepsy. Journal of the
Bremner, J. D., & Vermetten, E. (2001). Stress and development: International Neuropsychological Society, 3, 252–259.
Behavioral and biological consequences. Developmental Glosser, G., Cole, L., Khatri, U., DellaPietra, L., & Kaplan, E.
Psychopathology, 13, 473–489. (2002). Assessing nonverbal memory with the Biber Figure
Brewin, C. R., Kleiner, J. S., Vasterling, J. J., & Field, A. P. Learning Test–Extended in temporal lobe epilepsy patients.
(2007). Memory for emotionally neutral information in Archives of Clinical Neuropsychology, 17, 25–35.
posttraumatic stress disorder: A meta-analytic investigation. Goff, D., Brotman, A., Kindlon, D., Waites, M., & Amico, E.
Journal of Abnormal Psychology, 116, 448–463. (2003). Self-reports of child abuse in chronically psychotic
Carter, C. S., Perlstein, W., Ganguli, R., Brar, J., Mintun, M., patients. Psychiatry Research, 37, 73–80.
& Cohen, J. D. (1998). Functional hypofrontality and work- Goldstein, G., Allen, D. N., & Sanders, R. D. (2002). Sensory-
ing memory dysfunction in schizophrenia. American Journal perceptual dysfunction in patients with schizophrenia and
of Psychiatry, 155, 1285–1287. comorbid alcoholism. Journal of Clinical and Experimental
Cascardi, M., Mueser, K. T., DeGiralomo, J., & Murrin, M. Neuropsychology, 24, 1010–1016.
(1996). Physical aggression against psychiatric inpatients by Goodman, C., Finkel, B., Naser, M., Andreyev, P., Segev, Y.,
family members and partners. Psychiatric Services, 47, 531–533. Kurs, R., et al. (2007). Neurocognitive deterioration in eld-
Craine, L. S., Henson, C. E., Coliver, J. A., & MacLean, D. G. erly chronic schizophrenia patients with and without PTSD.
(1988). Prevalence of a history of sexual abuse among Journal of Nervous and Mental Disease, 195, 415–420.
female psychiatric patients in a state hospital system. Hospi- Goodman, L. A., Dutton, M. A., & Harris, M. (1997a). The
tal and Community Psychiatry, 39, 300–304. relationship between violence dimensions and symptom
Crowell, T. A., Kieffer, K. M., Siders, C. A., & Vanderploeg, R. severity among homeless, mentally ill women. Journal of
D. (2002). Neuropsychological findings in combat-related Traumatic Stress, 10, 51–70.
posttraumatic stress disorder. The Clinical Neuropsycholo- Goodman, L. A., Rosenberg, S. D., Mueser, K. T., & Drake, R. E.
gist 16(3), 310–321. (1997b). Physical and sexual assault history in women with ser-
de Kloet, C. S., Vermetten, E., Geuze, E., Kavelaars, A., ious mental illness: Prevalence, correlates, treatment, and
Heijnen, C. J., & Westenberg, H. G. M. (2006). Assessment future directions. Schizophrenia Bulletin, 23, 685–696.
of HPA-axis function in posttraumatic stress disorder: Phar- Goodman, L. A., Slayers, M. P., Mueser, K. T., Rosenberg, S.
macological and non-pharmacological challenge tests, a D., Swartz, M., Essock, S. M., et al. (2001). Recent victimi-
review. Journal of Psychiatric Research, 40, 550–567. zation in women and men with severe mental illness: Prevalence
Delis, D. C., Kramer, J., Kaplan, E., & Ober, B. A. (1987). Cal- and correlates. Journal of Traumatic Stress, 14, 615–632.
ifornia Verbal Learning Test (CVLT) manual. San Antonio, Gurvits, T. V., Shenton, M. E., Hokama, H., Ohta, H.,
TX: Psychological Corporation. Lasko, N. B., & Gilbertson, M. W. (1996). Magnetic res-
Docherty, N. M., St-Hilaire, A., Aakre, J. M., & Seghers, J. P. onance imaging study of hippocampal volume in chronic,
(2009). Life events and high-trait reactivity together predict combat-related posttraumatic stress disorder. Biological
psychotic symptom increases in schizophrenia. Schizophre- Psychiatry, 40, 1091–1099.
nia Bulletin, 35, 638–645. Halstead, W. C. (1947). Brain and intelligence. Chicago, IL:
Eren-Kocak, E., Kilic, C., Aydin, I., & Hizli, F. G. (2009). Mem- University of Chicago Press.
ory and prefrontal function in earthquake survivors: Differ- Heaton, R. K., Chelune, G. J., Talley, J. L., Kay, G. G., &
ences between current and past post-traumatic stress disorder Curtis, G. (1993). Wisconsin Card Sorting Test (WCST)
patients. Acta Psychiatrica Scandinavica, 119, 35–44. manual revised and expanded. Odessa, FL: Psychological
Everly, G. S., & Horton, A. M. (1989). Neuropsychology of Assessment.
posttraumatic stress disorder: A pilot study. Perceptual and Heckers, S., Rauch, S. L., Goff, D., Savage, C. R., Schacter, D.
Motor Skills, 68, 807–810. L., & Fischman, A. J. (1998). Impaired recruitment of the
Fan, X., Henderson, D. C., Nguyen, D. D., Cather, C., Freu- hippocampus during conscious recollection in schizophre-
denreich, O., Evins, A. E., et al. (2008). Posttraumatic stress nia. Nature Neuroscience, 1, 318–323.
750 DUKE ET AL.

Heinrichs, R. W., & Zakzanis, K. K. (1998). Neurocognitive deficit posttraumatic stress disorder assessments in persons with
in schizophrenia: A quantitative review of the evidence. severe mental illness. Psychological Assessment, 13, 110–117.
Neuropsychology, 12, 426–445. Nelson, M. D., Saykin, A. J., Flashman, L. A., & Riordan, H.
Hirayasu, Y., Shenton, M. E., Salisbury, D. F., Kwon, J. S., J. (1998). Hippocampal volume reduction in schizophrenia
Wible, C. G., & Fischer, I. A. (1999). Subgenual cingulate as assessed by magnetic resonance imaging: A meta-analytic
cortex volume in first-episode psychosis. American Journal study. Archives of General Psychiatry, 55, 433–440.
of Psychiatry, 156, 1091–1093. Neylan, T. C., Lenoci, M., Rothlind, J., Metzler, T. J., Schuff,
Holowka, D. W., King, S., Saheb, D., Pukall, M., & Brunet, A. N., Du, A. T., et al. (2004). Attention, learning, and mem-
(2003). Childhood abuse and dissociative symptoms in adult ory in posttraumatic stress disorder. Journal of Traumatic
schizophrenia. Schizophrenia Research, 60, 87–90. Stress, 17(1), 41–46.
Horner, M. D., & Hamner, M. B. (2002). Neurocognitive Nopoulos, P., Torrer, I., Flaum, M., Andreasen, N. C.,
functioning in posttraumatic stress disorder. Europsychol- Ehrhardt, J. C., & Yuh, W. T. (1995). Brain morphology in
ogy Review, 12, 15–30. first-episode schizophrenia. American Journal of Psychiatry,
Hutchings, P. S., & Dutton, M. A. (1993). Sexual assault 152, 1721–1723.
history in a community mental health center clinical popula- Nuechterlein, K. H., Barch, D. M., Gold, J. M., Goldberg, T.
tion. Community Mental Health Journal, 29, 59–63. E., Green, M. F., & Heaton, R. K. (2004). Identification of
Jacobson, A. (1989). Physical and sexual assault histories separable cognitive factors in schizophrenia. Schizophrenia
among psychiatric outpatients. American Journal of Psychi- Research, 72, 29–39.
atry, 146, 755–758. Nuechterlein, K. H., Dawson, M. E., Gitlin, M., Ventura, J.,
Jaeger, J., Czobor, P., & Berns, S. M. (2003). Basic neuropsy- Goldstein, M. J., Snyder, K. S., et al. (1992). Developmen-
chological dimensions in schizophrenia. Schizophrenia tal processes in schizophrenic disorders: Longitudinal stud-
Research, 65, 105–116. ies of vulnerability and stress. Schizophrenia Bulletin, 18,
Jenkins, M. A., Langlais, P. J., Delis, D., & Cohen, R. (1998). 387–425.
Learning and memory in rape victims with posttraumatic stress O’Connor, M., Lasgaard, M., Spindler, H., & Elklit, A.
disorder. American Journal of Psychiatry, 155, 278–279. (2007). The impact of different diagnostic criteria on
Johnsen, G. E., & Asbjornsen, A. E. (2008). Consistent PTSD prevalence: A comparison of PTSD prevalence
impaired verbal memory in PTSD: A meta-analysis. Journal using the DSM-IV and ICD-10 PTSD-criteria on a popula-
of Affective Disorders, 111, 74–82. tion of 242 Danish social work students. Nordic Psychol-
Kelley, M. E., van Kammen, D. P., & Allen, D. N. (1999). ogy, 59(4), 317–331.
Empirical validation of primary negative symptoms: Inde- Overall, J. E., & Gorham, D. R. (1962). The Brief Psychiatric
pendence from effects of medication and psychosis. Ameri- Rating Scale. Psychological Reports, 10, 799–812.
can Journal of Psychiatry, 156, 406–411. Park, B. S., Allen, D. N., Barney, S. J., Ringdahl, E. N., &
Kim, D., Kaspar, V., Noh, S., & Nam, J. H. (2006). Sexual and Mayfield, J. (2009). Structure of attention in children with
physical abuse among Korean female inpatients with schizo- traumatic brain injury. Applied Neuropsychology, 16, 1–10.
phrenia. Journal of Traumatic Stress, 19, 279–289. Pelletier, M., Achim, A. M., Montoya, A., Lal, S., & Lepage,
Knight, R. A., & Silverstein, S. M. (1998). The role of cognitive M. (2005). Cognitive and clinical moderators of recognition
psychology in guiding research on cognitive deficits in schizo- memory in schizophrenia: A meta-analysis. Schizophrenia
phrenia: A process-oriented approach. In M. G. Lenzenweger Research, 74, 233–252.
& R. H. Dworkin (Eds.), Origins and development of schizophre- Perry, B. D., & Pate, J. E. (1994). Neurodevelopment and the
nia. Advances in experimental psychopathology. Washington, psychobiological roots of post-traumatic stress disorder. In
DC: American Psychological Association. L. F. Koziol & C. E. Stout (Eds.), The neuropsychology of
Lezak, M. D., Howieson, D. B., & Loring, D. W. (2004). Neu- mental disorders: A practical guide (pp. 129–146). New
ropsychological assessment. New York: Oxford University Press. York: Charles C. Thomas Publishers.
Liddle, P. F., & Pantelis, C. (2003). Neuroimaging studies in Petty, R. G., Barta, P. E., Pearlson, G. D., McGilchrist, I. K.,
schizophrenia. In S. R. Hirsch & D. Weinberger (Eds.), Lewis, R. W., & Tien, A. Y. (1995). Reversal of asymmetry
Schizophrenia. Oxford, UK: Blackwell Science. of the planum temporale in schizophrenia. American Journal
Lipschitz, D. S., Kaplan, M. L., Sorkenn, J. B., Faedda, G. L., of Psychiatry, 152, 715–721.
Chorney, P., & Asnis, G. M. (1996). Prevalence and charac- Read, J., Agar, K., Argyle, N., & Aderhold, V. (2003). Sexual
teristics of physical and sexual abuse among psychiatric and physical assault during childhood and adulthood as
outpatients. Comprehensive Psychiatry, 37, 261–266. predictors of hallucinations, delusions and thought disor-
Lysaker, P., Meyer, P., Evans, J., Clements, C., & Marks, K. der. Psychology and Psychotherapy, 76, 1–22.
(2001a). Childhood sexual trauma and psychosocial func- Read, J., & Ross, C. A. (2003). Psychological trauma and psy-
tioning in adults with schizophrenia. Psychological Services, chosis: Another reason why people diagnosed schizophrenic
52, 1485–1488. must be offered psychological therapies. Journal of the
Lysaker, P. H., Meyer, P., Evans, J. D., & Marks, K. A. (2001b). American Academy of Psychoanalysis and Dynamic Psychia-
Neurocognitive and symptom correlates of self-reported try, 31, 247–268.
childhood sexual abuse in schizophrenia spectrum disorders. Read, J., van Os, J., Morrison, A. P., & Ross, C. A. (2005).
Annals of Clinical Psychiatry, 13, 89–92. Childhood trauma, psychosis and schizophrenia: A literature
McNally, R. J. (1998). Experimental approaches to cognitive review with theoretical and clinical implications. Acta Psy-
abnormality in posttraumatic stress disorder. Clinical chiatrica Scandinavica, 112, 330–350.
Psychology Review, 18, 971–982. Reichenberg, A., & Harvey, P. D. (2007). Neuropsychological
Meewisse, M., Reitsma, J. B., De Vries, G., Gersons, B. P. R., impairments in schizophrenia: Integration of performance-
& Olff, M. (2007). Cortisol and post-traumatic stress disor- based and brain imaging findings. Psychological Bulletin,
der in adults: Systematic review and meta-analysis. British 133(5), 833–858.
Journal of Psychiatry, 191(4), 367–392. Reitan, R. M., & Wolfson, D. (1993). The Halstead–Reitan
Morgan, C., & Fisher, H. (2007). Environment and schizophre- Neuropsychological Test Battery: Theory & clinical inter-
nia: Environmental factors in schizophrenia: Childhood pretation (2nd ed.). Tucson, AZ: Neuropsychological
trauma—a critical review. Schizophrenia Bulletin, 33, 3–10. Press.
Mueser, K. T., Goodman, L. B., Trumbetta, S. L., Rosenberg, Resnick, S., Bond, G., & Mueser, K. (2003). Trauma and PTSD
S. D., Osher, C., Vidaver, R., et al. (1998). Trauma and in people with schizophrenia. Journal of Abnormal Psychol-
posttraumatic stress disorder in severe mental illness. Jour- ogy, 112, 415–423.
nal of Consulting and Clinical Psychology, 66, 493–499. Ross, C., Anderson, G., & Clark, P. (1994). Childhood abuse
Mueser, K. T., Salyers, M. P., Rosenberg, S. D., Ford, J. D., Fox, and positive symptoms of schizophrenia. Hospital and Com-
L., & Carty, P. (2001). Psychometric evaluation of trauma and munity Psychiatry, 45, 489–491.
SCHIZOPHRENIA PTSD COMORBIDITY 751

Roth, W. T., Pfefferbaum, A., Kelly, A. F., Berger, P. A., & Thoma, P., Wiebel, B., & Daum, I. (2007). Response inhibition
Kopell, B. S. (1981). Auditory event-related potentials in schiz- and cognitive flexibility in schizophrenia with and without
ophrenia and depression. Psychiatry Research, 4, 199–212. comorbid substance use disorder. Schizophrenia Research,
Semple, W. E., Goyer, P. F., McCormick, R., Comptom-Toth, 92, 168–180.
B., Morris, E., & Donovan, B. (1996). Attention and Tiffin, J., & Asher, E. J. (1948). The Purdue Pegboard: Norms
regional cerebral blood flow in posttraumatic stress disorder and studies of reliability and validity. Journal of Applied
patients with substance abuse histories. Psychiatry Psychology, 32, 234–247.
Research, 67, 17–28. Tischler, L., Brand, S. R., Stavitsky, K., Labinsky, E., New-
Shenton, M. E., Kikinis, R., Jolesz, F. A., Stechuchak, K. M., mark, R., Grossman, R., et al. (2006). The relationship
Oddone, E. Z., Swartz, M. S., et al. (1992). Abnormalities between hippocampal volume and declarative memory in a
of the left temporal lobe and thought disorder in schizophre- population of combat veterans with and without PTSD.
nia. A quantitative magnetic resonance imaging study. New Annals New York Academy of Sciences, 1071, 405–409.
England Journal of Medicine, 327, 604–612. Twamley, E. W., Hami, S., & Stein, M. B. (2004). Neuropsy-
Shin, L. M., Orr, S. P., Carson, M. A., Rauch, S. L., Macklin, chological function in college students with and without
M. L., Lasko, N. B., et al. (2004). Regional cerebral blood posttraumatic stress disorder. Schizophrenia Research, 126,
flow in the amygdala and medial prefrontal cortex during 265–274.
traumatic imagery in male and female Vietnam veterans Vasterling, J. J., Brailey, K., Constans, J. I., & Sutker, P. B.
with PTSD. Archives of General Psychiatry, 61, 168–176. (1998). Attention and memory dysfunction in posttraumatic
Smith, M. E. (2005). Bilateral hippocampal volume reduction in stress disorder. Neuropsychology, 12, 125–133.
adults with post-traumatic stress disorder: A meta-analysis Velakoulis, D., Pantelis, C., McGorry, P. D., Dudgeon, P.,
of structural MRI studies. Hippocampus, 15(6), 798–807. Brewer, W., & Cook, M. (1999). Hippocampal volume in
Spindler, K. A., Sullivan, E. V., Menon, V., Lim, K. O., & Pfef- first-episode psychoses and chronic schizophrenia: A high-
ferbaum, A. (1997). Deficits in multiple systems of working resolution magnetic resonance imaging study. Archives of
memory in schizophrenia. Schizophrenia Research, 27, 1–10. General Psychiatry, 56, 133–141.
Stein, M. B., Kennedy, C. M., & Twamley, E. W. (2002). Neu- Vignal, J. P., Maillard, L., McGonigal, A., & Chauvel, P.
ropsychological function in female victims of intimate part- (2007). The dreamy state: Hallucinations of autobiographic
ner violence with and without posttraumatic stress disorder. memory evoked by temporal lobe stimulations and seizures.
Recent Advances in Biological Psychiatry, 52, 1079–1088. Brain, 130, 88–99.
Stein, M. B., Koverola, C., Hanna, C., Torchia, M. G., & Weathers, F. W., Litz, B. T., Herman, D. S., Huska, J. A., &
McClarty, B. (1997). Hippocampal volume in women vic- Keane, T. M. (1993, October). The PTSD Checklist: Relia-
timized by childhood sexual abuse. Psychological Medicine, bility, validity, and diagnostic utility. Paper presented at
27, 951–959. Annual Meeting of the International Society for Traumatic
Strauss, G. P., Allen, D. N., Jorgensen, M. L., & Cramer, S. L. Stress Studies, San Antonio, TX.
(2005). Test–retest reliability of the Stroop and Emotional Wechsler, D. (1997a). Wechsler Adult Intelligence Scale (3rd
Stroop task: An investigation of color–word and picture– ed.). New York: Psychological Corporation.
word versions. Assessment, 12, 330–337. Wechsler, D. (1997b). Wechsler Memory Scale (3rd ed.). New
Strauss, G. P., Duke, L. A., Ross, S. A., & Allen, D. N. (in York: Psychological Corporation.
press). Posttraumatic stress disorder and negative symptoms Weinstein, S., Woodward, T. S., & Ngan, E. T. (2007). Brain
of schizophrenia. Schizophrenia Bulletin. activation mediates the association between structural
Strauss, J. L., Calhoun, P. S., Marx, C. E., Pollack, S. D., abnormality and symptom severity in schizophrenia. Neu-
LeMay, M., Martin, J., et al. (2006). Comorbid posttrau- roImage, 36, 188–193.
matic stress disorder is associated with suicidality in male Yehuda, R. (1999). Linking neuroendocrinology of posttrau-
veterans with schizophrenia or schizoaffective disorder. matic stress disorder with recent neuroanatomic findings.
Schizophrenia Research, 84, 165–169. Seminar in Clinical Neuropsychiatry, 4, 256–265.
Sutker, P. B., Vasterling, J. J., Brailey, K., & Allain, A. N. Yehuda, R., Golier, J. A., Halligan, S. L., & Harvey, P. D.
(1995). Memory and attention in posttraumatic stress disor- (2004). Learning and memory in holocaust survivors with
der. Neuropsychology, 12, 125–133. posttraumatic stress disorder. Biological Psychiatry, 55,
Teicher, M. H., Ito, Y., Glod, C. A., Surrey, J., & Sweet, C. 291–295.
(1997). Preliminary evidence for abnormal cortical develop- Zedkova, L., Woodward, N. D., Harding, I., Tibbo, P. G., &
ment in physically and sexually abused children using EEG Purdon, S. E. (2006). Procedural learning in schizophrenia
coherence and MRI. Annals of the New York Academy of investigated with functional magnetic resonance imaging.
Sciences, 821, 160–175. Schizophrenia Research, 88, 198–207.
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