The course of neurocognition and social functioning in individuals at ultra high risk for psychosis.
ABSTRACT This study evaluates longitudinal neuropsychological performance and its association with clinical symptomatology and psychosocial outcome in individuals identified as ultra high risk (UHR) for psychosis.
Thirty-five UHR individuals completed neurocognitive, clinical, and social/role functioning assessments at baseline and, on average, 8.3 months later.
UHR subjects showed significant cognitive deficits at baseline and 2 distinct profiles of cognitive change over time. On average, 50% demonstrated improvement in social and role functioning over the follow-up period, while the other half showed either stability or decline in functioning. Functional improvement was associated with improved processing speed and visual memory, as well as improvement in clinical symptoms over the follow-up period. In contrast, patients who did not improve functionally showed stable clinical symptoms and cognitive performance over time.
Although the degree of neurocognitive deficit at baseline in UHR patients does not predict psychosocial outcome, the course of neurocognitive change over the first 8 months of follow-up does differentiate patients with good and poor functional outcomes.
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ABSTRACT: Individuals at a clinical high risk (CHR) for psychosis have grey matter volume (GMV) abnormalities that are similar to, though less severe than, those in individuals with schizophrenia. Less GMV in schizophrenia is related to worse social cognition and social functioning, but the relationship between GMV and social functioning in CHR individuals has yet to be investigated. The aim of this study was to (1) investigate differences in GMV between healthy controls (HC) and CHR individuals, and (2) evaluate the relationship between GMV and social functioning in these two groups. Participants comprised 22 CHR and 21 HC individuals who completed a structural magnetic resonance imaging (MRI) scan as well as self-reported and interviewer-rated measures of social functioning. Processing and analysis of structural images were completed using voxel based morphometry (VBM). Results showed that the CHR group had less GMV in the left postcentral gyrus, bilateral parahippocampual gyri, and left anterior cingulate cortex. Reduced GMV in the postcentral gyrus and the anterior cingulate was related to self-reported social impairment across the whole group. This study has implications for the neurobiological basis of social dysfunction present before the onset of psychosis.Psychiatry Research Neuroimaging 08/2014; · 2.83 Impact Factor
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ABSTRACT: Symptom assessment in early psychosis research typically relies on scales validated in chronic schizophrenia samples. Our goal was to inform investigators who are selecting symptom scales for early psychosis research. We described measure characteristics, baseline scores, and scale inter-relationships in clinical-high-risk (CHR) and recent-onset psychotic disorder (RO) samples using the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms; for the CHR group only, we included the Scale of Prodromal Symptoms. For investigators selecting symptom measures in intervention or longitudinal studies, we also examined the relationship of symptom scales with psychosocial functioning. In both samples, symptom subscales in the same domain, across measures, were moderately to highly intercorrelated. Within all measures, positive symptoms were not correlated with negative symptoms, but disorganized symptoms overlapped with both positive and negative symptoms. Functioning was significantly related to negative and disorganized, but not positive, symptoms in both samples on most measures. Findings suggest strong overlap in symptom severity ratings among the most common scales. In recent-onset samples, each has strengths and weaknesses. In CHR samples, they appear to add little information above and beyond the SOPS.Psychiatry Research 08/2014; · 2.68 Impact Factor
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ABSTRACT: Transition to psychotic disorder has been the traditional outcome of interest for research in the at-risk mental state (ARMS). However, there is growing recognition that individuals with ARMS may function poorly regardless of whether they develop psychosis. We aimed to review the literature to determine whether there are specific factors associated with, or predictive of, functional impairment in the ARMS population.Schizophrenia Research 09/2014; · 4.43 Impact Factor
The Course of Neurocognition and Social Functioning in Individuals at Ultra High
Risk for Psychosis
Tara A. Niendam1,2, Carrie E. Bearden3, Jamie Zinberg2,
Jennifer K. Johnson4, Mary O’Brien3, and
Tyrone D. Cannon2,3
1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563;
California, Los Angeles, Box 956968, Los Angeles, CA 90095-6968;
4Department of Psychiatry, Stanford University School of
Medicine, 701A Welch Road, Suite 3325, Stanford, CA 94304
Objective: This study evaluates longitudinal neuropsy-
chological performance and its association with clinical
symptomatology and psychosocial outcome in individuals
identified asultra high risk (UHR) forpsychosis. Methods:
Thirty-five UHR individuals completed neurocognitive,
clinical, and social/role functioning assessments at baseline
and, on average, 8.3 months later. Results: UHR subjects
showed significant cognitive deficits at baseline and 2 dis-
tinct profiles of cognitive change over time. On average,
ing over the follow-up period, while the other half showed
either stability or decline in functioning. Functional im-
provement was associated with improved processing speed
and visual memory, as well as improvement in clinical
symptoms over the follow-up period. In contrast, patients
who did not improve functionally showed stable clinical
symptoms and cognitive performance over time. Conclu-
sions: Although the degree of neurocognitive deficit at
baseline in UHR patients does not predict psychosocial
outcome, the course of neurocognitive change over the first
8 months of follow-up does differentiate patients with good
and poor functional outcomes.
Key words: prodrome/cognition/high risk/social
The prodromal phase of schizophrenia is hypothesized to
deterioration coincident with emergence of subthreshold
psychotic symptoms. While most individuals with schizo-
phrenia experience onset during late adolescence and
early adulthood, deficits in cognition are evident years
before the development of psychotic symptoms, during
childhood and adolescence.1–5These cognitive deficits
are hypothesized to accelerate during the prodromal pe-
riod in association with changes in brain functioning that
may lead to the development of psychotic symptoms6,7as
well as functional decline in a variety of domains.8
Recent studies have shown that individuals thought
to be at ultra high risk (UHR) for developing psychosis
demonstrate neuropsychological deficits that are associ-
ated with poor social and role functioning. Dysfunction
in multiple cognitive domains has been reported in inves-
tigations of UHR samples,8–18with the most pronounced
deficits observed on measures of visual attention and
working memory, processing speed, verbal learning and
memory, and executive functioning, including measures
of verbal fluency and set shifting. In addition, we recently
are predictive of current social functioning in UHR
individuals, irrespective of negative or positive symptom
severity.18UHR individuals do not show the level of
cognitive impairment reported in studies of patients with
first-episode9,10,13,15or chronic schizophrenia,15and such
differences in cognitive performance between UHR and
processes in the period prior to psychosis onset. However,
very little empirical evidence is available to address this
question,19and it remains unclear whether any deteriora-
tion that does occur is specific to the prodromal period.
While these studies of UHR individuals confirm that
neuropsychological deficits and functional impairment
are detectable before the onset of psychosis, such inves-
tigations do not account for the clinical heterogeneity
that exists within UHR populations. As described by
Yung and colleagues,20UHR populations are a mixture
of 3 subgroups: at-risk individuals who will subsequently
do not transition to psychosis because of resiliency, treat-
ment, or protective factors (false false positives); and
those individuals whose at-risk state actually represents
a vulnerability for another type of psychological disorder
As a result of this inherent clinical heterogeneity,
UHR studies have begun to examine change in clinical
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Schizophrenia Bulletin vol. 33 no. 3 pp. 772–781, 2007
Advance Access publication on April 9, 2007
? The Author 2007. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
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symptoms and cognitive performance over follow-up
periods with the hope of identifying those individuals
at highest risk for subsequent conversion to psychosis.
While a few studies have highlighted a pattern of greater
baselinecognitiveimpairment thatis associatedwithsub-
sequent conversion,8,9,16no study to date has examined
the effects of cognitive and clinical change on psychoso-
cial functioning in UHR individuals.
with the previously delineated UHR subgroups by inves-
tigating the interrelated patterns of change in cognition,
clinical symptoms, and functioning that may occur for
UHR individuals over the critical period following ascer-
tainment. Specifically, we chose to focus on predictors of
sion to psychosis, in order to understand factors asso-
ciated with impairment in social and role functioning
at follow-up independent of final diagnostic outcome.
Based on previous findings in UHR8–18and first-episode
samples,21we predicted that a subgroup of UHR individ-
uals would show baseline cognitive deficits and that such
deficits would be associated with severity of negative
symptoms as well as poorer role and social functioning,
independent of positive symptom severity, at follow-up.
Furthermore, we hypothesized that this subset of UHR
individuals would show deterioration in cognitive per-
formance over the follow-up period and that such decline
would be associated with the deterioration in clinical
and functional status thought to predate the onset of
Participants in this study are part of a larger longitudinal
prospective study of adolescents and young adults en-
rolled in research at the Center for the Assessment and
Prevention of Prodromal States (CAPPS) at the Univer-
sity of California, Los Angeles (UCLA). Eligible individ-
application of the assessment instruments. Participants
also must meet criteria for 1 of the 3 prodromal syn-
dromes, as assessed by the Structured Interview for Pro-
dromal Syndromes (SIPS22), based on presence of (1)
attenuated psychotic symptoms (Attenuated Positive
Symptom Syndrome); (2) transient psychotic symptoms
(Brief Intermittent Psychotic Syndrome, BIPS); or (3)
a substantial drop in social/role functioning in conjunc-
tion with schizotypal personality disorder diagnosis or
presence of psychotic disorder in first-degree relative
(Genetic Risk & Deterioration Syndrome). For cases
in which the frequency of psychotic symptoms was diffi-
cult to determine, such individuals were included within
the BIPS category if their psychotic symptoms began
within the past 3 months and they did not meet criteria
for a schizophrenia-spectrum diagnosis.
At baseline, adolescents aged 15 and older also com-
pleted the Structured Clinical Interview for Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edi-
tion (DSM-IV) Axis I Disorders23while participants 14
years and younger were administered the Kiddie Sched-
ule for Affective Disorders and Schizophrenia24,25. Par-
ticipants were excluded from the study if they met
DSM-IV criteria for an Axis I schizophrenia-spectrum
diagnosis, such as schizophrenia, schizoaffective disor-
der, schizophreniform disorder, or delusional disorder.26
Additional exclusion criteria include the presence of
a neurological disorder, DSM-IV diagnosis of drug or al-
viduals with a Wechsler Abbreviated Scale of Intelligence
IQ was determined by a complete WISC-III28/WAIS-
previous assessment by a qualified professional. Detailed
information regarding SIPS prodromal criteria, interrat-
er reliability, and case consensus procedures have been
described in detail elsewhere.30
The participantscompletedinformed consentor assent
for the intake screening and were compensated for their
participation in all assessments. Parental informed con-
sent for minors was also obtained. Study protocol and
informed consent procedures were approved by the
UCLA Institutional Review Board.
Demographic data for UHR individuals included in
these analyses (n = 35) are shown in Table 1. Eighty per-
cent of study participants received psychotropic medica-
tion as part of their usual care at baseline, and 89% were
taking at least 1 medication at follow-up. These medica-
and SSRI antidepressants (34%, 40%). Over the follow-
up period, participants also received a variety of psycho-
social treatments that were provided in an unstructured
format by both CAPPS and community treatment
providers. These treatments included individual psycho-
therapy (83%), family therapy (34%), group therapy
(37%), and school-based therapy or counseling (57%).
Seventy-four percent of the participants received 2 or
more forms of psychotherapy (eg, individual therapy
plus group therapy) over the follow-up period. Ninety-
seven percent of the participants also received case man-
agement services from a CAPPS staff member.
In the SIPS interview,22,31symptoms are rated on 4 main
scales of the Scale of Prodromal Symptoms (SOPS): pos-
itive, negative, disorganized, and general symptoms. To
reduce the number of statistical comparisons, our hy-
potheses in the current investigation focus on the positive
Course of Neurocognition & Functioning in Prodrome
and negative symptom scales. The SOPS Positive Symp-
tom Scale assesses symptoms related to unusual thought
content, suspiciousness, perceptual disturbances/halluci-
nations, grandiosity, and disorganized communication.
Symptoms of anhedonia, avolition, flat affect, decreased
role functioning, and decreased verbal comprehension/
for use with the SIPS31,32,is also administered at intake.
At the time of the baseline interview, social and role
functioning were assessed with the Global Functioning:
Social Scale (GF:Social33), the Global Functioning: Role
Table 1. Demographics and Clinical Characteristics of Participants
Characteristic Participants (n = 35)
Age at examination, mean (6SD), [range] 17.26 (4.32), [12.5–29.00]
Average time (y) to follow-up, mean (6SD), [range] 0.68 (0.21), [0.34–1.33]
Years of education, mean (6SD), [range]
Estimated WASI IQ, mean (6SD), [range]
10.23 (2.97), [6–17]
105.49 (16.29), [73–135]
Gender, n (%)
Race, n (%)
Handedness, n (%)
Primary SIPS-defined prodromal status, n (%)
Brief Intermittent Psychotic Syndrome
Attenuated Positive Symptom Syndrome
Genetic Risk & Deterioration Syndrome
Diagnosis of schizotypal personality disorder, n (%) 3 (9)
First-degree family history of psychotic disorder, n (%) 8 (23)
Clinical characteristics of sample
GAF score, mean (6SD), [range]
42.43 (11.66), [17–70]
53.57 (11.68), [20–80]
SOPS Positive Symptom Total, mean (6SD), [range]
13.06 (4.37), [3–22]
9.06 (4.38), [1–18]
SOPS Negative Symptom Total, mean (6SD), [range]
13.66 (6.99), [2–30]
11.29 (8.12), [0–32]
Strauss-Carpenter Total Score, mean (6SD), [range]
8.57 (2.43), [4–12]
9.63 (2.77), [0–12]
Social Attainment Survey Total Score, mean (6SD), [range]
16.26 (5.14), [7–29]
19.14 (7.60), [7–33]
Global Functioning: Role Scale score, mean (6SD), [range]
5.00 (1.83), [1–8]
5.80 (1.88), [2–9]
Global Functioning: Social Scale score, mean (6SD), [range]
5.60 (1.68), [2–8]
6.09 (1.58), [2–9]
Note: WASI, Wechsler Abbreviated Scale of Intelligence; SIPS, Structured Interview for Prodromal Syndromes; GAF, Global
Assessment of Functioning; SOPS, Scale of Prodromal Symptoms.
T. A. Niendam et al.
Scale (GF:Role34), the Strauss-Carpenter Outcome Scale
(SCOS35), and the UCLA Social Attainment Survey
(SAS36). The GF:Social and GF:Role scales provide
ratings of functioning in both social and role domains
on 2 separate 10-point Likert scales, which are scored in-
dependently of symptom severity. The GF:Social and
GF:Role scales are 2 new measures (see Cornblatt et al
, this issue) that are designed to provide a global
measure of psychosocial functioning in younger popula-
tions. The SCOS contains three 4-point items assessing
duration and frequency of hospitalizations, social con-
tacts with individuals outside of the family, and useful
seven 5-point items evaluating peer and romantic rela-
tionships and participation in activities and organiza-
tions. Scores for each item on the SCOS and SAS were
summed into 1 total score for each measure. Ratings
for all scales described were based on the past month.
A comprehensive neuropsychological examination
assessing multiple domains of cognitive functioning
(Table 2) was also administered at baseline and follow-
up by supervised clinical psychology doctoral students or
forms for specific cognitive measures, when statistically
comparable versions were available, and raw scores
were converted to age-matched scaled scores before
z score transformation was completed using published
normative data. In order to reduce the number of statis-
tical comparisons, the measures were combined into 5
dimensions of cognitive functioning (processing speed,
reasoning and problem solving, visual learning and mem-
ory, verbal working memory, and verbal learning and
memory) that have been identified as domains of impair-
sure assessing the domain of motor speed was included in
The demographic variables of age, gender, handedness,
and parental education were examined to determine
if these variables showed a significant relationship to
WASI IQ at baseline. Preliminary analyses revealed that
based on gender [40% female; F(1, 34) = 0.32, P = .58],
handedness [89% right-handed; F(1, 34) = 0.89, P = .35]
or parental education [58% college educated; F(6,
32) = 2.24,P=.07].Participants’agewasnotsignificantly
To analyze the nature and severity of cognitive deficits
at baseline and follow-up, UHR participants’ average
performance within the 6 cognitive domains (speed
of processing, working memory, verbal learning and
memory, visual learning and memory, reasoning and
problem solving, and motor speed) was analyzed using
one-sample t tests, contrasting the observed score at
each time point with the normative mean of 0. Change
in participants’ performance on the 6 cognitive domains
from baseline to follow-up was analyzed in a paired-sam-
ples t test.
Independent-samples t tests were used to analyze dif-
ferences in the baseline cognitive performance of individ-
uals who demonstrated improvement in functioning by
Table 2. Neuropsychological Measures and Published Normative Data
Cognitive Domain Test Used Norms Used in z Score Transformation
Processing speedTrail-Making Test A and B63
Trail-Making Test: ages 12–1464; ages 15–39
(Tombaugh, Rees, & McIntyre 1996
as cited in Spreen & Srauss65)
Digit Symbol Coding: ages 12–15, WISC-III27;
ages 16þ, WAIS-III28
FAS Verbal Fluency: ages 12–1366; ages 15–4067
Ages 16 and over only: WMS-III68
WISC-III/WAIS-III Digit Symbol Coding
FAS subtest of the Verbal Fluency Test
Reasoning and problem solving WASI Matrix Reasoning
Visual learning and memoryWMS-III Visual Reproduction Immediate
and Delayed Recall
Verbal working memoryWISC-III/WAIS-III Digit Span Backward WISC-III27; WAIS-III28
Ages 12–15: CVLT-C69; ages 16þ: CVLT-II70
Ages 12–15: CMS71; ages 16þ: WMS-III68
Verbal learning and memoryCVLT-II/CVLT-C 1–5 Total
CMS Stories/WMS-III Logical Memory
Immediate and Delayed Recall
Motor speedFinger Tapping Test, Average of dominant
and nondominant hand scores
Ages 12–1563; Ages 15–3972
Note: WISC-III, Wechsler Intelligence Scale for Children-III; WAIS-III, Wechsler Adult Intelligence Scale-III; WASI, Wechsler
Abbreviated Scale of Intelligence; CVLT-II, California Verbal Learning Test-II; CVLT-C, California Verbal Learning
Test—Children’s Edition Trials; CMS, Children’s Memory Scale; WMS-III, Wechsler Memory Scale-III.
Course of Neurocognition & Functioning in Prodrome
or declined in functioning. In concordance with the stan-
dard level of change consideredto be clinically significant
in clinical trials, improvement in functioning was defined
score on the SCOS, SAS, GF:Social, or GF:Role func-
tioning scales. Group differences in performance on
the 6 cognitive domains and SOPS Positive and Neg-
ative Symptom Total scores at baseline were examined
using independent t tests for each of the functioning
To address the relationship between change in cogni-
tive performance and change in functioning over the
follow-up period, independent-samples t tests were
used to examine differences in the profile of cognitive
change scores for individuals who demonstrated 20%
improvement in functioning by follow-up when com-
ate cognitive change scores, UHR participants’ baseline
performance on each of the 6 cognitive domains was sub-
tracted from their follow-up performance, so that a pos-
itive change score reflected improvement in cognitive
functioning for that domain. Similarly, change in so-
cial/role functioning was determined by subtracting the
baseline total score from the follow-up total score on
each of the 4 functioning measures, so that a positive
functioning change score reflected improvement in social
or role functioning. In contrast, change scores for SOPS
ing follow-up presentation from baseline severity, such
that a positive symptom change score reflected a decrease
in symptom severity. Post hoc analyses addressed poten-
tial confoundingvariables, such as the potential effects of
personality disorder, use of antipsychotic medications,
and participation in psychosocial treatment.
All analyses were univariate and 2-tailed with alpha set
at P ? .05 to allow for recognition of smaller effects due
to small sample size and possible power limitations. This
exploratory approach sought to generate hypotheses for
future studies and encourage additional work in this area
ipants’ baseline performance revealed significant deficits
in speed of processing [t = ?3.59(33), P = .001] and motor
speed [t-= ?3.27(33), P = .003], with a trend toward
impaired verbal learning and memory [t-= ?1.82(31),
P = .08]. As shown in Figure 1, participants showed sig-
nificant improvement, on average, over the follow-up pe-
riod in the domains of processing speed [t = ?3.56(33),
P = .001], verbal learning and memory [t-= ?4.11(30),
P-< .001], visual learning and memory [t-= ?2.52(19),
P-= .02], and motor speed [t-= ?2.39(32), P = .02]. Par-
ticipants did not show significant change in performance
on measures of verbal working memory [t-= ?1.13(34),
P = .27] or reasoning and problem solving [t-= ?1.42(34),
P = .17].
On average, 50% of UHR individuals evidenced im-
provement in social and/or role functioning over the fol-
low-up period, with 37%–43% showing a 20% or greater
increase from their baseline functioning scores. Low to
moderate associations were observed between the base-
line and follow-up scores on each of the 4 functioning
measures (SAS r-= 0.63, P ? .001; SCOS r-= 0.25,
P = .15; GF:Social r- = 0.49, P = .003; GF:Role
r- = 0.51, P = .002), providing further evidence for
ing over time.
There were no significant relationships between base-
line cognitive functioning and level of clinical symptoms
or social/role functioning at follow-up. However, the rates
of improvement in symptoms and cognitive functioning
Profile of Change in Cognitive Functioning over Follow-up Period
Speed of Processing
Reasoning & Problem Solving
Visual Learning & Memory
Verbal Working Memory
Verbal Learning & Memory
Mean Change in Z-score ± SEM
Fig. 1. Change in Patients’ Mean Performance (z score 6 SEM) on 6 Cognitive Domains Between Baseline and Follow-up.
T. A. Niendam et al.
differentiated those UHR individuals who improved
functionally from those who did not. As shown in Figure
2, a 20% or greater improvement in baseline GF:Social
functioning was associated with significant improvement
in processing speed [t-= ?2.26(32), P = .03] and Visual
Learning and Memory [t-= ?2.56(18), P = 0.02] as indi-
viduals who improved in social functioning also showed
improved processing speed [change mean z score (SD) =
0.73 (0.53)] and visual learning and memory [change
mean z score (SD) = 1.22 (1.07)] over the follow-up pe-
riod when compared with those individuals who did
not show improvement on the GF:Social [processing
speed change mean z score (SD) = 0.20 (0.77); visual
learning change mean z score (SD) = 0.21 (0.68)]. Addi-
tionally, a 20% or greater improvement in SAS Total
Score was associated with differential change in SOPS
Positive Symptom Score [t-= 2.43(32), P = .02] because
individuals who improved on the SAS showed a larger
decrease in positive symptomatology [positive symptom
change mean z score (SD) = 6.62 (4.03)] than those indi-
viduals who did not show improvement in social func-
tioning according to the SAS [positive symptom
change mean z score (SD) = 2.76 (4.75)].
Finally, a 20% or greater improvement in role func-
tioning, according to SCOS total score, was significantly
associated with change in the SOPS Negative Symptom
Total Score [t-= 3.26(24.56), P = .003] and SOPS Positive
Symptom Total Score [t-= 2.24(32), P = .03] because
those individuals who showed functional improvement
also showed a larger decline in negative [negative symp-
tom change mean z score (SD) = 6.07 (2.81)] and positive
symptoms [positive symptom change mean z score
(SD) = 5.93 (3.39)] when compared with those who did
not improve on the SCOS [negative symptom change
mean z score (SD) = ?0.40 (8.24); positive symptom
change mean z score (SD) = 2.55 (5.49)].
Post hoc analyses of possible confounding factors
illness, diagnosis of schizotypal personality disorder, or
use of antipsychotic medication on cognition, clinical
tion or social/role functioning, participation in 2 or more
forms of psychosocial treatment during the follow-up
period was significantly associated with a 20% decline in
SOPS positive symptoms (v2= 6.41, P = .04).
This study confirms the presence of baseline neuropsy-
chological deficits in individuals at UHR for psychosis
and provides the first evidence of longitudinal associa-
tions between neuropsychological functioning, clinical
symptomatology, and social/role functioning in this
population. At baseline, UHR individuals demonstrated
a pattern of deficit in measures of speeded information
processing, with a trend toward impaired verbal learning
and memory. This profile is similar to that observed in
Profile of Cognitive Change by GF:Social Functioning Improvement
Speed of processing
Mean Change in Z-score ± SEM
(n = 20)
(n = 15)
Reasoning & Problem Solving
Visual Learning & MemoryVerbal Working Memory
Verbal Learning & MemoryMotor Speed
Fig. 2. Profiles of Change in Patients’ Mean Cognitive Performance (z score 6 SEM) associated with 20% Improvement on the Global
Functioning: Social scale.
Course of Neurocognition & Functioning in Prodrome
other UHR samples8–18as well as individuals with estab-
that individuals showing emerging clinical signs of illness
are on a continuum with fully psychotic individuals.
Additionally, this investigation is one of the first to
demonstrate that a subset of UHR individuals show a
pattern of improvement in multiple cognitive domains,
specifically processing speed, verbal and visual learning
and memory, and motor speed at follow-up approxi-
mately 8 months later. Although there is some evidence
for short-term improvement in some cognitive domains
in first-episode schizophrenia as a result of pharmacolog-
ical interventions,43,44the overall degree of cognitive
impairment appears relatively stable across the lifetime
course of the illness.45–48The current findings suggest
that the pattern of cognitive deficits observed at baseline
in a subset of putatively prodromal individuals may re-
flect difficulties associated with generalized psychiatric
distress, as opposed to a stable, underlying trait specifi-
cally associated with risk for psychosis. Therefore, some
UHR individuals share certain phenotypic features with
those who progress to psychosis, but possibly for differ-
ent underlying reasons.
Additionally, results of the current study revealed that
UHR individuals’ functional improvement at follow-up
was not predicted by their cognitive performance at base-
line, but functional improvement was associated with im-
provement in both cognition and clinical symptoms over
the follow-up period. In other words, those individuals
who showed improvement in social or role functioning
over the follow-up period also had improved cognitive
performance and decreased symptoms over time. Specif-
ically, improvement in social functioning was associated
with significant improvement in both processing speed
and visual learning and memory at follow-up. Given
that UHR participants in this sample show significant
cognitive improvement in many domains, these findings
reveal that it may be this pattern of change in cognition
over the follow-up period, rather than severity of cogni-
tive deficits at baseline, that is related to improvement in
functioning over time.
Furthermore, results showed that improvement in so-
cial functioning was associated with a larger decrease in
positive symptoms over the follow-up period, suggesting
that acute symptomatology may play a stronger role in
social functioning in UHR patients than is observed
ment in role functioning was associated with a larger
to the notion that negative symptoms have a notable
impact on role functioning in UHR individuals.
Several possible alternative explanations for the pat-
tern of cognitive improvement observed in this study
bear consideration. In particular, practice effects49and
the effects of interventions may arguably play a role. Re-
search shows improved functional outcome with earlier
intervention in the treatment of psychotic disorders,50–52
andmany ofthe studyparticipants receivedsomeform of
psychiatric or psychological treatment during the course
of the study. Such treatment is ethically necessary due to
the participants’ level of distress and functional impair-
ment, but these interventions likely affect the natural
course of the disorderand contributeto clinical and func-
tional improvement. In the current study, participants
who received 2 or more types of psychotherapy over
the follow-up period were significantly more likely to
show a 20% decrease in positive symptoms, suggesting
that psychosocialinterventions mayhave astrong impact
on clinical distress in this at-risk population. However,
such treatment was not associated with changes in cog-
nitive or psychosocial functioning. Unfortunately, sam-
ple size and the high percentage of study participants
receiving treatment prohibited comparison of individuals
receiving vs those who declined treatment and be-
tween individuals receiving different forms of treatment.
Nevertheless, longitudinal analyses of patients with
schizophrenia typically show a pattern of stable cognitive
functioning across the lifespan course of illness, despite
improvement in psychotic symptom severity in response
to psychosocial treatment,53,54which is in contrast to
the pattern of cognitive, clinical, and functional im-
provement observed here. In order to address these issues
definitively, future studies will need to use matched non-
UHR samples to control for practice effects, as well as
UHR individuals receiving alternative types of treatment
to examine the effects of psychotherapy and medication
on cognition and social/role functioning.
of improvement were driven by the subset of ‘‘false posi-
tives’’ within this sample, additional analyses revealed
disorder diagnoses (‘‘true positives,’’ n = 9, 25% of the
sample) showed the same patterns of baseline cognitive
symptoms, and functioning when compared with those
in first-episode treatment studies using novel atypical
antipsychotic compounds,43,44these results suggest that
early intervention may attenuate the effects of psychosis
on cognition and contribute to better outcome, even for
those who subsequently develop a psychotic disorder.
Many researchers have highlighted the potential of
pattern of cognitive improvement observed in this study
encourages critical examination of the potential utility
of baseline cognitive deficits as definitive markers for
heightened risk for psychotic illness in a clinical high-
risk sample. The observation of improvement in multiple
T. A. Niendam et al.
cognitive domains in association with clinical and func-
tional improvement suggests that baseline cognitive defi-
cits in a subgroup of UHR individuals may represent
a state-specific factor, associated with diffuse psychologi-
Alternatively, the pattern of deficits observed here could
represent an interaction between psychological state at
These competing explanations warrant further investiga-
tion in future studies.
A previous analysis30of DSM-IV diagnoses in this
sample revealed that many of the UHR participants
met criteria for a mood or anxiety disorder diagnosis
at ascertainment, diagnoses which other studies61–63
have found to be associated with cognitive impairment
in the domains observed here. Given that UHR popula-
tions are a mixture of true and false positives, the cogni-
tive deficits observed in UHR samples at ascertainment
may represent the manifestation of impairment associ-
ated with generalized risk for a variety of psychological
disorders rather than a vulnerability that is specific to
psychosis. Therefore, the results of this study suggest
that the pattern of change in cognition and functioning
over time may provide a more accurate means of separat-
ing the false positives, who show improvement in state-
related deficits over time, from the true positives, who
show more stable trait-like deficits representing endophe-
notypic markers of underlying risk.
Therefore, these findings provide novel evidence sug-
decline. To the contrary, the demonstration of improve-
ment in multiple cognitive domains highlights the power
ulation. Overall, the results of this study suggest that
UHR individuals should be examined over time because
stability that may differentiate those individuals who are
at highest risk for further psychological deterioration.
While this study offers support for early identification
as a means of improving functional outcome, results
should be interpreted with caution due to the small sam-
ple size. These findings provide the first glimpse into rela-
tionships between cognition, symptoms, and functioning
over time and are presented to generate hypotheses and
be noted that the lack of statistical power may have re-
Additionally, small sample size precluded the inves-
tigation of the different patterns of association between
cognitive, clinical, and social/role functioning measures
presented in the current study. Further analyses should
be pursued in larger samples to validate these findings,
examine specificity of deficits observed here, and uncover
additional relationships that may have been obscured in
the current analysis.
As noted previously, this current study is limited by its
lack of a normal comparison group and resulting use of
published normative data for comparison to this clinical
sample. However, such published normal samples were
developed and published in order to provide adequate
comparisons for clinical data. Given the difficulty in
obtaining well-matched adolescent control samples, re-
searchers commonly utilize such published norms.15
Nonetheless, comparison to a demographically matched
control sample, assessed at similar time points, would
strengthen the current findings and should be a priority
for future studies. As a related issue, this investigation
tests of the domains of cognition sampled, and it is pos-
sible that deficits in other domains, such as working
memory, would have been observed had we employed
experimental paradigms designed to isolate particular
aspects of these functions.
Finally, it is important to note that some proportion of
individuals within this sample will not progress to de-
velop a diagnosable psychotic disorder, and these indi-
viduals would consequently be labeled false positives.
As noted previously, the inclusion of such false positives
in the group analyses may obscure the presence of signif-
icant cognitive deficits in some of the hypothesized
domains, and the relationship between such deficits
and functional outcome, that may be present if only
true positives were examined. Although additional anal-
yses suggested that the pattern of improvement was also
characteristic of a small sample of true positives, longi-
tudinal follow-up in larger samples is needed to deter-
mine the pattern of neurocognitive, symptomatic, and
functional change most predictive of conversion to a
full-blown psychotic disorder and to elucidate the com-
plex relationship between such cognitive change, clinical
severity, and functional outcome over time.
This research was supported by the following grants:
NIMH MH65079, NIMH P50 MH066286, NIMH
MH14584 (Ruth L. Kirschstein National Research
Service Award Postdoctoral Fellowship to Niendam),
National Alliance for Research on Schizophrenia and
Depression Young Investigator Award (Maxine and
Jack Zarrow Investigator Award to Bearden), National
Science Foundation Graduate Fellowship, as well as
donations from the Rutherford Charitable Foundation
and Staglin Music Festival for Mental Health. The
authors would like to thank the following individuals
for their contributions to this project: Cindy Akin,
Peter Bachman, PhD, Tammy Beran, MA, Nicole
P. Connolly, MA, Melita Daley, MD, Lauren Ellman,
MA, Alison Greiner, LCSW, Jacqueline Horwitz, MA,
Course of Neurocognition & Functioning in Prodrome
Christopher Jetton, Tyler Lesh, MA, Rachel Loewy,
PhD, Sabrina Lux, Kristopher Mathis, Stephanie Meyer,
PhD, Caroline Miranda, LCSW, Keith Nuechterlein,
PhD, Leigh Sepeta, MA, David Shirinyan, MA, and
Natasha Thapar, MA.
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