Encoding and Retrieval
Processes in Declarative Memory Project At
the inception of the Memory Project, questions remained regarding
the development, nature (e.g., encoding, retrieval),
and neural underpinnings of the declarative memory deficit in
schizophrenia. Based on neuropsychological studies, there was
a general consensus that neurocognitive deficits do not progress
over time after illness onset, but little was known with regard
to putative deficits prior to the onset of illness. Our initial
studies focused on clinical and neuropsychogocal measures in
the prodrome and their continuity with first-episode schizophrenia
(Niendam et al. 2006; Willhite et al. 2008). We also started
to examine similar questions in the domain of working memory
(Karlsgodt et al. 2008; Karlsgodt et al. submitted). Within the
Center, we were able to translate the basic science remember-know
paradigm to evaluate the development, nature (e.g., encoding,
retrieval), and neural underpinnings of the declarative memory
deficit in schizophrenia. We published a study validating the
paradigm behaviorally in a chronic schizophrenia sample, and
are the first to interpret the schizophrenia memory deficit based
on the two most prominent basic science memory models to date
(Van Erp et al. 2008). The Center also allowed us to evaluate
at-risk for psychosis (prodromal) and first-episode schizophrenia
samples on this paradigm with fMRI. Collectively, these studies
reveal a progressive deficit in recollection across the phases
of illness. fMRI data indicate that both the first-episode and
prodromal samples show aberrant neural activation in the declarative
memory network during encoding and recognition (Van Erp et al.
submitted; Van Erp et al. submitted).
Attention and Dual-Task Interference
Project This project
has employed paradigms in which people are asked to complete
two tasks that overlap in time to isolate temporal relationships
among elementary cognitive processes that are impaired versus
intact in schizophrenia, particularly as they are related to
central executive processes. The project has translated to schizophrenia
research a series of dual-task interference paradigms from cognitive
psychology that (1) have particular promise to differentiate
between two distinctive models of attentional functioning and
(2) offer opportunities to isolate which elementary cognitive
processes are sources of attentional limitation because they
cannot be completed simultaneously (Nuechterlein et al, 2006).
Four studies have been carried out to examine alternative loci
for processing bottlenecks during divided attention in prodromal,
first episode, and chronic schizophrenia patients. Reaction time
studies detect a pause in Task 2 while central decision and response
selection is completed in Task 1. Briefly, the findings from
this Project indicate that a structural processing bottleneck
model accounts for divided attention in these paradigms in schizophrenia
better than a processing resource model. The divided attention
deficits in schizophrenia are evident in greater than normal
temporal interference when tasks overlap substantially. Exaggerated
structural processing bottlenecks are evident for response selection
and motor processes in schizophrenia, but perceptual encoding
seems to be completed in parallel without interference in schizophrenia
as it is in normal subjects (Nuechterlein et al, submitted; Nuechterlein
et al, in prep). A new paradigm to examine processing bottlenecks
in motivated, hedonic decision-making situations has also been
developed (Pashler et al, 2008).
Social Cognition Project The primary goal of this project
has been to examine specific components of social cognition across
phases of illness using performance-based measures. The areas
of social cognition included emotion processing, relationship
perception, and theory of mind, which are considered to be cognitive
constituents of social interactions. As no measure of relationship
perception was suitable for use in schizophrenia, we developed
one de novo. We currently have three papers in press from this
project (Kee et al 2003. for emotion processing, Sergi et al
in press. for relationship perception, and Kern et al in press
for theory of mind). These papers explore group differences,
clinical correlates, and relationships to functioning in the
chronic patients and their matched controls. All of the measures
were successful at group separation and show reasonable correlations
with functioning. Other analyses from the project are in preparation.
For the first episode patients, we found strong relationships
between social cognition and functioning at 12 months that were
larger than the cross-sectional relationships at baseline, perhaps
because the baseline functioning was more influenced by the initial
episode. Across phases of illness, there are consistent differences
between the clinical groups and their matched controls. Each
social cognitive test was sensitive to group differences (ranges
of.43 - .1.13 SDs) and there is no evidence of progression of
the size of the deficit across phase of illness.
Stress and Emotional Reactivity
Project
Emotional and motivational dysfunction is fundamental to
schizophrenia, and yet the precise nature and scope of the
associated deficits are not well understood. One of the primary
aims of this project was to assess the integrity of emotional
responding from the perspective of its underlying motivational
systems in patients with schizophrenia. Specifically, evaluative,
somatic, and autonomic responses were measured during viewing
of pictures with varied emotional content to examine core
motivational states during the prodromal, first-episode and
chronic phases of schizophrenia. Regardless of phase of illness,
patients showed a robust and normal pattern of affective
modulation across response systems, suggesting that identified
deficits in emotion and motivation likely involve higher
order processes (Yee et al., submitted). In addition, Sun
et al.
(submitted) determined that heart
rate variability (HRV), a measure of parasympathetic activity,
moderates the relationship between social cognition and role
functioning in chronic schizophrenia patients. Among those
with poor HRV, it appears that because these patients may
be less behaviorally and physiologically flexible, strong
social cognitive skills are more critical for performing
well at
work, living independently and engaging in self care. For
patients who show greater cardiovascular adaptability, better
functional outcome may be less contingent upon social cognitive
skills, as these
individuals may be more capable of taking advantage of other
resources. Papers are in preparation to report on group differences
in stress reactivity as a function of clinical state and
phase of illness, as reflected by resting levels of cortisol
and heart rate activity, as well as on key variables that
serve to moderate the stress response, including social support,
coping skills, life events and early life adversity.
Brief
Summary of Findings from Clinical Cores
Prodromal Research Program At
the inception of the Prodromal Research Program, very little
was known about the psychosis prodrome.
The initial set of publications from the Prodromal Resarch Program
focused on phenomenological aspects of the psychosis prodrome
(Meyer et al. 2005; Niendam et al. 2007), and continuity with
first episode schizophrenia in terms of symptomatology (Willhite
et al. 2008) and cognition (Niendam et al. 2006). In collaboration
with other researchers in this field, we developed a new measure
of social and role functioning that is better suited for use
in adolescent populations (Cornblatt et al. 2007). Recently,
we have taken advantage of our prospectively collected longitudinal
data to examine neurobiological (Karlsgodt et al. 2008; Sabb
et al., submitted; Sanz et al., submitted), cognitive (Niendam
et al. 2007) and clinical (Niendam et al., submitted) predictors
of functional outcome and conversion to psychosis in this at-risk
population. A parallel set of studies has focused on family factors
that predict outcome in at-risk youth (OBrien et al., 2007; OBrien
et al., under review).
Aftercare Research Program We examined the impact of medication
nonadherence on return of positive symptoms among the first-episode
schizophrenia patients in the Aftercare Research Program (Subotnik
et al. 2008). More frequent adherence assessments and better
operational criteria for nonadherence were utilized than those
found in most prior studies. Although we expected that medication
nonadherence would predict a return of psychotic symptoms, it
was noteworthy that even relatively brief periods of partial
antipsychotic nonadherence predicted psychotic symptom return
(risk ratio = 4.2). We also found that two types of formal thought
disorder (i.e., bizarre-idiosyncratic and concrete thinking)
were related to impairments in verbal learning, intrusions in
verbal memory, immediate auditory memory, sustained attention,
and social schema knowledge. The pattern of findings is consistent
with the view that neurocognitive and social cognitive deficits
underlie these two aspects of formal thinking disturbance in
schizophrenia. We also created and published an operational system
for identifying relapse, exacerbation, and remission of schizophrenia
for use within longitudinal studies that involve repeated symptom
assessments (Nuechterlein et al. 2006). A computer program is
available to facilitate its use. Use of these explicit definitions
of episodes may help to clarify relationships between episodic
outcome and other fundamental domains of illness outcome, particularly
other symptom dimensions, work functioning, and social functioning.
Chronic Schizophrenia Core It is unclear whether insight into
having a mental disorder deteriorates or improves over the course
of schizophrenia. We compared levels of insight between the first-episode
and chronic patients, and within a small subset of patients who
also had insight data available at two earlier time points from
participation in previous longitudinal studies (Subotnik 2006).These
results indicate that that schizophrenia patients’ insight
improved over time, but that most of the improvement occurred
during the initial year of outpatient treatment. We then examined
the associations between insight and measures of dual-task processing,
episodic memory, social cognition, and emotion reactivity among
the patients in the first-episode core and the chronic schizophrenia
core (Subotnik 2007).Results suggest that the awareness of having
a mental disorder shares some characteristics with understanding
what other people are thinking and the reasons for their behaviors.
Impairment in memory and attention resulted in difficulty in
being aware of one’s own problems in these domains. The
improvement seen over time might explain the attenuated relationships
seen among the chronic schizophrenia patients.
Copyright
2006 Center for Neurocognition and Emotion in Schizophrenia all rights
reserved.
Brief
Summary of Findings from Center Projects
