West Los Angeles,
Negative symptoms significantly interfere with daily functioning among individuals with
schizophrenia. They are strongly related to functional impairments  and contribute to the
poor community outcomes of Veterans with schizophrenia. Motivational negative symptoms
interfere with obtaining and maintaining employment , forming social relationships and
living independently . Developing treatments to effectively reduce negative symptoms is
important to achieve improvements in daily functioning. Recent empirical studies report that
psychosocial interventions for negative symptoms can have a moderate to large effect size on
community functioning and negative symptom severity. However, the treatments that have been
utilized so far are either cognitive-behavioral therapy interventions that require over a
year of weekly individual sessions and thus are very resource- and time-intensive, or they
are skills-training groups that do not address any of the cognitive and motivational aspects
of negative symptoms. Although group treatments are increasingly hailed as the gold standard
for schizophrenia, there is currently no group intervention explicitly for motivational
negative symptoms and functional deficits. Furthermore, treatment development and clinical
trials are increasingly reliant on neurophysiological measures of clinical severity and
treatment response and so far there are not identified negative symptom biomarkers.
The current CDA proposal will test a group-based treatment based on established motivational
enhancement (MI) techniques, augmented with cognitive-behavioral approaches, compared to an
active control group treatment, for improving motivational negative symptoms in Veterans with
schizophrenia. I will assess the efficacy of MI with measures from two outcome domains: 1)
negative symptoms (clinical ratings) and 2) functional outcomes (real-world improvements in
social, instrumental, and independent living). I will assess the relationship between these
outcomes and neurophysiological biomarkers (pupillometry and electroencephalography (EEG)).
Participants will be randomly assigned to the MI treatment or a control treatment for weekly
1-hour sessions for 12 weeks. The assessment battery will be administered at baseline, at
completion of treatment, and at 6-month follow-up. The investigators will enroll 60 Veterans
with schizophrenia that are low functioning and have high negative symptoms across the 4
years of the study.
This proposal is designed to examine group-based MI for reducing negative symptoms and
improving functioning in key domains (i.e., interpersonal, instrumental, and independent
living skills). Moreover, it will thoroughly investigate biomarkers of negative symptoms with
pupillometry and EEG. The development and evaluation of this recovery- oriented group MI
treatment for Veterans with disabling negative symptoms will yield results that can inform
larger treatment trials and neurophysiological measurement of negative symptoms in Veterans
Despite significant advances in pharmacological treatments for schizophrenia (SCZ), the rate
of disability among Veterans diagnosed with SCZ remains high. Functional disability among
Veterans with SCZ creates a huge and costly burden on the national VA healthcare system, and
interferes with community integration and quality of life. In particular, SCZ is associated
with low rates of employment, few social relationships, and poor independent living skills.
The negative symptoms of SCZ (i.e. avolition, anhedonia, asociality) are primary determinants
of functional impairments, and they have no validated treatments. Extensive work has been
devoted to treating positive symptoms and cognitive deficits, but much less has been done to
develop pharmacological and psychosocial treatments for negative symptoms. Developing such
interventions is a critical public health goal, as it would benefit one of the largest groups
of disabled Veterans.
The recently-emerging recovery-oriented approach to serious mental illness reflects a
fundamental shift from a focus on symptom reduction to a focus on patients' goals and
community functioning. Developing treatments for negative symptoms to augment community
functioning is a strong reflection of this shift. Importantly, preliminary research suggests
that motivational negative symptoms respond to novel evidence-based psychosocial
interventions. The primary goal of this proposal is to adapt and implement a
recovery-oriented evidence-based intervention, Motivational Interviewing (MI), for the
treatment of motivational negative symptoms in Veterans with SCZ. MI, originally developed
for substance use disorders, is effective to increase commitment to new behaviors in a range
of areas including treatment adherence, exercise, gambling, and depression. Importantly, it
has been shown to be applicable to Veterans with psychosis, but it is not known if MI can
reduce functional deficits that are attributable to motivational negative symptoms.
More specifically, the scientific goals of this proposal are to: 1) evaluate the efficacy of
a group-based MI intervention on motivational negative symptoms for Veterans with SCZ, and 2)
to examine potential biomarkers of negative symptoms and treatment response. I will assess
the efficacy of MI with measures from two outcome domains: 1) negative symptoms (clinical
ratings) and 2) functional outcomes (real-world improvements in social, instrumental, and
independent living). I will assess the relationship between these outcomes and
neurophysiological biomarkers (pupillometry and electroencephalography (EEG)). To address
these questions, 60 Veterans with SCZ who have at least moderate levels of motivational
negative symptoms will be randomly assigned in a 1:1 ratio to MI or a standard treatment
(relaxation skills training). Both treatments will consist of weekly 60-min group sessions
for twelve weeks. The assessment will be administered at baseline, at completion of
treatment, and at 6-month follow-up.
Specific Aim #1: To adapt the existing MI approach for group-based MI treatment for Veterans
Specific Aim #2: To examine the treatment effects of MI compared to the control procedure on
motivational negative symptoms and functional outcomes.
Hypothesis 2a: Individuals who receive MI will have significant improvements in motivational
negative symptoms, compared to those who receive the control.
Hypothesis 2b: Individuals who receive MI will have significant improvements in aspects of
functioning including social, instrumental, and independent living domains, compared to those
who receive the control.
Specific Aim #3: To examine neurophysiological biomarkers (i.e., EEG and pupillometry) of
motivational negative symptom severity and treatment response.
Hypothesis 3a: At baseline, subjects with more negative symptoms at baseline will have more
aberrant EEG and pupillary measures.
Hypothesis 3b: For subjects in the treatment group, change in the biomarkers (toward
normalization) over study duration will correlate with treatment related improvement in
motivational negative symptoms.
Exploratory Aim: To explore a causal model by examining whether MI improves defeatist beliefs
compared to a control procedure.
Although MI is a well-established intervention for a range of clinical populations and
conditions, the proposed project will be the first examination of MI in a group format for
motivational negative symptoms in SCZ. If validated, it could be disseminated throughout the
VA for other patient populations with motivational and functional deficits (e.g., traumatic
brain injury, post-traumatic stress disorder). Therefore, this CDA application will
facilitate my research independence and provide me with a unique combination of skills that
will equip me to be a local professional resource and long-term VA researcher.
- Diagnosis of schizophrenia or schizoaffective disorder
- No medication changes in the past six weeks
- No psychiatric hospitalization in the past three months
- No changes in housing in the past two months
- Neurological disorder
- history of serious head injury
- substance dependence in the past 6 months or abuse in the past month
- being insufficiently fluent in English