Motivational Negative Symptoms in Schizophrenia: Intervention and Biomarkers
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional

Summary: 
      Negative symptoms significantly interfere with daily functioning among individuals with
      schizophrenia. They are strongly related to functional impairments [1] and contribute to the
      poor community outcomes of Veterans with schizophrenia. Motivational negative symptoms
      interfere with obtaining and maintaining employment [2], forming social relationships[3] and
      living independently [4]. 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
      with schizophrenia.
    

Detailed description: 
      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
      with SCZ.

      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.
    

Intervention name(s): Motivational Interviewing and Cognitive Behavioral Therapy; Relaxation Skills
Intervention type(s): Behavioral; Behavioral
Intervention description(s): group-based recovery-oriented Motivational Interviewing combined with cognitive-behavioral therapy to target the negative symptoms of schizophrenia; Relaxation and mindfulness skills training group for comparison condition for negative symptoms of schizophrenia
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: recovery; rehabilitation