Motivational Negative Symptoms in Schizophrenia: Intervention and Biomarkers

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.

Conditions

• Schizophrenia
• Schizoaffective Disorder

Interventions

BEHAVIORAL

Motivational Interviewing and Cognitive Behavioral Therapy

group-based recovery-oriented Motivational Interviewing combined with cognitive-behavioral therapy to target the negative symptoms of schizophrenia

BEHAVIORAL

Relaxation Skills

Relaxation and mindfulness skills training group for comparison condition for negative symptoms of schizophrenia

Sponsors & Collaborators

• VA Office of Research and Development

  lead FED

Principal Investigators

• Lena F Reddy · VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-03-28

Primary Completion

2019-12-31

Completion

2020-06-30

Countries

• United States

Study Locations