One of the first NARSAD Grantees reflects on his long and fruitful relationship with the Foundation.

From The Quarterly, Spring 2012

When did your research career begin, and what made you pursue adolescent psychiatry and mood disorder research, specifically?



My first experiences with research occurred in the lab of Dr. Raymond Knight when I was an undergraduate at Brandeis University. Dr. Knight conducted research on emotion and cognition in schizophrenia, and because Brandeis didn’t have a graduate program, undergraduate students like me got to do things ordinarily reserved for grad students. I spent a fair amount of time doing clinical interviews and neuropsychological tests with inpatients at the VA Hospital in Bedford, MA. The patients were very ill, usually with schizophrenia or bipolar disorder, and had been hospitalized for much of their adult lives. But underneath their illness was a humanity that was always very striking to me. For example, they would express concerns for my feelings, suddenly tell a joke, or worry that they might not be able to help me with my studies. It was thrilling, challenging, and always very moving.



I became interested in bipolar disorder as a graduate student at UCLA under Professor Michael Goldstein’s mentorship. Dr. Goldstein took mentoring very seriously, and spent a lot of time with me. I knew I was interested in family interaction and family therapy, and first thought I’d make my career in schizophrenia research. But after exposure to patients with bipolar disorder during my UCLA clinical internship, and after working with their families, I knew I had found my niche.



You were amongst the very first to receive a NARSAD Grant in 1987 with your study “Does Expressed Emotion Index as Transactional Process?” What were the primary findings in this research? What do we know about mood disorders and the brain today that we didn’t know 25 years ago?



In 1983, I developed my dissertation idea: a comparison of family environments in patients with bipolar disorder and schizophrenia. I followed a cohort of young adult bipolar patients over time to see whether their family environments had a prognostic role in their outcomes. This study involved several meetings with family members during and immediately following the hospitalization.



What we learned from this NARSAD Grant-funded study was that when families are highly conflictual in the 1-2 months after a bipolar patient’s hospital discharge, the person’s chances of having a recurrence of mood disorder over the next 9 months increased five- or six-fold. Persons in these high conflict environments also had a tougher time functioning socially than those in more benign, less conflictual family environments. In many cases, parents and siblings had made peace with the bipolar disorder diagnosis and the need for medications, even though it made their own lives much more difficult. These findings led directly to our development of family-focused treatment (FFT), which is meant to help families and patients repair their relationships and learn to manage the disorder in the aftermath of an illness episode.



One thing that we didn’t know 25 years ago was that combining psychotherapy (of which FFT is only one type) with medication is a more powerful treatment for bipolar disorder than medication alone. Researchers in the US, Canada, the UK and Australia have observed benefits of various kinds of family, individual and group treatments, always in combination with pharmacotherapy. Although the most effective psychotherapy and its optimum length hasn’t been identified, we do know that people with bipolar disorder do better in terms of symptoms, recurrences, and life functioning when they’re in regular therapy as well as taking mood stabilizing medications.



What role has the Brain & Behavior Research Foundation and NARSAD Grants played in the development of your career?



Where do I start? The Foundation gave me my first research funding when I was a Postdoctoral Fellow in 1987 with the NARSAD Young Investigator Grant; a Distinguished Investigator Grant in 2001; and then this past Fall gave me a lifetime achievement award for my bipolar disorder research.  At each stage of my career, the Foundation has helped me achieve my goals, not only in terms of financial support but in terms of recognition and, more broadly, inviting me into the scientific community. Many of my closest colleagues are people who have been associated at one time or another with the Brain & Behavior Research Foundation. I can say without question that I would not have achieved my career goals or gone in the directions I’ve gone without the Foundation. I’m very grateful.



Over the course of the past 25 years, what role do you think NARSAD Grant funding has played in helping evolve the field overall—i.e., what we know about the brain and how to treat, prevent and cure mental illness?



The Brain & Behavior Research Foundation continues to recognize and nurture young investigators. Many young scientists who have an innovative idea, talent, and a good environment for carrying out their research have received NARSAD Grants, which has allowed them to collect the Dr. Miklowitz with wife Mary and Nikki their dog necessary pilot and feasibility data to make their first NIH grant successful. I think this initial success in grant writing has encouraged many to go into research careers rather than into purely clinical positions.



I also think the Foundation has highlighted the work of senior investigators who are often testing innovative genetic or neuroimaging methods or new treatments. My hat is off to the Brain & Behavior Research Foundation for recognizing basic scientists and clinical researchers who study both psychosocial and biological factors in major mental illnesses. I believe that the best treatments will continue to be combinations of new medications, brain technologies and targeted psychosocial interventions.



What research discovery have you made that you are the most proud of?



The finding I am most proud of is my team’s development of a family- based intervention for improving symptoms in the earliest phases of bipolar disorder. Our work shows that family psycho-education and skill training augments the effects of medications in young people who have just developed the disorder as well as those who have had multiple episodes. I think that the uptake of treatments like Functional

 

Family Therapy (FFT) in community mental health centers could make the lives of persons with bipolar disorder and their family members much less stressful and burdensome.



More specifically, I am proud of our finding that, in bipolar depression, patients who receive intensive psychosocial treatment (family or individual) in addition to mood stabilizing medications do better than patients who simply add on another medication (for example, an antidepressant) to their existing mood stabilizer regimen. This finding, which emerged from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), suggests that patients with bipolar depression who are on optimal dosages of mood stabilizers or atypical anti-psychotics may do better by choosing a targeted, well-planned psychotherapy instead of an SSRI augmentation. But I’d like to see our work replicated by others before this becomes part of the treatment guidelines.



What role do you see NARSAD Grant-funding playing in the next 25 years to come? Where do you expect to see breakthroughs?



I think we’ll be seeing more examples of matching treatments to individual patient characteristics (‘personalized medicine’). I think we’ll be learning more about how different disorders relate to differences in neural circuitry, and more and more examples of treatments based on neuroimaging (deep brain stimulation being a recent example). The promise of gene mapping suggests that one day, disorders may be more accurately diagnosed by genetic markers than by the subjective evaluation of symptoms by a clinician. More and more, I think we’ll see investigators mapping the common underlying dimensions of psychopathology rather than focusing exclusively on diagnostic categories like schizophrenia or bipolar disorder. I expect that NARSAD Grantees will be at the forefront of these novel developments.



I’m hoping there will come a day when, based on a blood test or a brain scan, we’ll be able to select medication options that are more likely to work for a specific person. I’m hoping we’ll see something similar with psycho- therapy, that clinicians will be able to use a combination of biological and psychosocial assessments to recommend the proper form—and length—of psychotherapy. Finally, I expect to see breakthroughs in the prevention of mental illness, the ability to intervene early with children who are not yet ill but are at risk for developing mood or psychotic disorders, so that they and their families lead more fulfilling lives.



Sure, it’s all very optimistic, but I can dream, can’t I?

David J. Miklowitz, Ph.D.

1987 NARSAD Young Investigator Grantee

2001 NARSAD Distinguished Investigator Grantee

2011 Brain & Behavior Research Foundation Mood Disorders Prizewinner

Professor of Psychiatry

Director, Child and Adolescent Mood Disorders Program Director, Integrative Study Center for Mood Disorders

UCLA Semel Institute for Neuroscience and Human Behavior Division of Child and Adolescent Psychiatry