A key finding from this study was that, in patients with bipolar disorder, obesity is a stronger influence on insulin resistance than is bipolar disorder itself. In other words, insulin resistance in these patients does not appear to be more severe after accounting for their obesity. This conclusion, however, should be tempered by the observation that these obese women with bipolar disorder had significantly more abdominal fat and were slightly more hypertensive than BMI-matched controls, allowing for the possibility that bipolar disorder may indeed be associated with altered metabolic profile.

Using tools to assess both energy expenditure and energy intake, this project indicates that, once these euthymic patients with bipolar disorder become obese, their energy imbalance is likely similar to non-patient controls. However, similar levels of insulin resistance in patients compared to BMI matched controls in this cross sectional study do not discount the possibility that bipolar disorder does not somehow predispose these patients towards weight gain and obesity. Comparing normal weight subjects perhaps provides some important clues in this regard.

Another finding in this study was that normal weight patients with bipolar disorder tended to have reduced rates of fat oxidation after an overnight fast. Thus, it is possible that reduced rates of fat oxidation in pre obese patients might contribute to greater weight gain in these patients. However, the physiological factors that may contribute to weight gain to cause them to become more obese than the general population remain unknown. Future prospective longitudinal studies are needed to address this hypothesis.

An important practical implication of the current study was that we were was able to recruit individuals diagnosed with the most severe form of bipolar disorder who were then able to tolerate and complete all procedures. This is the first study to show the feasibility of performing body composition and metabolic assessments in patients with bipolar disorder. Thus the demands of these specific studies are achievable in this patient population. Therefore, these tools may be useful to address important questions concerning the effects of lifestyle modifications, including diet and exercise programs, on obesity prevention and treatment in bipolar disorder.

CONTENTS

PREFACE
1.0 INTRODUCTION OBESITY
1.2 BIPOLAR DISORDER

1.2.1 Primary Specific Aims

2.0 SECOND CHAPTER
2.1 LITERATURE REVIEW

2.1.1 BACKGROUND

2.2 BIPOLAR DISORDER
2.3 METABOLIC SYNDROME

2.3.1 Metabolic Syndrome in Bipolar Disorder

2.4 INSULIN RESISTANCE

2.4.1 Insulin Resistance in Bipolar Disorder OBESITY

2.5 OBESITY

2.5.1 Obesity in Bipolar Disorder
2.5.2 Causes of Obesity in Bipolar Disorder
2.5.3 Central Obesity
2.5.4 Central Obesity in Bipolar Disorder

2.6 SKELETAL MUSCLE FATTY ACID METABOLISM

2.6.1 Mechanisms

2.7 MEDICATIONS IN BIPOLAR DISORDER

2.7.1 Antidepressants
2.7.2 Monoamine oxidase inhibitors (MAOI)
2.7.3 Tricyclic Antidepressants
2.7.4 Selective Serotonin Reuptake Inhibitors (SSRI)
2.7.5 Atypical Antipsychotics

3.0 CHAPTER 3
3.1 METHODS

3.1.1 Subjects
3.1.2 Bipolar Patients
3.1.3 Controls:

3.2 EXPERIMENTAL DESIGN AND METHODS

3.2.1 Screening Procedures
3.2.2 Physical Activity Measurement (Following Visit 1):
3.2.3 Visit 2<?ul>
3.3 DATA ANALYSES
4.0 CHAPTER 4
4.1 RESULTS
4.1.1 Subjects
4.1.2 Insulin Resistance
4.1.3 Metabolic Characteristics

4.2 OBESITY

4.2.1 Whole Body Fat and Lean Mass
4.2.2 Regional Fat Distribution

4.3 ENERGY EXPENDITURE:
4.4 FATTY ACID METABOLISM
4.5 NUTRITION BEHAVIOR
5.0 CHAPTER 5
5.1 DISCUSSION

5.1.2 Insulin Resistance

5.2 OBESITY

5.2.1 Generalized Obesity
5.2.2 Regional Fat Distribution

5.3 ENERGY EXPENDITURE
5.4 FATTY ACID METABOLISM
5.5 NUTRITION BEHAVIOR
5.6 SUMMARY AND CONCLUSIONS
5.7 LIMITATIONS AND FUTURE DIRECTION
APPENDIX A: INFORMED CONSENT
APPENDIX B: BASELINE DEMOGRAPHIC AND MEDICAL HISTORY FORM
BIBLIOGRAPHY

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