MHPC: Basic Mechanisms and Psychopathology

MHPG: Basic Mechanisms and Psychopathology discusses the interactions between clinical biological psychiatry and basic neuropsychopharmacology. Composed of 10 chapters, this book focuses on the role of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) in psychiatric disorders, particularly, in depression and mania. The book first examines the enzyme systems that produce MHPG in the brain and the features of these enzymes that could be used to reconcile several contradictions with regard to the origin of urinary MHPG. It then discusses the correlation between changes in impulse flow in central noradrenergic neurons of the locus ceruleus and MHPG levels in brain. The subsequent chapters cover the theoretical issues and empirical data dealing with the interrelationships between plasma and urinary measures of MHPG and central nervous system noradrenergic function. Measurement methods of MHPG in plasma, cerebrospinal fluid, and urine are also presented. The concluding chapters deal with the relevant human studies in patient and nonpatient populations concerning the role of MHPG in depressive disorders, with particular emphasis on clinical studies in childhood and adolescence. This book is of value to clinical biologists, psychiatrists, and neuropsychopharmacologists.

Contributors Preface 1. The Biochemical Pathways for Formation of 3-Methoxy-4-Hydroxyphenethyleneglycol in Man and Animals I. Introduction II. Sources of Urinary MHPG III. Oxidative Deamination and O-Methylation of NE IV. Enzymes Active in Producing the Alcohol Metabolites of NE V. Enzymes Active in Producing the Acid Metabolites of NE VI. Enzymes Active in Producing the Sulfate or Glucuronide Conjugates of MHPG VII. Estimates of CNS NE Metabolism by Measures of Urinary MHPG VIII. Summary References 2. Neuronal Activity, Impulse Flow, and MHPG Production I. Introduction II. Anatomy of NE Systems III. Impulse Flow and Transmitter Metabolism IV. Norepinephrine Metabolism V. Impulse Flow and Transmitter Turnover VI. Impulse Flow and MHPG Production VII. Plasma and CSF MHPG VIII. Summary References3. Relationships between Central Nervous System Noradrenergic Function and Plasma and Urinary MHPG and Other Norepinephrine Metabolites I. Introduction II. Theoretical Issues: The Peripheral versus Central Model as Opposed to a Central-Peripheral Interactive Paradigm III. Relationships between Brain, CSF, Plasma, and Urinary Concentrations of MHPG: The Empirical Data IV. Plasma and Urinary MHPG and Other NE Metabolites as Indices of Events in CNS NE Neurons V. Summary References 4. Effects of Pharmacological Agents on MHPG I. Introduction II. Effect of Antidepressants III. Effect of ECT IV. Effect of Lithium V. Effect of Neuroleptics VI. Effect of Stimulants VII. Effect of Narcotics VIII. Effect of 6-Hydroxydopamine IX. Effect of L-DOPA X. Effect of Adrenergic Agonists and Antagonists XI. Relationship between Norepinephrine Turnover and Adrenergic Receptors XII. Conclusion References 5. Methods for Determining MHPG in Plasma, CSF, and Urine I. Introduction II. Measurement of MHPG in CSF III. Measurement of MHPG in Plasma IV. Measurement of MHPG in Urine V. Hydrolysis of Conjugated MHPG VI. Synthesis of Stable Isotope-Labeled MHPG VII. Summary References 6. Preliminary Characterization of Plasma MHPG in Man I. Introduction II. Brain MHPG versus Other Metabolites as an Index of Brain NE Activity III. Factors That Influence Plasma MHPG Levels IV. The Role of the SNS: Interaction of Central and Peripheral NE Systems V. Correspondence of MHPG Levels in Brain, CSF, and Plasma VI. Plasma MHPG in Man: Emerging Clinical Applications VII. Summary References 7. Relationship between Psychiatric Diagnostic Groups of Depressive Disorders and MHPG I. Introduction II. Physiological Implications of Measurements of Urinary MHPG III. Longitudinal Studies of Urinary MHPG Levels in Patients with Bipolar Manic-Depressive Disorders IV. Urinary MHPG Levels in Bipolar Manic-Depressive and Other Clinically Defined Subgroups of Depressive Disorders V. Application of Multivariate Discriminant Function Analysis to Data on Urinary Catecholamines and Metabolites in Depressed Patients VI. Identification of Possible Subtypes of Unipolar Depressive Disorders VII. Recent Studies of Pre treatment Urinary MHPG Levels as Predictors of Responses to Noradrenergically Active Antidepressant Drugs VIII. Concluding Comments on Urinary MHPG Levels in Patients with Unipolar Major Depressive Disorders References 8. Sources of Variance in Clinical Studies of MHPG I. Introduction II. Interassay Variability III. Age, Sex, and Body Size IV. Environmental Factors V. Circadian and Annual Rhythms VI. Personality VII. Clinical State Differences VIII. Summary References 9. Urinary MHPG and Treatment Response: A Review I. Introduction II. Pretreatment MHPG and Drug-Response Prediction III.