Chapter 4 Mental Disorders and the Brain CONTENTS Page METHODS USED TO STUDY MENTAL DISORDERS. 71 Biochemistry . .. 72 Anatomy and Activity . 74 SCHIZOPHRENIA . 77 Biochemistry . .77 Anatomy and Activity . 79 Other Factors . 81 Synthesis . 82 MOOD DISORDERS . 82 Biochemistry . .. 82 Anatomy and Activity . 85 Other Factors . 86 Synthesis . 88 ANXIETY DISORDERS . .88 Obsessive-Compulsive Disorder . 88 Panic Disorder . 90 Synthesis . 92 IMPLICATIONS FOR TREATMENT . .92 SUMMARY AND CONCLUSIONS . 93 CHAPTER 4 REFERENCES . .94 Boxes Box Page 4-A. Cloning Dopamine Receptors . 75 4-B. Serotonin and Suicide . 83 Figures Figure Page 4-1. Neurons . 72 4-2. The Synapse . 73 4-3. Brain Structures Involved in Mental Disorders . 76 4-4. MRI Scan of an Individual With Schizophrenia . 79 4-5. PET Scan of an Individual With Schizophrenia . 80 4-6. PET Scans of an Individual With Bipolar Disorder . 86 4-7. PET Scan of an Individual With Obsessive-Compulsive Disorder . 89 4-8. PET Scan of an Individual With Panic Disorder . 92 Tables Table Page 4-1. Techniques for Imaging the Brain . 77 4-2. Drugs in Development for Mental Disorders . 93 Chapter 4 Mental Disorders and the Brain Studying the factors that play a role in mental are-but it does not explain what caused the disorders is like putting together a jigsaw puzzle. chemical disturbance. Thus, a correlated factor—in The pieces of the puzzle are bits of information about this case the chemical perturbation-is secondary to the workings of the human brain. This chapter the underlying cause of the disorder. The consistent considers the chemistry, structure, and function of association of either a causative or correlative factor the human brain in mental disorders. Another key with a disorder can provide a biological marker to piece in the puzzle is the heritability of these aid in the diagnosis of the disorder, which in turn can disorders, which is discussed in chapter 5. be critical to research and treatment. The identifica- tion of factors that are associated with a disorder can The nature and amount of information available also provide an understanding of the mechanisms about the biology of mental disorders reflects the underlying symptoms; this is crucial to the develop- course of neuroscience research over the years. ment of rational therapeutic interventions. Most During the 1960s and 1970s there were advances in basic of all is the identification of specific causes of the methods used to study the chemistry of the brain mental disorders. To date, research into the biology and a resulting increase in knowledge about brain of the mental disorders considered here has identi- pharmacology and biochemistry. Many scientists fied several factors that are associated with their therefore focused their work on the roles of natural symptoms; there is much less evidence regarding the chemicals and pharmaceuticals in mental disorders. causes of these disorders. The following decade, the 1980s, saw advances in molecular biology and imaging technologies, which To solve the puzzle of what causes and contrib- in turn led to study of brain anatomy and activity and utes to mental disorders, all of the pieces have to be the molecules involved. The pace and extent of studied and fit together. It is important to note that research into the biological components of mental not all of them will necessarily be biological. disorders mirror these developments, with the body Although beyond the scope of this report, psycho- of knowledge concerning the chemistry of the brain logical and social factors also contribute. Thus, being much larger than the growing database about when a biological factor is identified, research must other factors. Currently, some of the most active point out how it interacts with psychological and research involves techniques that enable investiga- social factors that may produce, modify, or deter- tors to study the activity of the brain in living mine how mental disorders are expressed. For subjects. These advances and the expectation of example, it may be that biological factors create a future discoveries have infused researchers in the predisposition to certain disorders. The psychologi- area of mental disorders with optimism that further cal and social experiences of an individual, such as studies will pay off in a greater knowledge of the exposure to stress or a negative life event, may then brain, a better understanding of disorders, and the shape the likelihood that that factor will manifest development of new treatments for them. itself as the clinical condition. Scientists examine the activity of the brain to METHODS USED TO STUDY determine its normal functioning and to see whether biological factors are associated with a given mental MENTAL DISORDERS disorder. When a factor is identified, an important To understand the involvement of biological distinction must be made as to whether it is factors in mental disorders, researchers conduct correlated with the disorder or in fact causes it. A experiments in animals, analyze biological samples correlated factor is one that is linked to the disorder from patients, and study patients’ biochemistry, and may result in some of its symptoms. For brain anatomy, behavior, and mental activities. In example, a perturbation of the chemical functioning general, basic mechanisms of the brain’s physiol- of an area of the brain may be correlated with ogy, chemistry, and anatomy are studied in either symptoms characteristic of a disorder. Understand- animal models that approximate aspects of a disor- ing the perturbation can explain how the symptoms der or in tissue samples from living persons and occur-that is, what the biological underpinnings brain samples from deceased ones. Patient popula- –71- 72 ● The Biology of Mental Disorders tions are examined to learn more about symptoms extent, the explosion in neuroscience research in and characteristics associated with disorders. Under- recent years and the development of new, sophisti- standing mental disorders depends on connecting cated techniques and methodologies for more pre- information from these diverse observations. Ulti- cise, complex analysis have reduced, and will mately, the most comprehensive information is continue to alleviate, many of these problems. derived from studies and techniques that permit direct measurements in humans, both those with and Biochemistry those without mental disorders. Although it is very Study of the biochemistry of the brain involves difficult to study the working brain in humans, new techniques enable investigators to observe some examining the many chemicals involved in commun- ication and processing of information in the brain. physiological processes in living subjects. Refine- Neurotransmitters are chemicals released by nerve ment of these techniques, and the development of additional ones, will most likely enhance the under- cells, or neurons, to communicate with each other. Neurons are the cells that process information in the standing of mental disorders. brain. A neuron consists of a cell body with long It is often difficult to put disparate biological extensions, much like the branches of a tree, called dendrites (figure 4-l). Also projecting out of the cell pieces together into a unified hypothesis about the body is a single fiber called the axon, which can biological underpinnings of a mental disorder. Many times, results from studies contradict each other or extend a great distance (figure 4-l). When a neuron is activated, it releases a neurotransmitter into the are inconsistent, which further complicates this process. A number of factors contribute to these synapse, the gap between two neurons (figure 4-2). contradictions and inconsistencies. A better under- The molecules of the neurotransmitter move across standing of the workings of the healthy brain is the synapse and attach themselves, or bind, to essential to understanding what might go wrong in proteins, called receptors, in the outer wall of an mental disorders. As a result, there is still much to be adjacent cell (figure 4-2). Usually, the axon terminal learned. Also, some older research techniques pro- is the part of the cell that releases neurotransmitters vide only crude measures of brain activity, produc- into the synapse, and the dendrites and cell body are ing less precise findings. Finally, the difficulty of the areas of the neuron which contain receptors that distinguishing specific mental disorders may result form synapses with the axons of other neurons. in a heterogeneous research population, which can Once the neurotransmitter has activated a recep- then produce difficult-to-interpret results. To some tor, it unbinds from the receptor. It then has to be Figure 4-l—Neurons Synapse Two neurons in synaptic contact. SOURCE: R. Brain (New York, NY: Bantam Books, 1984). Chapter Mental Disorders and the Brain ● 73 Figure 4-2—The Synapse axon terminal, the impulse causes the release of neurotransmitter from the neuron into the synapse. Sometimes a receptor for one neurotransmitter Nerve impulse can affect a receptor for another neurotransmitter. In such cases, the receptors are biochemically coupled: The activation of one modulates the functioning of the other, either increasing or decreasing its activity. A neuron can also have receptors for the neurotrans- mitter it releases; these are usually located near the breakdown Auto- site where the neurotransmitter is released into the receptor synapse (figure 4-2). Such receptors are acted on by the neuron’s own neurotransmitter to regulate the release of the neurotransmitter. Thus, these autorecep- tors, as they are called, act as a feedback mechanism to regulate a neuron’s activity. The activity of a neuron will be determined by the cumulative activity of all its various receptors. While receptors are specific for a neurotransmit- ter, there may be a variety of receptor subtypes, Receptors linked to different cellular mechanisms, that all Neurotransmitters Receiving cell respond to the same neurotransmitter. In this way, one neurotransmitter can have diverse effects in The synapse and associated structures.