5.1 Introduction
Research findings have made it abundantly clear that the brain is the organ of the mind. By the end of the twentieth century, equating a behavioral disorder with a dysfunctional brain had become a fundamental tenet in psychiatry. Just as the lungs exchange gases and the heart pumps blood, through a variety of mechanisms the brain influences and is responsible for behavior. Under the word “behavior” are subsumed all activities of the body, including respiration, fine and gross motor activity, sensory activity, as well as cognition or thought. More narrowly conceptualized, the brain is the major organ of the body that governs all forms of behavior which we observe in psychiatry and which our patients experience.
The goals of this chapter are to briefly summarize paradigms concerned with brain functions as they relate to psychiatric disorders. One operative word here is “brief,” meaning that the neuroanatomical and basic neurophysiology content is not presented comprehensively. Moreover, knowledge in this area is vast and expanding so rapidly that to do it justice in a single chapter is impossible. Detailed information on such topics as gray and white matter, membranes, myelin sheaths, and so forth can be found in neuroanatomy textbooks. This chapter is limited to “need-to-know” rather than “nice-to-know” material. It is designed to give useful conceptual material. Clinicians can use this material to facilitate their understanding of the neuroscientific foundations of psychiatric illnesses, inform what they see in their clinical settings, and think about their interventions more creatively than generically.
The chapter explores evidence for the view that disorders that have normally been considered to be distinct entities frequently have shared or overlapping biologic underpinnings. The general relationship between brain and behavior and disorders of brain function and psychiatric disease are discussed, providing examples of evidence for biologic commonalities among different disorders. The chapter also discusses how an awareness of normal functions of different brain circuits can facilitate an understanding of the consequences of their disruption in psychiatric disease, and how dysregulation of the same brain circuits across different disorders can help clinicians understand aspects of their overlapping symptomatology. This discussion only scratches the surface of the rich neurobiology of these structures and the larger networks in which they are embedded.
Another operative word for this chapter is “relate.” Because it is impossible to be exhaustive, the intention of this chapter is to relate (in a very broad sense) certain nervous system functioning to what clinicians might see in a clinical setting. For clinicians who want more in-depth information, the further reading list contains current textbooks and articles they may find especially useful.
During infancy and childhood, the human brain develops rapidly, acquiring an entire set of capabilities. This process of development is sequential, from less complex to more complex capabilities, and is guided by experience. The brain modifies and changes itself in response to new experiences, with neurons and neuronal connections evolving in an “activity-dependent” manner. In other words, the activity to which the neurons are exposed drive their response. Thus, development of the brain is use-dependent. As certain neural systems are activated repeatedly, an internal representation of the experience corresponding to the neuronal activity is created in the brain. The use-dependent capacity of the brain to make such internal representations of the internal or external world suggests a basis for learning and memory.
The capacity and desire to form emotional relationships is related to the organization and functioning of specific parts of the human brain. The systems in the human brain that allow persons to form and maintain emotional relationships develop during the first years of life. Experiences during this vulnerable period are critical to shaping the capacity to form intimate and emotionally healthy relationships. This capacity is at its peak during childhood, making children far more malleable and receptive to environmental stimuli than adults. By the time children are three years old, the brain is 90% of its adult size, and the emotional, behavioral, cognitive, and social foundation is in place for the rest of life. A child’s earlier repertoire of experiences provides an organizing framework or template through which subsequent experiences are filtered.
Human brains are most plastic (i.e., most receptive to environmental input) in early childhood. A child’s brain organizes in a use-dependent fashion, mirroring the pattern, timing, nature, frequency, and quality of experiences. For brain development to take place, children must be exposed to appropriate sensory experiences. The consequences of sequential development are that as different regions are organizing, they require specific kinds of experiences targeting the region’s specific function to develop properly. These developmental times are called critical periods.
The brain’s ability to develop and alter in response to experience is known as neuroplasticity. The brain adapts to new conditions during its maturation and during its constant interaction with its environment. Stimuli that arise in the internal or external environment trigger neuroplastic mechanisms. In a sense this means that, to some degree, humans can create their own brains by exposing them to certain experiences or substances (see Chapter 18). The concept of neuroplasticity provides the foundation for learning, memory, and other complex mental processes. Neuroplasticity accounts for the brain’s ability continue to grow connections, and exposure to new learning results in new brain changes, even into advanced old age.
5.3 Mind and Brain in Psychiatric Illness
Psychiatric illnesses have been called “brain disorders,” but that view masks enormous complexity. Clear, unitary, causes of symptoms are rare in psychiatry. More often, multiple causal factors, each with a small effect, act in concert to produce disease. The effects of causal factors for any one disorder include diverse genetic mechanisms, neurochemical systems, brain regions, and cellular abnormalities. The daunting complexity of psychiatric disorders poses a challenge to how one may meaningfully investigate biologic commonalities between disorders.
5.3.1 Endophenotypes
A way to come to terms with the complexity of the path from gene to mental illness is through the analysis of endophenotypes. These are important intermediaries along this path that assist in unraveling the contribution of genes. They are a measurable neurobiological or psychological parameter that meaningfully contributes to an aspect of a psychiatric disorder but is simpler, less heterogeneous, and more closely tied to measurable aspects of the underlying biology. Endophenotypes are inherited with, and closely linked to, the disease.
Endophenotypes may be shared across overtly distinct disorders, as can be seen by the presence of working memory impairments in schizophrenia, major depression, and attention-deficit hyperactivity disorder. Studies on endophenotypes may help bridge the explanatory gap between ultimate etiologic causes, such as genetic or environmental variables, and resulting psychiatric phenomenology.
There are two important classes of endophenotypes: biologic endophenotypes and symptom endophenotypes. Biologic endophenotypes are measurable biologic phenomena. There are many of these, ranging from the startle response to the neuroimaging response to information processing. Symptom endophenotypes are single symptoms associated with a mental illness and usually one of the DSM criteria for that illness. For example, guilt and insomnia are symptom endophenotypes that can be associated with major depressive disorder, and hallucinations and delusions are symptom endophenotypes that can be associated with schizophrenia.
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