Psychiatry and neurology have undergone revolutionary changes since the last edition of this book was published in 1985. There are now many new medications, discussed here, for the control of epilepsy, depression, mania, schizophrenia, obsessive-compulsive disorder, anxiety, and movement disorders. The discovery that the selective serotonin reuptake inhibitors (SSRIs) could control not only depression but also the symptoms of obsessive-compulsive disorder, phobia, and panic disorder has brought hope and relief to the sufferers from these conditions and their families and, perhaps even more importantly, has brought these illnesses into the realm of neuroscience. No one could argue today, as they did in the past, that these conditions are purely “psychological neuroses,” disorders of the mind not the brain.
New, atypical antipsychotic drugs have provided relief for many of the symptoms of schizophrenia. These drugs have a much lower rate of extra pyramidal side effects than the neuroleptics available in 1985, especially with regard to the risk of tardive movement disorders. We discuss these and their presumed mechanism of action.
The expanded understanding of Parkinson's disease, its etiology and treatment, has provided a paradigm for the understanding of the role of catecholamines and indoleamines in depression. It has also highlighted a flaw in the amine hypothesis of depression. The changes wrought by dopamine replacement therapy in Parkinson's are realized within minutes. The antidepressant drugs induce changes in brain amines within minutes, too, but the onset of their antidepressant effect is delayed for 2 to 3 weeks. The amine hypothesis and alternate hypotheses for depression are presented. The physiological effects of psychological stress on the brain may be mediated through steroids that damage and even kill neurons in the hippocampus and elsewhere.
Our understanding of reparative brain mechanisms is expanding and may apply to the recovery of brain cells from stress. The old idea that new neurons do not form during postnatal life has been challenged. There is strong and growing evidence that neurogenesis occurs in the adult human brain, especially in the hippocampus. Adult mice provided with enriched environmental living conditions grew 60 percent more granule cells in the dentate gyrus of the hippocampus than genetically identical controls and outperformed the controls in learning. There has been an astounding increase of our appreciation of the many links between the brain and behavior.
With the introduction of DSM-IV, the diagnostic criteria for psychiatric disease have sharpened. Clinical studies have become more focused and DSM-IV has broadened our understanding of mental illness. The new insights provided by DSM-IV are contrasted with some older ideas.
The newest categorization of epilepsy has abolished many imprecise, confusing terms that were in use a generation ago, such as petit mal, psychomotor, minor, focal, and grand mal. The new terminology is used in this edition. Many clinical studies have clarified the relationship of pseudoseizures to true epilepsy. It has proven very difficult to distinguish pseudoseizures from the behavioral abnormalities that are the manifestations of complex partial seizures that arise from the frontal and occipital lobes. We review these features and summarize the criteria that differentiate them.
There is increasing appreciation of the frequency with which dissociation occurs. It is the operative feature in many conversion reactions, including pseudoseizures. This insight has only recently emerged. As residents, we were taught that dissociation was rare. It is not rare. The role of child abuse, physical, sexual, or both, and the resulting dissociative defenses have been implicated in the development of many personality disorders (antisocial, borderline, hysterical, paranoid, multiple) and mood disorders. From the days of Freud until recently, the role of abuse in causing subsequent cognitive and behavioral abnormalities has been ignored, but now we know that abuse is an important factor in many of them. The focus of current approaches to this subject is turning toward understanding the brain mechanisms that are altered by abuse. The concept that abuse changes the brain has brought this experiential factor within the purview of neurology. The role of abuse in affecting the organization and the function of the brain is a new addition to this book.
Abuse, like any environmental factor that is remembered, changes the brain. One of the important themes of the first three editions of this book was that mental illnesses were the clinical manifestations of brain disease, most of it inherited. In this edition we emphasize that the environment changes the brain, sometimes permanently. Experience and heredity, together, shape the lasting connections in the brain that determine behavior and thought. Violence provides an example of a symptom that results from the interplay of experience, neurological disorders, and hereditary mental illness.
The role of the frontal lobes of the brain in modulating behavior and thought has achieved a new currency. Dysfunction of the executive capacities that are mediated through the frontal lobes is important in most of the psychiatric diseases, many movement and gait disorders, and some odd disorders that are located on the border between neurology and psychiatry, such as Tourette's syndrome. Violence and attention-deficit hyperactivity disorder are two symptomatic conditions that were not especially linked to frontal lobe disease in the past but are now thought to result largely from the loss of frontal control mechanisms.
Chronic dementias in the past were pretty much identified as “Alzheimer's,” but now many other dementias of clinical significance have been delineated. A sterile argument that regarded the diagnosis of Pick's disease as uncertain if rare inclusions called Pick bodies were not seen in the frontal and temporal cortex at autopsy has been sidestepped. The diagnosis of frontotemporal atrophy (read Pick's disease) is now common as tests that assess the executive and frontalcortical functions are more widely used. Lewy body dementia, a “new” condition, has bridged a gap between Alzheimer's and Parkinson's diseases.
The importance of badly made proteins to the dementias is now emerging. The abnormal proteins that seem to play a role in Parkinson's disease, Lewy body dementia, Alzheimer's disease, fronto temporal atrophy, Huntington's disease, and Creutzfeld-Jakob disease are variants of normal neuronal proteins, sometimes only a single amino acid different from the normal cellular constituent. The role of vascular dementia caused by small vessel disease in the symtomatology of Alzheimer's disease was not appreciated before the famous Nun's study. We have updated our discussion of the pathogenesis of Alzheimer's disease and the other dementias.
The tools to investigate brain disorders have advanced dramatically. It is now possible to see the brain at work in health and disease! Position emission tomography (PET), single photon emission computed tomography (SPECT), functional magnetic resonance (MR), and nuclear magnetic resonance (NMR) advances that were not available in 1985 for the investigation of brain disorders have become new research tools. Some (PET and SPECT) utilize radioactive isotopes. Though each technique is developing diagnostic niches in the fields of epilepsy, dementia, and vascular disease as the result of clinical research, none is easy to arrange. Positron emission tomography is expensive and is only done in a few large medical centers. Single photon emission computed tomography is more available but the need for coordination of physicians, radiologists, psychologists, nurses, and technicians has made SPECT unwieldy for its use in epilepsy. The need for isotopes has limited PET and SPECT in the evaluation of behavioral disorders in children and women of childbearing age. These limitations are being addressed increasingly by reaching out to functional MR techniques for the study of the brain.
This is to say that the uses of MRI have gone far beyond the superior static images that this technique provides. Even static MRI was not generally available in 1985. With functional MR, it is now possible to investigate the brain at work in real time without the radiation exposure that a radioisotope produces. The location of brain deficits in dyslexia and other cognitive deficits have been explored by this technique.
As dazzling as these techniques are for the investigation of behavioral disorders and as important as they may become in psychiatric and neurological diagnosis, at present the older techniques of clinical examination and neuro-psychological testing are still much more sensitive and specific in both psychiatry and neurology. Our understanding of the use of these older clinical techniques has also expanded. It is now clear that the standard mini-mental status examination (MMSE) and intelligence quotient (IQ) testing essentially ignore the anterior third of the brain. It is possible for a patient to become a social imbecile because of disease of his frontal lobes and still have a normal MMSE and IQ. How does a clinician assess the part of the frontal lobes that lie anterior to the motor strip? Calling this region prefrontal implies that it lies in front of the frontal lobes and that the frontal lobes end in the motor strip, their most posterior component. The clinical tools for investigation of this region are available and have been validated in adults (not in children). It is embarrassing that they are often unused by neurologists, psychiatrists, and psychologists who are investigating behavioral deviations. The clinical tests for assessing the frontal lobes and their connections are described in this edition in some detail.
At the time of this writing, we may be on the brink of exciting new advances in the diagnosis and therapy of some of humankind's oldest enemies. The concept that neurons do not multiply and cannot be replaced in the mature brain has been challenged by the finding that neurons in the hippocampus do multiply and stem cells (primitive, undifferentiated cells) exist in reservoirs either in the walls of the ventricles or among astrocytes a few cell layers away from the ventricular surface. These stem cells can become new neurons or glia and may become the vehicles for the repair of damaged myelin or systems that have suffered neuronal cell loss. The mechanisms that control the migration, growth, and differentiation of stem cells are now being studied. Stem cells have provided some repair in mice with a hereditary disease of myelin formation. The excitement that these advances engender must be tempered by acknowledgement that the tremendous advances in genetics over the last 15 years have not provided any treatment of genetic disorders of the brain, though some definitive genetic tests have become available, such as the one for Huntington's disease.
Until similar tests become available for the diagnosis of the major mental illnesses, the dementing disorders, the movement disorders, and many of the epilepsies, we must persist in using the clinical skills of history and physical examination and the nosology that has been based on them. In the fields of psychiatry and neurology, the clinician is still the main diagnostic instrument.