12.

Introduction and Overview

Carol A. Tamminga M.D.
Schizophrenia is arguably the most puzzling of psychiatric syndromes and one of its
most debilitating. It is characterized by disordered cognition, including a gain of function
in psychotic symptoms and a loss of function in specific cognitive functions, such as
working and declarative memory, but without the progressive dementia that characterizes
classical neurodegenerative disorders. Although its phenomenology is fascinating, its
pathophysiology and etiology remain unclear, and people with the illness suffer greatly. A
critical lack of knowledge about brain function underlies our inability to describe molecular
targets for definitive treatments or rational prevention strategies. This is the situation even at
the time when fundamental neuroscience and translational clinical methodologies have clearly
advanced our knowledge of aspects of the illness, most recently in the area of cognition. No
one knows which of the modern neuroscience methodologies or knowledge areas will
ultimately address schizophrenia pathophysiology. However, it is known which disease
elements will have to be accounted for by a mechanistic formulation. Those elements include
the clinical concepts and observations presented here in this schizophrenia chapter. These areas
of knowledge represent a rich resource characterizing the illness that focuses on its clinical
phenomenology, its evolving genetics, intermediate phenotypes, epidemiology, and its course
of illness. Despite this, the critical knowledge about the mechanisms and causes of
schizophrenia are lacking.
A phenomenological basis for defining dimensions of symptoms and actual phenotypes of the
illness exists, many of which are represented within the sections of this chapter. The
epidemiology of schizophrenia around the world has been examined and defined, along with
its distinctive disease characteristics such as the unusual age of onset and its lifelong symptom
course. Clinical genetics, postmortem tissue neurochemistry, and brain imaging characteristics
(structural, functional, and molecular) have advanced, if not yet defined, the illness
pathophysiology. Cognition in schizophrenia has been reconceptualized as a feature that is
critically important to outcome and to a full disease understanding. Current treatments have
come further than early scientists would have thought: Pharmacology, based on initial
serendipitous observations, has been taken to a sophisticated level of application, while
psychosocial approaches are demonstrating clear efficacy. The involvement of individuals with
the illness in the process of recovery has been gratifying to observe. And a dimensional
construct applied to psychiatric diagnoses is an emerging aspect within the field, particularly
as applied to schizophrenia.
It is always poignant to review the long history of this illness. Descriptions of schizophrenia
can be found in works of literature from earliest written history. Schizophrenia-like
symptoms are described in individuals labeled as seers and prophets, as well as witches and
devils. An understanding of schizophrenia as a human brain disease did not develop until the
19th century. Then, humane treatment was prescribed for insanity, an approach that
advocated care, protection, and human understanding for those afflicted. It was not until the
middle of the 20th century that antipsychotic drug treatments became widely available. Now
at the beginning of the 21st century, there have been two generations of antipsychotic
medications, several known risk genes, an evolving anatomy, but still no basic disease
formulation. Nonetheless, the focus on the illness has moved from diagnostic criteria to
domains of dysfunction (component symptom complexes), and there has been an emergence
of a fundamental understanding in the brain sciences. Therefore, it might be optimistically
predicted that it could be possible to describe the genes, cellular and molecular mechanisms,
and rational treatments for the condition within the next few decades.