CLINICAL HANDBOOK OF SCHIZOPHRENIA

CHAPTER 6GENETICSSTEPHEN J. GLATTThe goal of this text is to provide a concise, hands-on, up-to-date, authoritative book toassist clinicians in planning and delivering treatment for their clients with schizophrenia.As the title suggests, this chapter provides clinicians with an orientation to the subspecialtyof psychiatry known as psychiatric genetics, and to the types of clinically relevant informationthat psychiatric genetic research can yield for the early identification of—andintervention in—schizophrenia. Psychiatric genetics is an area of research in which humanbehavior and mental phenomena are studied in relation to inherited factors, orgenes. However, the term psychiatric genetics is actually shorthand for psychiatric geneticepidemiology, which more accurately reflects the discipline’s alignment with the largerfield of genetic epidemiology. Genetic epidemiology has been defined as “a science thatdeals with etiology, distribution, and control of disease in groups of relatives and with inheritedcauses of disease in populations” (Morton, 1982, Preface). Genetic epidemiologistsexamine the distribution of illness within families with the goal of finding geneticand environmental causes of illness. Thus, psychiatric genetic epidemiology, or psychiatricgenetics, considers both environmental and genetic factors—and their interactions—tobe on an equal footing and to have an equal likelihood of influencing a given behavior, untildata indicate otherwise. These assumptions are then tested empirically, of course, andthe relative environmental and genetic contributions to a behavior can be determined.Psychiatric genetic research on a particular disorder such as schizophrenia (or anyrelevant “phenotype,” including subthreshold psychopathology, biological traits, etc.)tends to follow a series of questions in a logical progression (Table 6.1). This sequence,which has been referred to as “the chain of psychiatric genetic research” (Faraone,Tsuang, & Tsuang, 1999), proceeds as follows: First we ask, “Is the phenotype familial?”or “Does it run in families?” Second, “What is the relative magnitude of genetic and environmentalcontributions to the phenotype?” Third, “How is the phenotype transmittedfrom generation to generation?” Fourth, “If genes mediate this transmission, where arethey located?” Fifth, “What specific genes influence risk for the phenotype?” These aredifficult questions to answer for any trait, but particularly so for phenotypes as complexas human behavior and psychiatric disorders. Fortunately, a wide variety of methods areavailable to help psychiatric genetic researchers resolve these issues. Those listed in Table55