CLINICAL HANDBOOK OF SCHIZOPHRENIA

26 I. CORE SCIENCE AND BACKGROUND INFORMATION“silly,” and catatonic. In 1908, Bleuler replaced the term dementia praecox with the modernterm schizophrenia. Basic symptoms included the “four A’s” of loosened associations,inappropriate affect, ambivalence, and autism. These criteria were widely used for 50years. In 1957, Schneider produced a new formulation that included “first-rank symptoms”:audible thoughts, voices arguing or discussing or commenting, thought control orthought broadcasting, “made” acts and emotion, and delusional perceptions. Thesephenomenological descriptions have influenced the current diagnostic systems around theworld. Current diagnostic approaches, such as the fourth edition of the Diagnostic andStatistical Manual of Mental Disorders (DSM-IV) and the 10th edition of the InternationalClassification of Diseases (ICD-10), describe not only the positive symptoms of delusions,hallucinations, and disorganized behavior and speech, but also negative symptomssuch as alogia, avolition, and flattened affect. The distinction between positive andnegative symptoms becomes important for some neurobiological theories of schizophrenia.Environmental FactorsMost of the identified risk factors for schizophrenia involve events occurring during preorperinatal rather than postnatal development. In rough order of strength, these includewinter birth; urban birth; intrauterine infections (rubella in particular, but also influenza,polio, and respiratory and central nervous system [CNS] infections); maternal stressors(bereavement in particular, but also famine, flood, unwanted gestation, and depression);obstetric complications (neonatal CNS injury in particular, but also low birthweight,preeclampsia, hypoxia, and Rhesus factor incompatibility). At present, it is unknownwhat common “mechanism of injury” leads from these risk factors to the onset of schizophrenia,or why symptoms such as psychosis only appear decades later.Postnatal environmental risk factors for schizophrenia are also beginning to be identified.Cannabis use, particularly in early adolescence, is associated with the developmentof psychosis. Certain individuals, comprising a “psychosis-prone” subpopulation, may beespecially vulnerable. It remains controversial whether cannabis use actually causes psychosis,or whether the association merely reflects higher use of cannabis in the psychosispronesubpopulation. One interpretation is that cannabis does not so much cause schizophreniain otherwise healthy individuals as it “unmasks” schizophrenia in those with agenetic predisposition toward the disease.Social and environmental stressors may have similar effects on individuals who arevulnerable to schizophrenia. A personal or family history of migration is an importantrisk factor, increasing the risk of schizophrenia threefold. Other environmental stressorsassociated with schizophrenia include urban residency, minority ethnicity, childhood trauma,and social isolation. It is suggested that discrimination, or other forms of social or economicadversity, may cause some individuals to develop a cognitive bias toward paranoid or delusionalthinking. In addition, the stress of such experiences, like the pharmacological stressof cannabis, may provide a final push that tips vulnerable individuals into developing adysregulated neurochemical state, with psychotic symptoms emerging as a result.Neuroanatomical AbnormalitiesMacroscopic AbnormalitiesComputed tomography (CT) and magnetic resonance imaging (MRI) neuroimaging studieshave identified abnormalities of brain structure in schizophrenia. Well-establishedfindings include enlarged lateral ventricles and reduced volumes of the hippocampus,parahippocampal gyrus, and amygdala. Some studies have also shown smaller prefrontal