8 In line with this observation, Mohamed et al9 and Bilder et al10 reported that worse neuropsychological performance was only weakly correlated with severity of negative symptoms and neuroleptic dose. Cognitive functioning in relatives of schizophrenia patients Numerous studies have demonstrated that relatives of patients with schizophrenia exhibit cognitive impairments that are milder than, yet similar to, those seen in schizophrenia patients. Studies of monozygotic Inhibitors,research,lifescience,medical twins discordant for schizophrenia have found that the nonpsychotic discordant twins manifested subtle impairments in memory attention, abstraction, and

IQ.16-18 Studies of siblings of patients with schizophrenia yielded similar results: both schizophrenia patients and their nonschizophrenic siblings were cognitively impaired compared with normal controls, and the nonschizophrenic siblings had a performance that was intermediate between Inhibitors,research,lifescience,medical the probands and normal controls. The cognitive deficits of the relatives included impairments in IQ and specific abnormalities in memory, attention, and abstraction.19-23 These

cognitive deficits in relatives were stable over time.24 Given that the cognitive abnormalities are also evident in the nonschizophrenic siblings, these abnormalities do not appear to be a result of longstanding illness; Inhibitors,research,lifescience,medical rather, they appear to represent longlasting markers of risk for the disorder, and possibly indicate a genetic predisposition. The origins of the cognitive impairment in schizophrenia It is clear from the studies reviewed above that schizophrenia is coupled with Inhibitors,research,lifescience,medical a severe and MM-102 order debilitating cognitive impairment, which is persistent and independent of positive or Inhibitors,research,lifescience,medical negative symptoms, and does not respond to neuroleptic treatment. However, cognitive impairments are also found in other, nonpsychotic psychiatric disorders, though they may be less severe than those seen in schizophrenia.25-27 Thus, a number of investigators have sought to determine whether lower cognitive functioning occurs as a precursor to, or risk factor for, schizophrenia or

only occurs concomitantly with the overt expression of the illness. A review of these early studies, mainly in clinical samples, can be found in Alyward et al.28 Below, I shall describe the main Isotretinoin epidemiological studies addressing the relationship between childhood and adolescence cognitive functioning and later schizophrenia. Epidemiological samples are representative of the population, and therefore protect against the ascertainment bias that often affects clinical samples. Schizophrenia In the British 1946 birth cohort A study of 5362 British subjects born in March 1946 has yielded 30 cases of narrowly defined (Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Reivsed [DSM-III-R] criteria) schizophrenia up to age 43 years.