Introduction

Schizophrenia is a chronic, debilitating mental disease, the etiology and pathophysiology of which is incompletely known.1'80 It affects approximately 1% of the global population and has no defined ethnic or social boundaries. Schizophrenia is characterized by a well-defined set of symptoms, a plethora of pathological and neurochemical brain alterations, and, despite diverse therapeutic options, a limited ability to treat the core dimensions of the illness other than psychotic symptoms, e.g., auditory and visual delusions and hallucinations. Despite the use of drug or electroconvulsive treatment, approximately 15% of schizophrenic patients have persistent moderate to severe positive symptoms.

While new insights into the disorder have appeared over the past decade, psychotic symptoms have been recognized throughout human history. In most societies, such aberrations have been considered to be signs of severe mental illness, although at times they have been interpreted as a sign of religious exaltation or possession. The clinical features of psychosis were noted in early literature and have remained remarkably unchanged over time. In the latter half of the nineteenth century, features of psychosis were variously categorized as 'folie circulaire' (cyclical madness), 'hebephrenia' (a silly, vacuous state of mind), and ultimately, due to the clinical acumen of Emil Kraepelin at the turn of the twentieth century, dementia praecox, or 'dementia of early onset.'2 Thus, Kraepelin deserves full credit for recognizing the relationship between psychosis and cognitive impairment. In 1911, Bleuler first used the term schizophrenia based upon an emphasis on nonpsychotic clinical symptomatology, specifically: blunted affect; loose associations; inability to experience pleasure; poverty of thought and a preoccupation with the self and one's own thoughts. The cognitive component of schizophrenia was all but forgotten from the time when chlorpromazine 1, the first antipsychotic drug, was serendipitously discovered in 19513 until resurrected recently. Indeed, cognitive dysfunction has now emerged as the major unmet medical need in developing novel therapies for the treatment of schizophrenia.

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