In all its variations, the spectrum concept remains critically dependent on the validity of the SPD concept. Accumulating

evidence from family and twin data indicates that SPD is multidimensional and may be genetically heterogeneous.33,35 Its manifestations fall into two genetically independent clusters: a “negative” cluster (odd speech and behavior, inappropriate affect, and Inhibitors,research,lifescience,medical social withdrawal), more common among relatives of schizophrenic probands, and a “positive” cluster (magical ideation, brief quasipsychotic episodes), associated with increased incidence of affective disorders in relatives. “Negative“ schizotypy may indeed represent a subclinical forme fruste of schizophrenia, manifesting attenuated cognitive deficits and brain structural abnormalities. Positive-negative schizophrenia (“Type I” and “Type II”) A general “weakening” of mental processes resulting in a “defect” was the cornerstone of Kraepelin’s dementia praecox, who suggested that precursors of “defect” could be detected early in the illness, coexisting with “productive” or “florid” symptoms.8 Inhibitors,research,lifescience,medical Since the 1970s, the terms “defect” and “productive” symptoms have been virtually replaced by “negative“

and “positive“ symptoms.” 36 Crow37 proposed a simple subclassification of schizophrenia, based on the predominance of either positive Inhibitors,research,lifescience,medical or negative symptomatology. “Type I” (positive) schizophrenia was characterized by Inhibitors,research,lifescience,medical hallucinations, delusions, and formal thought disorder, with a presumed underlying dopaminergic dysfunction, while patients with “Type II” (negative) schizophrenia displayed social withdrawal, loss of volition, affective flattening, and poverty of speech, presumed to be associated with structural brain abnormalities. Inhibitors,research,lifescience,medical Criteria and rating scales for positive (SAPS) and negative (SANS) schizophrenia were proposed by Andreasen and Olsen.38 The initial typology, implying discrete, mutually exclusive “types,”

was later replaced by a negative and a positive dimension, allowing the two kinds of symptoms to co-occur in the same individual.39 Deficit-nondeficit schizophrenia Carpenter and collaborators40,41 proposed the delineation of a subtype of schizophrenia characterized by enduring “primary” negative symptoms that could not be construed as sequelae of other psych opathology (Table III). This clinical construct, evocative of Kraepelin’s dementia praecox, was Sitaxentan termed “deficit schizophrenia” (DS) and hypothesized to be an etiologically distinct “disease” Alectinib research buy within the schizophrenia spectrum.42 Studies comparing DS cases with “nondeficit” (NDS) patients and controls, estimated the prevalence of the DS subtype at 16.5% in unselected epidemiological samples of schizophrenia cases and 25% to 30% within samples of chronic schizophrenia. DS and NDS do not differ on age at onset and length of illness, which argues against a progression leading from NDS to DS.