Is Schizotypy per se a Suitable Endophenotype of Schizophrenia? – Do Not Forget to Distinguish Positive from Negative Facets

In 2003, Gottesman and Gould advocated using the endophenotype concept in psychiatry genetics; describing it as a measurable component “along the pathway between disease and distal genotype” (p. 636). Especially in schizophrenia research, the idea of endophenotypes has gathered a wide following. Meehl’s definition of schizotaxia [Ref. (1), p. 829], as “an ‘integrative neural defect’ as the only direct phenotypic consequence produced by the genetic mutation” and “This neural integrative defect [. . .] is all that can properly be spoken of as inherited. The imposition of a social learning history upon schizotaxic individuals results in a personality organizationwhich I shall call, following Rado, the schizotype” (p. 830; my emphasis) reminds clearly of the aforementioned endophenotype description. Although there are a number of ongoing debates regarding the nature of schizotypy, its distribution throughout the population and its relation with schizophrenia, a few elements may be considered “agreed upon”: (1) schizotypy is a latent trait (partly) harboring individual risk for schizophrenia (2). (2) Schizotypy is (partly) influenced by genes considered relevant for schizophrenia; q.v. (3). (3) Schizotypic variance is best explained through gene–environment interactions of a kind also relevant for schizophrenia (4). (4) Schizotypy shares a factor-structure with symptoms of schizophrenia; with the most commonly replicated factors being the positive, negative, and disorganized facets (5, 6). It therefore appears that schizotypy and schizophrenia qualitatively share various similarities, albeit in a quantitatively different fashion. It is not surprising that a number of measures considered endophenotypes of schizophrenia [q.v. (7)] have also been shown to be associated with schizotypy (8). The question at hand (whether schizotypy per semay qualify as a suitable endophenotype for schizophrenia) has, to my knowledge, not been answered as yet. I have briefly argued thusly elsewhere (9) and will, here, further elaborate on this and continue discussing the implications of the debated link between schizophrenia-genetics and schizotypy in an attempt to provide a suitable answer to this question. First, it is necessary to distinguish two pairs of entities: on the one hand, although often used pseudo-synonymously, schizophrenia and psychosis are not the same. Schizophrenia is a psychotic disorder; featuring psychosis as a primary phenomenon, but being defined furthermore by having Krankheitswert. It has been shown repeatedly that (extremely) high schizotypic features and/or psychotic experiences are not limited to the clinical domain and, contrapositively, that psychotic experiences are found with considerably higher prevalence within the population [between 30 and 70% (10, 11)] than possible, if existing only in patient groups. Furthermore, it has been convincingly argued [review in Ref. (12)] that individuals, christened “happy schizotypes” (13), with considerably high positive schizotypy and often repeated psychotic experiences but significantly lower negative/disorganized schizotypic features (compared to the population!) are not only “not sick” but actually benefit from these experiences and are “more healthy.”