No support for linkage to the bipolar regions on chromosomes 4p, 18p, or 18q in 43 schizophrenia pedigrees.

Following the distinction proposed by Kraepelin[1919], who built on the work of Morel [1860], Hecker[1871] and Kahlbaum [1863], bipolar affective disorder(BPAD) and schizophrenia are generally thought of asseparate disorders. Modern epidemiological studiessupport this view since these disorders generally do notaggregate in the same families [Kendler et al., 1993;Maier et al., 1993]. An alternative view, originally putforward by Griesinger in 1861, is that schizophreniaand affective psychoses may be different expressions ofthe same disorder [Crow, 1986; Griesinger, 1861, asreferenced by Maier et al., 1993]. In support of thisview, cross prevalence studies have demonstrated asignificantly higher rate of unipolar affective illnessamongst the relatives of schizophrenia probands, com-pared with that observed amongst the relatives of con-trol probands [Kendler et al., 1993; Maier et al., 1993;Taylor et al., 1993]. Furthermore, commonality insymptomatology (with both schizophrenic and bipolarpatients experiencing Schneiderian first rank symp-toms), in illness course (deterioration in some severebipolar cases is more typical of the pattern seen inschizophrenia), and in effective treatments (neurolep-tics, lithium) raise the possibility of overlapping caus-ative factors, both genetic and nongenetic.Patients with schizoaffective disorder exhibit bothschizophrenic and affective symptoms in varying pat-terns over time, and in describing this group Kendelland Brockington [1980] raised four possible explana-tions: “that most are really schizophrenic illnesses,that most are really affective illnesses, that they are amixture of schizophrenic and affective illnesses, andthat they constitute a third independent type of psy-chosis” [Kendell and Brockington, 1980, p326]. Geneticstudies have forced the need for pragmatic distinctionsto be made within this group of patients for inclusion/exclusion in either schizophrenia or BPAD linkagestudies. For example, RDC [Endicott and Spitzer,1978] “schizoaffective, mainly schizophrenic” caseshave been included in schizophrenia linkage studies(including the present author’s study), while RDC“schizoaffective, mainly affective” cases have been in-cluded in BPAD linkage studies [Gershon et al., 1988]. Taken together, these factors suggest that, whetherclassified as separate disorders or as a continuum,overlap exists between affective and schizophrenic ill-nesses, and that the existence of this clinical and fa-milial overlap raises the possibility of overlapping ae-tiologies, and perhaps shared susceptibility genes.Blackwood and co-workers [Blackwood et al., 1996]reported a peak lod score of 4.1 coincident with D4S394(a40.35) on chromosome 4p16.1 in a cohort of 12 Scot-tish BPAD pedigrees. More recent genome screen re-sults provide additional support for a bipolar predispo-sition gene in this region, particularly withinCaucasian populations [Detera-Wadleigh et al., 1997;Ewald et al., 1998; McInnis, 1997; Nothen, 1997;Philibert et al., 1997]. As with most psychiatric genet-ics findings, there are also negative reports of linkageto bipolar disorder in this region [Raeymaekers, 1997;Rice, 1997; Schofield, 1997]. There is one report (an abstract) of a family withcases of schizophrenia and schizoaffective disorder thatgave a positive linkage score (lod 1.96) to markerD4S403, near DRD5, although analysis in an addi-tional 23 pedigrees collected by the same group failedto provide supportive evidence for this finding. [Asher-son et al., 1998]. On chromosome 18 there are two distinct regions ofinterest for affective psychoses. Berrettini and co-workers [Berrettini et al., 1994, 1997, 1998] reported asuggestive finding in the analysis of five chromosome18 pericentromeric marker loci (APM,