Subclinical microcrania, subclinical macrocrania, and fifth-month fetal markers (Of growth retardation or edema) in schizophrenia: A co-twin control study of discordant monozygotic twins

Objectives: We tested the hypothesis that gestational injuries in some patients with schizophrenia would leave their mark as a subtle reduction in head circumference (subclinical microcrania). It had been previously shown that prenatal injuries can differentially affect members of an MZ pair. We therefore examined the relationship between head circumference and a marker of prenatal injury (i.e. an in-utero, nonshared environmental effect) in monozygotic (MZ) twin pairs discordant for schizophrenia. Method: Twenty-two probands with DSM-III-R schizophrenia were compared to their unaffected MZ co-twins. Fetal-size discrepancy between MZ twins is a marker of differential-intrauterine injury to one of the two MZ members. Fingertip dermal cells migrate to form ridges during the fifth month of gestation. Finger-ridge count is lower in the MZ twin which was physically smaller during this fifth-month cell migration period. The intrapair-MZ-unsigned-percent difference in ridge count (MZu'frdRC) is thus an index of fifth-month fetal injury'- The variables of a priori focus in this study were two within-pair physical measures: MZu%dRC and "MZ percent difference in head circumference" (MZ%dHC). Results: There was no overall head-circumference-group difference in the 22 pairs between the affected and unaffected twins; however, we were able to draw some conclusions because of our access to genetically identical controls, which serve as an indicator of what each patient's head circumference and dermal-ridge count would have been if he or she were not afflicted with schizophrenia: among the 12 affected twins with subclinical wwewcrania. none had markers of second-trimester injury, but of the 10 affected MZ twins with subclinical microcrania, five had such injury markers (three had ridge-count markers of second-trimester edema and another two had ridge-count markers of second-trimester-growth retardation, p =.0228). Overall, in the 22 MZ twin pairs. a significant relationship was found between MZ%dHC and MZu%dRC (Spearman's rs = -0.45; p <.036). Of the variance in head circumference, 20.2% were predicted by within-pair discrepancy in ridge counts. Conclusions: The head circumferences of all subjects were in the normal range. Decreased head circumference in affected MZ co-twins (relative to unaffected MZ co-twin) characterizes discordant MZ pairs with larger finger-ridge-count differences (i.e., second-trimester fetal-size differences). This study using ideal genetic controls suggests that, while present only in some patients with schizophrenia, the decrease in head circumference is most likely a consequence of in-utero nonshared environmentaldeleterious events manifesting as growth retardation or as fetal edema and occurring around the fifth prenatal month.