Robert C. Alexander

Minor physical anomalies in schizophrenia

Using the Waldrop scale, minor physical anomalies were studied in 82 Caucasian subjects, including 41 schizophrenic and 8 bipolar adults, as well as 14 normal and 19 mentally retarded adults. An increased incidence of minor physical anomalies was found in the mentally retarded adults relative to the other groups. Consistent with previous studies, there was a trend for the total mean Waldrop score of the schizophrenic group to be higher than the mean score of the normal group. Minor physical anomalies (assessed by the Waldrop scale), however, appear to be of questionable utility in identifying “congenital” schizophrenia, at least as this putative subgroup of schizophrenia is currently conceptualized.

A study of oral morphine preference in inbred mouse strains.

C57BL/6J mice, in two-bottle choice paradigms, show increased oral morphine consumption, compared with DBA/2J mice. To determine whether this C57 morphine preference reflects differences in the receptor-mediated, reward-based action of morphine (as opposed to pharmacokinetic or gustatory differences), three experiments were performed. Consistent with previous two-bottle choice experiments, C57 mean (+/- S.D.) morphine consumption was 18 +/- 3 mg/kg/day, while the DBA mice consumed 1.4 +/- 1.2 mg/kg/day. Intraperitoneal naltrexone produced a 50% decrease in C57 morphine consumption (p < 0.01), while DBA mice showed no change. Consumption of fluid from the control bottle was not changed for either strain. Fifteen and 30 min after oral consumption of a morphine solution, plasma levels of morphine and its glucuronide derivative were not different between these two strains. C57 mice maintained a daily morphine intake of approximately 20 mg/kg across morphine concentrations of 0.05-0.4 mg/ml. These experiments suggest that the difference in oral morphine preference between C57 and DBA mice represents a reward-based mechanism which is mediated through opiate receptors.

Changing Patterns of Illicit Substance Use Among Schizophrenic Patients: 1984–1996

Over 1,700 psychiatric emergency room visits of schizophrenic and schizoaffective patients between 1984 and 1996 were reviewed, and urine drug screens (UDS) were recorded. Illicit drug use increased significantly over the 12-year period, with a large increase for cocaine (0% to 73% of positive UDS), a decline for amphetamines (60% to 0%), and a small increase for marijuana (0% to 27%). Opiate and sedative use remained unchanged. The results support the impression that cocaine use increased dramatically among urban schizophrenic patients beginning in 1988 and continuing to the present. Furthermore, cocaine seems to have replaced amphetamines as the preferred drug of abuse among schizophrenic persons following the crack epidemic.

Genomic screening for genes predisposing to bipolar disease

Twenty-one multiplex bipolar (BP) families, consisting of 365 informative persons (of whom 153 have BPI, schizoaffective, BPII with major depression or recurrent unipolar diagnoses) were studied in a systematic screening of chromosomes 1, 10q, 11q, 13, 15 and 17 for linkage, using DNA markers. Simulation research has indicated that this pedigree series has greater than 50% power to detect linkage when only 25% of families are linked (1% recombination) to the marker. Two and three-point linkage analysis (using the diagnoses mentioned above as affected and an autosomal dominant disease mode1) did not reveal any evidence for linkage (total lod scores less than - 2) under the hypothesis of homogeneity. Inspection of two-point lod scores by family did not reveal evidence for heterogeneity in nearly all cases. Heterogeneity analyses using the admixture test were conducted for a region of 11q13 (where inspection of 2-point analyses for individual families revealed several weakly positive lod scores) which yielded a maximum lod score of 1.5 when the fraction of linked families was estimated at 25%. These results indicate that a gene responsible for BP disease in a majority of the families studied is unlikely to originate within the chromosomal regions covered by the DNA markers used.

Schizencephaly associated with psychosis

Schizencephaly is a rare disorder of brain development resulting in the formation of abnormal unilateral or bilateral clefts in the cerebral hemispheres. It is often accompanied by partial seizures, mental retardation, and hemiparesis. Two patients are described with clear psychotic symptoms with either unilateral or bilateral schizencephaly. The implications of the association between schizencephaly and psychosis in these patients for understanding the biology of the psychoses are discussed.

Counter clockwise scalp hair whorl in schizophrenia

Recent work has suggested that schizophrenia may be a neurodevelopmental disorder (Weinberger !987; Murray and Lewis 1987; Benes et al 1986). Evidence for this hypothesis includes epidemiologic studies indicating that e~:posure to a physical insult during the second trimester of gestation may be associated with schizophrenia in later life (Torrey et al 1975; Huttunen and Niskanen 1978; Mednick et al 1988). In addition, several structures reported to be deviant in schizophrenia, ineluding the hippocampus, thalamus and basal ganglia, are formed during the second trimester (Lyon et al 1989). Braeha et al ( 1991), noting that development of the distal upper limb occurs in the second trimester, studied hand anomalies in a group of monozygotic twin pairs discordant for schizophrenia and found a higher frequency of hand maldevelopment scores in the schizophrenic twins than in the unaffected twins, implicating a second trimester insult in these patients. Scalp hair patterning is determined during