Loring J. Ingraham

Adoption studies of schizophrenia

The observation that schizophrenia is more commonly observed among the relatives of individuals with schizophrenia than in the general population does not indicate the mechanism that produces such familiality occurs. Adoption designs permit evaluation of the role of genetic factors in schizophrenia independently of the influence of family environments. Results from studies of adoptees with schizophrenia and their biological and adoptive relatives indicate that genetic factors play a highly significant role in the risk for schizophrenia. This genetically mediated risk to relatives includes an increased prevalence of both schizophrenia and a nonpsychotic syndrome analogous to schizophrenia, but does not represent a general liability to other forms of psychopathology. Although adoption studies have convincingly demonstrated an important role for genetic factors in schizophrenia, the necessity and specificity of such factors, their precise identity, and their interaction with environmental influences remain unknown.

Two novel polymorphic sequences in the glucocerebrosidase gene region enhance mutational screening and founder effect studies of patients with Gaucher disease

Gaucher disease, an inherited glycolipid storage disorder, is caused by a deficiency of the catabolic enzyme glucocerebrosidase (EC 3.2.1.45). The gene for human glucocerebrosidase is located on chromosome 1q21 and has a highly homologous pseudogene situated 16 kb downstream. We report two novel polymorphic sequences in the glucocerebrosidase gene region: the first consists of a variable number of dinucleotide (CT) repeats located 3.2 kb upstream from the glucocerebrosidase gene, and the second is a tetranucleotide (AAAT) repeat found between the glucocerebrosidase gene and its pseudogene, 9.8 kb downstream from the functional gene. These polymorphic sequences, along with a previously reported PvuII polymorphism in intron 6 of the glucocerebrosidase gene, were analyzed in patients with Gaucher disease (n=106) and in two normal control populations, one of Ashkenazi Jewish ancestry (n=72) and the second comprising non-Jewish individuals (n=46). In these samples, strong linkage disequilibrium was found between mutations N370S, c.84–85insG, and R463C and specific haplotypes; no significant linkage disequilibrium was found when examining haplotypes of patients with the L444P mutation. Studies of these polymorphic sites in several instances also led to the recognition of genotyping errors and the identification of unusual recombinant alleles. These new polymorphic sites provide additional tools for mutational screening and founder effect studies of Gaucher disease.

Genetic transmission and improved diagnosis of schizophrenia from pedigrees of adoptees

In previous investigations of the prevalence of schizophrenic illness among the biological relatives of schizophrenic adoptees in Copenhagen and the remainder of Denmark, the operation of heritable spectrum illness was clearly implicated. The findings supporting that conclusion are briefly summarized. Classical chronic schizophrenia was found almost exclusively in the biological relatives of chronic schizophrenic probands and its prevalence was ten times greater than that in the biological relatives of controls. These were global diagnoses, made without knowledge of the relationships and family histories of the subjects, and based upon the descriptions of dementia praecox or schizophrenia by Kraepelin and Bleuler. They showed considerably greater sensitivity and at least equal specificity in comparison with diagnoses made on the same material in accordance with operational criteria as exemplified by DSM-III. The prevalence of a disorder in the biological relatives of adoptees with that disorder in comparison with biological relatives of control adoptees offers a useful test for the expression of genetic factors in the disorder, but also a much needed evaluation of the validity of diagnoses based on clinical observation.

The relationship of occipital skull asymmetry to brain parenchymal measures in schizophrenia

It has long been hypothesized, but never proven that an organic brain injury early in life predisposes to schizophrenia. Since brain and cranial development are closely linked, if such an event occurred early enough in the premorbid course of schizophrenia, it could conceivably effect skull architecture. To approach this question, the occipital bone depth and the occipitomedian angle were measured in 50 patients with chronic schizophrenia and in 35 medical controls. Strong correlations emerged between the skull asymmetry indices and the occipital and temporal lobe parenchymal asymmetry indices. There were no statistically significant differences in cranial asymmetry measures between the patients with schizophrenia and the medical controls. However, when the comparison was limited to right handed individuals with homolateral sighting dominance, a weak, but statistically significant trend was observed for more symmetrical slanting along the sagittal suture in the schizophrenic patients. In addition, cranial asymmetry was weakly predictive of increased prefrontal markings in the schizophrenic patients. The congruence of skull findings with parenchymal variables suggests that certain aspects of skull and parenchymal architecture are co-determined.

A Cautionary Note on the Interpretation of Relationship Effects in the Social Relations Model

Kenny and La Voies Social Relations Model (1984) is a promising approach to the analysis of social interaction data which simultaneously and independently assesses individual differences and relationship-specific effects among interacting subjects. Unfortunately, some authors have used one-replication studies (which confound error and relationship-specific variance) and have interpreted the confounded relationshiplerror variance component as a relationship effect. We reanalyzed behaviorally coded data from four experiential groups. Side by side one-replication and two-replication Round Robin Analyses of Variance of two behaviors demonstrated the danger of interpreting the eonfounded relationship/error component of one-replication analyses as a relationship effect. With questioning behavior, one-replication analyses suggested a relationship-specific effect, but a two-replication analysis indicated that this finding was error variance. For self-disclosing behavior, the two-replication analysis confirmed the suggested relationship effect from the one-replication analyses. Researchers interested in relationship-specific effects using the Social Relations Model should design their studies to allow for two or more replications and report relationship variance terms unconfounded with error.

A social relations model test of Sullivan's anxiety hypothesis

Interpersonal relationships and mutual influence are important aspects of both personality and behavior. However, empirical tests of mutual influence in anxiety have not occurred because of difficulties in design and assessment. In this report, we present a study of two training groups of graduate students and a study of an outpatient psychotherapy group. In both studies relationship-specific variance was significant and accounted for a substantial proportion of the systematic variance. In the training groups, there were also significant individual differences in experienced anxiety. These studies support the importance of relationships in anxiety but not Sullivans hypothesis of the exclusive interpersonal nature of anxiety (Sullivan, 1964). The results address Endler and Magnussons (1976a, 1976b) interactional approach to anxiety by assessing dynamic interaction rather than mechanistic interaction. In addition, these studies extend the use of the Social Relations Model to a new area, anxiety, and demonstrate its use in separating relationship-specific adjustments in anxiety from individual differences in anxiety.

Skull asymmetry and handedness in adults: a possibility of their association with lateral head turning in infancy.

During the first two to three months after delivery infants when placed in the supine position commonly turn their heads laterally. This posture has been linked to the intrauterine orientation of the fetus. Skulls of adults were expected to bear a mark of this predominant head position in the form of occipital flattening. A blind examination of computerized axial tomography (CT) scans of 35 normal subjects assessed for handedness (20 right- and 15 mixed-handers) confirmed this prediction for the latter group only. Mixed-handers showed a slight, but reliable flattening of the tight occiput. Also, there was a small but significant inverse association between the size of the petrous ridge and handedness. Examining subtle variations in skull shape of adults may provide a glimpse into some aspects of pre- and early postnatal development.

Managing the pandemic of obesity: siding with the fox or the hedgehog?

Obesity is a major public health problem of pandemic proportion. Despite its high prevalence and widespread distribution (consistent with a common underlying etiology), clinical psychologists and primary care physicians routinely approach the problem with individualized but often ineffective treatments like psychotherapy and pharmacotherapy, or propose alterations to specific components of the ‘toxic environment’, cultural influences, and psychosocial factors purported to cause overeating. This paper presents an alternative perspective and proposes a potential framework for assisting health professionals in developing rational approaches to education about and preventive treatment of obesity based on the role of factors in early life that contribute to personality and behavior and which over time lead to obesity and its maintenance.

Genetic Risks in Schizophrenia: Cross-National Prospective Longitudinal High-Risk Studies

Prospective longitudinal studies are a powerful means to identify the causal chains of biological and environmental factors that underlie the development of serious mental disorders. Schizophrenia is one of these disorders. Schizophrenia is a multifactorial neurodevelopmental disorder whose specific molecular genetic, epigenetic, stochastic, and environmental bases remain elusive. The chronic debilitating nature of the disorder places a heavy emotional and financial burden on the individual, family, and society. Although the lifetime prevalence of schizophrenia is 1% in the general population that has passed through the risk period, it accounts for up to 3% of total national health-care expenditures in Western countries (Knapp, Mangalore, & Simon, 2004). The hypothetical ability to intervene in the developmental progression of the disorder at a point before breakdown is contingent upon the elucidation of early behavioral and other markers of genetic liability to the disorder and their triggers. In this chapter, we focus on research aimed at early detection of markers that may predict to the later onset of schizophrenia. Once these markers are identified, intervention can, at least in principle, be targeted to those individuals most at risk for the disorder.

Is There Psychopathology in the Coparents of Schizophrenic Adoptees' Half-Siblings?

An excess of schizophrenia has been observed in the biological relatives of adoptees with schizophrenia. The present analysis examined the possibility that illness observed among 90 half-siblings may have been influenced by assortative mating resulting in excess illness in the biological parents of the half-siblings not biologically related to the adoptees (the coparents). We found no difference in the prevalence of mental illness between 44 index and 26 control coparents.