Schizophrenia is associated with a number of anatomical and physiological abnormalities outside of the brain, as well as with a decrease in average life span estimated at 20% in the United States. Some studies suggest that this increased mortality is not entirely due to associated causes such as suicide and the use of psychotropic medications. In this article, in order to focus greater attention on the increased mortality associated with schizophrenia, we present a special case of the hypothesis that physiological abnormalities associated with schizophrenia make a contribution to the increased mortality of schizophrenia: specifically, the hypothesis that schizophrenia is a syndrome of accelerated aging. Evidence consistent with this hypothesis comes from several areas. The biological plausibility of the hypothesis is supported by the existence of established syndromes of accelerated aging and by the sharing of risk factors between schizophrenia and other age-related conditions. We propose methods for testing the hypothesis.

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Is Schizophrenia a Syndrome of Accelerated Aging

Somatotyping—Development and Applications

The involvement of Reelin in neurodevelopmental disorders.

Endophenotypes in schizophrenia: a selective review.

OBJECTIVE: In a previous study, the authors demonstrated an association between prenatal famine in middle to late gestation and major affective disorders requiring hospitalization. In this study, they sought to examine the association by using newly identified cases from the Dutch birth cohort used previously to examine the gender specificity of the association and to assess whether this relation is present for both unipolar and bipolar affective disorders. METHOD: The authors compared the risk of major affective disorder requiring hospitalization in birth cohorts who were and were not exposed, in each trimester of gestation, to famine during the Dutch Hunger Winter of 1944–1945. These cases of major affective disorder requiring hospitalization were newly ascertained from a national psychiatric registry. A larger data set from this registry was used for analysis by gender and diagnostic subtype. RESULTS: For the newly ascertained cases, the risk of developing major affective disorder requiring hospitaliza...

Further Evidence of Relation Between Prenatal Famine and Major Affective Disorder

The aim of the study is to investigate the rate and topographical pattern of minor physical anomalies in schizophrenic patients and normal subjects and determine their value in predicting the patient-control status. Seventy-six schizophrenic inpatients (43 men, 33 women) and 82 normal control subjects (42 men, 40 women) were examined for minor physical anomalies on the Waldrop scale. Schizophrenics showed a higher rate for almost all examined anomalies, the differences reaching statistical significance for six of them: fine electric hair, epicanthus, high/steepled palate, tongue with smooth/rough spots, third toe the second, and big gap between I and II toes. They have significantly higher values for 5 out of 6 body regions and for the total anomalies score. Anomalies in schizophrenics show higher prevalence in the craniofacial complex than the periphery, but the periphery is also considerably stigmatized. Seven anomalies distinguish patients from controls, classifying correctly 81.6% of the patients and 82.9% of the controls. Some anomalies show an almost equal rate in the schizophrenics and the controls, while the rate of others is more than 10 times greater in the patients (odds ratios range: 1.0 to 10.9). Viewed within the multifactorial-polygenic threshold model of liability to a disease, minor physical anomalies might reflect a type of neurodevelopmental risk factor, which by interaction with other genetic or environmental factors could result in passing a threshold and producing symptoms of the disorder, at least in one subpopulation of schizophrenics.

Minor physical anomalies in schizophrenic patients and normal controls

Minor physical anomalies (MPAs) are slight structural aberrations that are believed to be associated with abnormal neurodevelopment. Studies of schizophrenia patients show that these patients score higher in MPAs than normal controls. The present study attempted to assess the potential value of MPAs as a classifying test in the status schizophrenia patient versus normal control. Seventy-six schizophrenia patients and 82 normal controls were assessed for MPAs using the Waldrop Physical Anomaly Scale, and specificity, sensitivity, and predictive value of the total MPA score were determined. A significantly higher percentage of schizophrenia patients than normal controls had high numbers of MPAs. Total MPA scores higher than 4 showed the most balanced set of sensitivity (76.3%), specificity (72.0%), and positive (71.6%) and negative (76.6%) predictive values for schizophrenia and were the cutoff scores that optimally discriminate schizophrenia patients from normal controls. Schizophrenia patients showed a higher percentage of subjects with prominent MPA scores. The results are consistent with the hypothesis that MPAs might reflect extragenetic stressful events and present total MPA score as a reliable index in distinguishing between schizophrenia patients and normal controls.

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Discriminating value of total minor physical anomaly score on the Waldrop physical anomaly scale between schizophrenia patients and normal control subjects.

The aim of the study is to investigate the reliability (internal consistency) of the Waldrop Physical Anomaly Scale in patients with schizophrenia. The subjects were 76 schizophrenic patients (43 men, 33 women) and 82 normal controls (42 men, 40 women) of Bulgarian origin who were examined for minor physical anomalies. The correlations between the anomalies are low in schizophrenia, which indicates poor internal consistency of the scale, probably due to the heterogeneity of the anomalies in terms of location, character, and time of prenatal development. Some sex-related differences in the scale's reliability are indicated. The findings suggest the necessity of a more comprehensive scale by including informative morphogenetic variants, which can provide reliable anomaly assessment, distinguishing between minor malformations and phenogenetic variants and indicating the possible period of prenatal adversity.

Internal consistency of Waldrop Physical Anomaly Scale in schizophrenic patients.

Objectives
Minor physical anomalies (MPAs) have been investigated by numerous studies in patients with schizophrenia in support of the neurodevelopmental hypothesis of the disorder, but have rarely been examined in patients with bipolar disorder or in direct comparisons between the two conditions. The main objective of the present study was to compare the prevalence of MPAs in psychiatrically healthy controls, patients with bipolar I disorder, and patients with schizophrenia.

Methods
A slightly modified version of the Waldrop Physical Anomaly Scale was used to assess MPAs in psychiatrically healthy controls (n = 103), patients with bipolar I disorder (n = 61), and patients with schizophrenia (n = 128).

Results
In five out of six topographic regions (mouth, feet, head, eyes, and ears) there was a pattern of lowest regional MPA scores in controls, intermediate in bipolar I disorder, and highest in schizophrenia. The cephalofacial composite score and the total MPA score showed the same pattern, with all between-group differences being statistically significant. Seven individual MPAs in the discriminant analysis model contributed independently to the prediction of the triple-dependent status of ‘psychiatrically healthy control, bipolar I disorder patient, schizophrenia patient’: high/arched palate, fine electric hair, large gap between first and second toes, third toe ≥ second toe, epicanthus, malformed ears, and furrowed tongue.

Conclusions
Our findings support the existence of a continuum of neurodevelopmental adversity within the clinical spectrum of psychosis, with bipolar I disorder occupying an intermediate position between psychiatric health and schizophrenia.

Stefan T. Sivkov

Papers

Minor physical anomalies in schizophrenic patients and normal controls

Discriminating value of total minor physical anomaly score on the Waldrop physical anomaly scale between schizophrenia patients and normal control subjects.

Internal consistency of Waldrop Physical Anomaly Scale in schizophrenic patients.

Minor physical anomalies in schizophrenia and bipolar I disorder and the neurodevelopmental continuum of psychosis

Sexual dimorphism in minor physical anomalies in schizophrenic patients and normal controls