Minor physical anomalies in schizophrenia

This study was conducted to investigate the value of using physical anomalies (PAs) to evaluate early prenatal injury in schizophrenia. PAs are minor abnormalities in development of the head, hands, and feet that are presumably associated with insult during the first trimester. Sixty-seven schizophrenic inpatients and 88 normal controls were evaluated for PAs. The schizophrenic patients showed significantly more anomalies than the controls. The difference remained significant even when patients were compared to controls of low socioeconomic status. Both male and female patients showed a high incidence of mouth abnormalities, and female patients showed a high incidence of abnormalities in head circumference. Patients with early age of onset (less than or equal to 18 years) had more physical anomalies than did later onset patients. This relationship was most noticeable for males. Physical anomalies were not associated with deficits on measures of vigilance, selective attention, or orientation.     

Minor physical anomalies and behavior in children: A review

The recent literature concerning minor physical anomalies (MPA) and their relation to behavior is reviewed. Research seems to indicate that for males there is considerable consistency in the results but the finding with females is tenuous at best. It appears that a high number of MPA are evident in several pathological groups of boys, as compared with normal controls. In addition, there is a suggestion that MPA are correlated with severity of hyperactivity, IQ, and school achievement. Furthermore, there is also a relationship between a high number of MPA and obstetrical complications. The etiology of MPA and their utility in predicting pathological behavior is discussed.     

Minor physical anomalies in childhood autism

A group of autistic children have been found to have an excess of minor physical anomalies (MPA) and birth and pregnancy complications. However, there was not a significant positive correlation between the birth and pregnancy complications and the MPA. The relationship between MPA and maternal age in these autistic children was investigated. In the 45 autistic children studied, there was a significant positive correlation between MPA and maternal age at birth. The significance of the relationship between MPA and maternal age deserves further study. The author thanks M. Stockwell, Reg. N., F. Abichandani, M.D., and J. Simeon, M.D., for their work on the initial project, and A. Kopys and D. Offord, M.D., for their helpful assistance.     

Minor physical anomalies in schizophrenia: a meta-analysis

Numerous studies report an increased frequency of minor physical anomalies (MPAs) in schizophrenic individuals compared with controls. However, these studies vary considerably regarding the magnitude of the case-control disparity and the topographical distribution of the anomalies. A meta-analysis was carried out on the existing MPA literature in an effort to better understand the relationship between MPAs and schizophrenia. Following a literature search, 13 studies were identified that met our inclusion criteria. Mean total MPA scores were available for 11 of these studies, whereas only seven studies provided regional MPA scores. For both the total MPA and regional MPA analyses, pooled effect sizes (Hedges' g and pooled odds ratios, respectively) were calculated along with tests of heterogeneity. For the total MPA analyses, a meta-regression approach was used to explore the relationship between possible moderator variables (e.g., number of MPA scale items) and effect size heterogeneity. The magnitude of the pooled effect size for the total MPA scores was high (1.131; p<0.001), indicating significantly more overall MPAs in schizophrenic individuals. Significant effect size heterogeneity was present (p<0.001); however, this heterogeneity could not be explained by any of the included moderator variables. The regional MPA analysis revealed significantly increased MPAs in all six anatomical regions (p<0.05), although the pooled odds ratios for these regions did not differ significantly from one another. These results suggest a lack of regional specificity for MPAs in schizophrenia.     

Minor physical anomalies in autism: a meta-analysis

Autism is a complex neurodevelopmental disorder in which the interactions of genetic, epigenetic and environmental influences play a causal role. Despite the compelling evidence for a strong heritability, the etiology and molecular mechanisms underlying autism remain unclear. High phenotypic variability and genetic heterogeneity confounds the identification of susceptibility genes. The lack of robust indicators to tackle this complexity in autism has led researchers to seek for novel diagnostic tools to create homogenous subgroups. Several studies have indicated that patients with autism have higher rates of minor physical anomalies (MPAs) and that MPAs may serve as a diagnostic tool; however, the results have been inconsistent. Using the cumulative data from seven studies on MPAs in autism, this meta-analysis seeks to examine whether the aggregate data provide evidence of a large mean effect size and statistical significance for MPAs in autism. It covers the studies using multiple research methods till June 2007. The current results from seven studies suggested a significant association of MPAs in autism with a robust pooled effect size (d=0.84), and thereby provide the strongest evidence to date about the close association between MPAs and autism. Our results emphasize the importance of MPAs in the identification of heterogeneity in autism and suggest that the success of future autism genetics research will be exploited by the use of MPAs. Implications for the design of future studies on MPAs in autism are discussed and suggestions for further investigation of these important markers are proposed. Clarifying this relation might improve understanding of risk factors and molecular mechanisms in autism.     

Minor physical anomalies and vulnerability in prodromal youth

Because both the brain and craniofacial/limb features originate from the same germinal layer during early gestation, the postnatal presence of minor physical anomalies (MPAs) involving these physical features may be indicative of defects in prenatal neural migration and consequent brain abnormalities among individuals with psychosis. However, to date it is unknown what symptoms and characteristics MPAs may be associated with, or how these markers may reflect vulnerability among adolescents at high-risk for developing psychosis. This information is particularly vital for understanding susceptibility and informing etiological conceptualizations such as the neural diathesis-stress model. In this study, 50 adolescents with a prodromal syndrome were evaluated for MPAs, salivary cortisol, auditory and visual memory function, and attenuated positive, negative, and disorganized symptoms. Results indicated that the participants showing elevated MPAs (n=25) were distinguished by elevated cortisol, deficit immediate and delayed visual memory, and higher levels of disorganized prodromal symptoms when compared with those participants exhibiting a lower incidence of MPAs. This was supported by supplementary correlational analyses examining the entire sample. These findings provide preliminary support for a theory that MPAs may reflect hippocampal system vulnerability among prodromal patients.     

Minor physical anomalies in schizophrenic patients and normal controls

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 childhood and adolescent onset schizophrenia

A modified version of the Waldrop scale (WS) was used to assess the prevalence of minor physical anomalies in schizophrenic patients (n = 71) and healthy controls (n = 65). The mean total WS score was 3.32 (SD 1.98) for the schizophrenic patients, significantly higher than that for the controls (2.19, SD 1.18). Minor physical anomalies were compared between two schizophrenic groups, divided on the basis of age at onset, early onset schizophrenia (EOS, onset under age 18 years) group and late onset schizophrenia (LOS, onset at or above age 20 years) group. The mean total WS score was 3.92 (SD 1.86) in the EOS group, significantly higher than the 2.59 (SD 1.79) in the LOS group. Minor physical anomalies are an indirect index for early prenatal central nervous system (CNS) maldevelopment; the present study indicated association between minor physical anomalies and EOS, thus a relationship between early prenatal CNS maldevelopment and EOS. These results support the hypothesis that EOS constitutes a subset of schizophrenia in which neurodevelopmental damage is largely involved.     

Minor physical anomalies in normal,neurotic, learning disabled,and severely disturbed children

A high incidence of minor physical anomalies in a childhood schizophrenic population has been previously reported by Goldfarb. In the present study, 108 boys from four different clinical populations were examined, utilizing a standardized anomaly scoring system for which a high interrater reliability was obtained. The patient populations were: general pediatric ward patients (n=31), psychoneurotic outpatients at a university child guidance clinic (n =26), learning disabled children (n=23), and autistic, borderline, and atypical children (n=28) from two residential treatment centers. Both the learning disabled and residential treatment populations had higher mean anomaly scores than did the first two groups, but did not differ significantly from each other. There was a trend for patients with multiple anomalies to have had more frequent history of prenatal insults or paternal psychopathology. These results indicate that the development of these minor anatomical anomalies which are formed in the first three months of fetal development may parallel early developmental deviation of the central nervous system. The finding of high anomalies in the residential treatment groups supports the idea that some of these patients share a common etiology with the other early developmental deviations, such as speech delay or mental retardation, for which high anomaly scores have also been reported.     

Minor physical anomalies in schizophrenia and bipolar affective disorder.

OBJECTIVE: The prevalence of minor physical anomalies (MPAs) (prenatal errors of morphogenesis) was evaluated in patients with schizophrenia and bipolar affective disorder. METHOD: A new modification of the Waldrop-scale was used to detect the presence or absence of 57 MPAs in 30 patients with schizophrenia, 30 with bipolar disorder, and in 30 matched normal controls. RESULTS: Patients with schizophrenia compared to normal controls had significantly higher rates of three minor malformations (furrowed tongue, flat occiput, primitive shape of ears) and those of one phenogenetic variant (wide distance between toes 1 and 2), and they also had a significantly higher rate of one minor malformation (primitive shape of ears), as compared to patients with bipolar disorder. In patients with bipolar disorder, furrowed tongue was significantly more common than in controls. CONCLUSIONS: These results support an 'early' neuro-developmental model of schizophrenia.     

Minor physical anomalies in neurodevelopmental disorders: a twin study

Background

Minor physical anomalies (MPAs) are subtle anatomical deviations in one’s appearance and may suggest altered embryogenesis. MPAs have been shown to be more common in neurodevelopmental disorders (NDDs) compared with typical development. Still, further studies are needed on MPAs in NDDs, especially using twins to adjust for confounding familial factors.

Methods

Clinical assessments were conducted on 116 twins (61 NDD, 55 controls) from 51 monozygotic and 7 dizygotic pairs to examine MPAs and their association with DSM-5 defined NDDs. Additionally, the relationship between the number of MPAs within twins by zygosity was investigated.

Results

Within the cohort sample, a specific association was found between MPAs and autism spectrum disorder (ASD) diagnosis (crude odds ratio = 1.29, p = .047; adjusted odds ratios = 1.26–1.33, adjusted p values = .032–.073) and autistic traits (crude β = 3.02, p = .002; adjusted β = 2.28, p = .019), but not NDDs in general or ADHD, nor within-pairs. Identified MPAs in ASD included overweight, hypermobility, pes planus, straight eyebrows, vision impairment, arachnodactyly/long toes, long eyelashes, and microtia. The number of MPAs within all monozygotic pairs was highly correlated (r = .88, p < .001).

Conclusion

MPAs are more frequent in participants with ASD and may be influenced by genetics. The value of MPAs for (early) detection should be further explored, as they might index individuals at increased risk for ASD in particular.

     

Minor physical anomalies and recidivistic adult violent criminal behavior

Minor physical anomalies (MPA) result from disruptions of gestation, and may be used as signs of central nervous system defects in development. Utilizing a Danish birth cohort, we tested the hypothesis that MPA predict adolescent and adult recidivistic violent criminal behavior. The number of MPA was measured at 11 to 13 years of age and police records of criminal behavior were ascertained at 20 to 22 years of age. Recidivistic violent offenders evidenced an elevated level of MPA compared with subjects with one violent offense or subjects with no violent offenses.     

Minor physical anomalies across ethnic groups in a first episode psychosis sample

Minor physical anomalies (MPAs) are more prevalent amongst individuals with psychosis, supporting a neurodevelopmental model for psychotic disorders. The aim of this study was to investigate the possibility that neurodevelopmental adversity contributes to the excess of psychosis found in some ethnic groups in the UK. Subjects with first onset psychosis and healthy neighbourhood controls were enrolled in the AESOP study in South East London and Nottingham between 1997 and 1999. MPA rates were estimated in four broad ethnic groupings (White, African Caribbean, Black African and Other). Patients (n=245) had a higher mean total MPA score than healthy controls (n=158). This held true across each of the four ethnic groupings. The results of this study suggest that neurodevelopmental factors play a role in the aetiology of psychosis across all ethnic groups.     

Minor physical anomalies and schizophrenia spectrum disorders: a prospective investigation

OBJECTIVE: The authors prospectively assessed the relationship between minor physical anomalies identified in childhood and adult psychiatric outcome. METHOD: In 1972, minor physical anomalies were measured in a group of 265 Danish children ages 11-13. The examination was part of a larger study investigating early signs of schizophrenia spectrum disorders. Many of the subjects had a parent with schizophrenia, leaving them at high risk for developing a schizophrenia spectrum disorder. In 1991, adult psychiatric outcome data were obtained for 91.3% (N=242) of the original subjects, including 81 who were at high risk. RESULTS: Individuals with a high number of minor physical anomalies developed schizophrenia spectrum disorders significantly more often than they developed a no mental illness outcome. Further, individuals with a high number of minor physical anomalies tended to develop schizophrenia spectrum disorders more often than other psychopathology. Among individuals at genetic high risk, higher numbers of minor physical anomalies may interact with pre-existing vulnerabilities for schizophrenia to increase the likelihood of a schizophrenia spectrum disorder outcome. CONCLUSIONS: Minor physical anomalies may provide important clues to understanding schizophrenia spectrum disorders from a neurodevelopmental perspective. Minor physical anomalies appear to signal stressors relevant to schizophrenia spectrum development, especially in those at genetic risk for schizophrenia.     

Minor physical anomalies in familial and sporadic schizophrenia: the Maudsley family study

OBJECTIVES—(1) To test the hypothesis that minorphysical anomalies are increased in patients with schizophrenia and (2)to investigate differences in the prevalence of minor physicalanomalies in patients with familial and sporadic schizophrenia andtheir first degree relatives.
METHODS—A weighted Waldrop assessment was carriedout on 214 subjects in five groups: schizophrenic patients frommultiply affected families; first degree relatives of these familialschizophrenic patients; sporadic schizophrenic patients; first degreerelatives of these sporadic schizophrenic patients, and normalcontrols. Broad and narrow criteria for abnormality were defined basedon the distribution of minor physical anomalies in the control group.
RESULTS—(1) The total schizophrenic group did nothave a significant increase in minor physical anomalies using a narrowcriterion of abnormality, but did when a broader criterion was used.(2) A significant increase in the proportion of subjects with anabnormally high number of minor physical abnormalities was shown in thegroup of sporadic schizophrenic patients (uncorrected p<0.01).Separate analyses for males and females showed a significant increasein the male sporadic group (uncorrected p<0.05), and a smallernon-significant increase in the female sporadic group. Neither thefamilial schizophrenic group nor either group of first degree relativesshowed any significant increases in the proportion of patients withhigh abnormality scores.
CONCLUSION—This work supports prenataldevelopmental abnormality as a mechanism for sporadic, but notfamilial, schizophrenia.

     

Minor physical anomalies: potentially informative vestiges of fetal developmental disruptions in schizophrenia

Minor physical anomalies (MPAs) are subtle signs of developmental deviation that are observed at an elevated frequency among patients with schizophrenia. These minor morphological abnormalities of the craniofacial region and limbs arise during fetal development and represent a set of risk markers for schizophrenia. Although MPAs are not specific to schizophrenia, established findings about MPAs vis-à-vis schizophrenia include the replicated findings that MPAs are more prevalent among individuals with schizophrenia than healthy controls, MPAs are more prevalent among individuals with schizophrenia than unaffected relatives, and MPAs are not consistently associated with symptom domains or other risk markers, such as neurological soft signs. Unresolved questions include whether or not MPAs are more prevalent among unaffected relatives than healthy controls, and which specific MPAs are most associated with schizophrenia. This overview presents three promising avenues of further research on MPAs, including: (1) studies relying on traditional summary scores that combine multiple MPAs, which may have a role in prospective risk stratification in conjunction with other risk markers and endophenotypes; (2) research on specific, quantitatively assessed MPAs (especially in specific craniofacial structures) that may inform neurodevelopmental understandings of schizophrenia; and (3) genetic studies aimed at identifying the heritable and nonheritable determinants of specific MPAs, which may increase the field's understanding of the origins of MPAs and the nature of their association with schizophrenia.