Minor physical anomalies, palmar dermatoglyphics and somatotype: composite anthropometric biomarker predictors in schizophrenia. Mladen Y. Mantarkov1 ...
Minor physical anomalies, palmar dermatoglyphics and somatotype: composite anthropometric biomarker predictors in schizophrenia Mladen Y. Mantarkov1, Ferihan M. Ahmed-Popova2 1 2
Department of Psychiatry and Medical Psychology, Medical University of Plovdiv
Department of Anatomy, Histology and Embryology, Medical University of Plovdiv
Abstract Objective: In the last few decades the validity of psychiatric diagnoses has improved with the identification of biomarkers for a number of mental disorders. Biomarkers generally refer to measureable characteristics which may be used as indicators of a biological state or condition. The aim of the study was to assess the predictive value of composite quantitative anthropometric biomarkers (minor physical anomalies, palmar dermatoglyphics and somatotype) with regard to the group membership of patients with schizophrenia and psychiatrically healthy controls. Material and methods: We used a modified version of the Waldrop scale, the ink method and the Heath-Carter anthropometric method to evaluate minor physical anomalies, palmar dermatoglyphics and somatotype, respectively, in a sample of 141 schizophrenia patients (76 men and 65 women) and 120 psychiatrically healthy controls (54 men and 66 women). A logistic regression model was employed to determine the utility of quantitative anthropometric biomarkers in the prediction of group membership in men and women. Results: Regional minor physical anomaly scores for the head and mouth regions, mesomorphy and total a-b ridge count predicted correctly group membership in 80% of male schizophrenia patients and psychiatrically healthy controls. Regional minor physical anomaly scores for the mouth, ears and feet regions and total a-b ridge count predicted correctly group membership in 74% of female patients and controls. Conclusion: Quantitative anthropometric indices can be used as valid biomarker predictors in schizophrenia. Our findings lend additional support for the neurodevelopmental hypothesis in the etiology of the disorder. Key words: schizophrenia, minor physical anomalies, dermatoglyphics, somatotype, biomarkers
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Introduction In the last few decades the validity of psychiatric diagnoses has improved with the identification of biomarkers for a number of mental disorders. Biomarkers generally refer to measureable characteristics which may be used as indicators of a biological state or condition (1). In psychiatry the term has been used somewhat more specifically to denote characteristics that are distributed differently in psychotic subjects and normal controls, occur with higher frequencies in affected families and predict the onset of psychotic spectrum disorders in individuals at high risk. In order to be useful, biomarkers should be stable over time and lend themselves to non-invasive and reliable measurement (2). Candidate biomarkers at advanced stages of validation in schizophrenia include specific neurocognitive deficits, evoked potentials abnormalities, smooth pursuit eye tracking dysfunctions, neurological soft signs and structural and functional neuroimaging findings. A growing body of evidence supports the validity of certain anthropometric indices (minor physical anomalies, dermatoglyphics and somatotype) as putative biomarkers in schizophrenia (3-5). Evident long before the onset of psychosis, these biological markers sustain the etiological hypothesis of abnormal neurodevelopment in schizophrenia. Minor physical anomalies (MPAs) are considered phenotypic stigmata of developmental abnormality. They comprise a range of subtle, clinically and cosmetically insignificant errors in the development of morphological structures found in the eyes, ears, mouth, head, hands and feet. As the structures that express MPAs have the same embryonic origin as the central nervous system, MPAs may be valuable biological markers of abnormal brain development (6). Reflecting the impact of adverse events at critical stages of prenatal development (the first and early second trimester of pregnancy), MPAs may be informative of the nature and timing of intrauterine factors in the etiology of the disorder. A prerequisite for the utility of dermatoglyphics as biological markers is the stability in the organization of the papillary ridges on the skin of the fingers, palms and soles. Ridge patterns appear on the pads of the fingers, interdigital areas, thenar and hypothenar of the palms and soles during the first and early second trimester (10.5 – 22 gestational weeks) of pregnancy (7). Once developed, they remain unchanged throughout the postnatal period, which allows studying the impact of genetic, epigenetic and environmental factors during critical periods of intrauterine development.
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Since ancient times body build has been a factor that modifies the risk, presentation, course and treatment response of a number of different disease. Kretschmer was the first to acknowledge the association of certain marginal somatotypes with an increased risk for the major psychiatric disorders (8). Later on, Sheldon (9) introduced the concept of somatotype in an attempt to quantify the three components of human physique: mesomorphy (musculoskeletal robustness relative to height, representing meager mass, organs, and total fluid), endomorphy (relative fatness) and ectomorphy (relative linearity or slenderness) (5). Theoretically, Sheldon’s classification was based on the premise that the tissues that give rise to each of the somatotype components derive from the three embryonic germ layers. Meanwhile, it has generally been accepted that somatotype characteristics are determined by the interaction of multiple genetic, epigenetic and environmental factors during the intrauterine and postnatal development of the individual (10). The higher prevalence of MPAs and dermatoglyphic abnormalities in schizophrenia is supported by meta-analyses including large number of subjects (3, 4), while somatotype studies, though numerous, suffer from significant methodological limitations (5). The purpose of the study was to assess the predictive value of composite quantitative biomarker predictors (regional MPAs, ridge counts in the interdigital areas and somatotype components) with regard to the group membership of schizophrenia patients and psychiatrically healthy controls. Material and methods Participants The subjects for this study were patients with schizophrenia and psychiatrically healthy controls. The schizophrenia group consisted of 141 patients (76 men and 65 women), consecutively admitted to the Clinic of Psychiatry at UMHAT “Sveti Georgi” Plovdiv, Bulgaria with a mean age of 33.52 years (±10.72), a mean duration of illness of 9.39 years (± 9.07), and a mean number of hospitalizations of 5.09 (±5.28). The patients satisfied DSM-IV TR criteria for a diagnosis of schizophrenia on the basis of case records review, a semistructured interview based on a checklist of items from DSM-IV TR and information obtained from relatives to enhance the validity of the diagnosis. Potential subjects were excluded if they had any signs of mental retardation, a history of drug or alcohol abuse, an identifiable neurological disorder (seizure disorder, head injury, multiple sclerosis, etc.) or a general medical condition with direct effects on the central nervous system. Additional exclusion criteria were a clinically significant change in body weight (≥7% of original body weight) 3
within the last 6 months or any dermatological condition (e.g. psoriasis, vitiligo and alopecia areata), characterized by abnormal dermatoglyphic status. The control group consisted of 120 psychiatrically healthy subjects (54 men and 66 women) with a mean age of 39.07 years (±10.28), whose socioeconomic status was comparable to the patients’. Psychiatric health was defined as the absence of a major axis I or axis II disorder according to DSM-IV TR criteria (11). The controls satisfied exclusion criteria identical to those applied to the patients. In addition, potential controls were excluded if they had a first-degree relative with a history of psychotic disorder, major mood disorder or suicide. All patients and controls were of Bulgarian ethnicity in order to avoid the potential confounding effects of racial and ethnic variation in MPAs, palmar dermatoglyphics and somatotype. Individuals were excluded if their parental or grandparental ethnic group was other than Bulgarian. The study was approved by the Local Ethics Committee and all subjects gave written informed consent to participate. Assessments Assessment of MPAs The subjects were examined with a slightly modified version of the Waldrop Physical Anomaly Scale (12). The original scale includes 18 morphological abnormalities from six topographic regions: head, eyes, ears, mouth, hands, and feet. Most of the abnormalities are scored qualitatively as present (1) or absent (0). The variables fine electric hair, head circumference, epicanthus, intercanthal distance, low seated ears, high/arched palate and third toe ≥ second are scored in a graded manner - 1 or 2, according to severity. We introduced the following modifications. The categories adherent ear lobes and lower edges of the ears that extend backward/upward (two grades of a single item in the original scale) were defined as separate items because of the high prevalence of the former and only occasional occurrence of the latter. As a result of this distinction, our modification of the scale consisted of 19 items. Furrowed tongue was graded by scoring 1 for randomly furrowed tongue (a normal variant) and scoring 2 for transversely furrowed tongue (frequently observed in pathological conditions). In the original scale both types are scored 1. To determine the variable low seated ears we verified the ear canal position by the level of the ear canal on the head in relation to the midface with the head of the subject placed in the Frankfurt horizontal line. Intercanthal distance abnormality was also determined in cases of hypotelorism. The intercanthal distance as well as the head circumference were scored 1 if they differed from the same-sex mean for 4
psychiatrically healthy controls by 1.5 - 2 SD and 2 if they differed by more than 2 SD in both directions. Regional MPA scores were calculated by adding individual scores for each topographic region. Assessment of palmar dermatoglyphic patterns Rolled palmprints were obtained in a passive manner using an ink method and were read with light (6D) magnification in accordance with the methods proposed by Cummins and Midlo (13). Ridge count in II, III and IV interdigital areas (a-b, b-c and c-d ridge count) was calculated for each of the two hands by counting the number of ridges or points crossing or touching the line of Galton, which connects the central points of two adjacent deltas (a-b, b-c and c-d). Total palm ridge count of both hands was obtained as a total score of the palm ridge count of right and left hand. In cases of additional delta, the true - a - or d - delta was used. Assessment of somatotype Subjects’ somatotype was assessed using the Heath-Carter anthropometric method (10). This method provides three-number ratings representing endomorphy, mesomorphy and ectomorphy, respectively. Values between 0.5 and 2.5 are considered low, between 3 and 5 moderate, between 5.5 and 7 high and above 7.5 very high. The following anthropometric variables were assessed: height, weight, humerus biepicondylar breadth, femur biepicondylar breadth, upper arm girth with biceps brachii muscle maximally contracted, calf girth, skin folds (Harpenden caliper - 10 g/mm2 pressure, 0.5 mm accuracy) – triceps brachii, subscapular, suprailiac, medial calf. All measurements were performed on the right side. Ratings for the somatotype components (endomorphy, mesomorphy and ectomorphy) were calculated on the basis of these anthropometric variables using Heath-Carter formulas (10). Statistical analysis IBM SPSS v.20.0 for Windows was used for all statistical analyses. We used independent samples t-test for comparing the groups of the patients and controls and binary logistic regression (forward stepwise method using the Wald statistic) to determine the utility of quantitative anthropometric indices in the prediction of the patient-control status. In our regression model the six regional MPA scores, the three total ridge counts in II, III and IV interdigital areas (total a-b, b-c and c-d ridge counts) for both hands and the three somatotype components were the independent predictor variables, while the patient-control status was the binary dependent variable. All statistical analyses were performed separately for men and women in view of the available evidence for significant gender differences in MPAs, dermatoglyphics and somatotype (10, 14, 15). The level of statistical significance was set at P
