|Ahead of print publication
Minor physical anomalies in unipolar depression
Durva Balkrishna Sail, Sneh Babhulkar, Ninad Waghmare, Krishna Kadam
Department of Psychiatry, B.J.G.M.C and Sassoon General Hospital, Pune, Maharashtra, India
|Date of Submission||07-Nov-2020|
|Date of Decision||03-Feb-2021|
|Date of Acceptance||16-Apr-2021|
|Date of Web Publication||23-Jul-2021|
Department of Psychiatry, B.J.G.M.C and Sassoon General Hospital, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Minor physical anomalies (MPA), are mild errors of the morphogenesis, having prenatal origin and may bear major information for diagnostic and prognostic purposes. The notion that early brain insults predispose to depression is supported by findings that some patients with the disorder exhibit morphologic evidence of subtle developmental abnormalities. Aim: The aim is to study MPA in depression. Objectives: (1) To study the association of MPA in depression, if any. (2) To study the most common MPA in depression. Materials and Methods: The study was conducted on 60 patients suffering from depression attending outpatient services and 60 healthy controls. Patients were evaluated for MPA using the Waldrop and Halverson Scale. Data were tabulated and analyzed using unpaired t-test. Results: The scores in the study group are significant than the control group suggesting an association between MPA and depression. The score of anomalies in the head, ear, and in the study group was significant. Correlation between age of onset and MPA was negative which suggests that as age increases the frequency of MPA decreases. More physical anomalies were found in the patient with a positive family history of psychiatric illness than the control group. Conclusion: A few number of studies have stressed on the need to screen and identify the link between MPA with underlying etiopathogenetic mechanisms in depression. Therefore, this is one of the few studies where a physical endophenotypic marker was evaluated helping to support the neurodevelopmental hypothesis of depression.
Keywords: Minor physical anomalies, neurodevelopmental hypothesis, unipolar depression
| Introduction|| |
Minor physical anomalies (MPA), as the name suggests are mild errors of the morphogenesis which have a prenatal origin and may bear major information for diagnostic and prognostic purposes. They are subtle signs of developmental abnormalities, primarily involving the craniofacial region and limbs.,, Considering from the neurodevelopmental perspective, the central nervous system develops from the neuroectoderm; therefore, the presence of MPA may signal abnormal development of the central nervous system., Migration of the ectodermal cells of the fetal upper limb is simultaneous with neuronal migration to the cortex. The increased prevalence of MPA may reflect the operation of common aberrant genes responsible for disordered neurodevelopment as evidenced by its higher prevalence seen in schizophrenia, intellectual disabilities, and many neurodevelopmental syndromes. MPA are not known to affect the brain function or behavior directly but only serves to indicate the possibility of a first-trimester development anomaly in the fetus, the most critical period of development for the brain. Dermatoglyphics can also be used as tool to assess influences on the fetus in early developmental stages and also to assess heterogeneity of unipolar depression. Thus, MPAs are fixed markers that presumably signify gestational developmental insults that occur well before the occurrence of symptoms of the disorder itself.,, However, many of these physical traits are partly genetically determined as well.
Taking into consideration depression has multifactorial etiology, probability of deficits due to the environmental and genetic interactions can not be denied. Some patients with depression exhibit morphologic evidence of subtle developmental abnormalities that presumably have occurred during embryogenesis. This might support the notion that early brain insults predispose to depression. A study pioneered its way into this subject, by Lohr and Flynn. However, the affective groups were not analyzed individually, and they could not prove that patients with mood disorders were having higher MPA's than controls. Pediatric Surgery defines at least 50 MPA's, however Waldrop Minor Congenital anomaly Scale (Waldrop and Halverson 1971) enlists only 18 anomalies, including features of head, eyes, ears, mouth, hands, and feet. Considering the scarcity of studies, establishing, MPA in depression we decided to conduct this study with the following aims and objectives.
| Materials and Methods|| |
A cross-sectional, observational, noninterventional, single time assessment, hospital-based study was carried out. Sixty patients suffering from unipolar depression attending outpatient services unit in the Department of Psychiatry affiliated to tertiary health care multi-specialty teaching hospital were included in the study along with 60 healthy controls matched with a study group in relation to age and gender. An approval from the institutional ethics committee and informed consent from patients were taken. Patients of either gender, between 18 years and 80 years who are diagnosed cases of unipolar depression according to the International Classification of Disease-10 criteria and who were willing to give written informed consent were included in the study. Patients with intellectual disability, history of comorbid diagnosed neurological disorder such as epilepsy or neurodegenerative disorders, comorbid substance abuse except nicotine use, history of head injury or having undergone recent neurosurgery, suicidal, homicidal, catatonic patients, female patients with pregnancy, and whosoever refused to be a part of our study for any reason after due explanations for obtaining consent were excluded.
After written informed consent was taken in their local language, sociodemographic data was collected on a semi-structured proforma. Patients were evaluated and clinically examined for the evaluation of minor physical anomaly using the Waldrop Physical Anomaly Scale (WPAS). This scale is the standard instrument in assessing MPA developed by Waldrop and associates which standardizes the measurement of 18 different anomalies of the head, eyes, ears, mouth, hands, and feet. The scale can be used in two different ways unweighted and weighted. In this study, we have used weighted method to measure MPA. Results were obtained and tabulated. Data were tabulated and analyzed using unpaired t-tests. Statistical analysis was done using SPSS 17 (IBM SPSS version17:0 Chicago USA).
| Results and Observations|| |
In this study, we studied the association of the WPAS score between study and control. In addition, the association of different components of WPAS between the study and control group was studied separately. The correlation between age of onset and total score in the study group as well in the control group was studied using Pearson's correlation coefficient. We also analyzed the correlation of Waldrop score with a family history of psychiatric illness in the study group and controls by using Pearson's correlation coefficient.
As shown in [Table 1], our study found that the patients with unipolar depression have significantly greater anomalies than control subjects. As depicted in [Table 2], the score of anomalies in the head (P - 0.00), ear (P - 0.04), and feet (P - 0.00), in the study group were clearly specific and distinctly significant. In addition, the majority of anomalies were found in the head. As shown in [Figure 1], negative co-relation between the age of onset of illness and MPA was observed. This means as the age of onset of unipolar depression increases the frequency of MPA decreases. A moderate positive correlation between family history of psychiatric illness and total score of MPA in study group the value of r that is co-efficient of correlation being 0.6827. While as shown in [Figure 2], the value of r that is co-efficient of correlation for the control group is 0.1177. This indicates the relationship between family history of psychiatric illness and the total score of MPA in the control group is weak.
|Table 2: Association between study and control group for different component of Waldrop physical anomaly scale|
Click here to view
|Figure 1: Correlation between the age of onset of unipolar depression and Waldrop score in the study group|
Click here to view
|Figure 2: Correlation between age of onset of unipolar depression and Waldrop score in control group|
Click here to view
| Discussion|| |
Unipolar depression probably has a multifactorial etiology, reviews on structural neuroimaging studies in unipolar depression point at deficits during brain development due to interactions of environmental and genetic factors, which could result in hypodevelopment of particular brain areas. As the neurodevelopmental alternative of etiology has got some support from neuroimaging studies in a subgroup of patients, it seems important to develop investigations on clinical stigmata, probably relating to altered brain development. Furthermore, multiple twin study and family studies serve as evidence for the genetic contribution to unipolar depression.
Our study concluded that the scores in the study group [Table 1] were clearly specific and distinctly significant that is study patients with unipolar depression have been found to have significantly greater anomalies than controls. Our finding corroborates with the study conducted by Lohr et al. which also found to have significantly greater anomalies than controls. However, our results for total WPAS scores in depression are in disagreement with the study conducted by Tényi et al. which did not able to establish the association between MPA and nonfamilial unipolar recurrent major depression. As per [Table 2], the score of anomalies in the head, ear, and feet in the study group were also clearly specific and distinctly significant. The WPA scores for patients with depression in this study the majority of anomalies found in this group involved the head which differs from study findings by Lohr et al. who found the majority of anomalies in the ear. In fact anomalies in the ear were significant in controls than in the study group. Correlation between age of onset and MPA was negative which suggests that as age increases the frequency of MPA decreases. To our best knowledge, none of the studies evaluated the correlation between age of onset and frequency of MPA. A moderate positive correlation was found between Waldrop scores and family history of psychiatric illness which reflects that more physical anomalies were found in the patient with positive family history of psychiatric illness than the control group where the weak correlation was found between the same. In a study done by Balgir which suggested a significant difference in qualitative dermatoglyphic features of patients with familial unipolar depressive and sporadic unipolar depressive disorder. Considering the findings of our study as well as study done by Balgir and contradictory findings the study conducted by Tényi et al. which did not able to establish the association between MPA and nonfamilial unipolar recurrent major depression there is a possibility of genetic and/or neurodevelopmental background for unipolar depression.
Our study is not devoid of limitations if we analyze it critically. Among several limitations, one of the major limitations which includes cross-sectional study design in the hospital setting because most severe cases of depression come to our hospital and one-time cross-sectional evaluation to establish the fair degree of correlation can never be sufficient. Since, the appearance of MPA is a broader concept, which might probably take some time to evolve, may have fallen out of reach if the patient presents with an acute depressive illness and complete and adequate co-operation has always remained a practical concern and therefore is subjected to examiners' bias. Also, specific psychiatric illnesses with regard to family history and degree of family history were not correlated.
| Conclusion|| |
Considering genetic factors as one of the causes of depression among multifactorial etiology this study will help in supporting the neurodevelopmental hypothesis in unipolar depression.
As the number of cases of depression are increasing day by day, early diagnosis and treatment can be useful for early recovery and subsequently improved quality of life. A few number of studies have stressed on the need to screen and identify link/bridge between endophenotypes like MPA with the underlying etiopathogenetic mechanism in depression. Therefore this is one of the few studies where a physical endophenotypic marker was evaluated.
As data on neurodevelopmental hypothesis in unipolar depression are scarce as compared to that available on Schizophrenia and Bipolar Affective Disorder, this field demands more extensive research for establishing the same as well as to evaluate the potential of MPA as a new diagnostic biomarker.
The study protocol was approved by the Institutional Ethics committee with reference number ND-Dept 0718095095 obtained on 31/07/2018.
Declaration of patient consent
Patient consent statement was taken from each patient as per institutional ethics committee approval along with consent taken for participation in the study and publication of the scientific results/clinical information/image without revealing their identity, name, or initials. The patient is aware that though confidentiality would be maintained anonymity
cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gutiérrez B, Van Os J, Vallès V, Guillamat R, Campillo M, Fañanás L. Congenital dermatoglyphic malformations in severe bipolar disorder. Psychiatry Res 1998;78:133-40.
Buckley PF. The clinical stigmata of aberrant neurodevelopment in schizophrenia. J Nerv Ment Dis 1998;186:79-86.
Sivkov ST, Akabaliev VH. Discriminating value of total minor physical anomaly score on the Waldrop physical anomaly scale between schizophrenia patients and normal control subjects. Schizophr Bull 2004;30:361-6.
Weinberg SM, Jenkins EA, Marazita ML, Maher BS. Minor physical anomalies in schizophrenia: A meta-analysis. Schizophr Res 2007;89:72-85.
Weinberger DR, Wyatt RJ. Cerebral ventricular size: a biological marker for sub-typing chronic schizophrenia. InBiological markers in psychiatry and neurology 1982 Jan 1 (pp. 505-512). Pergamon.
Quitkin F, Rifkin A, Klein DF. Neurologic soft signs in schizophrenia and character disorders. Organicity in schizophrenia with premorbid asociality and emotionally unstable character disorders. Arch Gen Psychiatry 1976;33:845-53.
Watt NF. Longitudinal changes in the social behavior of children hospitalized for schizophrenia as adults. J Nerv Ment Dis 1972;155:42-54.
Compton MT, Walker EF. Physical manifestations of neurodevelopmental disruption: Are minor physical anomalies part of the syndrome of schizophrenia? Schizophr Bull 2009;35:425-36.
Green MF, Satz P, Gaier DJ, Ganzell S, Kharabi F. Minor physical anomalies in schizophrenia. Schizophr Bull 1989;15:91-9.
Lane A, Kinsella A, Murphy P, Byrne M, Keenan J, Colgan K, et al
. The anthropometric assessment of dysmorphic features in schizophrenia as an index of its developmental origins. Psychol Med 1997;27:1155-64.
McNeil TF, Cantor-Graae E. Minor physical anomalies and obstetric complications in schizophrenia. Aust N Z J Psychiatry 2000;34 Suppl: S65-73.
McNeil TF, Cantor-Graae E. Neuromotor markers of risk for schizophrenia. Aust N Z J Psychiatry 2000;34 Suppl: S86-90.
Lohr JB, Flynn K. Minor physical anomalies in schizophrenia and mood disorders. Schizophr Bull 1993;19:551-6.
Green MF, Satz P, Christenson C. Minor physical anomalies in schizophrenia patients, bipolar patients, and their siblings. Schizophr Bull 1994;20:433-40.
Petronis A. Schizophrenia, neurodevelopment, and epigenetics. In: Neurodevelopmental and Schizophrenia. Cambridge, UK: Cambridge University Press; 2004. p. 174-90.
Guy JD, Majorski LV, Wallace CJ, Guy MP. The incidence of minor physical anomalies in adult male schizophrenics. Schizophr Bull 1983;9:571-82.
Méhes K. Minor malformations in the neonate: Utility in screening infants at risk of hidden major defects. Prog Clin Biol Res 1985;163C: 45-9.
Firestone P, Peters S. Minor physical anomalies and behavior in children: A review. J Autism Dev Disord 1983;13:411-25.
Waldrop MF, Goering JD. Hyperactivity and minor physical anomalies in elementary school children. Am J Orthopsychiatry 1971;41:602-7.
Johnson L, Andersson-Lundman G, Aberg-Wistedt A, Mathé AA. Age of onset in affective disorder: Its correlation with hereditary and psychosocial factors. J Affect Disord 2000;59:139-48.
Soares JC, Mann JJ. The anatomy of mood disorders—review of structural neuroimaging studies. Biological psychiatry. 1997 Jan 1;41:86-106.
Flint J, Kendler KS. The genetics of major depression. Neuron 2014;81:484-503.
Lohr JB, Alder M, Flynn K, Harris MJ, McAdams LA. Minor physical anomalies in older patients with late-onset schizophrenia, early-onset schizophrenia, depression, and Alzheimer's disease. Am J Geriatr Psychiatry 1997;5:318-23.
Tényi T, Trixler M, Csábi G, Jeges S. Minor physical anomalies in non-familial unipolar recurrent major depression. J Affect Disord 2004;79:259-62.
Balgir RS. Dermatoglyphics in unipolar depression. Relevance of family history. Hum Hered 1982;32:428-31.
[Figure 1], [Figure 2]
[Table 1], [Table 2]