Mirror finger patterns of apparent monozygotic twins and sib pairs with Schizophrenia.

BACKGROUND: Although mirror images are noted in some twins, no such reports are available for twins and subjects with schizophrenia. AIM: The study was to assess the occurrence of mirror image finger patterns in apparent monozygotic twins with schizophrenia. Another objective was to elucidate these characteristics among sib pairs with schizophrenia for comparison with those of the twins.
MATERIALS AND METHODS: Eight apparent monozygotic twin pairs and eight sib pairs with schizophrenia were investigated. The frequency of identical patterns in the right side finger of one twin and the corresponding left side finger of the other twin was assessed, and similarly on other sides. Similar assessment was made in sib pairs with schizophrenia and normal sib pairs.
RESULTS: The left middle finger pattern of one of the twin pair was found to be the mirror image of the right middle finger of the other twin in all the twin pairs studied and so was in seven of the sib pairs with schizophrenia. These mirror images of sib pairs with schizophrenia was more than those of normal sib pairs. This difference was accentuated with significantly more of these patterns in the twins in comparison to those among normal sib pairs. Notably, no difference emerged between the sib pairs with schizophrenia and the twins in any of their finger pairs.
CONCLUSION: Mirror images that are probably due to factors like abnormal genotypes and L- DNA, appear to be promising tools to study the etiology of schizophrenia. Copyright:

INTRODUCTION

In a small category of twins, termed as mirror twins, a characteristic manifested in a twin on one side, for example, on the right side, is noted in the other twin on the other side, i.e., on the left side. Some examples of the characteristics that are found to be mirror images are birthmarks, moles, freckles, dimples, eyebrow shape, nostril shape, ear shape, and cowlicks. Gestures or movements may also be manifestations of mirror-image twinning. One twin may be right handed and the other left handed.[12] Furthermore, mirror images might occur in the direction of hair whorls and eye dominance.[1] Mirror images of dental fusion have also been described.[3] In some extreme cases, which are exceptionally rare, mirror twins display situs inversus, where internal organs such as the heart, liver, lungs, or stomach are situated on the opposite side of their normal anatomical position.

There is a paucity of reports on mirror images in twins with schizophrenia and so is in the case of sibs and other pair of patients with schizophrenia, which had prompted this study.

MATERIALS AND METHODS

Subjects

The study participants were twins recruited over a period of 30 years (1979–2008), selected from three psychiatric centers, all located within a radius ranging from 5 to 15 km in the city of Chennai, State of Tamil Nadu, India. After eliciting the presenting complaints and the history of their illness from the close relatives, the patients were undertaken for mental status examination. Each individual was interviewed independently by two senior psychiatrists (RP and JJ) with the structured clinical interview for Present State Examination[4] that was designed for the WHO to serve as a diagnostic instrument for international studies. Although this instrument was used for selection of participants up to early 1990s, later samples were interviewed with the complete Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R, patient version (Structured Clinical Interview for DSM-P)[5] and also by using the schedule for affective disorders and schizophrenia.[6] The history obtained from the reliable informants and the clinical interview revealed that among the 12 twin pairs selected, two had to be excluded on the ground that one in each of the two pairs were normal at the time of selection. Another two pairs also had to be excluded as one of each pair were found to be affected with somatization disorder and personality disorder (not otherwise specified), respectively. Hence, after exclusion of these four twin pairs, only eight pairs of twins (males – 6, females – 2) could be recruited. Although the sample had to be selected using different criteria at different times as per Feighner et al.,[7] DSM III R[8] and DSM IV,[9] a retrospective application, showed that all of them fulfilled DSM IV criteria for schizophrenia, and there was consensus in the diagnosis among the two senior psychiatrists (RP and JJ).

All of the twin pairs were considered to be apparently monozygotic (MZ), as determined by physical similarities such as facial appearance, height, hair texture, iris color, and also by assessing their blood groups (A, B, AB, Rh antigens). These similarities were determined by two of the authors (SI and AR) independently, and there was consensus about the identical features of the twins. Of the eight affected twin pairs, two had schizophrenia paranoid type, three had schizophrenia disorganized type, and three had undifferentiated type. There was also consensus among the psychiatrists over the concordance of diagnosis in each of the pairs.

For the purpose of comparison eight sib pairs (males – 6, females – 2) who were affected with schizophrenia and matched for the sex of the twin pairs, were selected from among the new cases of schizophrenia of Government General Hospital, Chennai, from January 1981 to April 1982, after adopting the same previous procedures. For ascertaining their family history, Family History Research Diagnostic Criteria[10] was used. Although these patients were selected as per the Feighner's criteria for schizophrenia, retrospective analysis showed that they also fulfilled the DSM IV criteria for schizophrenia, and there was also consensus among the two psychiatrists over the diagnosis. For the control group, eight sib pairs (males – 6, females – 2) who reported to the same hospital for ordinary physical illnesses but had no mental illness either in them or in their first- and second-degree relatives were selected. It was ensured that these normal sibs were elders in their age than the twin and sib pairs with schizophrenia. Some of these patients were actually subjected to a different type of analysis reported elsewhere.[1112] Altogether, three groups formed the study participants, i.e., eight twin pairs with schizophrenia, eight sib pairs with schizophrenia, and the eight normal sib pairs.

Dermatoglyphic analysis

The method used to take the rolled fingerprints was the ink and pad method. The classification and analysis of the finger patterns was done as per the guidelines of Cummins and Midlo[13] and also wherever needed by following the pictorial descriptions provided by Schaumann and Alter.[14] Of the three usual pattern types, namely arch/tented arch, loop (ulnar or radial), whorls of different configuration, and also of the unusual complex pattern types, whichever type is displayed on the distal phalange on a particular finger of one of the pairs on one side and if the same pattern type is noted in the distal phalange of the corresponding finger of the other pair on its opposite side, the concerned fingers having these similar patterns were considered to be having mirror-image finger patterns. In this study, only the pattern types, but not the ridge counts, are considered, as even when two members of the pairs have the same genetic inheritance factors, their fingerprint ridge characteristics are never identical.

As one of the twins had lost his left hand in an accident, that hand alone had to be excluded in this sample and furthermore, another one of the twin's left thumb that had syndactyly of two thumbs had also necessarily led to the omission of this thumb for analysis.

The identification of the pattern type was made independently by the two authors (RP and JJ), and there was complete agreement between the two authors on the interpretation of pattern types. Prior training was obtained in analyzing the dermatoglyphic data from the Director, Finger Prints Bureau, Government of Tamil Nadu, India, who is primarily involved in crime detection.

Data analysis

The frequency of identical patterns on the right side finger of one twin and the left side corresponding finger of the other twin was assessed, and similarly on other sides. Similar assessment was made in sib pairs with schizophrenia and normal sib pairs. The difference between the frequency distribution of the mirror-image finger patterns of the corresponding finger pairs of the different groups was assessed using the Chi-square test.

RESULTS

The left middle finger pattern of one of the twin pair was found to be the mirror image of the right middle finger of the other twin in all the twin pairs studied [Table 1]. Similar was our observation in all but one sib pair with schizophrenia in these finger pairs, which was actually more in comparison to those found in the group of normal sibs [Table 2]. This observed difference interestingly became accentuated on comparison of the frequency of these mirror image finger patterns of the normal sib pairs with those of the twin pairs with schizophrenia [Table 1]. In the six twin pairs studied, the left thumb pattern of each one of twin pairs was found to be the mirror image of the right thumb pattern of the other twin. However, this frequency was only marginally more than those of the eight normal sib pairs analyzed, in whom four had such mirror image patterns and hence the noted difference could not be unequivocally considered as significant. Furthermore, such a difference was not noted when those of the normal sib pairs were compared with the sib pairs with schizophrenia, where the number of finger pairs studied was also equal in both the groups. Notably, no difference emerged between the sib pairs with schizophrenia and the twin pairs in the frequency distribution of mirror image patterns in any of their finger pairs [Table 3].

Table 1

Frequency distribution of mirror finger patterns of twin pairs with schizophrenia and normal sib pairs

	With mirror patterns	Without mirror patterns	χ2/P
Right-hand fingers of Group 1 and left-hand fingers of Group 2 samples
Right thumb of and left thumb of
Twin 1 and Twin 2	5	3	0.000/1.000
Sib 1 and Sib 2	5	3
Right index finger of and left index finger of
Twin 1 and Twin 2	6	2	2.286/0.131
Sib 1 and Sib 2	3	5
Right middle finger of and left middle finger of
Twin 1 and Twin 2	4	4	0.254/0.614
Sib 1 and Sib 2	5	3
Right ring finger of and left ring finger of
Twin 1 and Twin 2	7	1	0.410/0.522
Sib 1 and Sib 2	6	2
Right little finger of and left little finger of
Twin 1 and Twin 2	4	4	2.618/0.106
Sib 1 and Sib 2	7	1
Left hand fingers of Group 1 and right hand fingers of Group 2 samples
Left thumb of and right thumb of
Twin 1 and Twin 2	6	0	4.200*/0.040 (Yates corrected - 2.807, P - 0.147; Mantel-Haenszel - 4.000, P - 0.046)
Sib 1 and Sib 2	4	4
Left index finger of and right index finger of
Twin 1 and Twin 2	4	3	0.286/0.593
Sib 1 and Sib 2	3	4
Left middle finger of and right middle finger of
Twin 1 and Twin 2	7	0	6.563*/0.010 (Yates corrected - 4.051, P - 0.044; Mantel-Haenszel - 6.125, P - 0.013)
Sib 1 and Sib 2	3	5
Leftt ring finger of and right ring finger of
Twin 1 and Twin 2	6	1	0.010/0.919
Sib 1 and Sib 2	7	1
Left little finger of and right little finger of
Twin 1 and Twin 2	4	3	1.759/0.185
Sib 1 and Sib 2	7	1

*Significant

Table 2

Frequency distribution of mirror finger patterns of sib pairs with schizophrenia and normal sib pairs

	With mirror patterns	Without mirror patterns	χ2/P
Right-hand fingers of Group 1 and left-hand fingers of Group 2 samples
Right thumb of and left thumb of
Sib 1 and Sib 2 (+)	4	4	0.254/0.614
Sib 1and Sib 2 (−)	5	3
Right index finger of and Left index finger of
Sib 1 and Sib 2 (+)	5	3	1.000/0.317
Sib 1 and Sib2 (−)	3	5
Right middle finger of and left middle finger of
Sib 1 and Sib 2 (+)	4	4	0.254/0.614
Sib 1 and Sib 2 (−)	5	3
Right ring finger of and left ring finger of
Sib 1 and Sib 2 (+)	5	3	0.291/0.590
Sib 1 and Sib 2 (−)	6	2
Right little finger of and left little finger of
Sib 1 and Sib 2 (+)	7	1	0.000/1.000
Sib 1 and Sib 2 (−)	7	1
Left hand fingers of Group 1 and right hand fingers of Group 2 samples
Left thumb of and right thumb of
Sib 1 and Sib 2 (+)	6	2	1.067/0.302
Sib 1 and Sib 2 (−)	4	4
Left index finger of and right index finger of
Sib 1 and Sib 2 (+)	5	3	0.579/0.447
Sib 1 and Sib 2 (−)	3	4
Left middle finger of and right middle finger of
Sib 1 and Sib 2 (+)	7	1	4.267*/0.039 (Yates corrected - 2.400, P - 0.121; Mantel-Haenszel - 4.000, P - 0.046)
Sib 1 and Sib 2 (−)	3	5
Left ring finger of and right ring finger of
Sib 1 and Sib 2 (+)	5	3	1.333/0.248
Sib 1 and Sib 2 (−)	7	1
Left little finger of and right little finger of
Sib 1 and Sib 2 (+)	7	1	0.000/1.000
Sib 1 and Sib 2 (−)	7	1

Sib 1 and Sib 2 (+) with schizophrenia, Sib 1 and Sib 2 (−) normal. *Significant

Table 3

Frequency distribution of mirror finger patterns of twin pairs and sib pairs with schizophrenia

	With mirror patterns	Without mirror patterns	χ2/P
Right-hand fingers of Group 1 and left-hand fingers of Group 2 samples
Right thumb of and left thumb of
Twin 1 and Twin 2	5	3	0.254/0.614
Sib 1 and Sib 2	4	4
Right index finger of and left index finger of
Twin 1 and Twin 2	6	2	0.291/0.590
Sib 1 and Sib 2	5	3
Right middle finger of and left middle finger of
Twin 1 and Twin 2	4	4	0.000/1.000
Sib 1 and Sib 2	4	4
Right ring finger of and left ring finger of
Twin 1 and Twin 2	7	1	1.333/0.248
Sib 1 and Sib 2	5	3
Right Little finger of and left little finger of
Twin 1 and Twin 2	4	4	2.618/0.106
Sib 1 and Sib 2	7	1
Left-hand fingers of Group 1 and right-hand fingers of Group 2 samples
Left thumb of and right Thumb of
Twin 1 and Twin 2	6	0	1.750/0.186
Sib 1 and Sib 2	6	2
Left index finger of and right index finger of
Twin 1 and Twin 2	4	3	0.045/0.833
Sib 1 and Sib 2	5	3
Left middle finger of and right middle finger of
Twin 1 and Twin 2	7	0	0.938/0.333
Sib 1 and Sib 2	7	1
Left ring finger of and right ring finger of
Twin 1 and Twin 2	6	1	1.029/0.310
Sib 1 and Sib 2	5	3
Left little finger of and right little finger of
Twin 1 and Twin 2	4	3	1.759/0.185
Sib 1 and Sib 2	7	1

DISCUSSION

It has been argued persuasively that MZ twinning itself is a reflection of abnormal and poorly controlled coordinate mapping, and particularly, of midline specification.[15] The occurrence of MZ twinning has been described as a congenital defect and the congenital defects noted in MZ twins have been well documented.[16] A population-based study has shown that twins, in particular MZ twins, have an increased risk of congenital anomalies than singletons.[17] Of the MZ twins, 25% of them are mirror images. Mirror imaging occurs when pathologic conditions are present on opposite sides of the body.[18] The difference between singletons and twins of both zygosities represent a coherent system of rearranged embryonic asymmetries.[19] Common knowledge has it that MZ twins share 100% of their genes, whereas the siblings share 50% of their genes. The MZ twinning “splits” embryos that not only lead to 100% sharing of their genes, but also produce anomalously rearranged asymmetries between the twins. The offspring singletons begin with independent ovulation and inherit their genes from their parents with their gene sharing occurring as part of the process of their inheritance from their parents. Where as in MZ twins, after whatever is inherited from their parents, the same are being shared. Hence, the gene-sharing event among the MZ twins, and among the singleton siblings, occurs by unrelated mechanisms.

It has been hypothesized that there are two types of twinning events, one being independent of genetic factors, associated with high birth weight and lack of mirror imaging, the other being partly genetic, associated with low birth weight and mirror imaging.[20] Furthermore, it has been pointed out that the monochorionic MZ twins are significantly at risk for nongenetic prenatal environmental influences that distinguish them from dichorionic MZ twins. The genetically mediated twinning represents an abnormal genotype, lacking in some degree, good control over specification coordinate. Hence, a reasonable interpretation is that increased occurrence of the mirror image characteristics in the twins could be the result of genetically mediated twinning and perhaps such mirror image characteristics are under control of abnormal genotypes. In MZ twinning, it is easy to see that craniocaudal and dorsoventral axes (or gradients) could be transmitted faithfully from a single zygote to the two gastrulation process, but left-right asymmetry might well be disturbed. This could account for some cases of abnormal heart looping, situs inversus/ambiguous/heterotaxy, and proposed mirror imaging in MZ twins.[21] Thus, mitigation of left-right, and right-left, asymmetrical distribution of characteristics between the pairs might result in augmentation of mirror image of these characteristics in the pairs. In sib pairs with schizophrenia, the influence of different abnormal genotypes is speculated on each of the siblings in the pairs during the process of inheritance causing more mirror image patterns of the left middle finger of one sib and that of the right middle finger of the other. Of relevance is also the polygenic theory for schizophrenia that has already been proposed by some.[222324] The role played by the L-DNA, the mirror image of natural DNA that controls the formation of structures of opposite chirality[25] is yet to be established in schizophrenia. Furthermore, therea is dearth of reports on L-DNA and abnormal genotypes in schizophrenia. Even in a large study involving 37,000 patients and 114,000 normal individuals, the Schizophrenia Working Group of the Psychiatric Genomics Consortium that found 108 gene loci to be associated with schizophrenia[26] have apparently ignored about the possible association of schizophrenia with either L-DNA or with the abnormal genotypes. Notwithstanding at this stage, the increased occurrence of the observed finger pattern mirror images in the twin pairs as well as in the sib pairs with schizophrenia remains inexplicable.

We were unable to undertake DNA analysis and other blood group assessments for want of the required facilities that might also be needed for the ascertainment of zygosity of the twins. Nevertheless, it should also be noted that many classic publications about MZ twins and twinning are, in fact, lacking in the appropriate criteria for the diagnosis of MZ status. As pointed out elsewhere,[21] while it is true that most of MZ twins are phenotypically very similar, there is significant number of MZ pairs who are neither phenotypically nor genotypically identical: postzygotic genetic events of various types and severity result in striking within-pair dissimilarity. However, like-sex twins can be tested for DNA restriction fragment length polymorphism differences, using placenta, cord, and membranes, which could at best be done at or before birth for diagnosing zygosity. More recently, the use of ultra-deep, next-generation sequencing has been advocated that claims to distinguish the identical twins. However, to circumvent these lacunae, the twins in this study were considered only as apparently MZ.

Interestingly, the normal sib pairs displayed only less number of mirror-image patterns in their left and right middle fingers, in comparison to their corresponding mirror-image trait of twin pairs and sib pairs with schizophrenia. In fact, the noted difference between the sib pairs with schizophrenia and normal sib pairs was accentuated when the twin pairs with schizophrenia were compared with these normal sib pairs. Perhaps, molecular genetic studies inclusive of also L-DNA and abnormal genotypes of larger samples of twin pairs with proven nature of zygosity and sib pairs with schizophrenia displaying such dermatoglyphic mirror image parameters are needed to draw reasonably valid conclusion. This study also pleads for the assessment of other mirror image characteristics of twin pairs and sib pairs with schizophrenia.

Limitations

Despite the collection of twins sample was spread over nearly three decades, the sample size could not be enlarged since the twins with schizophrenia could be collected from a few centers of Chennai city only. Furthermore, the sample sizes of sib pairs were restricted to suit that of the twin pairs, to avoid any possibility of sampling bias. In view of the small sample size of the twin pairs, no conclusion could be drawn and our findings require to be interpreted with caution.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.