Marfan’s syndrome (MFS) is an autosomal dominant systemic disorder with defects in the connective tissue in multiple organ systems, characterized by abnormalities in the skeletal, ocular, and cardiovascular systems. Mutation of fibrillin-1 on chromosome 15 has been considered the cause for MFS in many cases.[2,3] Schizophrenia is a neuropsychiatric disorder of multifactorial etiology characterized by delusions, hallucinations, disorganized thinking, memory problems, apathy, and poor social functioning.
The prevalence of MFS is 2–3/10,000 people, whereas the prevalence of schizophrenia is 100/10,000 people[5,6] Several reports have described cases of co-occurrence of MFS, or isolated marfanoid features and schizophrenia[4–9] and have hinted at an association between the two disorders due to the gene loci they share on chromosome 15.
Although existing literature does not have robust scientific evidence to support such an association, the possibility of such should be explored because:
- Both MFS and schizophrenia cause significant degrees of disabilities in patients
- Patients suffering from MFS do have a higher degree of psychiatric comorbidities than the general population[4,5]
- Co-occurrence of MFS and schizophrenia in certain ethnic populations is higher than what is expected by chance
- MFS have numerous anthropometric signs and symptoms which may serve as warning signs for schizophrenia.
Existing literature consists mostly of individual case reports, and does mention the need for systemic examination of an association if any between the two disorders. Looking at the significant difference between the prevalence rates for MFS and schizophrenia, a small proof of concept study is warranted to test the possibility of an association between MFS and schizophrenia. Therefore, this study was undertaken to find whether any co-occurrence of marfanoid features exists in patients diagnosed with schizophrenia.
MATERIALS AND METHODS
The observational study was performed from January 2018 to April 2019 with the sample being 50 patients visiting diagnosed with schizophrenia according to the International Classification of Diseases-10 diagnostic criteria (World Health Organization, 2004) at the psychiatric Department in a Tertiary Care Centre at Kolhapur. Patients were recruited with a random number table. Other inclusion criteria were, (1) Patients in the age group of 18–65 years and (2) Having both parents alive at the time of recruitment. The control group comprised of patients’ both parents recruited at the same time as patients. Exclusion criteria for the patient as well as control groups were (1) Presence of comorbid psychiatric disorders, (2) History of any surgery for lens or any other anomaly of the eye, and (3) History of any structural or functional illness of the heart. Institutional ethical clearance and informed consent from parents or caretakers of the patients were obtained before the initiation of the study.
We used the revised Ghent Nosological Criteria (rGNC) as the reference for making the assessment protocol for patients. The rGNC includes major and minor criteria for diagnosing MFS, and includes anthropometric signs and symptoms, as well as certain genetic testing-related markers.
After discussing, the study aims and objectives with subject experts from the departments of internal medicine, pediatrics, and ophthalmology, it was decided to include those anthropometric measurements from rGNC, which can be clinically examined in an outpatient setting or bedside manner.
After recruitment, patients as well as the controls were evaluated in detail by a panel of subject experts from three medical specialties: (1) Psychiatry, (2) General medicine, and (3) Ophthalmology.
A detailed psychiatric evaluation followed the first assessment. Patients were assessed for the severity of their symptoms of schizophrenia using the Positive and Negative Symptoms Scale (PANSS) for schizophrenia.
All patients and controls were examined by an ophthalmologist for the (1) Presence of lens abnormalities and (2) Refractory errors with routinely used clinical methods and a slit-lamp examination (AIA-11 Dynamic by Appasamy Associates Haag Streit Style). Ophthalmologists were provided with a copy of the checklist developed as reference for recording the presence of any ophthalmological sign suggestive of MFS.
Internal medicine and cardiology assessment
A physician with more than 20 years of experience in clinical medicine, and more than 15 years of experience of undergraduate and postgraduate teaching assessed the patient and the control groups. A copy of the structured checklist was also given to the physician for reference.
Anthropometric measurements were taken using a standard scale for the assessment of the upper and lower segment (US/LS) ratio and arm span-to-height ratio. Marfanoid features such as wrist sign, thumb sign, high-arched palate, dolichocephaly, arachnodactyly, and other skeletal abnormalities were looked for with clinical examination and measurements.
A physician who is well trained, and has more than 15 years of experience in clinical two-dimensional (2D) echocardiography examined all patients and controls. Parameters checked were the presence of any valvular defects and aortic root Z score. The instrument used for 2D echocardiography was GE Medical Systems.
Data were analyzed using Microsoft Excel 2007. Continuous variables were expressed in mean ± standard deviation and categorical variables were expressed in frequency and percentage.
The study population of 50 patients comprised a majority of males (56%). The mean age of the patient group was 27.38 ± 4.48 years (Range 20–38 years), whereas that of the control group was 48.12 ± 5.2 years (Range 38–61 years). The mean duration of illness was 3.22 (2.09) years (Median 3 years). The mean PANSS score was 73.78 (12.30) [Table 1].
Scores on anthropometric measurements
All the patients and their parents had normal US/LS ratio and arm span/height span [Table 2].
No marfanoid feature was observed in most of the patients (98%), whereas high-arched palate was observed in one patient. A family history of schizophrenia was observed in nine patients. No family history of MFS was noted in any of the patients.
Scores on ophthalmological assessment
No patient or control had any finding suggestive of MFS or connective tissue disorder on clinical examination or slit-lamp examination. A total of 18 (15 patients and three parents) participants had myopia on refraction; however, none of them had severity higher than three diopters required for a diagnosis of MFS.
None of the patients or controls had any valvular defect including mitral valve prolapse detected after the clinical or echocardiographical examination. All study participants had aortic root Z scores lower than 2.
There was no significant difference in US/LS ratio, arm span/height ratio, and aortic root Z scores between patients and controls.
This study examined systematically whether patients diagnosed with schizophrenia and their biological parents demonstrate any concurrent clinical signs suggestive of MFS. To the best of our knowledge, this is the first study of its kind and it attempts to address a lacuna in the literature.
So far, evidence supporting the hypothetical link between MFS and schizophrenia can be described as indirect at best. Theories hypothesized include: (1) A defect on the gene encoding a microfibrillar protein (fibrillin) and related impaired growth factor signaling leading to neurodevelopmental abnormalities (which could explain neuropsychiatric manifestations of MFS.) (2) Altered transforming growth factor beta function is linked with psychiatric disorders, mutations in which could cause symptomatology of MFS and increased susceptibility to schizophrenia. (3) The fact that female patients with nonaffective psychosis may have altered skeletal growth trajectory This study, however, found no significant difference in US/LS ratio, arm span/height ratio, and aortic root Z score between male and female participants. Similarly, in our study, we found none of the patients to have any anthropometric or cardiovascular markers necessary for diagnosis of MFS except the presence of high-arched palate as well as neither patients nor controls had any abnormalities of the lens, retina, or the facial anatomy on the clinical examination required for diagnosing MFS. Thus, despite sharing the same chromosome locus, marfanoid features were not prominent and possible explanation for such co-occurrences in some case reports is still elusive.
This is one of the few studies of its kind to systematically examine patients diagnosed with schizophrenia for any clinical signs suggestive of MFS. We believe another strength of the study is the inclusion of patients’ biological parents in the study sample to give more credibility to the observations. Limitations of this study are, (1) A small sample size which can be explained by this being one of the fewer studies done on this topic. The prevalence rates for MFS have been reported in high variance across the globe[13,14] and precise statistics regarding its prevalence in India are not readily available. (2) Absence of genetic testing and imaging in study protocol; although the decision to avoid X-rays for skeletal deformities and any investigations at this stage of investigations without any solid evidence of a link between the two diagnoses was taken with due care at the time of protocol design.
We understand that these observations are just a step in the direction of understanding the relationship between MFS and schizophrenia. This study, however, tries to fulfill the lacuna in research highlighted by existing reports and case studies on this topic. A study with a larger sample size and follow-up including family history and genetic tests is the further recommendation of the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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