A comparative study on neurological soft signs in patients suffering from schizophrenia, their first-degree relatives and healthy control

Durva Balkrishna Sail; Sneh Babhulkar; Nitesh H Mishra; Krishna Kadam; Prasanna Vinayak Phutane; Akash Kumar Nema; Pooja Dubey

doi:10.4103/tjp.tjp_24_21

ORIGINAL ARTICLE

Year : 2021 | Volume : 7 | Issue : 2 | Page : 105-108

A comparative study on neurological soft signs in patients suffering from schizophrenia, their first-degree relatives and healthy control

Durva Balkrishna Sail, Sneh Babhulkar, Nitesh H Mishra, Krishna Kadam, Prasanna Vinayak Phutane, Akash Kumar Nema, Pooja Dubey
Department of Psychiatry, B.J.G.M.C and Sassoon General Hospital, Pune, Maharashtra, India

Date of Submission	28-May-2021
Date of Decision	07-Sep-2021
Date of Acceptance	16-Sep-2021
Date of Web Publication	12-Jan-2022

Correspondence Address:
Dr. Sneh Babhulkar
Department of Psychiatry, B.J.G.M.C and Sassoon General Hospital, Pune, Maharashtra
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjp.tjp_24_21

Abstract

Introduction: Neurological soft signs (NSS) can be defined as a group of minor nonlocalizable neurological abnormalities, including simple motor coordination, complex motor sequencing, and sensory integration dysfunctions. Research has postulated complex etiopathogenesis of schizophrenia which is amalgamation of various genetic, biological, and psychosocial factors. This study provides us opportunity to endorse the neurodevelopmental hypothesis in schizophrenia.
Aim: The aim of this study is to study and compare NSS in patients suffering from schizophrenia, first-degree relatives and healthy controls.
Methods: A cross-sectional, observational, noninterventional, single time assessment, and hospital-based study was carried out on 60 patients, 60 first-degree relatives, and 60 healthy controls. Evaluation was done using the Positive and Negative Syndrome Scale and the Cambridge Neurological Inventory (Part 2). Results were obtained, tabulated, and analyzed.
Results: We observed that patients with schizophrenia had more NSS than healthy control as well as their first-degree relatives. Similarly, first-degree relatives of patients with schizophrenia had more NSS than healthy control. The most common soft sign in patients as well as relatives was Oseretsky test. Most of the patients performed poorly on tests for motor coordination and sensory integration so did their first-degree relatives.
Conclusion: NSS can be potential endophenotype for patients suffering from schizophrenia. Patients with schizophrenia had more NSS than healthy control as well as their first-degree relatives. Similarly, first-degree relatives of patients with schizophrenia had more NSS than healthy control. This suggests a role of common genetic and/or environmental factors in the pathogenesis of these abnormalities in the two groups. This is in with support neurodevelopmental hypothesis of schizophrenia.

Keywords: First-degree relatives, neurodevelopmental hypothesis, neurological soft signs, schizophrenia

How to cite this article:
Sail DB, Babhulkar S, Mishra NH, Kadam K, Phutane PV, Nema AK, Dubey P. A comparative study on neurological soft signs in patients suffering from schizophrenia, their first-degree relatives and healthy control. Telangana J Psychiatry 2021;7:105-8

How to cite this URL:
Sail DB, Babhulkar S, Mishra NH, Kadam K, Phutane PV, Nema AK, Dubey P. A comparative study on neurological soft signs in patients suffering from schizophrenia, their first-degree relatives and healthy control. Telangana J Psychiatry [serial online] 2021 [cited 2023 Mar 30];7:105-8. Available from: https://tjpipstsb.org/text.asp?2021/7/2/105/335636

Introduction

Neurological soft signs (NSS) can be defined as a group of minor nonlocalizable neurological abnormalities, including simple motor coordination, complex motor sequencing, and sensory integration dysfunctions.^[1] In psychiatric disorders, NSS partly reflects developmental abnormalities which is a result of genetic and nongenetic processes.^[2] The neurodevelopmental hypothesis of schizophrenia was put forward in the late 20^th century and suggested that a combination of genetic and environmental factors led to neurobiological changes in the pre- and perinatal period, increasing risk for the disorder later in life.^[3],[4] This hypothesis is supported by various studies done to study epidemiological, cognitive, and imaging studies done since then showing increased NSS, minor physical anomalies, premorbid cognitive deficits, and obstetric complications in the patients suffering from schizophrenia.^[3],[4],[5] Studies comparing neurological abnormalities in patients, relatives, and healthy controls have shown that relatives of schizophrenic patients have shown rates of neurological abnormality somewhere in between those of the patients and normal comparison subjects which denotes that these measures could serve as intermediate phenotypes for schizophrenia.^[6],[7] Although genetic or early environmental factors can influence this intrafamilial similarity, a number of investigators focusing on the nonpsychotic close relatives of patients have pointed out that there is a genetic diathesis to NSS as a higher rate of NSS was observed in these groups.^[8],[9],[10]Twin study can be helpful to study a theory of gene–environment interactions. Cantor Graae et al.,^[11] in their study with monozygotic twins discordant for schizophrenia, reported neurological signs in both twins; however, they were more pronounced in the affected twin, highlighting that genetic and other variables such as perinatal trauma may have role in the etiology of the neurological signs. As relatively less Indian studies as available, this study was taken up with the aim to determine the NSS scores in patients with schizophrenia, their first-degree relatives compared with healthy controls.

Methods

A cross-sectional, observational, noninterventional, single time assessment, and hospital-based study was carried out. Sixty patients suffering from schizophrenia diagnosed as per the International Classification of Diseases (ICD) 10 attending outpatient services unit in the Department of Psychiatry affiliated to tertiary healthcare multispecialty teaching hospital were included in the study. Sixty first-degree relatives of patients suffering from schizophrenia along with 60 healthy controls were assessed after an approval from the institutional ethics committee. Informed consent from patients, first-degree relatives, and healthy controls was taken. Appropriate ethical approval procedures were followed while taking consent from subjects and also in conducting the research. Patients in the state of symptomatic remission only were assessed for NSS. The Positive and Negative Syndrome Scale (PANSS) was published in 1987 by Stanley Kay, Lewis Opler, and Abraham Fiszbein.^[10] It includes the 30 items, 7 constitute a positive scale, 7 a negative scale, and the remaining 16 a general psychopathology scale. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers. The scores for these scales are arrived at summation of ratings across component items. The α coefficients for the Positive and Negative Scales were 0.73 and 0.83, respectively (P < 0.001). The General Psychopathology Scale similarly revealed high internal consistency, producing an α coefficient of 0.79 (P < 0.001).^[10] Patients and their relatives with previous or current substance abuse except nicotine, dementia, mental retardation, epilepsy, Parkinson's disease, or other chronic neurological illnesses were excluded from the study.^[12] Healthy controls having any of the above as well as any of the first-degree relatives with psychiatric illness were excluded from the study. Healthy controls were chosen randomly mostly from hospital staff of tertiary care center who were meeting inclusion and exclusion criteria. Sociodemographic data were collected using semi-structured pro forma. ICD 10^th revision^[13] (diagnostic and clinical research criteria) was used for the diagnosis of schizophrenia and bipolar affective disorder. The presence and severity of soft neurological signs were assessed using part 2 of the Cambridge Neurological Inventory.^[14] The Cambridge Neurological Inventory is given by Chen et al. in 1995 and is clinical instrument for the assessment of soft neurological signs in psychiatry patients. It has been subdivided into three parts, the first part can be used for the assessment of speech, the second part assesses soft neurological signs, and the third part can be used for the assessment of posture and movements.^[14] Soft signs assessment is done mainly in three groups. The first group of soft signs test assesses some “primitive reflexes.” The second group is concerned with repetitive sequential motor execution. The third group consists of test related to the integration of sensory information. They are rated from 0 to 2.^[14] Results were obtained and tabulated. Data were tabulated and analyzed using the Chi-square test. Statistical analysis was done using IBM SPSS version 17:0 Chicago, USA.

Results

A study involved 60 patients suffering from schizophrenia, 60 first-degree relatives as well as 60 healthy controls. The mean age of schizophrenia patients was 39.23 ± 14.20 years while that of schizophrenia relatives was 41.33 ± 13.85 years. The mean age of controls was 23.1 ± 2.52 years. 51.67% (n = 31) of schizophrenia patients and relatives were male while 48.33% (n = 29) were female. 51.67% (n = 31) of controls were female while 48.33% (n = 29) were male. We observed that patients with schizophrenia had more NSS than healthy control (P < 0.001) as well as their first-degree relatives (P < 0.001). Similarly, first-degree relatives of patients with schizophrenia had more NSS than healthy control (P < 0.001). As [Table 1] depicts, most common soft sign in patients as well as relatives was Oseretsky test. Most of the patients performed poor on tests for motor coordination and sensory integration so did their first-degree relatives. Patients had statistically significant higher score in tests for palmomental reflex (P < 0.05), finger nose test (P < 0.001), fist-edge-palm test (P < 0.001), Oseretsky test (P < 0.05), rhythm tapping test (P < 0.001), go/no go test (P < 0.001), and finger agnosia (P < 0.05) than first-degree relatives. They also had statistically significant higher score in tests for palmomental reflex (P < 0.05), finger nose test (P < 0.001), fist-edge-palm test (P < 0.001), Oseretsky test (P < 0.001), rhythm tapping test (P < 0.001), go/no go test (P < 0.001), finger agnosia (P < 0.001), finger thumb tapping (P < 0.05), mirror movements -1 (P < 0.05), diadochokinesis (P < 0.05), and graphesthesia (P < 0.05) than healthy controls.

Table 1: Comparison of neurological soft signs in schizophrenia patients, relatives, and controls

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Discussion

The mean age of patients with schizophrenia in our study was 39.23 ± 14.20 years which was comparable with some studies. In a study done by Chrobak et al.,^[15] the mean age was 37 years, while in Rigucci et al.'s study,^[12] the mean age was 34.9 years. The mean age in multiple studies was ranging from 15.4–37 years.^[16] This wide range could be the result of various inclusion and exclusion criteria. Most of the abovementioned studies, patients were on antipsychotics as in our study. Several studies found the presence of NSS in antipsychotic naïve patients and they are not known to be induced by antipsychotics. Furthermore, no statistically significant difference was observed between NSS scores in patients taking antipsychotics and those who are antipsychotic naïve.^[17] Our study found higher prevalence of NSS in patients with schizophrenia than healthy controls. Nasrallah et al.^[18] found that there was statistically significant difference in NSS in patients with schizophrenia than healthy controls. Similar finding was replicated in a study done by Zhao et al.^[19] and Bansal et al.^[20] This was in line with our study. We found higher prevalence of NSS in first-degree relatives than healthy controls. Similar to our study, several studies have found an excess of NSS in first-degree relatives of patients with schizophrenia suggested that the presence of NSS in relatives increases with the potential genetic loading.^[8],[9] A systematic review done by Neelam et al.^[21] also concluded higher prevalence of NSS in patients as well as their first-degree relatives than healthy controls. In comparison with our study, Ismail et al.^[8] and Chen et al.^[22] also found higher prevalence of NSS in patients than their first-degree relatives. This further suggests familial association of the same. Based on their study, Gourion et al.^[23] reported that the NSS total score could be used to distinguish between relatives who were thought to be carriers of the genetic vulnerability to schizophrenia and those who might not. Considering all these findings together, it can be said that these have the important implication that neurological impairment in schizophrenia may be familial and trait-like in nature. This suggests that the presence of NSS may be indicative of being a “gene-carrier” for psychosis.^[24] Among various domains of NSS, Mechri et al.^[24] found high levels of neurological abnormality mainly in motor coordination abnormalities and involuntary movements. Mirror movements were more prominent than other domains in the siblings. Chen et al. found higher frequency of sensory integration signs in the nonpsychotic siblings of schizophrenics than control subjects.^[22] We also found more impaired scores in motor coordination and sensory integration. Contrary finding was reported by Yazici et al.^[9] suggesting frequency of sensory integration signs are similar in the nonpsychotic siblings of schizophrenics and control subjects. This also implies that different functional circuits responsible for producing NSS are involved to some degree in the pathophysiological processes of schizophrenia.^[9]

Ours is one of the fewer Indian studies that has compared NSS in schizophrenia patients, their first-degree relatives, and healthy controls using standard instruments.

One of the major limitations of our study was it was a cross-sectional, hospital-based study hence need not represent the general population. Furthermore, the duration of illness, number of episodes, and history of perinatal trauma were not taken into consideration. Another possible limitation of this study may be that the examiner was not blind to the diagnoses of the subjects being examined.

Conclusion

Patients with schizophrenia had more NSS than healthy control as well as their first-degree relatives. Similarly, first-degree relatives of patients with schizophrenia had more NSS than healthy control. We found more impaired scores in scales for motor coordination and sensory integration. This is suggestive of common genetic and/or environmental factors underlying these abnormalities. This further is in support of the neurodevelopmental hypothesis of schizophrenia. In line with systematic review by Neelam et al.,^[21] higher prevalence of NSS in patients than first-degree relatives and healthy controls has added to evidence for hypothesis of familial association. Further increased NSS in first-degree relatives can be an indicator of potential genetic loading helping to distinguish from those having genetic vulnerability those who do not. However, some do not agree with the same.^[25] As it is easy and less time-consuming to assess them, they could be used in ordinary clinical settings to identify at-risk individuals, especially in cases of diagnostic dilemmas such as prodrome of schizophrenia. Considering of limitations of our study, further research is required in line of the validity and predictive power of NSS as intermediate phenotype. From the clinical point of view, it will help to include physical training as involvement of motor and sensory cerebral sites considered to be underlying pathophysiology.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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