Accepted Manuscript Does latitude as a zeitgeber affect the course of bipolar affective disorder? Janardhanan C Narayanaswamy, Nagaraj Moily, Shobana Kubendran, Y.C. Janardhan Reddy, Sanjeev Jain PII: DOI: Reference:
S0306-9877(14)00252-7 http://dx.doi.org/10.1016/j.mehy.2014.06.017 YMEHY 7640
To appear in:
Medical Hypotheses
Received Date: Accepted Date:
23 January 2014 14 June 2014
Please cite this article as: J.C. Narayanaswamy, N. Moily, S. Kubendran, Y.C. Janardhan Reddy, S. Jain, Does latitude as a zeitgeber affect the course of bipolar affective disorder?, Medical Hypotheses (2014), doi: http:// dx.doi.org/10.1016/j.mehy.2014.06.017
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Does latitude as a zeitgeber affect the course of bipolar affective disorder? Janardhanan C Narayanaswamy, M.D., Nagaraj Moily, MBBS, Shobana Kubendran, MBBS, Y.C. Janardhan Reddy, M.D., Sanjeev Jain, M.D. Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India. Corresponding Author: Dr. Janardhanan. C. Narayanaswamy, Assistant Professor (DST-INSPIRE faculty), Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India- 560029 Phone: 91-80-26995267 Email: [email protected]
Word Count Abstract: 234 Manuscript (excluding references): 2259 Table: 1
Conflict of interest: none Funding: nil
Acknowledgements: Dr. Janardhanan C. Narayanaswamy is supported by the INSPIRE faculty award programme of the Department of Science And Technology, Government of India.
1
Background Several long-term follow-up studies suggest that bipolar disorder (BD) is characterized by frequent recurrences (1, 2) and that depression is the most common phase of illness in the course of BD. Two reports from the NIMH Collaborative Depression Study (3, 4) have demonstrated that patients with BD experience depression much more frequently than hypomania or mania. Judd et al focusing on subjects with BD I (3) reported on a follow-up of 146 patients over an average period of 12.8 years. Assessing weekly symptom status, the authors found that patients experienced depressive symptoms for 32% of weeks during the study period. Only 9% of the time accounted for by hypomanic or manic symptoms and 6% for rapid cycling or mixed presentations. In a study on BD II subjects (4) from the same cohort, depression was even more prevalent than in the BD I sample, accounting for 50% of weeks, compared with 1% of weeks in hypomania and 12% cycling or mixed. The functional outcome of subjects with BD correlated significantly with their depressive, but not manic symptoms(5). Hence depressive episodes have been considered to be the greatest unmet need with respect to the treatment and functional outcome in BD according to the literature so far (3, 6-9). Early observations of the contrasting course of BD Studies from tropical countries which have evaluated the longitudinal course of BD (10-14) suggest that the patients experience a greater proportion of manic episodes. This was earlier hinted at by some observations in the 19th and 20th centuries; better outcomes for mania acuta have been reported (Editorial, Indian Medical Gazette, 6: 268; 1871). In 1936, after discussions with psychiatrists all over India, one of the major queries Sir Edwin Mapother suggested for research, was to examine whether in India
2
there was an ‘apparent reversal of the proportion in which manic and depressive states occur in Europe’. Rates of admission for mania were higher in Egypt, India and Ceylon, with differences in sunlight suggested as one of speculative causes, and in any case, the question was of wider interest in relation to both ‘psychogenesis’ and ‘physiogenesis’ (Royal Bethlem Hospital Archive. EM-01 Papers of Edward Mapother, p24). Circadian biology and the hypothesis Converging evidence suggests association between disrupted circadian system and pathogenesis of BD (15). It has been hypothesized that the evolutionary origin of circular BD could be related to biological adaptations to the severe climatic conditions of the northern temperate zone and based on this theory, it has been suggested that this disorder also would have an “epidemiology” of adaptation (16). Sunlight, an important circadian zeitgeber could thus be responsible for the contrasting course across many BD study cohorts. Latitude, which is one of the most important determinants of sunlight, would be an important parameter to explain the difference in BD course related differences across geographical locations. We evaluated the course of BD in a sample of patients from India and compared the course parameters with those of other earlier reported cohorts from other parts to examine our hypothesis.
3
Methods
The data is derived from the phenotypic characteristics of BD subjects recruited for BD genetics study in the Molecular genetics laboratory of the department of psychiatry in the National Institute of Mental Health And Neurosciences (NIMHANS) situated in the city of Bangalore in southern India. The data was collected with the approval of ethics committee of the Institute. Demographic details and the parameters about the course of illness were elicited by a retrospective recall after detailed interviews of the subjects and a reliable informant (a family member) as well as by the review of their case records. They were interviewed with the Diagnostic Interview for Genetic studies (17) and a life chart was drawn to ascertain the episodes of illness. The mean total episode frequency and the mean manic and depressive episode frequency were recorded for this study.
Results: There were 517 subjects with BD. Fifty six of them were excluded for the analysis since they had a rapid cycling course and hence calculation of episode frequency would be imprecise. The data of the remaining 461 subjects were used for the present study. However, data on the number of total episodes, manic and depressive episodes separately was reliably recalled in 439 subjects. Table 1 shows the episode related parameters in these subjects. The number of males and females were 247 and 192 respectively. Overall, in an average duration of 7.45 years of illness, there was a much higher mean frequency of manic episodes (3.29) when compared to depressive episodes (1.08).
4
--------------- Table1 here---------------
Discussion The present study reveals that mania is the commonest mode of recurrence of BD in this sample, in the first decade following onset of illness. This is in contrast to several studies which report that depressive episodes are the more common mode of recurrence in BD. The role of sunlight could be one factor contributing this. Ambient sunlight and its variation are related to the latitude. There are several evidences implicating the role of sunlight as an important biological determinant of BD pathogenesis. The effect of light determining the illness characteristics in mood disorders can be inferred in different ways. The evidence from seasonal affective disorder, seasonal variations in hospital admissions and examining the geographical locale and characteristics of the cohort studied are some of the methods. We discuss the evidence for these factors in the course of mood disorders and suggest that latitude may influence the course of BD. Evidence from Seasonal Affective disorder (SAD) and the role of light therapy SAD is a form of mood disorder exhibiting a substantial role of season and light related factors in the causation and treatment of mood episodes. Patients with SAD have episodes of depression which tend to occur during specific periods of the year, usually in winter (18). Light therapy forms an important form of treatment for SAD. Difference in exposure to ambient sunlight has been found to be a critical aspect in SAD (19). This may however also be related to the individual mood vulnerability based on sunlight received(20). For instance, perinatal photoperiod causing imprinting on the circadian clock in animal models simulating SAD have been demonstrated (21). In a 10 year follow
5
up study, seasonal pattern was observed in BD and such a pattern was associated with BD II subtype with predominant depressive content (22). Light therapy and its effect of producing mania symptoms indicating that light plays a significant role in the expression of illness in BD (23, 24). Seasonal trends for hospital admissions and relapses An indirect measure of the effect of season on the relapse of BD would be data on the hospital admission rates across seasons. Admissions for mania were more frequent in late spring or summer (25, 26) whereas those for depression were frequent in winter (27). This observation was made in both temperate as well as tropical climatic zones (28, 29). Yang et al reported that in a cohort based in Taiwan which is situated at a latitude 25 degrees north, manic or mixed episodes peaked during spring or summer and depressive episodes peaked during winter (30). Taiwan lies in a latitude of about 25 degree N. Similarly, summer peak for mania and winter peak for depression was reported in a cohort from Birmingham (latitude: 52 degrees North) (28). In the above study, Asians in UK also experienced similar seasonal variations of bipolar disorder and it might indicate that this effect is not related to cultural and lifestyle factors. Admission rates provide a surrogate measure of the illness relapse rate based on the sunlight and other environmental factors. However, limitation in studying the admission rate of affective disorders to hospitals is that it might not always reflect the start of an affective episode or it might indicate only severe episodes.
6
Influence of study cohort’s latitude: a better way of understanding the effect of sunlight In the subsequent section, we would like to discuss the bipolar course related differences based on difference in latitude since latitude is the parameter which is intricately linked to sunlight exposure variations. Data on sunlight exposure on earth has been released by the US National Aeronautics and Space Administration (NASA) on the Surface Meteorology and Solar Energy (SSE) Version 6.0 database (NASA Surface meteorology and Solar Energy (SSE)nRelease 6.0 Methodology, 2011. available from: http:⁄⁄eosweb.larc.nasa.gov⁄sse⁄). This reference has been used by Bauer et al in their paper on Latitude and its influence on age of onset of bipolar disorder (31). The variation in sunlight is best expressed according to the “solar insolation”, which is a measure of the electromagnetic energy from the sun received for a given surface area on earth at a given time, expressed in kilowatt hours⁄square meter⁄day(kWh⁄m2⁄day). The solar insolation is known to vary according to latitude. For example, as demonstrated by Bauer et al in their paper on the effect of latitude on age at onset of bipolar disorder, the solar insolation values at latitudes 64 and 6 are 4.5 and
S0306-9877(14)00252-7 http://dx.doi.org/10.1016/j.mehy.2014.06.017 YMEHY 7640
To appear in:
Medical Hypotheses
Received Date: Accepted Date:
23 January 2014 14 June 2014
Please cite this article as: J.C. Narayanaswamy, N. Moily, S. Kubendran, Y.C. Janardhan Reddy, S. Jain, Does latitude as a zeitgeber affect the course of bipolar affective disorder?, Medical Hypotheses (2014), doi: http:// dx.doi.org/10.1016/j.mehy.2014.06.017
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Does latitude as a zeitgeber affect the course of bipolar affective disorder? Janardhanan C Narayanaswamy, M.D., Nagaraj Moily, MBBS, Shobana Kubendran, MBBS, Y.C. Janardhan Reddy, M.D., Sanjeev Jain, M.D. Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India. Corresponding Author: Dr. Janardhanan. C. Narayanaswamy, Assistant Professor (DST-INSPIRE faculty), Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India- 560029 Phone: 91-80-26995267 Email: [email protected]
Word Count Abstract: 234 Manuscript (excluding references): 2259 Table: 1
Conflict of interest: none Funding: nil
Acknowledgements: Dr. Janardhanan C. Narayanaswamy is supported by the INSPIRE faculty award programme of the Department of Science And Technology, Government of India.
1
Background Several long-term follow-up studies suggest that bipolar disorder (BD) is characterized by frequent recurrences (1, 2) and that depression is the most common phase of illness in the course of BD. Two reports from the NIMH Collaborative Depression Study (3, 4) have demonstrated that patients with BD experience depression much more frequently than hypomania or mania. Judd et al focusing on subjects with BD I (3) reported on a follow-up of 146 patients over an average period of 12.8 years. Assessing weekly symptom status, the authors found that patients experienced depressive symptoms for 32% of weeks during the study period. Only 9% of the time accounted for by hypomanic or manic symptoms and 6% for rapid cycling or mixed presentations. In a study on BD II subjects (4) from the same cohort, depression was even more prevalent than in the BD I sample, accounting for 50% of weeks, compared with 1% of weeks in hypomania and 12% cycling or mixed. The functional outcome of subjects with BD correlated significantly with their depressive, but not manic symptoms(5). Hence depressive episodes have been considered to be the greatest unmet need with respect to the treatment and functional outcome in BD according to the literature so far (3, 6-9). Early observations of the contrasting course of BD Studies from tropical countries which have evaluated the longitudinal course of BD (10-14) suggest that the patients experience a greater proportion of manic episodes. This was earlier hinted at by some observations in the 19th and 20th centuries; better outcomes for mania acuta have been reported (Editorial, Indian Medical Gazette, 6: 268; 1871). In 1936, after discussions with psychiatrists all over India, one of the major queries Sir Edwin Mapother suggested for research, was to examine whether in India
2
there was an ‘apparent reversal of the proportion in which manic and depressive states occur in Europe’. Rates of admission for mania were higher in Egypt, India and Ceylon, with differences in sunlight suggested as one of speculative causes, and in any case, the question was of wider interest in relation to both ‘psychogenesis’ and ‘physiogenesis’ (Royal Bethlem Hospital Archive. EM-01 Papers of Edward Mapother, p24). Circadian biology and the hypothesis Converging evidence suggests association between disrupted circadian system and pathogenesis of BD (15). It has been hypothesized that the evolutionary origin of circular BD could be related to biological adaptations to the severe climatic conditions of the northern temperate zone and based on this theory, it has been suggested that this disorder also would have an “epidemiology” of adaptation (16). Sunlight, an important circadian zeitgeber could thus be responsible for the contrasting course across many BD study cohorts. Latitude, which is one of the most important determinants of sunlight, would be an important parameter to explain the difference in BD course related differences across geographical locations. We evaluated the course of BD in a sample of patients from India and compared the course parameters with those of other earlier reported cohorts from other parts to examine our hypothesis.
3
Methods
The data is derived from the phenotypic characteristics of BD subjects recruited for BD genetics study in the Molecular genetics laboratory of the department of psychiatry in the National Institute of Mental Health And Neurosciences (NIMHANS) situated in the city of Bangalore in southern India. The data was collected with the approval of ethics committee of the Institute. Demographic details and the parameters about the course of illness were elicited by a retrospective recall after detailed interviews of the subjects and a reliable informant (a family member) as well as by the review of their case records. They were interviewed with the Diagnostic Interview for Genetic studies (17) and a life chart was drawn to ascertain the episodes of illness. The mean total episode frequency and the mean manic and depressive episode frequency were recorded for this study.
Results: There were 517 subjects with BD. Fifty six of them were excluded for the analysis since they had a rapid cycling course and hence calculation of episode frequency would be imprecise. The data of the remaining 461 subjects were used for the present study. However, data on the number of total episodes, manic and depressive episodes separately was reliably recalled in 439 subjects. Table 1 shows the episode related parameters in these subjects. The number of males and females were 247 and 192 respectively. Overall, in an average duration of 7.45 years of illness, there was a much higher mean frequency of manic episodes (3.29) when compared to depressive episodes (1.08).
4
--------------- Table1 here---------------
Discussion The present study reveals that mania is the commonest mode of recurrence of BD in this sample, in the first decade following onset of illness. This is in contrast to several studies which report that depressive episodes are the more common mode of recurrence in BD. The role of sunlight could be one factor contributing this. Ambient sunlight and its variation are related to the latitude. There are several evidences implicating the role of sunlight as an important biological determinant of BD pathogenesis. The effect of light determining the illness characteristics in mood disorders can be inferred in different ways. The evidence from seasonal affective disorder, seasonal variations in hospital admissions and examining the geographical locale and characteristics of the cohort studied are some of the methods. We discuss the evidence for these factors in the course of mood disorders and suggest that latitude may influence the course of BD. Evidence from Seasonal Affective disorder (SAD) and the role of light therapy SAD is a form of mood disorder exhibiting a substantial role of season and light related factors in the causation and treatment of mood episodes. Patients with SAD have episodes of depression which tend to occur during specific periods of the year, usually in winter (18). Light therapy forms an important form of treatment for SAD. Difference in exposure to ambient sunlight has been found to be a critical aspect in SAD (19). This may however also be related to the individual mood vulnerability based on sunlight received(20). For instance, perinatal photoperiod causing imprinting on the circadian clock in animal models simulating SAD have been demonstrated (21). In a 10 year follow
5
up study, seasonal pattern was observed in BD and such a pattern was associated with BD II subtype with predominant depressive content (22). Light therapy and its effect of producing mania symptoms indicating that light plays a significant role in the expression of illness in BD (23, 24). Seasonal trends for hospital admissions and relapses An indirect measure of the effect of season on the relapse of BD would be data on the hospital admission rates across seasons. Admissions for mania were more frequent in late spring or summer (25, 26) whereas those for depression were frequent in winter (27). This observation was made in both temperate as well as tropical climatic zones (28, 29). Yang et al reported that in a cohort based in Taiwan which is situated at a latitude 25 degrees north, manic or mixed episodes peaked during spring or summer and depressive episodes peaked during winter (30). Taiwan lies in a latitude of about 25 degree N. Similarly, summer peak for mania and winter peak for depression was reported in a cohort from Birmingham (latitude: 52 degrees North) (28). In the above study, Asians in UK also experienced similar seasonal variations of bipolar disorder and it might indicate that this effect is not related to cultural and lifestyle factors. Admission rates provide a surrogate measure of the illness relapse rate based on the sunlight and other environmental factors. However, limitation in studying the admission rate of affective disorders to hospitals is that it might not always reflect the start of an affective episode or it might indicate only severe episodes.
6
Influence of study cohort’s latitude: a better way of understanding the effect of sunlight In the subsequent section, we would like to discuss the bipolar course related differences based on difference in latitude since latitude is the parameter which is intricately linked to sunlight exposure variations. Data on sunlight exposure on earth has been released by the US National Aeronautics and Space Administration (NASA) on the Surface Meteorology and Solar Energy (SSE) Version 6.0 database (NASA Surface meteorology and Solar Energy (SSE)nRelease 6.0 Methodology, 2011. available from: http:⁄⁄eosweb.larc.nasa.gov⁄sse⁄). This reference has been used by Bauer et al in their paper on Latitude and its influence on age of onset of bipolar disorder (31). The variation in sunlight is best expressed according to the “solar insolation”, which is a measure of the electromagnetic energy from the sun received for a given surface area on earth at a given time, expressed in kilowatt hours⁄square meter⁄day(kWh⁄m2⁄day). The solar insolation is known to vary according to latitude. For example, as demonstrated by Bauer et al in their paper on the effect of latitude on age at onset of bipolar disorder, the solar insolation values at latitudes 64 and 6 are 4.5 and
