32
The Influence of Latitude on Imipramine Platelet Binding Sites
In arecent WHO multicentre eollaborative study on imipramine platelet binding sites in depression, no statistieally signifieant ditTerenees were observed in the platelet 3H-imipramine binding in eontrols and in depressed patients in any of the nine research centres (Mellerup and Langer, 1990). However, the results of this study show a large eentre etTeet on platelet 3H-imipramine binding: the mean Bmax values in the eontrol group ranged from 2514 (Irvine) to 360 (Tokyo), and in the patients group from 2006 (lrvine) to 388 (Tokyo). This large ditTerenee eannot be explained by differenees in the c1inical estimation of the persons studied, sinee the same diagnostie eriteria were used in all the research centres. In the diseussion the authors note the seasonal, geographie, ethnie and eultural faetors as the possible explanation of this variability. The term "geographie faetor" is too broad, and in my opinion this large eentre etTeet is nothing other than a c1ear refleetion of the influenee of the geographie latitude. If, however, we list the ditTerent research centres not in alphabetieal order, but aeeording to geographie latitude, an interesting and impressive positive relationship emerges between the degree of latitude and mean Bmax values either in healthy eontrols or in depressed patients: persons Iiving in eities c10ser to the equator showed lower mean Bmax values in vice versa (Table 1). (Beeause of the ditTerent sampling and homogenization proeedure used in Irvine this eentre was excluded from my re-analysis.) In spite ofthe small number ofthe remaining centres (N = 8) this relationship is signifieant in the depressed population (Sperman rank test, R s = 0.881, p< 0.0 I).
This etTeet of latitude on imipramine binding was not unexpeeted for me. Re-analysing the data of the WHO eollaborative multicentre study on the dexamethasone suppression test (OST) in depression 3 years ago, I demonstrated a similar latitude etTeet, i. e. a positive relationship between the degree of latitude and the rate of abnormal OST response, and postdexamethasone serum eortisol levels (Rihmer, 1987). There is no relationship between 3H-imipramine binding and OST (Desmedt et al., 1987), probably beeause the first refleets primarily the disturbanee of the serotoninergie, and the seeond that of the noradrenergie system. Sinee it was previously demonstrated that either the OST in depressed patients (Arat6 etal., 1987),orthe 3H-imipramine binding sites both in normal eontrols and in depressed patients (Egrise et al., 1986; Goziotis and Tang, 1987) show seasonal variation, I suggest that all ("state or trait-dependent") biological markers that show seasonality may also be a subjeet of a latitude etTeet (ditTerent geographie plaee at the same time ofyear). This latitude etTeet may be related to ditTerent light/dark eycles, and sinee 3H-imipramine binding does not seem to be under genetie eontrol ~Arora and Meltzer, 1990), it would be interesting to estimate H-imipramine binding again in the 5 healthy Japanese eontrols after they had been in Moseow for several weeks, of course in the same season when the original blood sampIes were eolleeted in Tokyo. Interestingly, this latitude etTeet on imipramine binding (higher Bmax values at higher latitude where the dark part ofthe day is longer) is the opposite to what would be expeeted from two eireadian and seasonal studies: the
T8bls 1 Mean Bmax values of controls and depressed patients in different research centres according to latitude Centre Moscow Copenhagen Brussels Munich Basle Milan/Naples Athens Tokyo
Latitude
55.5 55.4 50.5 48.1 47.3 45.4 40.8 37.6 35.4
Controls n
mean Bmax
Depressed patients n mean Bmax
12 26 14 14 11
1223 1237 919 1300 1237
11 27 14 14 19
1342 1282 1026 1305 1268
9 12 5
745 619 360
17
603
20
544
5
388
n = number of persons studied
Pharmacopsychiat. 24 (1991) 32 - 33 © Georg Thieme Verlag Stuttgart· N ew York
Received:
7.9.1990
Downloaded by: Universite de Sherbrooke. Copyrighted material.
Z. Rihmer
The Influence 0/Latitude on Imipramine Platelet Binding Sites
mean Bmax values were low in the dark phase of the day and in winter, and high during the daylight hours and in summer (Egrise et al. , 1986; Nankai et al., 1986) in both normal eontrols and depressed patients. On the other hand, in the third study, Whitaker et a1. (1984) found the highest Bmax values in 4 healthy eontrols between November and January, and the lowest between May and September.
Pharmacopsychiat. 24 (1991)
33
Dr. Z Rihmer National Institute for Nervous and Mental Diseases Budapest 27, Pf I H-1281 Hungary
There is no doubt that 3H-imipramine binding is a subjeet of eireadian, seasonal (eireannual) and latitude effeets, but the exploration of the nature of their interrelationship needs further, milticentre eollaborative projeets.
Arat6. M .• Z Rihmer. E. Szadoczky: Seasonal dexamethasone suppression test results. Arch. Gen. Psychiat. 44 (1987) 920 - 921 Arora. R. c., H. Y. Me/tzer: 3H-imipramine binding in the blood plateletsofnormal twins. Psychiat. Res. 32 (1990) 265 - 273 Desmedt. D. H.. E. Egrise. J. Mend/ewicz: Tritiated imipramine binding sites in affective disorders and schizophrenia. J. Affect. Dis. 12 (1987)193 - 198 Egrise. D.. M. Rubinstein. A. Schoutens. F. Cantraine. J. Mend/ewicz: Seasonal variation of platelet serotonin uptake and 3H-imipramine binding in normal and depressed subjects. Biol. Psychiat. 21 (1986)283 - 292 Goziotis. A., S. W. Tang: A longitudinal study ofintact platelet 3H-imipramine binding in 12 normal human subjects. Psychiat. Res. 26 (1988)157-162 Mellerup. E.. Langer. S. Z: Validity of imipramine binding sites as a biological marker of endogenous depression. A World Health Organization Collaborative Study. Pharmacopsychiat. 23 (1990) 113-117 Nankai. M.. S. Yoshimoto. K. Narita, R. Takahashi: Platelet 3H-imipramine binding in depressed patients and its circadian variations inhealthycontrols.J. Aff. Disord. 11 (1986) 207 - 212 Rihmer, Z:The goegraphy ofDST. Biol. Psychiat. 22 (1987) 1044-1045 Whitaker. P. M.. J. J. Warsh. H. C. Stancer, E. Persad. C. K. Vint: Seasonal variation in platelet 3H-imipramine binding: comparable values in control und depressed populations. Psychiat. Res. 1l (1984)127-131
Downloaded by: Universite de Sherbrooke. Copyrighted material.
References
The Influence of Latitude on Imipramine Platelet Binding Sites
In arecent WHO multicentre eollaborative study on imipramine platelet binding sites in depression, no statistieally signifieant ditTerenees were observed in the platelet 3H-imipramine binding in eontrols and in depressed patients in any of the nine research centres (Mellerup and Langer, 1990). However, the results of this study show a large eentre etTeet on platelet 3H-imipramine binding: the mean Bmax values in the eontrol group ranged from 2514 (Irvine) to 360 (Tokyo), and in the patients group from 2006 (lrvine) to 388 (Tokyo). This large ditTerenee eannot be explained by differenees in the c1inical estimation of the persons studied, sinee the same diagnostie eriteria were used in all the research centres. In the diseussion the authors note the seasonal, geographie, ethnie and eultural faetors as the possible explanation of this variability. The term "geographie faetor" is too broad, and in my opinion this large eentre etTeet is nothing other than a c1ear refleetion of the influenee of the geographie latitude. If, however, we list the ditTerent research centres not in alphabetieal order, but aeeording to geographie latitude, an interesting and impressive positive relationship emerges between the degree of latitude and mean Bmax values either in healthy eontrols or in depressed patients: persons Iiving in eities c10ser to the equator showed lower mean Bmax values in vice versa (Table 1). (Beeause of the ditTerent sampling and homogenization proeedure used in Irvine this eentre was excluded from my re-analysis.) In spite ofthe small number ofthe remaining centres (N = 8) this relationship is signifieant in the depressed population (Sperman rank test, R s = 0.881, p< 0.0 I).
This etTeet of latitude on imipramine binding was not unexpeeted for me. Re-analysing the data of the WHO eollaborative multicentre study on the dexamethasone suppression test (OST) in depression 3 years ago, I demonstrated a similar latitude etTeet, i. e. a positive relationship between the degree of latitude and the rate of abnormal OST response, and postdexamethasone serum eortisol levels (Rihmer, 1987). There is no relationship between 3H-imipramine binding and OST (Desmedt et al., 1987), probably beeause the first refleets primarily the disturbanee of the serotoninergie, and the seeond that of the noradrenergie system. Sinee it was previously demonstrated that either the OST in depressed patients (Arat6 etal., 1987),orthe 3H-imipramine binding sites both in normal eontrols and in depressed patients (Egrise et al., 1986; Goziotis and Tang, 1987) show seasonal variation, I suggest that all ("state or trait-dependent") biological markers that show seasonality may also be a subjeet of a latitude etTeet (ditTerent geographie plaee at the same time ofyear). This latitude etTeet may be related to ditTerent light/dark eycles, and sinee 3H-imipramine binding does not seem to be under genetie eontrol ~Arora and Meltzer, 1990), it would be interesting to estimate H-imipramine binding again in the 5 healthy Japanese eontrols after they had been in Moseow for several weeks, of course in the same season when the original blood sampIes were eolleeted in Tokyo. Interestingly, this latitude etTeet on imipramine binding (higher Bmax values at higher latitude where the dark part ofthe day is longer) is the opposite to what would be expeeted from two eireadian and seasonal studies: the
T8bls 1 Mean Bmax values of controls and depressed patients in different research centres according to latitude Centre Moscow Copenhagen Brussels Munich Basle Milan/Naples Athens Tokyo
Latitude
55.5 55.4 50.5 48.1 47.3 45.4 40.8 37.6 35.4
Controls n
mean Bmax
Depressed patients n mean Bmax
12 26 14 14 11
1223 1237 919 1300 1237
11 27 14 14 19
1342 1282 1026 1305 1268
9 12 5
745 619 360
17
603
20
544
5
388
n = number of persons studied
Pharmacopsychiat. 24 (1991) 32 - 33 © Georg Thieme Verlag Stuttgart· N ew York
Received:
7.9.1990
Downloaded by: Universite de Sherbrooke. Copyrighted material.
Z. Rihmer
The Influence 0/Latitude on Imipramine Platelet Binding Sites
mean Bmax values were low in the dark phase of the day and in winter, and high during the daylight hours and in summer (Egrise et al. , 1986; Nankai et al., 1986) in both normal eontrols and depressed patients. On the other hand, in the third study, Whitaker et a1. (1984) found the highest Bmax values in 4 healthy eontrols between November and January, and the lowest between May and September.
Pharmacopsychiat. 24 (1991)
33
Dr. Z Rihmer National Institute for Nervous and Mental Diseases Budapest 27, Pf I H-1281 Hungary
There is no doubt that 3H-imipramine binding is a subjeet of eireadian, seasonal (eireannual) and latitude effeets, but the exploration of the nature of their interrelationship needs further, milticentre eollaborative projeets.
Arat6. M .• Z Rihmer. E. Szadoczky: Seasonal dexamethasone suppression test results. Arch. Gen. Psychiat. 44 (1987) 920 - 921 Arora. R. c., H. Y. Me/tzer: 3H-imipramine binding in the blood plateletsofnormal twins. Psychiat. Res. 32 (1990) 265 - 273 Desmedt. D. H.. E. Egrise. J. Mend/ewicz: Tritiated imipramine binding sites in affective disorders and schizophrenia. J. Affect. Dis. 12 (1987)193 - 198 Egrise. D.. M. Rubinstein. A. Schoutens. F. Cantraine. J. Mend/ewicz: Seasonal variation of platelet serotonin uptake and 3H-imipramine binding in normal and depressed subjects. Biol. Psychiat. 21 (1986)283 - 292 Goziotis. A., S. W. Tang: A longitudinal study ofintact platelet 3H-imipramine binding in 12 normal human subjects. Psychiat. Res. 26 (1988)157-162 Mellerup. E.. Langer. S. Z: Validity of imipramine binding sites as a biological marker of endogenous depression. A World Health Organization Collaborative Study. Pharmacopsychiat. 23 (1990) 113-117 Nankai. M.. S. Yoshimoto. K. Narita, R. Takahashi: Platelet 3H-imipramine binding in depressed patients and its circadian variations inhealthycontrols.J. Aff. Disord. 11 (1986) 207 - 212 Rihmer, Z:The goegraphy ofDST. Biol. Psychiat. 22 (1987) 1044-1045 Whitaker. P. M.. J. J. Warsh. H. C. Stancer, E. Persad. C. K. Vint: Seasonal variation in platelet 3H-imipramine binding: comparable values in control und depressed populations. Psychiat. Res. 1l (1984)127-131
Downloaded by: Universite de Sherbrooke. Copyrighted material.
References
