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Serum cholesterol concentration in suicide attempters: a case-control study
430 It is interesting to speculate on the importance of the above finding for the use of Li-pilocarpine seizures as a model for the testing of Berridge's inositol depletion theory of Li action. Contraction of guinea pig ileum was a key model for the study of serotonin receptors, even though guinea pig ileum is uniquely suited for these experiments. The underlying biochemical principles were generalizable to other species and other serotonin receptors, including brain. Li-pilocarpine seizures may be such a model with no face validity but useful for mechanistic study.
Table 1. Lithium-pilocarpine synergism? LDso Li (mEq/kg)
Convulsive dose (Pi) (mg/kg)
LiC1 (mEq/kg)
Pilocarpine (mg/kg)
Time from Li to Pi (h)
Rats Mice Rabbits Guinea pigs
15-20 30M0
20(P400 >400
Chicks
> 10
3 10 6 6 6 10 10 3 6 10
20 100 30 30 60 100 150 100 100 80
6~ 30 17 20 23 17 18 17 18 6 6 2 2 17
0.96 mM
1.25 mg physo
Goldfish Human (Oppenheim et al., 1979)
>60 > 150 >200
Pi % seized 0 0 ( n - 10) 0 (n-2) 11 ( n - 9 ) 54 ( n - 13) 25 ( n - 4 ) 0 (n - 5) 0 (n-5)
0 (n=5)
Pi + Li % seized 8(~ 100 70 (n = 10) 0 (n - 2) 0 (n-2) 11 ( n - 9 ) 44 ( n - 9 ) 25 ( n - 6 ) 60 (n - 5) 40 (n-5) 80 (n-5)
0 (n=5)
References Lee, C.H., Dixon, J.F., Reichman, M., Moummi, C., Los, G. and Hokin, L.E. (1992) Li + increases accumulation of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in cholinergically stimulated brain cortex slices in guinea pig, mouse and rat. Biochem. J. 282, 377 385. Oppenheim, G., Ebstein, R.P. and Belmaker, R.H. (1979) Effect of lithium on the physostigmine-induced behavioral syndrome and plasma cyclic G M P . J. Psychiatr. Res. 15, 133-138. Sherman, W.R. (1991) Lithium and the phosphoinositide signalling system In: N.J. Birch (Ed.), Lithium and the Cell. Academic Press, London, pp. 121 157.
Serum cholesterol concentration in suicide attempters: a case-control study
M. Abbar, P. Courtet, M.C. Picot a, J. Sultan b a n d D. C a s t e l n a u b Service de Psychiatrie, CHU CarOmeau, rue du Professeur DebrO, 30000 Nimes, France, aDdpartement d'information mOdicale and bService de Psychiatrie, CHU Lapeyronie, route de Ganges, 34000 Montpellier, France Key words. Suicidal behavior; Suicide attempters; Cholesterol; Serotonin
Primary prevention trials have shown that lowering the serum cholesterol concentration in middle-aged subjects by diet, drugs or both leads to a decrease in mortality from coronary heart disease but to an increase in deaths due to suicide or violence (Muldoon et al., 1990). Secondary prevention trials revealed the same trend. Furthermore, a strong negative association between original serum cholesterol levels and short-term suicide in men was found in the largest naturalistic followup study (Lindberg et al., 1992). However, earlier follow-up studies among smaller samples had not revealed this association (Pekkanen et al., 1989; Smith et al., 1990; Chen et al., 1991, cited in Lindberg et al., 1992). The objective of this study was to determine whether total serum cholesterol concentration is associated with a past history of suicide attempts, through a casecontrol study with comparison of total serum cholesterol concentrations among psychiatric inpatients with (n = 509) and without (n = 275) a history of past suicide attempts and non-psychiatric inpatient controls (n = 2421). Mean cholesterol concentration was statistically significantly lower after sex and age adjustment in past suicide attempters when compared with other psychiatric patients. The same difference was found between suicide attempters and sex and age
431 matched control subjects, while no difference was observed between sex and age matched controls and psychiatric patients without a history of suicide attempts. Our data among suicide attempters are concordant with those found with complete suicide and suggest an association between suicidal behavior and low serum cholesterol levels. The nature of this association remains unknown but a decreased activity of brain serotonin pathways and poorer suppression of aggressive behavior with low serum cholesterol level have been proposed as possible explanations (Engelberg, 1992). This hypothesis is consistent with previous studies reporting that subjects with antisocial personalities and aggressive conduct disorders had lower blood cholesterol than did control groups (Virkkunen, 1979, 1983, 1984, cited in Engelberg, 1992). References
Engelberg, H. (1992) Low serum cholesterol and suicide. Lancet 339, 727-729. Lindberg, G., Rfistam, L., Gullberg, B. and Eklund, G.A. (1992) Low serum cholesterol concentration and short term mortality from injuries in men and women. Br. Med. J. 305, 277-279. Muldoon, M.F., Manuck, S.B. and Mathews, K.M. (1990) Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. Br. Med. J. 301,309-314.
Involvement of L-type voltage-dependent calcium channel in apomorphine motility but not stereotypy
J. Michaluk, J. Vetulani and L. Antkiewicz-Michaluk Institute of Pharrnacology, Polish Academy of Sciences, 31-343 Cracow, Poland Key words." Electroconvulsive shock; Morphine abstinence; Neuroleptic; Calcium channel; Apomorphine hypermotility; Apomorphine stereotypy; Nifedipine
The involvement of the voltage-dependent calcium channel in behavioral effects of apomorphine was tested in naive rats and in animals which were morphine-abstinent or were subjected to chronic electroconvulsive (ECS) or neuroleptic (haloperidol) treatment. In naive rats a calcium channel blocker, nifedipine, which by itself does not affect locomotor activity, completely antagonized the locomotor stimulation induced by apomorphine, while it facilitated stereotyped behavior. Morphine-abstinent as well as ECS- and neuroleptic-treated rats displayed elevated responsiveness to apomorphine, reflected by hypermotility and stereotyped behavior after a dose of 1 mg/kg i.p., which does not produce overt behavioral effects in naive animals. Nifedipine, 5 mg/kg i.p., significantly reduced hypermotility produced by apomorphine in morphine-abstinent or ECS- and neuroleptic-treated rats. The calcium channel blocker did not, however, antagonize enhanced stereotyped behavior. The results indicate that apomorphine hypermotility is controlled by dihydropyridine calcium channels and that enhancement of calcium channel density produced by morphine abstinence and by chronic ECS potentiates the hypermotility response. Calcium channels seem to be differently involved in control of apomorphine-induced hypermotility and stereotypy.
Table 1. Lithium-pilocarpine synergism? LDso Li (mEq/kg)
Convulsive dose (Pi) (mg/kg)
LiC1 (mEq/kg)
Pilocarpine (mg/kg)
Time from Li to Pi (h)
Rats Mice Rabbits Guinea pigs
15-20 30M0
20(P400 >400
Chicks
> 10
3 10 6 6 6 10 10 3 6 10
20 100 30 30 60 100 150 100 100 80
6~ 30 17 20 23 17 18 17 18 6 6 2 2 17
0.96 mM
1.25 mg physo
Goldfish Human (Oppenheim et al., 1979)
>60 > 150 >200
Pi % seized 0 0 ( n - 10) 0 (n-2) 11 ( n - 9 ) 54 ( n - 13) 25 ( n - 4 ) 0 (n - 5) 0 (n-5)
0 (n=5)
Pi + Li % seized 8(~ 100 70 (n = 10) 0 (n - 2) 0 (n-2) 11 ( n - 9 ) 44 ( n - 9 ) 25 ( n - 6 ) 60 (n - 5) 40 (n-5) 80 (n-5)
0 (n=5)
References Lee, C.H., Dixon, J.F., Reichman, M., Moummi, C., Los, G. and Hokin, L.E. (1992) Li + increases accumulation of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in cholinergically stimulated brain cortex slices in guinea pig, mouse and rat. Biochem. J. 282, 377 385. Oppenheim, G., Ebstein, R.P. and Belmaker, R.H. (1979) Effect of lithium on the physostigmine-induced behavioral syndrome and plasma cyclic G M P . J. Psychiatr. Res. 15, 133-138. Sherman, W.R. (1991) Lithium and the phosphoinositide signalling system In: N.J. Birch (Ed.), Lithium and the Cell. Academic Press, London, pp. 121 157.
Serum cholesterol concentration in suicide attempters: a case-control study
M. Abbar, P. Courtet, M.C. Picot a, J. Sultan b a n d D. C a s t e l n a u b Service de Psychiatrie, CHU CarOmeau, rue du Professeur DebrO, 30000 Nimes, France, aDdpartement d'information mOdicale and bService de Psychiatrie, CHU Lapeyronie, route de Ganges, 34000 Montpellier, France Key words. Suicidal behavior; Suicide attempters; Cholesterol; Serotonin
Primary prevention trials have shown that lowering the serum cholesterol concentration in middle-aged subjects by diet, drugs or both leads to a decrease in mortality from coronary heart disease but to an increase in deaths due to suicide or violence (Muldoon et al., 1990). Secondary prevention trials revealed the same trend. Furthermore, a strong negative association between original serum cholesterol levels and short-term suicide in men was found in the largest naturalistic followup study (Lindberg et al., 1992). However, earlier follow-up studies among smaller samples had not revealed this association (Pekkanen et al., 1989; Smith et al., 1990; Chen et al., 1991, cited in Lindberg et al., 1992). The objective of this study was to determine whether total serum cholesterol concentration is associated with a past history of suicide attempts, through a casecontrol study with comparison of total serum cholesterol concentrations among psychiatric inpatients with (n = 509) and without (n = 275) a history of past suicide attempts and non-psychiatric inpatient controls (n = 2421). Mean cholesterol concentration was statistically significantly lower after sex and age adjustment in past suicide attempters when compared with other psychiatric patients. The same difference was found between suicide attempters and sex and age
431 matched control subjects, while no difference was observed between sex and age matched controls and psychiatric patients without a history of suicide attempts. Our data among suicide attempters are concordant with those found with complete suicide and suggest an association between suicidal behavior and low serum cholesterol levels. The nature of this association remains unknown but a decreased activity of brain serotonin pathways and poorer suppression of aggressive behavior with low serum cholesterol level have been proposed as possible explanations (Engelberg, 1992). This hypothesis is consistent with previous studies reporting that subjects with antisocial personalities and aggressive conduct disorders had lower blood cholesterol than did control groups (Virkkunen, 1979, 1983, 1984, cited in Engelberg, 1992). References
Engelberg, H. (1992) Low serum cholesterol and suicide. Lancet 339, 727-729. Lindberg, G., Rfistam, L., Gullberg, B. and Eklund, G.A. (1992) Low serum cholesterol concentration and short term mortality from injuries in men and women. Br. Med. J. 305, 277-279. Muldoon, M.F., Manuck, S.B. and Mathews, K.M. (1990) Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. Br. Med. J. 301,309-314.
Involvement of L-type voltage-dependent calcium channel in apomorphine motility but not stereotypy
J. Michaluk, J. Vetulani and L. Antkiewicz-Michaluk Institute of Pharrnacology, Polish Academy of Sciences, 31-343 Cracow, Poland Key words." Electroconvulsive shock; Morphine abstinence; Neuroleptic; Calcium channel; Apomorphine hypermotility; Apomorphine stereotypy; Nifedipine
The involvement of the voltage-dependent calcium channel in behavioral effects of apomorphine was tested in naive rats and in animals which were morphine-abstinent or were subjected to chronic electroconvulsive (ECS) or neuroleptic (haloperidol) treatment. In naive rats a calcium channel blocker, nifedipine, which by itself does not affect locomotor activity, completely antagonized the locomotor stimulation induced by apomorphine, while it facilitated stereotyped behavior. Morphine-abstinent as well as ECS- and neuroleptic-treated rats displayed elevated responsiveness to apomorphine, reflected by hypermotility and stereotyped behavior after a dose of 1 mg/kg i.p., which does not produce overt behavioral effects in naive animals. Nifedipine, 5 mg/kg i.p., significantly reduced hypermotility produced by apomorphine in morphine-abstinent or ECS- and neuroleptic-treated rats. The calcium channel blocker did not, however, antagonize enhanced stereotyped behavior. The results indicate that apomorphine hypermotility is controlled by dihydropyridine calcium channels and that enhancement of calcium channel density produced by morphine abstinence and by chronic ECS potentiates the hypermotility response. Calcium channels seem to be differently involved in control of apomorphine-induced hypermotility and stereotypy.