Abstract
A 26-year-old male, the index patient, presented with persecutory delusions and suicidal behavior. He had 10 paternal male relatives in two prior generations. Five of them died by violent suicide and one, of the five, also committed a double homicide. The index patient was found to be hypocholesterolemic due to being heterozygous for a novel mutation of apolipoprotein B (apoB-29.4). His mother and paternal grandmother were normocholesterolemic, whereas a surviving paternal uncle was hypocholesterolemic and heterozygous for the apoB-29.4 mutation. This indicated that the index patient's father and paternal grandfather, both of which died by violent suicide, were obligate heterozygotes for the apoB-29.4 mutation and that the index patient inherited the mutation from his paternal grandfather. The odds ratio for the association between hypocholesterolemia and violent behavior in this family, where cholesterol status was known, was 16.9 (95% confidence interval 1.1–239.3). Therefore, our results support an inheritable relationship between violent behavior and hypocholesterolemia.
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References
Martinez R . Injury prevention. A new perspective. JAMA 1994; 272: 1541–1542.
Muldoon MF, Rossouw JE, Manuck SB, Glueck CJ, Kaplan JR, Kaufmann PG . Low or lowered cholesterol and risk of death from suicide and trauma. Metabolism 1993; 42: 45–56.
Golomb BA . Cholesterol and violence: is there a connection? Ann Intern Med 1998; 128: 478–487.
Golomb BA, Stattin H, Mednick S . Low cholesterol and violent crime. J Psychiatr Res 2000; 34: 301–309.
Muldoon MF, Manuck SB, Mendelsohn AB, Kaplan JR, Belle SH . Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials. BMJ 2001; 322: 11–15.
Paavola P, Repo-Tiihonen E, Tiihonen J . Serum lipid levels and violence among Finnish male forensic psychiatric patients. J Foren Psychiatry 2002; 13: 555–568.
Ormiston T, Wolkowitz OM, Reus VI, Manfredi F . Behavioral implications of lowering cholesterol levels: a double-blind pilot study. Psychosomatics 2003; 44: 412–414.
Golomb BA, Kane T, Dimsdale JE . Severe irritability associated with statin cholesterol-lowering drugs. Q J Med 2004; 97: 229–235.
Dumais A, Lesage AD, Lalovic A, Seguin M, Tousignant M, Chawky N et al. Is violent method of suicide a behavioral marker of lifetime aggression? Am J Psychiatry 2005; 162: 1375–1378.
Brent DA, Bridge J, Johnson BA, Connolly J . Suicidal behavior runs in families. A controlled family study of adolescent suicide victims. Arch Gen Psychiatry 1996; 53: 1145–1152.
Turecki G . Suicidal behavior: is there a genetic predisposition? Bipolar Disord 2001; 3: 335–349.
Parhofer KG, Barrett PHR, Aguilar-Salinas CA, Schonfeld G . Positive linear correlation between the length of truncated apolipoprotein B and its secretion rate: in vivo studies in human apoB-89, apoB-75, apoB-54.8, and apoB-31 heterozygotes. J Lipid Res 1996; 37: 844–852.
Yao Z, McLeod RS . Synthesis and secretion of hepatic apolipoprotein B-containing lipoproteins. Biochim Biophys Acta 1994; 1212: 152–166.
Segrest JP, Jones MK, Dashti N . N-terminal domain of apolipoprotein B has structural homology to lipovitellin and microsomal triglyceride transfer protein: a ‘lipid pocket’ model for self-assembly of apob-containing lipoprotein particles. J Lipid Res 1999; 40: 1401–1416.
Kane JP, Havel R . Disorders of the biogenesis and secretion of lipoproteins containing the B apoliproteins. In: Scriver C, Beaudet A, Sly W, Valle D, Childs B, Kinzler K et al. (eds). The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill: New York, 2001, pp 2717–2752.
Schonfeld G . Familial hypobetalipoproteinemia: a review. J Lipid Res 2003; 44: 878–883.
Whitfield AJ, Barrett PH, van Bockxmeer FM, Burnett JR . Lipid disorders and mutations in the APOB gene. Clin Chem 2004; 50: 1725–1732.
Hixson JE, Vernier DT . Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990; 31: 545–548.
Enkin M, Keirse MJC, Chalmers I . Effective Care in Pregnancy and Childbirth. Oxford University Press: Oxford, 1989.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, 4th edn, text revision. ed. American Psychiatric Press Inc.: Washington, DC, 1994.
Welty FK, Lahoz C, Tucker KL, Ordovas JM, Wilson PW, Schaefer EJ . Frequency of apoB and apoE gene mutations as causes of hypobetalipoproteinemia in the Framingham offspring population. Arterioscler Thromb Vasc Biol 1998; 18: 1745–1751.
Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 1992; 258: 999–1001.
Homer VM, George PM, du Toit S, Davidson JS, Wilson CJ . Mental retardation and ataxia due to normotriglyceridemic hypobetalipoproteinemia. Ann Neurol 2005; 58: 160–163.
Burnett JR, Shan J, Miskie BA, Whitfield AJ, Yuan J, Tran K et al. A novel nontruncating APOB gene mutation, R463W, causes familial hypobetalipoproteinemia. J Biol Chem 2003; 278: 13442–13452.
Collins DR, Knott TJ, Pease RJ, Powell LM, Wallis SC, Robertson S et al. Truncated variants of apolipoprotein B cause hypobetalipoproteinaemia. Nucleic Acids Res 1988; 16: 8361–8375.
Huang LS, Ripps ME, Korman SH, Deckelbaum RJ, Breslow JL . Hypobetalipoproteinemia due to an apolipoprotein B gene exon 21 deletion derived by Alu–Alu recombination. J Biol Chem 1989; 264: 11394–11400.
Young SG, Hubl ST, Smith RS, Snyder SM, Terdiman JF . Familial hypobetalipoproteinemia caused by a mutation in the apolipoprotein B gene that results in a truncated species of apolipoprotein B (B-31). A unique mutation that helps to define the portion of the apolipoprotein B molecule required for the formation of buoyant, triglyceride-rich lipoproteins. J Clin Invest 1990; 85: 933–942.
Cham BE, Smith JL, Colquhoun DM . Interdependence of serum concentrations of vitamin K1, vitamin E, lipids, apolipoprotein A1, and apolipoprotein B: importance in assessing vitamin status. Clin Chim Acta 1999; 287: 45–57.
Group SSR . Smoking habits and plasma lipid peroxide and vitamin E levels in never-treated first-episode patients with schizophrenia. Br J Psychiatry 2000; 176: 290–293.
Owen AJ, Batterham MJ, Probst YC, Grenyer BF, Tapsell LC . Low plasma vitamin E levels in major depression: diet or disease? Eur J Clin Nutr 2005; 59: 304–306.
Taylor PJ, Gunn J . Violence and psychosis. I. Risk of violence among psychotic men. BMJ (Clin Res Ed) 1984; 288: 1945–1949.
Taylor PJ, Gunn J . Violence and psychosis. II – Effect of psychiatric diagnosis on conviction and sentencing of offenders. BMJ (Clin Res Ed) 1984; 289: 9–12.
Taylor PJ . When symptoms of psychosis drive serious violence. Soc Psychiatry Psychiatr Epidemiol 1998; 33 (Suppl 1): S47–S54.
Suicide facts: provisional 2003 all-ages statistics. New Zealand Government: Wellington, 2005.
Lovell-Badge R . Aggressive behavior: contributions from genes on the Y chromosome. Novartis Found Symp 2005; 268: 20–33.
Kaplan JR, Manuck SB, Shively C . The effects of fat and cholesterol on social behavior in monkeys. Psychosom Med 1991; 53: 634–642.
Kaplan JR, Shively CA, Fontenot MB, Morgan TM, Howell SM, Manuck SB et al. Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behavior in monkeys. Psychosom Med 1994; 56: 479–484.
Muldoon MF, Kaplan JR, Manuck SB, Mann JJ . Effects of a low-fat diet on brain serotonergic responsivity in cynomolgus monkeys. Biol Psychiatry 1992; 31: 739–742.
Acknowledgements
This work was supported by grants from the Health Research Council of New Zealand (04/141R), the Schizophrenia Fellowship of New Zealand (to PFE and NRP), the Royal Perth Hospital Medical Research Foundation, the Raine Medical Research Foundation, the National Health & Medical Research Council (403908) and the National Heart Foundation of Australia (G 139 115) (to JRB). We are indebted to Dr K Ungerer (Canterbury District Health Board Laboratories) for his assistance.
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Edgar, P., Hooper, A., Poa, N. et al. Violent behavior associated with hypocholesterolemia due to a novel APOB gene mutation. Mol Psychiatry 12, 258–263 (2007). https://doi.org/10.1038/sj.mp.4001910
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DOI: https://doi.org/10.1038/sj.mp.4001910
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