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P.8.066 An inherited mutation of apoliprotein B is associated with violent suicide in a pedigree
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inherited mutation of apoliprotein B is associated with violent suicide in a pedigree
RE Edgar 1 *, K. Ungerer 2, A. Whitfield 3, J. 13urnett3, N.R. Poa 1 .
] University of Otago, Molecular Psychiatty Group, Christchurch, New Zealand; 2 University of Otago, Canterbuty District Health Board Laboratories, New Zealand; 3Royal Perth Hospital, Core Clinical Pathology and Biochemistty, Australia Apolipoproteins are increasingly implicated as causes of neuropsychiatric disorder. Apolipoprotein E allelic variants indicate the risk of developing Alzheimer's disease, and recently Apolipoprotein D concentrations in specific human brain tissue regions have been found to be altered by antipsychotic drugs. A consequence of some mutations of another Apolipoprotein, Apolipoprotein t3, is hypocholesterolemia. Both epidemiological and animal studies have converged to provide evidence that hypocholesterolemia is associated with non-illness mortality, suicidal behaviour, violent crime, impulsive aggression and antisocial personality disorder. Studies in primates suggested this effect is mediated by serotonin, a neurotransmitter. Therefore, the widespread use of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), to lower cholesterol in patients, lead to concern that rates of suicide could increase. Subsequent meta-analyses indicated that hypocholesterolemia was associated with increased rates of suicide when produced by diet and non-statin drugs but not with statin drug use. We investigated a young man who was diagnosed with a psychotic illness, Schizoaffective Disorder Bipolar Type. He had made one suicide attempt, and was hypocholesterolemic. His father, two paternal uncles, his paternal grandfather and a paternal great uncle had all died by suicide, using firearms. In addition, one of the uncles perpetrated a double-murder prior to his suicide. This pedigree included seven paternal uncles and one paternal aunt. The proband also had low plasma vitamin E and approximately 10% of his red blood cells had deformed cell membranes, acanthocytes. On further investigation he proved to be hypobetalipoproteinemic as a result of a heterozygous mutation of Apolipoprotein t3, truncated Apo13 29.4 (1336Tyr Stop, TACTAA), previously undescribed. A surviving uncle carried the same mutation, was hypocholesterolemic and had low vitamin E levels, indicating the Apo13 29.4 mutation was inherited paternally. Upon clinical examination this uncle demonstrated a hyperthymic temperament, considered to be a subclinical expression of the Bipolar Disorder spectrum. The inheritance of truncated Apo13 mutants are known to cause familial hypocholesterolemia, and resistance to atherosclerosis. However, there is convergent evidence from both epidemiological and animal studies that hypocholesterolemia is associated with impulsive violence and this Apo13 29.4 mutation is associated in this family with violent suicide and homi cide. Therefore, inheritance of this Apo13 29.4 mutation may be the cause of this family's tragic history and an inherited risk factor for bipolar spectrum major mental illness.
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$635
Associations between vascular risk factors and incidence of late-life depression
S.W. Kim 1 *, J.M. Kim 1, R. Stewart 2, I.S. Shin 1, S.J. Yang 1 , J.S. Yoon 1 . ] Chonnam National University Hospital, Psychiatty,
Kwang-ju, Republic of Korea; 2Institute of Psychiatty, London, Section of Epidemiology, United Kingdom Objective: Associations between vascular risk factors and late-life depression are controversial at a population level. Moreover, there has been very little prospective investigation of this issue. The objective of the present study was to investigate the longitudinal associations between vascular disease/risk and late-life depression. Methods: This was a two year prospective study with a community dwelling elderly cohort. O f 661 non-depressed peoples aged 65 or over, 521 (79%) were reevaluated two years later. Both at the time of baseline and follow up, a diagnostic interview for depression (GMS) was carried out and information on vascular disease/risk (stroke, heart disease, hypertension, diaetes), examination for vascular risk status (blood pressure, fasting blood tests for glucose and lipid profiles), disability (WHODAS II), and cognitive function (MMSE) were gathered. Results: Pre-existing heart disease, incident stroke and lower baseline high density lipoprotein cholesterol level were significantly associated with incidence of late-life depression independent of demographic characteristics, disability, and cognitive function. Conclusion: These results provide some support for a vascular etiology of late-life depression, particularly with respect to overt clinical vascular disease. An adverse lipid profile might be a risk factor for depression but might also be secondary to earlier episodes of affective disorder.
References [1] Kim J.M., Stewart R., Shin I.S., Yoon J.S., 2002. Previous stroke but not vascular risk factors are associated with depression in a cognitively impaired older Korean population. Int J Geriatr Psychiatry. 17:453 458. [2] Camus V., Kraehenbuhl H., Preisig M., Bula C.J., Waeber G.J., 2004. Geriatric depression and vascular diseases: what are the links? Affect Disord. 81, 1 16.
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Efficacy and tolerability of pharmacological treatments for personality disorders: a meta-analysis
M. Nosb *, A. Cipriani, C. B arbui. Clinica Psichiatrica, University
of Verona, Department of Medicine and Public Health, Verona, Italy Purpose: In everyday clinical practice psychotropic drugs are often prescribed for patients with personality disorders, and rates of intensive polypharmacy are not uncommon. Although randomised controlled trials have shown that drug treatments could effectively be employed to tackle specific symptoms (depression, anxiety, agitation), clear clinically meaningful data are still lacking. The aim of the present systematic review is to establish whether psychotropic drugs are effective in improving cognitive, emotional, and impulsive symptoms in patients with personality disorders. Method: The Cochrane Controlled Trials Register, Medline, Embase, PsycINFO were searched up to March 2005. Reference lists of relevant papers and previous systematic reviews were hand searched for punished reports and citations of unpunished
inherited mutation of apoliprotein B is associated with violent suicide in a pedigree
RE Edgar 1 *, K. Ungerer 2, A. Whitfield 3, J. 13urnett3, N.R. Poa 1 .
] University of Otago, Molecular Psychiatty Group, Christchurch, New Zealand; 2 University of Otago, Canterbuty District Health Board Laboratories, New Zealand; 3Royal Perth Hospital, Core Clinical Pathology and Biochemistty, Australia Apolipoproteins are increasingly implicated as causes of neuropsychiatric disorder. Apolipoprotein E allelic variants indicate the risk of developing Alzheimer's disease, and recently Apolipoprotein D concentrations in specific human brain tissue regions have been found to be altered by antipsychotic drugs. A consequence of some mutations of another Apolipoprotein, Apolipoprotein t3, is hypocholesterolemia. Both epidemiological and animal studies have converged to provide evidence that hypocholesterolemia is associated with non-illness mortality, suicidal behaviour, violent crime, impulsive aggression and antisocial personality disorder. Studies in primates suggested this effect is mediated by serotonin, a neurotransmitter. Therefore, the widespread use of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), to lower cholesterol in patients, lead to concern that rates of suicide could increase. Subsequent meta-analyses indicated that hypocholesterolemia was associated with increased rates of suicide when produced by diet and non-statin drugs but not with statin drug use. We investigated a young man who was diagnosed with a psychotic illness, Schizoaffective Disorder Bipolar Type. He had made one suicide attempt, and was hypocholesterolemic. His father, two paternal uncles, his paternal grandfather and a paternal great uncle had all died by suicide, using firearms. In addition, one of the uncles perpetrated a double-murder prior to his suicide. This pedigree included seven paternal uncles and one paternal aunt. The proband also had low plasma vitamin E and approximately 10% of his red blood cells had deformed cell membranes, acanthocytes. On further investigation he proved to be hypobetalipoproteinemic as a result of a heterozygous mutation of Apolipoprotein t3, truncated Apo13 29.4 (1336Tyr Stop, TACTAA), previously undescribed. A surviving uncle carried the same mutation, was hypocholesterolemic and had low vitamin E levels, indicating the Apo13 29.4 mutation was inherited paternally. Upon clinical examination this uncle demonstrated a hyperthymic temperament, considered to be a subclinical expression of the Bipolar Disorder spectrum. The inheritance of truncated Apo13 mutants are known to cause familial hypocholesterolemia, and resistance to atherosclerosis. However, there is convergent evidence from both epidemiological and animal studies that hypocholesterolemia is associated with impulsive violence and this Apo13 29.4 mutation is associated in this family with violent suicide and homi cide. Therefore, inheritance of this Apo13 29.4 mutation may be the cause of this family's tragic history and an inherited risk factor for bipolar spectrum major mental illness.
•
$635
Associations between vascular risk factors and incidence of late-life depression
S.W. Kim 1 *, J.M. Kim 1, R. Stewart 2, I.S. Shin 1, S.J. Yang 1 , J.S. Yoon 1 . ] Chonnam National University Hospital, Psychiatty,
Kwang-ju, Republic of Korea; 2Institute of Psychiatty, London, Section of Epidemiology, United Kingdom Objective: Associations between vascular risk factors and late-life depression are controversial at a population level. Moreover, there has been very little prospective investigation of this issue. The objective of the present study was to investigate the longitudinal associations between vascular disease/risk and late-life depression. Methods: This was a two year prospective study with a community dwelling elderly cohort. O f 661 non-depressed peoples aged 65 or over, 521 (79%) were reevaluated two years later. Both at the time of baseline and follow up, a diagnostic interview for depression (GMS) was carried out and information on vascular disease/risk (stroke, heart disease, hypertension, diaetes), examination for vascular risk status (blood pressure, fasting blood tests for glucose and lipid profiles), disability (WHODAS II), and cognitive function (MMSE) were gathered. Results: Pre-existing heart disease, incident stroke and lower baseline high density lipoprotein cholesterol level were significantly associated with incidence of late-life depression independent of demographic characteristics, disability, and cognitive function. Conclusion: These results provide some support for a vascular etiology of late-life depression, particularly with respect to overt clinical vascular disease. An adverse lipid profile might be a risk factor for depression but might also be secondary to earlier episodes of affective disorder.
References [1] Kim J.M., Stewart R., Shin I.S., Yoon J.S., 2002. Previous stroke but not vascular risk factors are associated with depression in a cognitively impaired older Korean population. Int J Geriatr Psychiatry. 17:453 458. [2] Camus V., Kraehenbuhl H., Preisig M., Bula C.J., Waeber G.J., 2004. Geriatric depression and vascular diseases: what are the links? Affect Disord. 81, 1 16.
•
Efficacy and tolerability of pharmacological treatments for personality disorders: a meta-analysis
M. Nosb *, A. Cipriani, C. B arbui. Clinica Psichiatrica, University
of Verona, Department of Medicine and Public Health, Verona, Italy Purpose: In everyday clinical practice psychotropic drugs are often prescribed for patients with personality disorders, and rates of intensive polypharmacy are not uncommon. Although randomised controlled trials have shown that drug treatments could effectively be employed to tackle specific symptoms (depression, anxiety, agitation), clear clinically meaningful data are still lacking. The aim of the present systematic review is to establish whether psychotropic drugs are effective in improving cognitive, emotional, and impulsive symptoms in patients with personality disorders. Method: The Cochrane Controlled Trials Register, Medline, Embase, PsycINFO were searched up to March 2005. Reference lists of relevant papers and previous systematic reviews were hand searched for punished reports and citations of unpunished