The +1444C>T polymorphism in the CRP gene: a study on personality traits and suicidal behaviour

Objectives Numerous studies have shown associations between an on-going depression and elevated serum levels of the acute-phase reactant C-reactive protein (CRP). Also, in suicidal behaviour, a proinflammatory state has been suggested to be of importance for the pathophysiology. There is a genetic susceptibility to suicidal behaviour, but studies with respect to genes related to inflammation are sparse. We have previously reported an association between a polymorphism located in the CRP gene, +1444C>T (rs1130864), and the personality trait impulsiveness in women assessed using the Karolinska Scales of Personality. The present study aims to replicate these results in suicide attempters and examine whether the polymorphism is associated with suicidal behaviour. Materials and methods The +1444C>T polymorphism was genotyped in suicide attempters from two cohorts (a total of 106 patients) and healthy controls (n=517). Results We could replicate our previous finding, as the +1444T allele was associated with higher scores in the Karolinska Scales of Personality factor extraversion and its subscale impulsiveness in one of the patient cohorts. Furthermore, the +1444T allele was significantly more common among suicide attempters compared with the +1444C allele. Conclusion The present results lend further support to the relevance of inflammation for suicidal behaviour. The association between the polymorphism and personality trait impulsiveness reinforces our hypothesis of the importance of immune-related genes also for normal mental functions such as personality traits. Given the fact that impulsiveness is a well-known risk factor for suicidal behaviour, we further hypothesize that the polymorphism studied may in part explain this relationship.

[1]  K. Peter,et al.  Amyloid Plaques Dissociate Pentameric to Monomeric C‐Reactive Protein: A Novel Pathomechanism Driving Cortical Inflammation in Alzheimer's Disease? , 2012, Brain pathology.

[2]  G. Holm,et al.  Personality traits and the R668Q polymorphism located in the MMP-9 gene , 2012, Behavioural Brain Research.

[3]  E. Jönsson,et al.  Is the Gly82Ser polymorphism in the RAGE gene relevant to schizophrenia and the personality trait psychoticism? , 2012, Journal of psychiatry & neuroscience : JPN.

[4]  M. Perola,et al.  CRP gene variation affects early development of Alzheimer's disease-related plaques , 2011, Journal of Neuroinflammation.

[5]  B. Ekici,et al.  Asthma and suicide: possible role of brain-derived neurotrophic factor. , 2011, Medical hypotheses.

[6]  S. Janelidze,et al.  Cytokine levels in the blood may distinguish suicide attempters from depressed patients , 2011, Brain, Behavior, and Immunity.

[7]  Inbal Goshen,et al.  Immune modulation of learning, memory, neural plasticity and neurogenesis , 2011, Brain, Behavior, and Immunity.

[8]  J. Jokinen,et al.  Cholesterol and CSF 5-HIAA in attempted suicide. , 2010, Journal of affective disorders.

[9]  A. Raine,et al.  Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy. , 2010, The British journal of psychiatry : the journal of mental science.

[10]  Y. Ko,et al.  Asthma and suicide mortality in young people: a 12-year follow-up study. , 2010, The American journal of psychiatry.

[11]  D. Clarke,et al.  Seasonal allergies and suicidality: results from the National Comorbidity Survey Replication , 2010, Acta psychiatrica Scandinavica.

[12]  M. Timonen,et al.  Cardiovascular Diseases among Suiciders: A Population-Based Study in Northern Finland Population , 2010, Cardiovascular psychiatry and neurology.

[13]  E. Ringelstein,et al.  Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function , 2010, Neurology.

[14]  E. Baca-García,et al.  Is impulsivity a link between childhood abuse and suicide? , 2010, Comprehensive psychiatry.

[15]  S. Manuck,et al.  Polymorphisms in the CRP gene moderate an association between depressive symptoms and circulating levels of C-reactive protein , 2010, Brain, Behavior, and Immunity.

[16]  L. Boulanger,et al.  Immune Proteins in Brain Development and Synaptic Plasticity , 2009, Neuron.

[17]  N. O’Rourke,et al.  Impulsivity and Hopelessness as Predictors of Suicide-Related Ideation among Older Adults , 2009, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[18]  Martin Samuelsson,et al.  Interleukin-6 Is Elevated in the Cerebrospinal Fluid of Suicide Attempters and Related to Symptom Severity , 2009, Biological Psychiatry.

[19]  C. R. Cloninger,et al.  Individual differences in personality traits reflect structural variance in specific brain regions , 2009, Brain Research Bulletin.

[20]  A. Sposito,et al.  Association between suicide and cardiovascular disease: time series of 27 years. , 2009, International journal of cardiology.

[21]  A. Halaris Comorbidity between depression and cardiovascular disease. , 2009, International angiology : a journal of the International Union of Angiology.

[22]  R. Rosmond,et al.  Genetic variability within the innate immune system influences personality traits in women , 2009, Genes, brain, and behavior.

[23]  D. F. Drake,et al.  Activation of Central Nervous System Inflammatory Pathways by Interferon-Alpha: Relationship to Monoamines and Depression , 2009, Biological Psychiatry.

[24]  Y. F. Neelagund,et al.  Bacterial meningitis: rapid diagnosis and microbial profile: a multicentered study. , 2008, The Journal of communicable diseases.

[25]  R. Rosmond,et al.  Behavioral and Brain Functions Association between Serum Levels of C-reactive Protein and Personality Traits in Women , 2022 .

[26]  D. Rujescu,et al.  Elevated cytokine expression in the orbitofrontal cortex of victims of suicide , 2008, Acta psychiatrica Scandinavica.

[27]  A. Beekman,et al.  Inflammatory markers in late-life depression: results from a population-based study. , 2008, Journal of affective disorders.

[28]  T. Lehtimäki,et al.  C-reactive protein genetics is associated with carotid artery compliance in men in The Cardiovascular Risk in Young Finns Study. , 2008, Atherosclerosis.

[29]  M. Rizzo,et al.  Prediction of Cerebrovascular and Cardiovascular Events in Patients With Subclinical Carotid Atherosclerosis , 2008, Journal of Investigative Medicine.

[30]  V. Meyer-Rochow,et al.  The Association Between C-Reactive Protein Levels and Depression: Results from the Northern Finland 1966 Birth Cohort Study , 2006, Biological Psychiatry.

[31]  C. Caruso,et al.  Association between +1059G/C CRP Polymorphism and Acute Myocardial Infarction in a Cohort of Patients from Sicily , 2006, Annals of the New York Academy of Sciences.

[32]  M. Alda,et al.  Risk factors for suicide completion in major depression: a case-control study of impulsive and aggressive behaviors in men. , 2005, The American journal of psychiatry.

[33]  I. Janszky,et al.  Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease , 2005, Brain, Behavior, and Immunity.

[34]  S. Humphries,et al.  C-reactive protein (+1444C>T) polymorphism influences CRP response following a moderate inflammatory stimulus. , 2005, Atherosclerosis.

[35]  Avshalom Caspi,et al.  Personality development: stability and change. , 2005, Annual review of psychology.

[36]  T. Erlinger,et al.  Depression and C-reactive protein in US adults: data from the Third National Health and Nutrition Examination Survey. , 2004, Archives of internal medicine.

[37]  Viola Vaccarino,et al.  Association Between Depression and Elevated C-Reactive Protein , 2003, Psychosomatic medicine.

[38]  Jarmo Hietala,et al.  Personality traits and striatal dopamine synthesis capacity in healthy subjects. , 2003, The American journal of psychiatry.

[39]  P. Mcgeer,et al.  Human neurons generate C-reactive protein and amyloid P: upregulation in Alzheimer’s disease , 2000, Brain Research.

[40]  P. Björntorp,et al.  Psychiatric ill-health of women and its relationship to obesity and body fat distribution. , 1998, Obesity research.

[41]  H. Ohtani,et al.  Levels of interleukin‐6, CRP and α2 macroglobulin in cerebrospinal fluid (CSF) and serum as indicator of blood‐ CSF barrier damage , 1997, Biochemistry and molecular biology international.

[42]  T. Duong,et al.  C-reactive protein-like immunoreactivity in the neurofibrillary tangles of Alzheimer's disease , 1997, Brain Research.

[43]  M. Åsberg,et al.  Origins of individual differences in anxiety proneness: a twin/adoption study of the anxiety‐related scales from the Karolinska Scales of Personality (KSP) , 1996, Acta psychiatrica Scandinavica.

[44]  P. Björntorp,et al.  Mental distress, obesity and body fat distribution in middle-aged men. , 1996, Obesity research.

[45]  L. Träskman-bendz,et al.  Increased soluble interleukin‐2 receptor concentrations in suicide attempters , 1993, Acta psychiatrica Scandinavica.

[46]  B. Hazenberg,et al.  The effect of interleukin-1, interleukin-6 and its interrelationship on the synthesis of serum amyloid A and C-reactive protein in primary cultures of adult human hepatocytes. , 1988, Biochemical and biophysical research communications.

[47]  M. Åsberg,et al.  Markers for vulnerability to psychopathology: Temperament traits associated with platelet MAO activity , 1987, Acta psychiatrica Scandinavica.

[48]  F. Crumley Adolescent suicide attempts. , 1979, JAMA.

[49]  R. Marioni,et al.  Genetic Variants Associated With Altered Plasma Levels of C-Reactive Protein are not Associated With Late-Life Cognitive Ability in Four Scottish Samples , 2010, Behavior genetics.

[50]  A. Zinsmeister,et al.  Relationships between C-reactive protein concentration and genotype in healthy volunteers , 2009, Clinical chemistry and laboratory medicine.

[51]  B. Bogerts,et al.  Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. , 2008, Journal of psychiatric research.

[52]  Jianfeng Huang,et al.  −717A>G polymorphism of human C-reactive protein gene associated with coronary heart disease in ethnic Han Chinese: the Beijing atherosclerosis study , 2004, Journal of Molecular Medicine.

[53]  N. Shimetani,et al.  Levels of three inflammation markers, C-reactive protein, serum amyloid A protein and procalcitonin, in the serum and cerebrospinal fluid of patients with meningitis. , 2001, Scandinavian journal of clinical and laboratory investigation.

[54]  M. First,et al.  Structured clinical interview for DSM-IV axis I disorders : SCID-I: clinical version : administration booklet , 1996 .