Article thumbnail

Endophenotypes in the personality disorders

By Larry J. Siever


The identification of endophenotypes in the personality disorders may provide a basis for the identification of underlying genotypes that influence the traits and dimensions of the personality disorders, as well as susceptibility to major psychiatric illnesses. Clinical dimensions of personality disorders that lend themselves to the study of corresponding endophenotypes include affective instability impulsiwity aggression, emotional information processing, cognitive disorganization, social deficits, and psychosis. For example, the propensity to aggression can be evaluated by psychometric measures, interview, laboratory paradigms, neurochemical imaging, and pharmacological studies. These suggest that aggression is a measurable trait that may be related to reduced serotonergic activity. Hyperresponsiveness of amygdala and other limbic structures may be related to affective instability, while structural and functional brain alterations underlie the cognitive disorganization in psychoticlike symptoms of schizotypal personality disorder. Thus, an endophenotypic approach not only provides clues to underlying candidate genes contributing to these behavioral dimensions, but may also point the way to a better understanding of pathophysiological mechanisms

Topics: Clinical Research
Publisher: Les Laboratoires Servier
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. 5HTTLPR polymorphism in schizophrenic patients: further support for association with violent suicide attempts.
  2. (2005). A fenfluramine-activated FDG-PET study of borderline personality disorder. Biol Psychiatry. 2000;47:540-547.Endophenotypes in the personality disorders - Siever Dialogues in Clinical Neuroscience -
  3. (2005). A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia.
  4. A multidimensional scaling of the DSM-III personality disorders. Arch Gen psychiatry.
  5. (2002). A polymorphism in the dopamine beta-hydroxylase gene is associated with “paranoid ideation” patients with major depression. Biol Psychiatry.
  6. (1991). A psychobiological perspective on the personality disorders.
  7. A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res.
  8. A twin study of personality disorders.
  9. (1993). Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A.
  10. (1988). Acting out hostility in normal volunteers: negative correlation with levels of 5HIAA in cerebrospinal fluid. Psychiatry Res.
  11. Affect intensity and reactions to daily life events.
  12. Affective and impulsive personality disorder traits in the relatives of patients with borderline personality disorder.
  13. Aggressive behavior and physiological arousal as a function of provocation and the tendency to inhibit aggression.
  14. (2000). An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder. Psychiatr Genet.
  15. An inventory for assessing different kinds of hostility.
  16. (1994). Anxiety and growth disturbance: is there a connection? A review of biological studies in social phobia. J Clin Psychiatry.
  17. Association between allelic variation of serotonin transporter function and neuroticism in anxious cluster C personality disorders.
  18. Association between the adrenergic alpha 2A receptor gene (ADRA2A) and measures of irritability, hostility, impulsivity and memory in normal subjects.
  19. Association of a duplicated repeat polymorphism in the 5'-untranslated region of the DRD4 gene with novelty seeking.
  20. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.
  21. (1991). Avoidant and dependent personality traits in relatives of patients with panic disorder, patients with dependent personality disorder and normal controls. Psychiatry Res.
  22. (2002). Blunted prefrontal cortical 18F-fluorodeoxyglucose positron emission tomography response to metachlorophenylpiperazine in impulsive aggression. Arch Gen Psychiatry.
  23. Borderline psychopathology in the first-degree relatives of borderline and axis II comparison probands.
  24. Brain serotonin transporters distribution in subjects with in impulsive aggression: a positron emission study with [ 11C]McN5652.
  25. Characterizing affective instability in borderline and other personality disorders.
  26. (1988). Childhood derivatives of inhibition and lack of inhibition to the unfamiliar. Child Dev.
  27. Coccaro EF. Assessment of behavioral and cognitive impulsivity: development and validation of the Lifetime History of Impulsive Behaviors Interview. Psychiatry Res.
  28. (2004). cognitive, and neuroimaging intermediate phenotypes in impulsive personality disorders. Biol Psychiatry.
  29. CSF homovanillic acid in schizotypal personality disorder.
  30. d,1-Fenfluramine response in impulsive personality disorder assessed with [ 18F]flurodeoxyglucose positron emission tomography.
  31. Deliberate self-harm is associated with allelic variation in the tryptophan hydroxylase gene (TPH A779C), but not with polymorphisms in five other serotonergic genes. Psychol Med.
  32. Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder. Schizophr Res.
  33. Dopamine D3 receptor gene polymorphism and violent behavior: relation to impulsiveness and ADHD-related psychopathology.
  34. (2001). Dopamine D4 receptor (DRD4) gene polymorphism in the first psychotic episode. Arch Med Res.
  35. DRD4 exon variants associated with delusional symptomatology in major psychoses: a study on 2011 affected subjects.
  36. Effect of COMT Val 108/158Met genotype on frontal lobe function and risk for schizophrenia.
  37. Effects of smoking different doses of nicotine on human aggressive behavior.
  38. (2004). Emotion processing in borderline personality disorder: a functional MRI perspective. Neuropsychopharmacology.
  39. (2001). Evidence of abnormal amygdale functioning in borderline personality disorder: a functional MRI study. Biol Psychiatry.
  40. Executive functioning and alcohol-related aggression.
  41. Fractionating impulsivity: contrasting effects of central 5-HT depletion on different measures of impulsive behavior.
  42. (1984). Genetic and nosological aspects of schizotypal and borderline personality disorders. Arch Gen Psychiatry.
  43. (1991). Growth hormone resonses to intravenous clonidine challenge correlates with behavioral irritability in psychiatric patients and in healthy volunteers. Psychiatry Res.
  44. (1997). Heritability of aggression and irritability: a twin study of the Buss-Durkee Aggression Scales in adult male subjects. Biol Psychiatry.
  45. Impulsiveness and aggression.
  46. (2003). Impulsiveness as the intermediate link between the dopamine receptor D2 gene and alcohol dependence. Psychiatr Genet.
  47. Impulsiveness subtraits: arousal and information processing.
  48. Insensitivity to future consequences following damage to human prefrontal cortex.
  49. (1997). Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus.
  50. Looking at pictures: affective, facial, visceral, and behavioral reactions.
  51. (1976). Measuring facial movement. Environ Psychol Nonverbal Behav.
  52. (2000). Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits.
  53. Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity. Biol Psychiatry.
  54. (1992). Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry.
  55. Personality similarity in twins reared apart and together.
  56. Physical anhedonia, perceptual aberration, and psychosis proneness.
  57. Polymorphisms of DRD4 and DRD3 and risk of avoidant and obsessive personality traits and disorders. Psychiatry Res.
  58. (1992). Prefrontal structural and functional deficits associated with individual differences in schizotypal personality. Schizophr Res.
  59. Prefrontal structural and functional deficits in schizotypal personality disorder.
  60. (1998). Psychiatric genetics: search for phenotypes. Trends Neurosci.
  61. Relationship between positive and negative symptoms of schizophrenia and schizotypal symptoms nonpsychotic relatives. Arch Gen Psychiatry.
  62. Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors.
  63. (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry.
  64. (1997). Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission topography method.
  65. (1999). Schizophrenia: a review of genetic studies. Harv Rev Psychiatry.
  66. Searching for alternative phenotypes in psychiatric genetics. Methods Mol Med.
  67. Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder.
  68. (1989). Serotonergic studies in patients with affective and personality disorders: correlates with suicidal and impulsive aggressive behavior. Arch Gen Psychiatry.
  69. (2004). Serotonin transporter gene polymorphism and personality traits in primary alcohol dependence. World J Biol Psychiatry.
  70. Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior. Biol Psychiatry.
  71. (2000). Serotonin transporter gene regulatory region polymorphism (5-HTTLPR), [ 3H]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity. Psychiatry Res.
  72. Serotonin transporter promoter polymorphism is associated with attenuated prolactin response to fenfluramine.
  73. (1998). Serotonin transporter protein gene polymorphism and personality measures in African American and European American subjects.
  74. (1992). Social phobia: biological aspects and pharmacotherapy. Prog Neuropsychopharmacol Biol Psychiatry.
  75. (1992). Stable behavioral inhibition and its association with anxiety disorder.
  76. Studies of interference in serial verbal reactions.
  77. (1997). Studies of violent and nonviolent male parolees: I. Laboratory and psychometric measurements of aggression. Biol Psychiatry.
  78. (1994). Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. Arch Gen Psychiatry.
  79. (2001). Suicide, impulsive aggression and the HTR1B genotype. Biol Psychiatry.
  80. The 5HTTLPR polymorphism, psychopathologic symptom and platelet [ 3H]paroxetine binding in bulimic syndromes.
  81. The affective lability scales: development reliability and validity.
  82. (1992). The aggression questionnaire.
  83. (2002). The borderline diagnosis III: identifying endophenotypes for genetic studies. Biol Psychiatry.
  84. The endophenotype concept in psychiatry: etymology and strategic intentions.
  85. The meanings of personality predicates.
  86. The pathophysiology of schizophrenia disorders: perspectives from the spectrum.
  87. The pathophysiology of the schizophrenic disorders: perspective from the spectrum.
  88. (1991). The relationship of social phobia subtypes and avoidant personality disorder. Compr Psychiatry.
  89. (1993). The roscommon family study I. Methods, diagnosis of probands and risk of schizophrenia in relatives. Arch Gen Psychiatry.
  90. (1991). The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophr Bull.
  91. (1991). The structure of schizotypy: a pilot multitrait twin study. Psychiatry Res.
  92. (1991). The Swedish Adoption/Twin Study of Aging: an update. Arch Gen Med.
  93. True” schizotypal personality disorder: a study of co-twins and relatives of schizophrenic probands.
  94. (1998). Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study.
  95. Variation in catechol-Omethyltransferase val 58met genotype associated with schizotypy but not cognition: a population study in 543 young men. Biol Psychiatry.
  96. (1998). Verbal learning and memory in schizotypal personality disorder. Schizophr Bull.
  97. (2000). Visuospatial working memory in schizotypal personality disorder patients. Schizophr Res.