Hostname: page-component-8448b6f56d-mp689 Total loading time: 0 Render date: 2024-04-22T13:37:35.468Z Has data issue: false hasContentIssue false

Neurobiologic Function and Temperament in Subjects With Personality Disorders

Published online by Cambridge University Press:  07 November 2014



Personality traits have been hypothesized to involve specific neurotransmitter systems. In order to test this model, the relationship between the responses to serotonergic and noradrenergic probes, central cerebrospinal fluid (CSF) measures of monoamine neurotransmitters and the Tridimensional Personality Questionnaire (TPQ) were evaluated in a cohort of personality disorder subjects.


A total of 142 patients meeting at least one personality disorder (meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition–Revised criteria) participated in these studies. The prolactin response to fenfluramine (a measure of serotonin function) was obtained for 110 subjects; growth hormone response to clonidine (a measure of noradrenergic function) was obtained for 77 subjects, while homovanillic acid (HVA) at baseline, an index of dopaminergic function, was available for 103 subjects. Measures of central neurotransmitter function (dopaminergic, serotonergic, and noradrenergic: HVA, 5-hydroxyindolacetic acid, and 3-methoxy-4-hydroxyphenylglycol, respectively) were available for 36 subjects. Separate regression analyses utilizing each of the hypothesized associations, where the TPQ total scores were used as the dependent measures and the biologic indices were the independent measures were conducted. Exploratory correlational analyses between these biologic measures and the four dimensions of the TPQ (and its subscales) were also conducted. (Correlations are reported if they would remain significant at P<.01 level after Bonferroni correction for multiple comparisons across the six neuroendocrine measures).


In the regression analyses, there was a trend association between CSF and plasma HVA in predicting novelty-seeking (P<.07). No other significant associations were found in the other three measures. Regarding the individual correlational analyses, the persistence scale of the TPQ was significantly positively correlated with the growth hormone response to clonidine (r=.30, P<.008). The sentimentality subscale (reward dependence) was positively correlated with CSF 5-hydroxyindolacetic acid (r=0.45, P<.001), while the attachment subscale (also reward dependence) was correlated with CSF 3-methoxy-4-hydroxyphenylglycol (r=0.49, P<.002).


Limited support was provided for a relationship between monoamines, particularly dopamine and novelty-seeking as well as norepinephrine and reward dependence but other hypothesized relationships were not supported by these measures.

Original Research
Copyright © Cambridge University Press 2003

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



1.Cloninger, CR. A systematic method for clinical description and classification of personality variants. A proposal. Arch Gen Psychiatry. 1987;44:573588.CrossRefGoogle ScholarPubMed
2.Cloninger, CR, Svrakic, DM, Przybeck, TR. A psychobiological model of temperament and character. Arch Gen Psychiatry. 1993;50:975990.CrossRefGoogle ScholarPubMed
3.Cloninger, CR, Bayon, C, Svrakic, DM. Measurement of temperament and character in mood disorders: a model of fundamental states as personality types. J Affect Disord. 1998;51:2132.CrossRefGoogle Scholar
4.Tancer, ME, Ranc, J, Golden, RN. Pharmacological challenge test of the Tridimensional Personality Questionnaire in patients with social phobia and normal volunteers. Anxiety. 19941995;1:224226.CrossRefGoogle ScholarPubMed
5.Waller, DA, Gullion, CM, Petty, F, Hardy, BW, Murdock, MV, Rush, AJ. Tridimensional Personality Questionnaire and serotonin in bulimia nervosa. Psychiatry Res. 1993;48:915.CrossRefGoogle ScholarPubMed
6.Wiesbeck, GA, Mauerer, C, Thome, J, Jakob, F, Boening, J. Neuroendocrine support for a relationship between “novelty seeking” and dopaminergic function in alcohol-dependent men. Psychoneuroendocrinology. 1995;20:755761.CrossRefGoogle ScholarPubMed
7.Evans, J, Platts, H, Lightman, S, Nutt, D. Impulsiveness and the prolactin response to d-fenfluramine. Psychopharmacology (Berl). 2000;149:147152.CrossRefGoogle ScholarPubMed
8.Nelson, EC, Cloninger, CR, Przybeck, TR, Csernansky, JG. Platelet serotonergic markers and Tridimensional Personality Questionnaire measures in a clinical sample. Biol Psychiatry. 1996;15;40:271278.CrossRefGoogle Scholar
9.Pfohl, B, Black, D, Noyes, R Jr, Kelley, M, Blum, N. A test of the tridimensional personality theory: association with diagnosis and platelet imipramine binding in obsessive-compulsive disorder. Biol Psychiatry. 1990;28:4146.CrossRefGoogle ScholarPubMed
10.Hansenne, M, Ansseau, M. Harm avoidance and serotonin. Biol Psychol. 1999;51:7781CrossRefGoogle ScholarPubMed
11.Hennig, J, Toll, C, Schonlau, P, Rohrmann, S, Netter, P. Endocrine responses after d-fenfluramine and ipsapirone challenge: further support for Cloninger's tridimensional model of personality. Neuropsychobiology. 2000;41:3847.CrossRefGoogle ScholarPubMed
12.Benjamin, J, Osher, Y, Kotler, M, et al.Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol-O-methyltransferase (COMT). Mol Psychiatry. 2000;5:96100.CrossRefGoogle ScholarPubMed
13.Malhotra, AK, Virkkunen, M, Rooney, W, Eggert, M, Linnoila, M, Goldman, D. The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking. Mol Psychiatry. 1996;1:388391.Google ScholarPubMed
14.Mulder, RT, Joyce, PR. Relationship of temperament and behaviour measures to the prolactin response to fenfluramine in depressed men. Psychiatry Res. 2002;109:221228.CrossRefGoogle Scholar
15.Ruegg, RG, Gilmore, J, Ekstrom, RD, et al.Clomipramine challenge responses covary with Tridimensional Personality Questionnaire scores in healthy subjects. Biol Psychiatry. 1997;42:11231129.CrossRefGoogle ScholarPubMed
16.Gerra, G, Zaimovic, A, Timpano, M, Zambelli, U, Delsignore, R, Brambilla, F. Neuroendocrine correlates of temperamental traits in humans. Psychoneuroendocrinology. 2000;25:479496.CrossRefGoogle ScholarPubMed
17.Limson, R, Goldman, D, Roy, A, et al.Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls. Arch Gen Psychiatry. 1991;48:437441.CrossRefGoogle ScholarPubMed
18.Diagnostic and Statistical Manual of Mental Disorder. 3rd ed rev. Washington, DC: American Psychiatric Association; 1987.Google Scholar
19.Spitzer, RL, Endicott, J. Schedule for Affective Disorders and Schizophrenia (SADS). New York, NY: New York State Psychiatric Institute, Biometrics Research; 1978.Google Scholar
20.Pfohl, B, Stangl, D, Zimmerman, M. Semi-structured interview for DSM-III-R Personality Disorder. Iowa City, IA: University of Iowa Press; 1989.Google Scholar
21.Coccaro, EF, Siever, LJ, Klar, HM, et al.Serotonergic studies in patients with affective and personality disorders. Correlates with suicidal and impulsive aggressive behavior. Arch Gen Psychiatry. 1989;46:587599.CrossRefGoogle ScholarPubMed
22.Trestman, RL, Coccaro, EF, Mitropoulou, V, Gabriel, SM, Horvath, T, Siever, LJ. The cortisol response to clonidine in acute and remitted depressed men. Biol Psychiatry. 1993;15;34:373379.CrossRefGoogle Scholar
23.Siever, LJ, Amin, F, Coccaro, EF, et al.CSF homovanillic acid in schizotypal personality disorder. Am J Psychiatry. 1993;150:149151.Google ScholarPubMed
24.Amin, F, Davidson, M, Davis, KL. Homovanillic acid measurement in clinical research: a review of methodology. Schizophr Bull. 1992;18:123148.CrossRefGoogle ScholarPubMed
25.Scheinin, M, Chang, WH, Jimerson, DC, Linnoila, M. Measurement of 3-methoxy-4-hydroxyphenylglycol in human plasma with high-performance liquid chromatography using electrochemical detection. Anal Biochem. 1983;132:165170.CrossRefGoogle ScholarPubMed
26.Cloninger, CR, Przybeck, TR, Svrakic, DM. The Tridimensional Personality Questionnaire: U.S. normative data. Psychol Rep. 1991;69(3 pt 1):10471057.CrossRefGoogle ScholarPubMed
27.Eysenck, HJ. The Biological Basis of Personality. Springfield, Ill: Charles C. Thomas; 1967.Google Scholar
28.Siever, LJ, Davis, KL. A psychobiological perspective on the personality disorders. Am J Psychiatry. 1991;148:1647–658.Google ScholarPubMed
29.Virkkunen, M, Nuutila, A, Goodwin, FK, Linnoila, M. Cerebrospinal fluid monoamine metabolite levels in male arsonists. Arch Gen Psychiatry. 1987;44:241247.CrossRefGoogle ScholarPubMed
30.Roy, A, Agren, H, Pickar, D, et al.Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression. Am J Psychiatry. 1986;143:15391545.Google ScholarPubMed
31.New, AS, Trestman, RL, Mitropoulou, V, et al.Serotonergic function and self-injurious behavior in personality disorder patients. J Psychiatry Res. 1997;69:1726.CrossRefGoogle ScholarPubMed
32.Manuck, SB, Flory, JD, McCaffery, JM, Matthews, KA, Mann, JJ, Muldoon, MEAggression, impulsivity, and central nervous system serotonergic responsivity in a nonpatient sample. Neuropsychopharmacology. 1998;19:287299.CrossRefGoogle Scholar
33.Goldman, RG, Skodol, AE, McGrath, PJ, Oldham, JM. Relationship between the Tridimensional Personality Questionnaire and DSM-III-R personality traits. Am J Psychiatry. 1994;151:274276.Google ScholarPubMed
34.Svrakic, DM, Whitehead, C, Przybeck, TR, Cloninger, CR. Differential diagnosis of personality disorders by the seven-factor model of temperament and character. Arch Gen Psychiatry. 1993;50:991999.CrossRefGoogle ScholarPubMed
35.Maggini, C, Ampollini, P, Marchesi, C, Gariboldi, S, Cloninger, CR. Relationships between Tridimensional Personality Questionnaire Dimensions and DSM-III-R personality traits in Italian adolescents. Compr Psychiatry. 2000;41:426431.CrossRefGoogle ScholarPubMed
36.Agren, H, Mefford, IN, Rudorfer, MV, Linnoila, M, Potter, WZ. Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF. J Psychiatr Res. 1986;20:175193.CrossRefGoogle Scholar