BIOL PSYCI~IATRY 1990;28:41--46
41
A Test of the Tridimensional Personality Theory: Association with Diagnosis and Platelet Imipramine Binding in Obsessive-Compulsive Disorder Bruce Pfohl, Donald Black, Russell Noyes, Jr., Michael Kelley, and Nancee Blum
We administered the Tridimensional Personality Questionnaire (TPQ) to a sample of 25 individuals with obsessive-compulsive disorder (OCD) and 35 norn~al controls. As predicted, OCD cases scored much higher on the harm avoidance dimension than normal controls. Findings for the novelty seeking and reward dependence dimensions were less dramatic, although compatible with the underlying theory. Despite a theoretical link between tlw harm avoidance dimension and serotonin-mediated neuropathways, we failed to find an association between ~;hisdimension and platelet imipramine binding in either OCD cases or controls. Introduction The Tridimensional Personality Questionnaire (TPQ) has been developed to measure three fundamental dimensions of personality: novelty seeking, harm avoidance, and reward dependence (Cloninger 1987). Cloninger developed the TPQ in order to operationalize behavioral dimensiens that have been correlated with the activity of several neurotransmitter systems by previous resean~h. Thus, each dimension is hypothesized to relate to a specific neurotransmitter system. In theory~ variations in the activity level of the three neurotransmitter systems are manifested as changes in the three corresponding behavioral dimensions and extreme vm'iations are expressed as specific psychiatric disorders. The TPQ is thus a useful tool for operationalizing key behavio~L variables in order to test hypotheses regarding the link between behavior and central nervous system (CNS) neurotransmitter activity. The three TPQ dimensions and the neurochemical and psychopharmacologicaI studies on which they are based have been previously described in greater detail (Cloninger 1986, 1987). In brief, individuals with higher-than-average scores on novelty seeking tend to be impulsive, excitable, extravagant, and di:;orderly. This dimens,.'on is theoretically associated with low basal dopaminergic activity which leads to a predis.~ position towards novel and exploratory behaviors which ~ : then reinfow~! by an acute
From the Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA. Supported in part by the Ciba.Geigy Co. Address reprint requests to Bruce Pfohl, M.D., Dept. of Psychiatry, Uaiversity of Iowa College of Medicine, 500 Newton Road, Iowa City, IA 52242. Received August 15, 1988; revised December 14, 1989. © 1990 Society of Biological Psychiatry
0006-3223/90/$03.50
42
BIOL PSYCHIATRY
B. Pfohl et al.
1990;28:41--46
increase in dopaminergic activity. This relationship is supported by the finding that dopamine receptor antagonists reduce h--npulsive behavior in patients with borderline personality disorder as, presumably, dopamine blockade reduces the reinforcement for exploration of novel stimuli (Soloff et al. 1986; Cowdry and Gardner 1988). Cloainger (1987) also describes studies of dopamine depleting lesions in the nucleus accombens and ventral tegmentum of rats which are associated with a reduced tendency to explore novel stimuli. Individuals with high scores on harm avoidance tend to be characterized by anticiipatory worry, fear of uncertainty, shyness, and fatigability. This dimension is theoretically related to increased serotonin activity as suggested by the negative correlation between CSF 5HIAA and risk-taking/suicidal behavior in patients with a va~riety of diagnoses f~Brown et al. 1982). Individuals with high scores on reward dependence tend to be sentimental, persistent, dependent, and readily form attachments with others. This dimension is said to correlate with low basal noradrenergic activity as suggested by studies link/rig noradrenergic activity to resistance to extinction in learning paradigms (Cloninger 1987; Mason and Iversen 1979). Theoretically, the low basal norepinephrine activity leads to greater persistence in seeking rewards which result in norepinephrine-mediated reinforcement. The study of a group of patients with a well-defined diagnosis such as obsessive compulsive disorder (OCD) and healthy controls can be used to test the TPQ and associated theory in several ways. First, the theory conceptualizes OCD as representkig certain extremes of behavior on the three operationalized dimensions. Most of these predictions make common sense. A clinician familiar with the obsessive compulsive patient's typical concerns about germs or sharp, knives could easily predict that OCD patients would score high on the harm avoidance dimensions. Likewise, the tendency to maintain order and follow well-defined rituals suggests that such pati,mts would score low on novelty seeking. Predictions for the reward dependence dimension is more problematic. The tendency to persist with repetitive behaviors would suggest high-reward dependence. On the other hand, OCD patients appear to be more likely than controls to have obsessive-compulsive personality (Pfohl et al. in press) and Cloninger (1986) has previously predicted that such patients would have low reward dependence based on the lack of sentimentali,ty and social sensitivity associated with this personality diagnosis. To the extent that the OCD patients differ from controls in the predicted direction on these dimensions, the TPQ can be considered a valid operational measure of those behaviors associated with OCD on clinical and theoretical grounds. An even more critical test is to determine whether the behavioral extremes captured by the TPQ are associated with available measures of activity of the specified neurotransmitter systems. A positive finding would validate both the TPQ as an instrument and the associated theory. Because medications that act on the serotonergic system appear to redu~c¢ OCD symptoms (Charney et al. 1988), several investigators have reported on biological measures thought to reflect serotonin neurotransmitter activity in OCD patients compared with controls. These reports include increased levels of the serotonin metabolite 5-HIAA in the cerebrospinal fluid of OCD patients (Insel et al. 1985), reduction in serotonin receptor sensitivity as suggested by a reduced response to an exogenous sero~,3niin agonist (Zohar et al. 1987), and reduction in platelet imipramine bh',ding (Weizm0~r~ et al. 1986). If Cloninger's Tridimensional PersonalRy Theory is correct, not only ~oald obsessivecompulsive patients show evidence of increased serotonergic activity, b,_~tthose OCD
Personality and lmipramine Binding in OCD
BIOL PSYCHIATRY
1990;28:41-45
43
patients with the highest level of serotonergic activity ought to have the highest scores on harm avoidance. The relevance of platelet imipramine binding as an indicator of central serotonin function is based on the fact that both sites bind imipramine and serotonin. Changes in receptor density measured peripherally -are thought to reflect changes in central serotonin sites, and be inversely related to long-term serotonin availability (Zohar et al. 1988). The association is based on several assumptions for which there is at least partial empirical support. It is assumed that the hypothesized increased activity in the serotonergic systems is mediated presynaptically, that platelet receptor density correlates with CNS serotonin receptor density, and that platelet receptor density is not substantially influenced by activity of other neurotransmitters such as norepinephrine OVeizman et al. 1986; Langer et al. 1980). Given these assumptions, it is predicted that the harm avoidance dimension of the TPQ should be inversely correlated with the density of platelet imipramine binding sites on platelets. Methods Between December 1986 and March 1987 we recruited subjects with OCD using accepted procedures for informed consent. Cases were located by referral from clinical staff and diagnosis was established by two psychiatrists (DB, RN) using the Schedule for Affective Disorders and Schizophrenia (SADS) (Spitzer and Endicott 1975). Cases had to meet DSMIII-R criteria for OCD (American Psychiatric Association 1987) and be ill with OCD symptoms for at least the last year. Cases also had to score 16 or higher on the Yale-Brown Obsessive Compulsive Scale (Y-BOC) (Goodman et al. 1986). A history of major depression was allowed if the onset occurred after the beginning of OCD symptoms, and if the current 17-item Hamilton Depression Score (HDS) (ltamilton 1967) was less than or equal to 21. Exclusion criteria included significant medical illness, a history of seizures, current alcohol or drug abuse, and a history of psychosurgery. Information on family history of psychiatric disorders was collected using the FH-RDC. Controls were located by advertisement in a newsletter that circulates among hospital staff and by word of mouth to members of the surrounding community. Exclusion criteria for controls included a lifetime diagnosis of any psychiatric disorder on the SADS or past psychiatric treatment for any reason. Controls were recruited to represent a distribution in age and gender similar to the patient volunteers. TPQ was added about halfway through the study period. Some of the OCD cases participated in a placebo-controlled crossoover study with elomipramine. In all cases the TPQ was administered several weeks to months after the drug trial. At the time of blood collection, patients were free of tricyclic antidepressants for at least 4 weeks and free of MAO inhibitors or depot antipsychotics for at least 6 weeks prior to testing. Thirty milliliters of blood was collected in tubes containing edetic acid as an anticoagulant. All samples were obtained between 12:00 noon and 4:00 PM and were immediately placed on ice and transported for centrifugation and storage at 70°C. The platelet imipramine-binding assay was based on the use of tritiated imipramine and is described elsewhere (Black et al. in press). Statistical analysis was carried out using the Statistical Analysis Subroutines (SAS) system using the TTEST and General Linear Models (GLM) procedures. Two-tailed tests were used and a p value of 0.05 or less was required to reject the null hypothesis unless otherwise noted. All means are reported as mean +- standard deviation (SD). -
44
B . P f o h l e t al.
BIOL PSYCHIATRY 1990;28:41-46
Table 1. Tridimensi~.,~J Personality Scale Score Differences Between OCD Cases and I1. . . . . . 1NOEIili~
!
fq
~-
J....~l~
~,..U~m m uto
Normal controls (n -- 35)
O C D cases (n =- 25)
m
Novelty seeking Harm avoidance Reward dependence
X -4- SD
X -4- SD
t
p"
~5.0 -4- 3.6 10.3 -4- 3.6 19.1 ± 3.9
13.0 -4- 5.5 22.4.4- 6.7 22.0 -4- 3.7
1.68 9.10 2.97
0.0973 0.0001 0.0044
"Probabilities based on two-Udled Student's t-tests with 58° of freedom.
Results At the time of this report, 40 cases with OCD and 37 controls had been recraitod into the study. Because the TPQ was added after the study began, scores were available on only 25 cases and 35 controls. Cases and controls were similar on age (37.9 ± 11.8 versus 38.2 -+ 9.8) and proportion of females [16/25 (64%) versus 22/35 (63%)]. The cases had slightly fewer total years of education than controls (13.0 -+ 5.5 versus 15.0 -+ 3.6) but the difference was not significant (t - 1.67, p = 0.101). All but one of the cases had received prior treatment for OCD, including medications or psychotherapy, and 11 (44%) had a history of inpatient treatment. Table 1 summarizes the TPQ results. Novelty seeking was lower in OCD cases as predicted, but the difference was not significant using a two-tailed t-test. If the directional nature of the prediction were used to justify a one-tailed test, the results would barely reach significance (p = 0.0486). Harm avoidance was much higher among OCD cases than controls and the difference was highly significant. Finally, reward dependence was significantly higher among OCD cases versus normal controls. The findings for the controls are similar to the national norms repotted for the TPQ. However, because demographic variables such as gender, age, and education may effect TPQ scores, we did an additional comparison of OCD cases with controls using a multivariate regression in which variation due to age, gender, and education was included in the model. There was no substantial change in the p values for any of the three dimensions. Table 2 shows the results for maximum platelet imipramine binding capacity. TPQ scores and platelet binding results were available on 11 OCD cases and 19 controls. Although the theory predicts that only the harm avoidance dimension should correlate with imipramine binding, we examined correlations between each of the dimensions and imipramine binding in OCD cases, in normal controls, and in both groups combined. In
Table 2. Correlation Between Imipramine Binding Capacity and TPQ Dimension Normal controls ( n - 19)
Novelty seeking Harm avoidance Reward dependence
O C D cases (n = 11)
Combined (n = 30)
r
F~
r
F°
r
Fa
0.01 - 0.16 - 0.19
0.00 0.45 0.67
0.02 - 0.36 0. !5
0.00 1.32 0.21
- 0.15 0.04 0.09
0.38 0.04 0.24
°All correlations were not significant based on two-tailed F tests with I/(N-2)° of freedom.
Personality and Imipramine Binding in OCD
BIOLPSYCHIATRY 1990;28:41-46
45
theory, the combined groups represent a very powerful test of the association between harm avoidance and platelet imipramine binding as a range of scores is represented. Unfortunately, none of the findings reached significance. Among OCD cases, the correlation coefficient was 0.36, with harm avoidance in the predicted direction. However, even if a one-tailed t-test is u s ~ , the result fails to reach significance (p = 0.140). These cases and controls represent a small subset of a larger study on the associatioL between OCD and platelet imipramine binding which has been reported separately (Bla~k et al. in press). The larger study found no significant difference in ~latelet imipramine binding between OCD cases and normal controls. Other predictions based on the tridimensional personality theory were tested. In~tividuals with high scores on reward dependence are postulated to be at higher risk for rea~ ~ive dysphoria. Though secondary depression developing after the onset of OCD m~y not be identical with reactive dysphoria, we compared mean reward dependence scores for the 20 OCD cases with a past history of major depression with the 5 0 C D cases with no history of deple~icn. There was no signi~cant difference and the trend ~.,as in the opposite direction to that predicted (21.8 - 2.4 ";,ersus 23.2 _ 2.38, t = 0.77, p = 0.447), although the small sample size for cases without depression provided limited statistical power to test the prediction. Discussion Cloninger's tridimensional personality theory proposes to unify data from n:,arobiological and behavioral studies. As appealing as this is, the ultimate test of any theory is its ability to predict the results of new research. This study first attempted to demonstrate that a self-report measure, the TPQ, could be successfully employed to identify specific behavioral differences between obsessivecompulsive patients and normal controls which are predicted by clinical experience and by the tridimensional personality theory. Scores on harm avoidance were highly significantly elevated in OCD, as predicted. Scores on novelty seeking were lower in OCD, as predicted, but only at a marginally significant level. Scores on reward dependence, for which conflicting predictions could be made, were significantly increased. In the absence of comparison groups with other diagnosis one might question whether significantly elevated harm avoidance may simply be a nonspecific index of general psychopathology. This is not likely, as individuals with other diagnoses such as alcoholism and antisocial personality score in the opposite direction on harm avoidance, whereas normal controls score somewhere in between (Cloninger 1988). Thus, tested against OCD, the TPQ appears to have moderate face validity and concurrent validity. Our study also attempted to find evidence of a predicted link between harm avoidance and ~ e serotonergic neuropathways using platelet imipramine binding. No significant correlations were found. However, given the co:~plexity of the neurotransmitter systems, this cannot be considered convincing evidence against such a relationship. Platelet imipraml._~ binding may not be an adequate model for serotonin receptor activity or the abnormality could exist at some other functional or anatomic level of the serotonin-mediated neuropathways. Future studies attempting to validate the tridimensional personality theory should examine correla:ion between TPQ din~ensio~s and a broader range of parameters thought to reflect centrai serotonin pathway activity, including CSF 5-HIAA and behavioral responses to serotonin agonists and antagonists (Zohar et a!. 1988).
46
BIOLPSYCHIATRY 1990;28:41--46
B. Pfohl et al.
References American Psychiatric Association (1987): Diagnostic and Statistical Manual of Mental Disorders (ed 3, revised). Washington, DC: American Psychiatric Association. Black D, Kelly M, Myers C, Noyes R Jr (1988): Tritiated imipramine binding in obsessive compulsive volunteers and psychiatrically normal controls. Biol Psychiatry, in press. Brown GL, Ebort MH, Goyer PF, et al (1982): Aggression, suicide, and serotonin. Relationships to CSF amine metabolites. Am J Psychiatry 139:741-746. Charney DS, Goodman WK, ~rice LH, Woods SW, Rasmussen SA, Heninger GR (1988): Serotonin function in obsessive-compulsive disorder. Arch Gen Psychiatry 45:177-185. Cloninger CR (1986): A unified biosocial theory of personality and its role in the development of anxiety states. Psychiat Dev 3:167-226. Cloninger CR (1987): A systematic method for clinical description and classification of personality variants: A proposal. Arch Gen Psychiatry 44:573-588. Cloninger CR, Sigvardsson S, Bohman M (1988): Childhood personality predicts M¢ohol abuse in young adults. Alcoholism: Clin Exp Res 12:494-505. CowdD" RW, Gardner DL (1988): Pharmacotherapy of borderline personality disorder. Arch Gen Psychiatry 45:111-119. Goodman WK, Rasmussen SA, Price LH, Mazure C, Heminger G, Charney DS (1986): YaleBrown obsessive-compulsb~e scale (Y-BOCS). New Haven: Department of Psychiatry, Yale University, Clinical Neuroscience Research Unit. Hamilton M (1967): Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278-296. Insel TR, Mueller EA, Alterman I, Linnoile M, Murphy DL (1985): Obsessive-compulsive disorder and serotonin: Is there a connection? Bwl Psychia~j 20:1174-1185 Langer SZ, Moret C, Raisman R (1980): High affinity imipramine binding in rat hypothalamus: Association with uptake of serotonin but not of norepine~hrine. Science 210:1133-1135. Mason ST, Iversen ST (1979): Theories of the dorsal bundle extinction effect. Brain Res Rev 1:107-137. Pfohl B (1989): Axis I/Axis II comorbidity findings: Implications for validity. In Oldham J (ed), Axis II: New Persp~ctives on Validity. Washit~gton, DC: American Psychiatric Association Press (in press). Soloff PH, George A, Nathan S, Schulz PM, Ulrich RF, Perel JM (1986): Progress in pharrnacotherapy of borderline disorders. Arch Gen Psychiatry 43:691-697. Spitzer RL, Endicott JR (1975): The Schedule for Affective Disorders and Schizophrenia. New York State Department of Mental Hygiene, New York State Psychiatric Institute, Biometrics Research. Weizman AW, Carmi M, Hermesh H, et al (1986): High-affinity imipramine binding and semtol~in uptake in platelets of eight adolescent and ten adult obsessive-compulsive patients. Am J Psychiatry 143:335-339. Zohar J, Insel TR, Zohar-Kadouch RC, Hill JL, Murphy DL (1988): Serotonergic responsivity in obsessive-compulsive disorder. Arch Gen Psychiatry 45:167-172. Zohar J, Mueller EA, lnsel TR, Zohar-Kadouch RC, Murphy DL (1987): Serotonergic responsivity in obsessive-compulsive disorder: Comparison of patients and healthy controls. Arch Gen Psychiatry 44:946-951.
41
A Test of the Tridimensional Personality Theory: Association with Diagnosis and Platelet Imipramine Binding in Obsessive-Compulsive Disorder Bruce Pfohl, Donald Black, Russell Noyes, Jr., Michael Kelley, and Nancee Blum
We administered the Tridimensional Personality Questionnaire (TPQ) to a sample of 25 individuals with obsessive-compulsive disorder (OCD) and 35 norn~al controls. As predicted, OCD cases scored much higher on the harm avoidance dimension than normal controls. Findings for the novelty seeking and reward dependence dimensions were less dramatic, although compatible with the underlying theory. Despite a theoretical link between tlw harm avoidance dimension and serotonin-mediated neuropathways, we failed to find an association between ~;hisdimension and platelet imipramine binding in either OCD cases or controls. Introduction The Tridimensional Personality Questionnaire (TPQ) has been developed to measure three fundamental dimensions of personality: novelty seeking, harm avoidance, and reward dependence (Cloninger 1987). Cloninger developed the TPQ in order to operationalize behavioral dimensiens that have been correlated with the activity of several neurotransmitter systems by previous resean~h. Thus, each dimension is hypothesized to relate to a specific neurotransmitter system. In theory~ variations in the activity level of the three neurotransmitter systems are manifested as changes in the three corresponding behavioral dimensions and extreme vm'iations are expressed as specific psychiatric disorders. The TPQ is thus a useful tool for operationalizing key behavio~L variables in order to test hypotheses regarding the link between behavior and central nervous system (CNS) neurotransmitter activity. The three TPQ dimensions and the neurochemical and psychopharmacologicaI studies on which they are based have been previously described in greater detail (Cloninger 1986, 1987). In brief, individuals with higher-than-average scores on novelty seeking tend to be impulsive, excitable, extravagant, and di:;orderly. This dimens,.'on is theoretically associated with low basal dopaminergic activity which leads to a predis.~ position towards novel and exploratory behaviors which ~ : then reinfow~! by an acute
From the Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA. Supported in part by the Ciba.Geigy Co. Address reprint requests to Bruce Pfohl, M.D., Dept. of Psychiatry, Uaiversity of Iowa College of Medicine, 500 Newton Road, Iowa City, IA 52242. Received August 15, 1988; revised December 14, 1989. © 1990 Society of Biological Psychiatry
0006-3223/90/$03.50
42
BIOL PSYCHIATRY
B. Pfohl et al.
1990;28:41--46
increase in dopaminergic activity. This relationship is supported by the finding that dopamine receptor antagonists reduce h--npulsive behavior in patients with borderline personality disorder as, presumably, dopamine blockade reduces the reinforcement for exploration of novel stimuli (Soloff et al. 1986; Cowdry and Gardner 1988). Cloainger (1987) also describes studies of dopamine depleting lesions in the nucleus accombens and ventral tegmentum of rats which are associated with a reduced tendency to explore novel stimuli. Individuals with high scores on harm avoidance tend to be characterized by anticiipatory worry, fear of uncertainty, shyness, and fatigability. This dimension is theoretically related to increased serotonin activity as suggested by the negative correlation between CSF 5HIAA and risk-taking/suicidal behavior in patients with a va~riety of diagnoses f~Brown et al. 1982). Individuals with high scores on reward dependence tend to be sentimental, persistent, dependent, and readily form attachments with others. This dimension is said to correlate with low basal noradrenergic activity as suggested by studies link/rig noradrenergic activity to resistance to extinction in learning paradigms (Cloninger 1987; Mason and Iversen 1979). Theoretically, the low basal norepinephrine activity leads to greater persistence in seeking rewards which result in norepinephrine-mediated reinforcement. The study of a group of patients with a well-defined diagnosis such as obsessive compulsive disorder (OCD) and healthy controls can be used to test the TPQ and associated theory in several ways. First, the theory conceptualizes OCD as representkig certain extremes of behavior on the three operationalized dimensions. Most of these predictions make common sense. A clinician familiar with the obsessive compulsive patient's typical concerns about germs or sharp, knives could easily predict that OCD patients would score high on the harm avoidance dimensions. Likewise, the tendency to maintain order and follow well-defined rituals suggests that such pati,mts would score low on novelty seeking. Predictions for the reward dependence dimension is more problematic. The tendency to persist with repetitive behaviors would suggest high-reward dependence. On the other hand, OCD patients appear to be more likely than controls to have obsessive-compulsive personality (Pfohl et al. in press) and Cloninger (1986) has previously predicted that such patients would have low reward dependence based on the lack of sentimentali,ty and social sensitivity associated with this personality diagnosis. To the extent that the OCD patients differ from controls in the predicted direction on these dimensions, the TPQ can be considered a valid operational measure of those behaviors associated with OCD on clinical and theoretical grounds. An even more critical test is to determine whether the behavioral extremes captured by the TPQ are associated with available measures of activity of the specified neurotransmitter systems. A positive finding would validate both the TPQ as an instrument and the associated theory. Because medications that act on the serotonergic system appear to redu~c¢ OCD symptoms (Charney et al. 1988), several investigators have reported on biological measures thought to reflect serotonin neurotransmitter activity in OCD patients compared with controls. These reports include increased levels of the serotonin metabolite 5-HIAA in the cerebrospinal fluid of OCD patients (Insel et al. 1985), reduction in serotonin receptor sensitivity as suggested by a reduced response to an exogenous sero~,3niin agonist (Zohar et al. 1987), and reduction in platelet imipramine bh',ding (Weizm0~r~ et al. 1986). If Cloninger's Tridimensional PersonalRy Theory is correct, not only ~oald obsessivecompulsive patients show evidence of increased serotonergic activity, b,_~tthose OCD
Personality and lmipramine Binding in OCD
BIOL PSYCHIATRY
1990;28:41-45
43
patients with the highest level of serotonergic activity ought to have the highest scores on harm avoidance. The relevance of platelet imipramine binding as an indicator of central serotonin function is based on the fact that both sites bind imipramine and serotonin. Changes in receptor density measured peripherally -are thought to reflect changes in central serotonin sites, and be inversely related to long-term serotonin availability (Zohar et al. 1988). The association is based on several assumptions for which there is at least partial empirical support. It is assumed that the hypothesized increased activity in the serotonergic systems is mediated presynaptically, that platelet receptor density correlates with CNS serotonin receptor density, and that platelet receptor density is not substantially influenced by activity of other neurotransmitters such as norepinephrine OVeizman et al. 1986; Langer et al. 1980). Given these assumptions, it is predicted that the harm avoidance dimension of the TPQ should be inversely correlated with the density of platelet imipramine binding sites on platelets. Methods Between December 1986 and March 1987 we recruited subjects with OCD using accepted procedures for informed consent. Cases were located by referral from clinical staff and diagnosis was established by two psychiatrists (DB, RN) using the Schedule for Affective Disorders and Schizophrenia (SADS) (Spitzer and Endicott 1975). Cases had to meet DSMIII-R criteria for OCD (American Psychiatric Association 1987) and be ill with OCD symptoms for at least the last year. Cases also had to score 16 or higher on the Yale-Brown Obsessive Compulsive Scale (Y-BOC) (Goodman et al. 1986). A history of major depression was allowed if the onset occurred after the beginning of OCD symptoms, and if the current 17-item Hamilton Depression Score (HDS) (ltamilton 1967) was less than or equal to 21. Exclusion criteria included significant medical illness, a history of seizures, current alcohol or drug abuse, and a history of psychosurgery. Information on family history of psychiatric disorders was collected using the FH-RDC. Controls were located by advertisement in a newsletter that circulates among hospital staff and by word of mouth to members of the surrounding community. Exclusion criteria for controls included a lifetime diagnosis of any psychiatric disorder on the SADS or past psychiatric treatment for any reason. Controls were recruited to represent a distribution in age and gender similar to the patient volunteers. TPQ was added about halfway through the study period. Some of the OCD cases participated in a placebo-controlled crossoover study with elomipramine. In all cases the TPQ was administered several weeks to months after the drug trial. At the time of blood collection, patients were free of tricyclic antidepressants for at least 4 weeks and free of MAO inhibitors or depot antipsychotics for at least 6 weeks prior to testing. Thirty milliliters of blood was collected in tubes containing edetic acid as an anticoagulant. All samples were obtained between 12:00 noon and 4:00 PM and were immediately placed on ice and transported for centrifugation and storage at 70°C. The platelet imipramine-binding assay was based on the use of tritiated imipramine and is described elsewhere (Black et al. in press). Statistical analysis was carried out using the Statistical Analysis Subroutines (SAS) system using the TTEST and General Linear Models (GLM) procedures. Two-tailed tests were used and a p value of 0.05 or less was required to reject the null hypothesis unless otherwise noted. All means are reported as mean +- standard deviation (SD). -
44
B . P f o h l e t al.
BIOL PSYCHIATRY 1990;28:41-46
Table 1. Tridimensi~.,~J Personality Scale Score Differences Between OCD Cases and I1. . . . . . 1NOEIili~
!
fq
~-
J....~l~
~,..U~m m uto
Normal controls (n -- 35)
O C D cases (n =- 25)
m
Novelty seeking Harm avoidance Reward dependence
X -4- SD
X -4- SD
t
p"
~5.0 -4- 3.6 10.3 -4- 3.6 19.1 ± 3.9
13.0 -4- 5.5 22.4.4- 6.7 22.0 -4- 3.7
1.68 9.10 2.97
0.0973 0.0001 0.0044
"Probabilities based on two-Udled Student's t-tests with 58° of freedom.
Results At the time of this report, 40 cases with OCD and 37 controls had been recraitod into the study. Because the TPQ was added after the study began, scores were available on only 25 cases and 35 controls. Cases and controls were similar on age (37.9 ± 11.8 versus 38.2 -+ 9.8) and proportion of females [16/25 (64%) versus 22/35 (63%)]. The cases had slightly fewer total years of education than controls (13.0 -+ 5.5 versus 15.0 -+ 3.6) but the difference was not significant (t - 1.67, p = 0.101). All but one of the cases had received prior treatment for OCD, including medications or psychotherapy, and 11 (44%) had a history of inpatient treatment. Table 1 summarizes the TPQ results. Novelty seeking was lower in OCD cases as predicted, but the difference was not significant using a two-tailed t-test. If the directional nature of the prediction were used to justify a one-tailed test, the results would barely reach significance (p = 0.0486). Harm avoidance was much higher among OCD cases than controls and the difference was highly significant. Finally, reward dependence was significantly higher among OCD cases versus normal controls. The findings for the controls are similar to the national norms repotted for the TPQ. However, because demographic variables such as gender, age, and education may effect TPQ scores, we did an additional comparison of OCD cases with controls using a multivariate regression in which variation due to age, gender, and education was included in the model. There was no substantial change in the p values for any of the three dimensions. Table 2 shows the results for maximum platelet imipramine binding capacity. TPQ scores and platelet binding results were available on 11 OCD cases and 19 controls. Although the theory predicts that only the harm avoidance dimension should correlate with imipramine binding, we examined correlations between each of the dimensions and imipramine binding in OCD cases, in normal controls, and in both groups combined. In
Table 2. Correlation Between Imipramine Binding Capacity and TPQ Dimension Normal controls ( n - 19)
Novelty seeking Harm avoidance Reward dependence
O C D cases (n = 11)
Combined (n = 30)
r
F~
r
F°
r
Fa
0.01 - 0.16 - 0.19
0.00 0.45 0.67
0.02 - 0.36 0. !5
0.00 1.32 0.21
- 0.15 0.04 0.09
0.38 0.04 0.24
°All correlations were not significant based on two-tailed F tests with I/(N-2)° of freedom.
Personality and Imipramine Binding in OCD
BIOLPSYCHIATRY 1990;28:41-46
45
theory, the combined groups represent a very powerful test of the association between harm avoidance and platelet imipramine binding as a range of scores is represented. Unfortunately, none of the findings reached significance. Among OCD cases, the correlation coefficient was 0.36, with harm avoidance in the predicted direction. However, even if a one-tailed t-test is u s ~ , the result fails to reach significance (p = 0.140). These cases and controls represent a small subset of a larger study on the associatioL between OCD and platelet imipramine binding which has been reported separately (Bla~k et al. in press). The larger study found no significant difference in ~latelet imipramine binding between OCD cases and normal controls. Other predictions based on the tridimensional personality theory were tested. In~tividuals with high scores on reward dependence are postulated to be at higher risk for rea~ ~ive dysphoria. Though secondary depression developing after the onset of OCD m~y not be identical with reactive dysphoria, we compared mean reward dependence scores for the 20 OCD cases with a past history of major depression with the 5 0 C D cases with no history of deple~icn. There was no signi~cant difference and the trend ~.,as in the opposite direction to that predicted (21.8 - 2.4 ";,ersus 23.2 _ 2.38, t = 0.77, p = 0.447), although the small sample size for cases without depression provided limited statistical power to test the prediction. Discussion Cloninger's tridimensional personality theory proposes to unify data from n:,arobiological and behavioral studies. As appealing as this is, the ultimate test of any theory is its ability to predict the results of new research. This study first attempted to demonstrate that a self-report measure, the TPQ, could be successfully employed to identify specific behavioral differences between obsessivecompulsive patients and normal controls which are predicted by clinical experience and by the tridimensional personality theory. Scores on harm avoidance were highly significantly elevated in OCD, as predicted. Scores on novelty seeking were lower in OCD, as predicted, but only at a marginally significant level. Scores on reward dependence, for which conflicting predictions could be made, were significantly increased. In the absence of comparison groups with other diagnosis one might question whether significantly elevated harm avoidance may simply be a nonspecific index of general psychopathology. This is not likely, as individuals with other diagnoses such as alcoholism and antisocial personality score in the opposite direction on harm avoidance, whereas normal controls score somewhere in between (Cloninger 1988). Thus, tested against OCD, the TPQ appears to have moderate face validity and concurrent validity. Our study also attempted to find evidence of a predicted link between harm avoidance and ~ e serotonergic neuropathways using platelet imipramine binding. No significant correlations were found. However, given the co:~plexity of the neurotransmitter systems, this cannot be considered convincing evidence against such a relationship. Platelet imipraml._~ binding may not be an adequate model for serotonin receptor activity or the abnormality could exist at some other functional or anatomic level of the serotonin-mediated neuropathways. Future studies attempting to validate the tridimensional personality theory should examine correla:ion between TPQ din~ensio~s and a broader range of parameters thought to reflect centrai serotonin pathway activity, including CSF 5-HIAA and behavioral responses to serotonin agonists and antagonists (Zohar et a!. 1988).
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