Prediction of Detached Personality in Healthy Subjects by Low Dopamine Transporter Binding

Individual variations in the human temperament and character affecting one’s social relationships most probably have a complex background influenced by both psychosocial and biological factors. The first pieces of evidence connecting human personality to underlying biological phenomena at the neurotransmitter level in vivo have been reported. Two independent research groups have determined that subjects who score high on the detachment scale of the Karolinska Scales of Personality self-report questionnaire, supposedly indicating that they avoid involvement with others (1), have low dopamine D₂ receptor density in the striatum, especially in the putamen (2, 3). Dopamine transporter is a protein located on the presynaptic membrane of dopaminergic nerve terminals. Its density has been shown to reflect the density of dopaminergic innervation in the brain, especially when measured with radiolabeled CFT (also known as WIN 35,428) (4, 5). In this study, we investigated whether there is a relationship between detached personality and interindividual differences in brain dopamine transporter binding studied with [¹⁸F]CFT and positron emission tomography (PET) (6).

METHOD

The study was approved by the ethics committee of the Turku University and University Central Hospital, Turku, Finland, and was performed in accordance with the ethical standards of the Declaration of Helsinki. After a complete description of the study to the subjects, written informed consent was obtained. Eighteen healthy volunteers (10 men and eight women) who were between 18 and 43 years old participated in the study. The mean age of the men was 27.6 years (SD=7.1); the mean age of the women was 29.2 years (SD=8.1). Four subjects were left-handed according to the Edinburgh Handedness Inventory. None had a history of psychiatric or neurological illness, chronic somatic illness, or substance abuse. None had a close relative with a known psychiatric illness. Dopamine transporter density was measured with PET and [¹⁸F]CFT as described previously (6). PET experiments were performed with a whole-body PET scanner (ECAT 931/08-12, Computer Technology & Imaging, Knoxville, Tenn.). The mean injected dose of [¹⁸F]CFT was 4.1 mCi (SD=0.7). Each subject also underwent a T₁-weighted 1.5-T MRI scan (Siemens Magnetom, Iselin, N.J.). Anatomical regions of interest (the caudate, putamen, and cerebellar cortex) were drawn without knowledge of personality scores on magnetic resonance images resliced according to PET slices. The tracer uptake was quantified by calculating a mean binding potential ratio during a 1-hour interval containing the transient equilibrium of CFT uptake (from 3.5 to 4.5 hours after the tracer injection).

Each subject also completed the Karolinska Scales of Personality self-report questionnaire (1), which has 15 personality subscales. Each answer was scored from 1 (does not apply) to 4 (applies completely). The detachment subscale has 10 items (e.g., “I avoid people who are interested in my personal life” or “I feel best when I keep people at a certain distance”). Since sex and age may affect personality trait scores, the relationships were also studied after T-score transformation of the scores according to normative data (2).

Since a negative correlation between brain dopamine transporter binding and age is well documented (7, 8), correlations between striatal [¹⁸F]CFT binding potentials and personality scores were studied by using multivariate analysis of covariance with age as a covariate. Because there was an a priori hypothesis for the relationship between dopamine transporter binding and detached personality, we considered a p value less than 0.05 to be statistically significant despite multiple comparisons. More stringent criteria (p<0.01) were used for comparisons between dopamine transporter binding and the other 14 personality scores.

RESULTS

Detachment scores on the Karolinska Scales of Personality correlated negatively with [¹⁸F]CFT binding in the putamen (r=–0.43, df=15, p<0.05), especially in the right hemisphere (figure 1) (r=–0.36, df=15, p<0.12, in the left putamen). This correlation remained significant in the right putamen also after T-score transformation of the personality data (r=–0.44, df=15, p<0.05). No other personality scores correlated with [¹⁸F]CFT binding in the striatum, except social desirability, which correlated positively with [¹⁸F]CFT binding in the putamen (r=0.61, df=15, p=0.009), especially in the right hemisphere (r=0.68, df=15, p=0.003, in the right putamen, r=0.47, df=15, p<0.06, in the left putamen, T-score transformed data). However, there was a highly significant negative correlation between social desirability and detachment subscales (r=–0.73, df=15, p=0.001). In the caudate, no correlation was observed between [¹⁸F]CFT binding and the detachment score (r=–0.27, df=15, p<0.21, for the right caudate, r=–0.21, df=15, p<0.35, for the left caudate) or any other of the personality scores.

DISCUSSION

The current data indicate that low putamen dopamine transporter density is associated with the detached personality trait in healthy human subjects. Putamen dopamine transporter density also correlated significantly with social desirability scores. This is clearly a related finding because there was a highly significant negative correlation between social desirability and detachment scales.

Our results are essentially in line with previous studies indicating an association between low dopamine D₂ receptor density and detachment (2, 3). Although dopamine D₂ receptor binding potential measurements in vivo may be subject to numerous factors affecting the results, including endogenous dopamine, the dopamine transporter density seems to be a relatively stable index for the integrity of dopaminergic innervation (4, 5). In fact, we suggest that the low density of dopamine D₂ receptors and the low density of dopamine transporter are associated with the detached personality trait and are explained by the same underlying phenomenon: low density of dopaminergic nerve terminals innervating striatum and the putamen in particular (2). This neurobiological phenomenon may predispose a person to a behavioral pattern characterized by withdrawal and aloofness. This relationship between detachment and dopamine most likely has a heterogenous basis, probably partly explained by genetic factors. It is also entirely possible that the formation of the dopaminergic system is under substantial environmental influence during brain development and may even be affected by social interactions in childhood and adolescence. It can also be speculated that low dopaminergic activity is associated with detached behavior because of relative deficits in the dopamine-driven brain circuits responsible for motivational and rewarding processes.

In conclusion, this report provides further evidence of the influence of the dopaminergic system on personality traits and also provides one possible explanation for the previously observed association between dopamine D₂ receptor density and human personality. Further research is warranted to clarify the role of the dopaminergic system in various personality disorders, especially schizoid personality disorder. The greatest importance of our findings, however, may lie in the fact that they show a connection between the development of a specific neurotransmitter system and a psychological trait that probably has a profound influence on an individual’s social life. However, because the number of subjects in our study was small, these results need to be replicated in a larger group.

Received Dec. 7, 1998; revision received June 15, 1999; accepted June 18, 1999. From the Department of Pharmacology and Clinical Pharmacology, University of Turku; Turku PET Centre; and the Department of Psychiatry, University of Turku. Address reprint requests to Dr. Laakso, Department of Pharmacology and Clinical Pharmacology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; [email protected] (e-mail)