Skip to main content Accessibility help
×
Home

Serotonin and dopamine transporters in relation to neuropsychological functioning, personality traits and mood in young adult healthy subjects

  • S. M. Burke (a1) (a2), E. van de Giessen (a2), M. de Win (a3), T. Schilt (a4), M. van Herk (a5), W. van den Brink (a4) and J. Booij (a2)...

Abstract

Background

Serotonin and dopamine neurotransmitter systems are implicated in the regulation of mood, cognition and personality traits and their dysfunction is thought to be implicated in diverse psychopathologies. However, in healthy subjects the relationship between the serotonin and dopamine systems and neuropsychological functioning and personality traits is not clearly established. In the present study we investigated whether neuropsychological functioning, personality traits and mood states of a group of healthy subjects are associated with in vivo measures of serotonin transporters (SERTs) and dopamine transporters (DATs).

Method

A total of 188 young healthy subjects underwent neuropsychological and subjective measurements of memory function, depression and impulsivity. Participants' SERT and DAT availability in predefined regions of interest were assessed using single photon emission computed tomography (SPECT) with the radiotracer [123I]β-CIT. Individual magnetic resonance imaging (MRI) scans served as anatomic reference.

Results

We did not find any significant association between SERT or DAT availability and neuropsychological test performance or self-reported impulsivity and mood. There were no significant sex differences in SERT or DAT availability, but men performed significantly better on some tests of visuospatial functioning than women.

Conclusions

Robust negative findings for striatal DAT availability seriously question earlier findings of positive associations between DAT availability and cognitive functions in healthy subjects. Our results also suggest that subcortical SERT availability is not associated with the neuropsychological functions and personality traits assessed. In summary, the present study suggests that neuropsychological and personality measurements in young healthy people are not associated with subcortical SERT or striatal DAT availabilities in the brain.

Copyright

Corresponding author

*Address for correspondence: Dr J. Booij, Department of Nuclear Medicine F2-N, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. (Email: j.booij@amc.uva.nl)

References

Hide All
Acton, PD, Meyer, PT, Mozley, PD, Plossl, K, Kung, HF (2000). Simplified quantification of dopamine transporters in humans using [99mTc]TRODAT-1 and single-photon emission tomography. European Journal of Nuclear Medicine 27, 17141718.
Aouizerate, B, Guehl, D, Cuny, E, Rougier, A, Burbaud, P, Tignol, J, Bioulac, B (2005). Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder. Neuropsychiatric Disease and Treatment 1, 231243.
Bechara, A, Damasio, AR, Damasio, H, Anderson, SW (1994). Insensitivity to future consequences following damage to human prefrontal cortex. Cognition 50, 7–15.
Bechara, A, Damasio, H, Damasio, AR (2000). Emotion, decision making and the orbitofrontal cortex. Cerebral Cortex 10, 295307.
Bechara, A, Damasio, H, Damasio, AR, Lee, GP (1999). Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making. Journal of Neuroscience 19, 54735481.
Beck, AT, Steer, RA, Brown, GK (2002). Beck Depression Inventory II. In Manual of the Dutch Version of the BDI [in Dutch] (ed. van der Does, AJW.). The Psychological Corporation/Swets Test Publishers: San Antonio, TX/Lisse, The Netherlands.
Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561571.
Benton, AL, Varney, NR, Hamsher, KD (1987). Visuospatial judgment: a clinical test. Archives of Neurology 35, 364367.
Borg, J, Henningsson, S, Saijo, T, Inoue, M, Bah, J, Westberg, L, Lundberg, J, Jovanovic, H, Andree, B, Nordstrom, AL, Halldin, C, Eriksson, E, Farde, L (2009). Serotonin transporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in humans. International Journal of Neuropsychopharmacology 12, 783792.
Cloninger, CR (1987). A systematic method for clinical description and classification of personality variants: a proposal. Archives of General Psychiatry 44, 573588.
de Win, MML, Habraken, JBA, Reneman, L, van den Brink, W, den Heeten, GJ, Booij, J (2005 a). Validation of [123I]β-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram. Neuropsychopharmacology 30, 996–1005.
de Win, MML, Jager, G, Booij, J, Reneman, L, Schilt, T, Lavini, C, Olabarriaga, SD, den Heeten, GJ, van den Brink, W (2008). Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users. Brain 131, 29362945.
de Win, MML, Jager, G, Vervaeke, HKE, Schilt, T, Reneman, L, Booij, J, Verhulst, FC, den Heeten, GJ, Ramsey, NF, Korf, DJ, van den Brink, W (2005 b). The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance. International Journal of Methods in Psychiatric Research 14, 167185.
de Win, MML, Reneman, L, Jager, G, Vlieger, EJ, Olabarriaga, SD, Lavini, C, Bisschops, I, Majoie, CBLM, Booij, J, den Heeten, GJ, van den Brink, W (2007). A prospective cohort study on sustained effects of low-dose ecstasy use on the brain in new ecstasy users. Neuropsychopharmacology 32, 458470.
Edmonds, CJ, Isaacs, EB, Visscher, PM, Rogers, M, Lanigan, J, Singhal, A, Lucas, A, Gringras, P, Denton, J, Deary, IJ (2008). Inspection time and cognitive abilities in twins aged 7 to 17 years: age-related changes, heritability and genetic covariance. Intelligence 36, 210255.
Feij, JA, Van Zuilen, RW, Gazendam, A (1982). The development of a Dutch questionnaire for sensation seeking: the sensation seeking scale [in Dutch]. Gedrag: Tijdschrift voor Psychologie 10, 364383.
Friedman, NP, Miyake, A, Young, SE, De Fries, JC, Corley, RP, Hewitt, JK (2008). Individual differences in executive functions are almost entirely genetic in origin. Journal of Experimental Psychology: General 137, 201225.
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636645.
Graham, FK, Kendall, BS (1960). Memory-For-Designs Test: revised general manual. Perceptual and Motor Skills 11, 147188.
Gronwall, DMA (1977). Paced Auditory Serial-Addition Task: a measure of recovery from concussion. Perceptual and Motor Skills 44, 367373.
Gudelsky, GA, Yamamoto, BK (2008). Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons. Pharmacology, Biochemistry, and Behavior 90, 198207.
Hariri, AR, Holmes, A (2006). Genetics of emotional regulation: the role of the serotonin transporter in neural function. Trends in Cognitive Sciences 10, 182191.
Hosmer, L, Lemeshow, S (2001). Applied Logistic Regression: Textbook and Solutions Manual. John Wiley & Sons: New York.
Howes, OD, Kapur, S (2009). The dopamine hypothesis of schizophrenia: version III – the final common pathway. Schizophrenia Bulletin 35, 549562.
Ichimiya, T, Suhara, T, Sudo, Y, Okubo, Y, Nakayama, K, Nankai, M, Inoue, M, Yasuno, F, Takano, A, Maeda, J, Shibuya, H (2002). Serotonin transporter binding in patients with mood disorders: a PET study with [11C](+)McN5652. Biological Psychiatry 51, 715722.
Innis, RB, Cunningham, VJ, Delforge, J, Fujita, M, Giedde, A, Gunn, RN, Holden, J, Houle, S, Huang, SC, Ichise, M, Lida, H, Ito, H, Kimura, Y, Koeppe, RA, Knudsen, GM, Knuuti, J, Lammertsma, AA, Laruelle, M, Logan, J, Maguire, RP, Mintun, MA, Morris, ED, Parsey, R, Price, JC, Slifstein, M, Sossi, V, Suhara, T, Votaw, JR, Wong, DF, Carson, RE (2007). Consensus nomenclature for in vivo imaging of reversibly binding radioligands. Journal of Cerebral Blood Flow and Metabolism 27, 15331539.
Joensuu, M, Tolmunen, T, Saarinen, PI, Tiihonen, J, Kuikka, J, Ahola, P, Vanninen, R, Lehtonen, J (2007). Reduced midbrain serotonin transporter availability in drug-naïve patients with depression measured by SERT-specific [123I] nor-β-CIT SPECT imaging. Psychiatry Research: Neuroimaging 154, 125131.
Johanson, CE, Frey, KA, Lundahl, LH, Keenan, P, Lockhart, N, Roll, J, Galloway, GP, Koeppe, RA, Kilbourn, MR, Robbins, T, Schuster, CR (2006). Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers. Psychopharmacology (Berlin) 185, 327338.
Kalbitzer, J, Frokjaer, VG, Erritzoe, D, Svarer, C, Cumming, P, Nielsen, FA, Hashemi, SH, Baare, WF, Madsen, J, Hasselbalch, SG, Kringelbach, ML, Mortensen, EL, Knudsen, GM (2009). The personality trait openness is related to cerebral 5-HTT levels. NeuroImage 45, 280285.
Koch, W, Schaaff, N, Pöpperl, G, Mulert, C, Juckel, G, Reicherzer, M, Ehmer-von Geiso, C, Moeller, H-J, Hegerl, U, Tatsch, K, Pogarell, O (2007). [123I]ADAM and SPECT in patients with borderline personality disorder and healthy control subjects. Journal of Psychiatry and Neuroscience 32, 234240.
Laruelle, M, Wallace, E, Seibyl, JP, Baldwin, RM, Zea-Ponce, Y, Zoghbi, SS, Neumeyer, JL, Charney, DS, Hoffer, PB, Innis, RB (1994). Graphical, kinetic, and equilibrium analyses of in vivo [123I]beta-CIT binding to dopamine transporters in healthy human subjects. Journal of Cerebral Blood Flow and Metabolism 14, 982994.
Lehto, SM, Tolmunen, T, Joensuu, M, Saarinen, PI, Valkonen-Korhonen, M, Vanninen, R, Ahola, P, Tiihonen, J, Kuikka, J, Lehtonen, J (2008 a). Changes in midbrain serotonin transporter availability in atypically depressed subjects after one year of psychotherapy. Progress in Neuro-Psychopharmacology and Biological Psychiatry 32, 229237.
Lehto, SM, Tolmunen, T, Kuikka, J, Valkonen-Korhonen, M, Joensuu, M, Saarinen, PI, Vanninen, R, Ahola, P, Tiihonen, J, Lehtonen, J (2008 b). Midbrain serotonin and striatum dopamine transporter binding in double depression: a one-year follow-up study. Neuroscience Letters 441, 291295.
Lindström, M, Ryding, E, Bosson, P, Ahnlide, JA, Rosén, I, Träskman-Bendz, L (2004). Impulsivity related to brain serotonin transporter binding capacity in suicide attempters. European Neuropsychopharmacology 14, 295300.
Maron, E, Kuikka, JT, Shlik, J, Vasar, V, Vanninen, E, Tiihonen, J (2004). Reduced brain serotonin transporter binding in patients with panic disorder. Psychiatry Research 132, 173181.
McCann, UD, Szabo, Z, Vranesic, M, Palermo, M, Mathews, WB, Ravert, HT, Dannals, RF, Ricaurte, GA (2008). Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (±)3,4-methylenedioxymethamphetamine (‘ecstasy’) users: relationship to cognitive performance. Psychopharmacology 200, 439450.
Meneses, A (1999). 5-HT system and cognition. Neuroscience and Biobehavioral Reviews 23, 11111125.
Meyer, JH, Houle, S, Sagrati, S, Carella, A, Hussey, DF, Ginovart, N, Goulding, V, Kennedy, J, Wilson, AA (2004). Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. Archives of General Psychiatry 61, 12711279.
Mozley, LH, Gur, RC, Mozley, PD, Gur, RE (2001). Striatal dopamine transporters and cognitive functioning in healthy men and women. American Journal of Psychiatry 158, 14921499.
Nelson, HE, O'Connell, A (1978). Dementia: the estimation of premorbid intelligence levels using the New Adult Reading Test. Cortex 14, 234244.
Newberg, AB, Amsterdam, JD, Wintering, N, Ploessl, K, Swanson, RL, Shults, J, Alavi, A (2005). I-123-ADAM binding to serotonin transporters in patients with major depression and healthy controls: a preliminary study. Journal of Nuclear Medicine 46, 973977.
Oades, RD (2008). Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD). Progress in Brain Research 172, 543565.
Parsey, RV, Hastings, RS, Oquendo, MA, Huang, YY, Simpson, N, Arcement, J, Huang, Y, Ogden, RT, Van Heertum, RL, Arango, V, Mann, JJ (2006). Lower serotonin transporter binding potential in the human brain during major depressive episodes. American Journal of Psychiatry 163, 5258.
Pattij, T, Vanderschuren, LJMJ (2008). The neuropharmacology of impulsive behaviour. Trends in Pharmacological Sciences 29, 192199.
Patton, JH, Stanford, MS, Barratt, ES (1995). Factor structure of the Barratt Impulsiveness Scale. Journal of Clinical Psychology 51, 768774.
Pirker, W, Asenbaum, S, Hauk, M, Kandlhofer, S, Tauscher, J, Willeit, M, Neumeister, A, Praschak-Rieder, N, Angelberger, P, Brucke, T (2000). Imaging serotonin and dopamine transporters with I-123-beta-CIT SPECT: binding kinetics and effects of normal aging. Journal of Nuclear Medicine 41, 3644.
Reneman, L, Booij, J, de Bruin, K, Reitsma, JR, de Wolff, FA, Gunning, WB, den Heeten, GJ, van den Brink, W (2001 a). Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet 358, 18641869.
Reneman, L, Lavalaye, J, Schmand, B, de Wolff, FA, van den Brink, W, den Heeten, G, Booij, J (2001 b). Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’). Archives of General Psychiatry 58, 901906.
Rey, A (1964). The Clinical Examination in Psychology [in French]. Presses Universitaires de France: Paris, France.
Robbins, TW, Roberts, AC (2007). Differential regulation of fronto-executive function by the monoamines and acetylcholine. Cerebral Cortex 17, I151I160.
Roiser, JP, Rogers, RD, Cook, LJ, Sahakian, BJ (2006). The effect of polymorphism at the serotonin transporter gene on decision-making, memory and executive function in ecstasy users and controls. Psychopharmacology 188, 213227.
Ryding, E, Ahnlide, JA, Lindström, M, Rosén, I, Träskman-Bendz, L (2006). Regional brain serotonin and dopamine transporter binding capacity in suicide attempters relate to impulsiveness and mental energy. Psychiatry Research: Neuroimaging 148, 195203.
Schilt, T, de Win, MML, Koeter, M, Jager, G, Korf, DJ, van den Brink, W, Schmand, B (2007). Cognition in novice ecstasy users with minimal exposure to other drugs: a prospective cohort study. Archives of General Psychiatry 64, 728736.
Schmand, BA, Bakker, D, Saan, RJ, Louman, J (1991). The Dutch reading test for adults: a measure of premorbid intelligence level [in Dutch]. Tijdschrift voor Gerontologie en Geriatrie 22, 1519.
Seibyl, JP, Laruelle, M, van Dyck, CH, Wallace, E, Baldwin, RM, Zoghbi, S, Zea-Ponce, Y, Neumeyer, JL, Charney, DS, Hoffer, PB, Innis, RB (1996). Reproducibility of iodine-123-beta-CIT SPECT brain measurement of dopamine transporters. Journal of Nuclear Medicine 37, 222228.
Shepard, RN, Metzler, J (1971). Mental rotation of three-dimensional objects. Science 171, 701703.
Stahl, SM (2000). Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 2nd edn. Cambridge University Press: New York.
Suhara, T, Yasuno, F, Sudo, Y, Yamamoto, M, Inoue, M, Okubo, Y, Suzuki, K (2001). Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking. NeuroImage 13, 891895.
Takano, A, Arakawa, R, Hayashi, M, Takahashi, H, Ito, H, Suhara, T (2007). Relationship between neuroticism personality trait and serotonin transporter binding. Biological Psychiatry 62, 588592.
Tiihonen, J, Kuikka, JT, Bergstrom, KA, Karhu, J, Viinamaki, H, Lehtonen, J, Hallikainen, T, Yang, JW, Hakola, P (1997). Single-photon emission tomography imaging of monoamine transporters in impulsive violent behaviour. European Journal of Nuclear Medicine 24, 12531260.
Tsai, HC, Yeh, TL, Hsieh, MH, Lee, IH, Chen, KC, Chen, PS, Yang, YK, Yao, WJ (2009). Association between serotonin transporter availability and overall rating scores of quality of life in healthy volunteers. Progress in Neuro-Psychopharmacology and Biological Psychiatry 33, 711714.
Van den Burg, W, Saan, RJ, Deelman, BG (1985). 15-Woordentest: Provisional Manual. University Hospital: Groningen, The Netherlands.
van der Wee, NJ, van Veen, JF, Stevens, H, van Vliet, IM, van Rijk, PP, Westenberg, HG (2008). Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by 123I-beta-(4-iodophenyl)-tropane SPECT. Journal of Nuclear Medicine 49, 757763.
van Dyck, CH, Malison, RT, Seibyl, JP, Laruelle, M, Klumpp, H, Zoghbi, SS, Baldwin, RM, Innis, RB (2000). Age-related decline in central serotonin transporter availability with [I-123]beta-CIT SPECT. Neurobiology of Aging 21, 497501.
van Herk, M, de Jaeger, K, de Munck, J, Hoogeman, M, Meinders, JPL, Zijp, L (2000). A delineation system for N modalities – software aspects (Extended Abstract). In Proceedings XIII International Conference on the Use of Computers in Radiation Therapy (XII ICCR) (ed. Schlegel, W. and Bortfelt, T.), pp. 7375. Springer-Verlag: Heidelberg, Germany.
Wechsler, D (1981). WAIS-R Manual. The Psychological Corporation: San Antonio, TX.
Zhu, J, Reith, ME (2008). Role of the dopamine transporter in the action of psychostimulants, nicotine, and other drugs of abuse. CNS and Neurological Disorders Drug Targets 7, 393409.
Zuckerman, M, Kuhlman, DM (2000). Personality and risk-taking: common biosocial factors. Journal of Personality 68, 999–1029.
Zuckerman, M, Link, K (1968). Construct validity for the sensation-seeking scale. Journal of Consulting and Clinical Psychology 32, 420426.

Keywords

Type Description Title
WORD
Supplementary materials

Burke supplementary material
Table S1.doc

 Word (71 KB)
71 KB

Serotonin and dopamine transporters in relation to neuropsychological functioning, personality traits and mood in young adult healthy subjects

  • S. M. Burke (a1) (a2), E. van de Giessen (a2), M. de Win (a3), T. Schilt (a4), M. van Herk (a5), W. van den Brink (a4) and J. Booij (a2)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed