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Higher striatal dopamine transporter density in PTSD: an in vivo SPECT study with [99mTc]TRODAT-1

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Abstract

Rationale

Some evidence suggests a hyperdopaminergic state in posttraumatic stress disorder (PTSD). The 9-repetition allele (9R) located in the 3′ untranslated region of the dopamine transporter (DAT) gene (SLC6A3) is more frequent among PTSD patients. In vivo molecular imaging studies have shown that healthy 9R carriers have increased striatal DAT binding. However, no prior study evaluated in vivo striatal DAT density in PTSD.

Objectives

The objective of this study was to evaluate in vivo striatal DAT density in PTSD.

Methods

Twenty-one PTSD subjects and 21 control subjects, who were traumatized but asymptomatic, closely matched comparison subjects evaluated with the Clinician-Administered PTSD Scale underwent a single-photon emission computed tomography scan with [99mTC]-TRODAT-1. DAT binding potential (DAT-BP) was calculated using the striatum as the region of the interest and the occipital cortex as a reference region.

Results

PTSD patients had greater bilateral striatal DAT-BP (mean ± SD; left, 1.80 ± 0.42; right, 1.78 ± 0.40) than traumatized control subjects (left, 1.62 ± 0.32; right, 1.61 ± 0.31; p = 0.039 for the left striatum and p = 0.032 for the right striatum).

Conclusions

These results provide the first in vivo evidence for increased DAT density in PTSD. Increases in DAT density may reflect higher dopamine turnover in PTSD, which could contribute to the perpetuation and potentiation of exaggerated fear responses to a given event associated with the traumatic experience. Situations that resemble the traumatic event turn to be interpreted as highly salient (driving attention, arousal, and motivation) in detriment of other daily situations.

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Acknowledgments

This study received financial support in the form of grants provided by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of São Paulo) to Dr. Mari (grant: 2004/15039-0) and from Instituto do Cérebro, Instituto de Ensino e Pesquisa do Hospital Israelita Albert Einstein to Dr. Bressan (grant: 148-06). This work was presented at the 65th Annual Meeting of the Society of Biological Psychiatry, May 20–22 in New Orleans, LA, USA.

Conflicts of interest

Drs. Hoexter, Fadel, Felício, Calzavara, Batista, Reis, Shih, Pitman, Andreoli, Mello, and Mari have declared no conflict of interest. Dr. Bressan has received honoraria and/or consultations fees from Astra Zeneca, Bristol, Janssen, and Lundbeck; has received research funding from Janssen, Eli Lilly, Lundbeck, Novartis, and Roche; and is a shareholder of Biomolecular Technology Ltda.

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Authors and Affiliations

  1. Instituto do Cérebro, Instituto de Ensino e Pesquisa do Hospital Israelita Albert Einstein, São Paulo, Brazil

    Marcelo Q. Hoexter, André C. Felício, Ilza R. Batista, Marilia A. Reis, Ming C. Shih & Rodrigo A. Bressan

  2. Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), Rua Pedro de Toledo, 669-3° andar fundos, CEP: 04039-032, São Paulo, SP, Brazil

    Marcelo Q. Hoexter, Gustavo Fadel, André C. Felício, Mariana B. Calzavara, Ilza R. Batista, Marilia A. Reis, Ming C. Shih, Jair J. Mari & Rodrigo A. Bressan

  3. Núcleo de Estatística e Metodologia Aplicadas (NEMAP), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

    Sérgio B. Andreoli

  4. Programa de Atendimento e Pesquisa em Violência (PROVE), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

    Marcelo F. Mello

  5. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Marcelo Q. Hoexter & Roger K. Pitman

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  1. Marcelo Q. Hoexter
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  2. Gustavo Fadel
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  3. André C. Felício
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  4. Mariana B. Calzavara
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  5. Ilza R. Batista
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  6. Marilia A. Reis
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  7. Ming C. Shih
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  8. Roger K. Pitman
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  9. Sérgio B. Andreoli
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  10. Marcelo F. Mello
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  11. Jair J. Mari
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  12. Rodrigo A. Bressan
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Correspondence to Marcelo Q. Hoexter.

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Hoexter, M.Q., Fadel, G., Felício, A.C. et al. Higher striatal dopamine transporter density in PTSD: an in vivo SPECT study with [99mTc]TRODAT-1. Psychopharmacology 224, 337–345 (2012). https://doi.org/10.1007/s00213-012-2755-4

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