Reduced volumes of the external and internal globus pallidus in male heroin addicts: a postmortem study
- 209 Downloads
Deep brain stimulation (DBS) of the globus pallidus internus was recently proposed as a potential new treatment target for opioid addiction. DBS requires computer-assisted-3D planning to implant the stimulation electrode precisely. As volumes of brain regions may differ in addiction compared to healthy controls, our aim was to investigate possible volume differences in addicts compared to healthy controls. Volumes of the globus pallidus externus (PE) and internus (PI) in heroin addicts (n = 14) and healthy controls (n = 12) were assessed using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1479 ± 62 cm3 vs. mean 1352 ± 103 cm3), as the heroin group was more than 10 years younger (p = 0.001). Despite larger mean whole brain volume, the mean relative volume of the PE and PI was smaller in addicted subjects compared to healthy controls (PE 0.658 ± 0.183 × 10−3 vs. 0.901 ± 0.284 × 10−3; ANOVA F(1, 24) = 6.945, p = 0.014, η2 = 0.224; PI 0.253 ± 0.095 × 10−3 vs. 0.345 ± 0.107 × 10−3; ANOVA F(1, 24) = 5.374, p = 0.029, η2 = 0.183). These findings were not significantly confounded by age, duration of autolysis, and fixation time. Our results provide further evidence for structural and not only functional deficits of the globus pallidus in addiction. In the context of previous studies, our findings support the idea of shared pathophysiological processes between comorbid depression and impulsivity in opioid addiction.
KeywordsHeroin Addiction Globus pallidus internus Globus pallidus externus Postmortem Volumetry Morphometry Deep brain stimulation DBS
Renate Stauch, Sieglinde Funke and Gabriela Meyer-Lotz provided excellent technical assistance.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflicts of interest.
Sampling and preservation of the human brain material were done in accordance with the Declaration of Helsinki, German Law and approval by the local institutional review board.
- 3.Kuhn J, Lenartz D, Huff W, Lee S, Koulousakis A, Klosterkoetter J, Sturm V (2007) Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications? J Neurol Neurosurg Psychiatry 78:1152–1153. https://doi.org/10.1136/jnnp.2006.113092 CrossRefGoogle Scholar
- 4.Müller U, Sturm V, Voges J, Heinze H-J, Galazky I, Büntjen L, Heldmann M, Frodl T, Steiner J, Bogerts B (2016) Nucleus accumbens deep brain stimulation for alcohol addiction—safety and clinical long-term results of a pilot trial. Pharmacopsychiatry 49:170–173. https://doi.org/10.1055/s-0042-104507 CrossRefGoogle Scholar
- 5.Kuhn J, Möller M, Treppmann JF, Bartsch C, Lenartz D, Gruendler TOJ, Maarouf M, Brosig A, Barnikol UB, Klosterkötter J, Sturm V (2014) Deep brain stimulation of the nucleus accumbens and its usefulness in severe opioid addiction. Mol Psychiatry 19:145–146. https://doi.org/10.1038/mp.2012.196 CrossRefGoogle Scholar
- 6.Muller UJ, Truebner K, Schiltz K, Kuhn J, Mawrin C, Dobrowolny H, Bernstein H-G, Bogerts B, Steiner J (2015) Postmortem volumetric analysis of the nucleus accumbens in male heroin addicts: implications for deep brain stimulation. Eur Arch Psychiatry Clin Neurosci. 265:647–653. https://doi.org/10.1007/s00406-015-0617-x CrossRefGoogle Scholar
- 7.Muller UJ, Schiltz K, Mawrin C, Dobrowolny H, Frodl T, Bernstein H-G, Bogerts B, Truebner K, Steiner J (2017) Total hypothalamic volume is reduced in postmortem brains of male heroin addicts. Eur Arch Psychiatry Clin Neurosci 268:243–248. https://doi.org/10.1007/s00406-017-0809-7 CrossRefGoogle Scholar
- 8.Jaeger D, Kita H (2011) Review functional connectivity and integrative properties of globus pallidus neurons. Neuroscience 198:44–53. https://doi.org/10.1016/j.neuroscience.2011.07.050 CrossRefGoogle Scholar
- 9.Goldberg JA, Bergman H (2011) Review computational physiology of the neural networks of the primate globus pallidus: function and dysfunction. Neuroscience 198:171–192. https://doi.org/10.1016/j.neuroscience.2011.08.068 CrossRefGoogle Scholar
- 12.Bernstein HG, Stanarius A, Baumann B, Henning H, Krell D, Danos P, Falkai P, Bogerts B (1998) Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. Neuroscience 83:867–875CrossRefGoogle Scholar
- 19.Bernstein H-G, Trübner K, Krebs P, Dobrowolny H, Bielau H, Steiner J, Bogerts B (2014) Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: possible implications for heroin neurotoxicity. Acta Histochem 116:182–190. https://doi.org/10.1016/j.acthis.2013.07.006 CrossRefGoogle Scholar
- 24.Gos T, Krell D, Bielau H, Steiner J, Trübner K, Brisch R, Bernstein H-G, Jankowski Z, Bogerts B (2009) Demonstration of disturbed activity of external globus pallidus projecting neurons in depressed patients by the AgNOR staining method. J Affect Disord 119:149–155. https://doi.org/10.1016/j.jad.2009.03.010 CrossRefGoogle Scholar