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Effects of sedative antidepressants on prefrontal cortex activity during verbal fluency task in healthy subjects: a near-infrared spectroscopy study

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Abstract

Rationale

Japanese researchers have recently conducted studies using near-infrared spectroscopy (NIRS) to help diagnose psychiatric disorders based on changes in brain activity. However, the influence of psychotropic drugs on NIRS measurements has not been clarified.

Objective

To assess the effects of sedative antidepressants on prefrontal cortex activity in healthy subjects using NIRS in a double-blinded, placebo-controlled, crossover trial.

Methods

Nineteen healthy males received nocturnal doses of mirtazapine 15 mg, trazodone 25 mg, or placebo for eight consecutive days in rotation, with a washout period of more than 1 week between each rotation. Subjects performed a verbal fluency task during NIRS on a total of seven occasions during the study period: more than a week prior to receiving the first dose of the first medication; and on days 2 and 9 of each rotation. The number of words correctly generated during the task (behavioral performance) was also recorded. Stanford Sleepiness Scale (SSS) scores were determined each day.

Results

Mirtazapine 15 mg significantly increased oxyhemoglobin (oxy-Hb) concentration change in NIRS on day 9, compared to trazodone 25 mg and placebo. Mirtazapine 15 mg significantly increased SSS on day 2, compared to the other conditions. No significant differences in behavioral performance were observed.

Conclusions

Administration of mirtazapine for eight consecutive days affected oxy-Hb changes on NIRS. This result indicates that researchers should consider how certain types of antidepressant could influence brain function when the brain activity of patients with psychiatric disorders is assessed.

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References

  • Hampson E (1990) Variations in sex-related cognitive abilities across the menstrual cycle. Brain Cogn 14:26–43

    Article  PubMed  CAS  Google Scholar 

  • Herrmann MJ, Ehlis AC, Fallgatter AJ (2004) Bilaterally reduced frontal activation during a verbal fluency task in depressed patients as measured by near-infrared spectroscopy. J Neuropsychiatry Clin Neurosci 16(2):170–175

    Article  PubMed  CAS  Google Scholar 

  • Hock C, Villringer K, Muller-Spahn F, Wenzel R, Heekeren H, Schuh-Hofer S, Hofmann M, Minoshima S, Schwaiger M, Dirnagl U, Villringer A (1997) Decrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer's disease monitored by means of near-infrared spectroscopy (NIRS)—correlation with simultaneous rCBF-PET measurements. Brain Res 755:293–303

    Article  PubMed  CAS  Google Scholar 

  • Kameyama M, Fukuda M, Uehara T, Mikuni M (2004) Sex and age dependencies of cerebral blood volume changes during cognitive activation: a multichannel near-infrared spectroscopy study. Neuroimage 22:1715–1721

    Article  PubMed  Google Scholar 

  • Kameyama M, Fukuda M, Yamagishi Y, Sato T, Uehara T, Ito M, Suto T, Mikuni M (2006) Frontal lobe function in bipolar disorder: a multichannel near-infrared spectroscopy study. Neuroimage 29:172–184

    Article  PubMed  Google Scholar 

  • Kleinschmidt A, Obrig H, Requardt M, Merboldt KD, Dirnagl U, Villringer A, Frahm J (1996) Simultaneous recording of cerebral blood oxygenation changes during human brain activation by magnetic resonance imaging and near-infrared spectroscopy. J Cereb Blood Flow Metab 16:817–826

    Article  PubMed  CAS  Google Scholar 

  • Maki PM, Rich JB, Rosenbaum RS (2002) Implicit memory varies across the menstrual cycle: estrogen effects in young women. Neuropsychologia 40:518–529

    Article  PubMed  Google Scholar 

  • Mehagnoul-Schipper DJ, van der Kallen BF, Colier WN, van der Sluijs MC, van Erning LJ, Thijssen HO, Oeseburg B, Hoefnagels WH, Jansen RW (2002) Simultaneous measurements of cerebral oxygenation changes during brain activation by near-infrared spectroscopy and functional magnetic resonance imaging in healthy young and elderly subjects. Hum Brain Mapp 16:14–23

    Article  PubMed  Google Scholar 

  • Millan MJ, Gobert A, Rivet JM, Adhumeau-Auclair A, Cussac D, Newman-Tancredi A, Dekeyne A, Nicolas JP, Lejeune F (2000) Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of alpha2-adrenergic and serotonin2C receptors: a comparison with citalopram. Eur J Neurosci 12:1079–1095

    Article  PubMed  CAS  Google Scholar 

  • Miyata S, Noda A, Ozaki N, Hara Y, Minoshima M, Iwamoto K, Takahashi M, Iidaka T, Koike Y (2010) Insufficient sleep impairs driving performance and cognitive function. Neurosci Lett 469:229–233

    Article  PubMed  CAS  Google Scholar 

  • Mochizuki H, Tashiro M, Tagawa M, Kano M, Itoh M, Okamura N, Watanabe T, Yanai K (2002) The effects of a sedative antihistamine, d-chlorpheniramine, on visuomotor spatial discrimination and regional brain activity as measured by positron emission tomography (PET). Hum Psychopharmacol 17:413–418

    Article  PubMed  CAS  Google Scholar 

  • Nakayama K, Sakurai T, Katsu H (2004) Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation. Brain Res Bull 63:237–241

    Article  PubMed  CAS  Google Scholar 

  • Okamoto M, Dan H, Sakamoto K, Takeo K, Shimizu K, Kohno S, Oda I, Isobe S, Suzuki T, Kohyama K, Dan I (2004) Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10–20 system oriented for transcranial functional brain mapping. Neuroimage 21:99–111

    Article  PubMed  Google Scholar 

  • Okamura N, Yanai K, Higuchi M, Sakai J, Iwata R, Ido T, Sasaki H, Watanabe T, Itoh M (2000) Functional neuroimaging of cognition impaired by a classical antihistamine, d-chlorpheniramine. Br J Pharmacol 129:115–123

    Article  PubMed  CAS  Google Scholar 

  • Peran P, Demonet JF, Cardebat D (2008) Paroxetine-induced modulation of cortical activity supporting language representations of action. Psychopharmacology (Berl) 195:487–496

    Article  CAS  Google Scholar 

  • Phillips SM, Sherwin BB (1992) Variations in memory function and sex steroid hormones across the menstrual cycle. Psychoneuroendocrinology 17:497–506

    Article  PubMed  CAS  Google Scholar 

  • Sadock BJ, Sadock VA, Sussman N, Cancro R (2005) Kaplan and Sadock's pocket handbook of psychiatric drug treatment. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  • Schecklmann M, Ehlis AC, Plichta MM, Boutter HK, Metzger FG, Fallgatter AJ (2007) Altered frontal brain oxygenation in detoxified alcohol dependent patients with unaffected verbal fluency performance. Psychiatry Res 156:129–138

    Article  PubMed  CAS  Google Scholar 

  • Strangman G, Culver JP, Thompson JH, Boas DA (2002) A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation. Neuroimage 17:719–731

    Article  PubMed  Google Scholar 

  • Suda M, Sato T, Kameyama M, Ito M, Suto T, Yamagishi Y, Uehara T, Fukuda M, Mikuni M (2008) Decreased cortical reactivity underlies subjective daytime light sleepiness in healthy subjects: a multichannel near-infrared spectroscopy study. Neurosci Res 60:319–326

    Article  PubMed  Google Scholar 

  • Suda M, Uehara T, Fukuda M, Sato T, Kameyama M, Mikuni M (2010) Dieting tendency and eating behavior problems in eating disorder correlate with right frontotemporal and left orbitofrontal cortex: a near-infrared spectroscopy study. J Psychiatr Res 44:547–555

    Article  PubMed  Google Scholar 

  • Suto T, Fukuda M, Ito M, Uehara T, Mikuni M (2004) Multichannel near-infrared spectroscopy in depression and schizophrenia: cognitive brain activation study. Biol Psychiatry 55:501–511

    Article  PubMed  Google Scholar 

  • Tomioka H, Yamagata B, Takahashi T, Yano M, Isomura AJ, Kobayashi H, Mimura M (2009) Detection of hypofrontality in drivers with Alzheimer's disease by near-infrared spectroscopy. Neurosci Lett 451:252–256

    Article  PubMed  CAS  Google Scholar 

  • Toronov V, Webb A, Choi JH, Wolf M, Michalos A, Gratton E, Hueber D (2001) Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging. Med Phys 28:521–527

    Article  PubMed  CAS  Google Scholar 

  • Tsujii T, Yamamoto E, Ohira T, Saito N, Watanabe S (2007) Effects of sedative and non-sedative H1 antagonists on cognitive tasks: behavioral and near-infrared spectroscopy (NIRS) examinations. Psychopharmacology (Berl) 194:83–91

    Article  CAS  Google Scholar 

  • Tsujii T, Masuda S, Yamamoto E, Ohira T, Akiyama T, Takahashi T, Watanabe S (2009) Effects of sedative and nonsedative antihistamines on prefrontal activity during verbal fluency task in young children: a near-infrared spectroscopy (NIRS) study. Psychopharmacology (Berl) 207:127–132

    Article  CAS  Google Scholar 

  • Tsuzuki D, Jurcak V, Singh AK, Okamoto M, Watanabe E, Dan I (2007) Virtual spatial registration of stand-alone fNIRS data to MNI space. Neuroimage 34:1506–1518

    Article  PubMed  Google Scholar 

  • Vollm B, Richardson P, McKie S, Elliott R, Deakin JF, Anderson IM (2006) Serotonergic modulation of neuronal responses to behavioural inhibition and reinforcing stimuli: an fMRI study in healthy volunteers. Eur J Neurosci 23:552–560

    Article  PubMed  Google Scholar 

  • Wingen M, Kuypers KP, van de Ven V, Formisano E, Ramaekers JG (2008) Sustained attention and serotonin: a pharmaco-fMRI study. Hum Psychopharmacol 23:221–230

    Article  PubMed  Google Scholar 

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Acknowledgments

We wish to offer our sincere thanks to the healthy volunteers who participated in our study. This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Ministry of Health, Labor and Welfare of Japan, the Academic Frontier Project for Private Universities, Comparative Cognitive Science Institutes, Meijo University, the Yokoyama Foundation for Clinical Pharmacology, and the Japan Research Foundation for Clinical Pharmacology.

Conflict of interest

None of the authors have any conflicts of interest directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi, Japan

    Kunihiro Kohmura, Kunihiro Iwamoto, Branko Aleksic, Kazumi Sasada, Naoko Kawano, Hiroto Katayama, Tetsuya Iidaka & Norio Ozaki

  2. Research Team for Promoting Independence of the Elderly, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Naoko Kawano

  3. Division of Clinical Science and Neuropsychopharmacology, Graduate School of Pharmacy, Meijo University, Nagoya, Aichi, Japan

    Yukihiro Noda

  4. The Academic Frontier Project for Private Universities, Comparative Cognitive Science Institutes, Meijo University, Nagoya, Aichi, Japan

    Yukihiro Noda

  5. Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan

    Akiko Noda

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  1. Kunihiro Kohmura
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  2. Kunihiro Iwamoto
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  9. Tetsuya Iidaka
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  10. Norio Ozaki
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Correspondence to Kunihiro Iwamoto.

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Kohmura, K., Iwamoto, K., Aleksic, B. et al. Effects of sedative antidepressants on prefrontal cortex activity during verbal fluency task in healthy subjects: a near-infrared spectroscopy study. Psychopharmacology 226, 75–81 (2013). https://doi.org/10.1007/s00213-012-2885-8

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  • DOI: https://doi.org/10.1007/s00213-012-2885-8

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