Minocycline Modulates Human Social Decision-Making: Possible Impact of Microglia on Personality-Oriented Social Behaviors

Kato, Takahiro A.; Watabe, Motoki; Tsuboi, Sho; Ishikawa, Keisuke; Hashiya, Kazuhide; Monji, Akira; Utsumi, Hideo; Kanba, Shigenobu

doi:10.1371/journal.pone.0040461

Cited by 32 publications

(26 citation statements)

References 56 publications

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“…Interestingly, we have recently reported that minocycline modulates human social decision-making in healthy volunteers [186,187]. Therefore, minocycline may effect not only on psychiatric patients but also on healthy persons.…”

Section: Minocyclinementioning

confidence: 99%

Neurotransmitters, Psychotropic Drugs and Microglia: Clinical Implications for Psychiatry

Kato¹,

Yamauchi²,

Horikawa³

et al. 2013

Current Medicinal Chemistry

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Psychiatric disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters. Thus, the effects of psychotropic drugs such as antipsychotics and antidepressants have been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as dopamine and serotonin. Recently, microglia, immunological/inflammatory cells in the brain, have been indicated to have positive links to psychiatric disorders. Positron emission tomography (PET) imaging and postmortem studies have revealed microglial activation in the brain of neuropsychiatric disorders such as schizophrenia, depression and autism. Animal models of neuropsychiatric disorders have revealed the underlying microglial pathologies. In addition, various psychotropic drugs have been suggested to have direct effects on microglia. Until now, the relationship between microglia, neurotransmitters and psychiatric disorders has not been well understood. Therefore, in this review, at first, we summarize recent findings of interaction between microglia and neurotransmitters such as dopamine, serotonin, norepinephrine, acetylcholine and glutamate. Next, we introduce up-to-date knowledge of the effects of psychotropic drugs such as antipsychotics, antidepressants and antiepileptics on microglial modulation. Finally, we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders. Further investigations and clinical trials should be conducted to clarify this perspective, using animal in vivo studies and imaging studies with human subjects.

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Section: Minocyclinementioning

confidence: 99%

Neurotransmitters, Psychotropic Drugs and Microglia: Clinical Implications for Psychiatry

Kato¹,

Yamauchi²,

Horikawa³

et al. 2013

Current Medicinal Chemistry

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“…As the first step to clarify this unexplored field, we have started to conduct a series of social decision-making experiments with healthy human subjects using minocycline, a microglial inhibitor (59–61). Healthy Japanese adult males made a monetary decision about whether or not to trust an anonymous partner after a 4-day oral administration of minocycline.…”

Section: Possible Glial Roles In Human Mental Functionsmentioning

confidence: 99%

“…Therefore, this first trial has indicated that microglial activation may cause “unconscious noises” against appropriate social decision-making, and inhibiting microglial activity may reduce such noise (60). In a next trial with larger samples, we additionally measured the effects of anxiety and personality as candidates for “noise” factors, by using Temperament and Character Inventory (TCI) and State-Trait Anxiety Inventory (STAI) (59). The monetary score in trust game was significantly lower in the minocycline group.…”

Section: Possible Glial Roles In Human Mental Functionsmentioning

confidence: 99%

Neuron-Glia Interaction as a Possible Glue to Translate the Mind-Brain Gap: A Novel Multi-Dimensional Approach Toward Psychology and Psychiatry (R1)

2013

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Neurons and synapses have long been the dominant focus of neuroscience, thus the pathophysiology of psychiatric disorders has come to be understood within the neuronal doctrine. However, the majority of cells in the brain are not neurons but glial cells including astrocytes, oligodendrocytes, and microglia. Traditionally, neuroscientists regarded glial functions as simply providing physical support and maintenance for neurons. Thus, in this limited role glia had been long ignored. Recently, glial functions have been gradually investigated, and increasing evidence has suggested that glial cells perform important roles in various brain functions. Digging up the glial functions and further understanding of these crucial cells, and the interaction between neurons and glia may shed new light on clarifying many unknown aspects including the mind-brain gap, and conscious-unconscious relationships. We briefly review the current situation of glial research in the field, and propose a novel translational research with a multi-dimensional model, combining various experimental approaches such as animal studies, in vitro & in vivo neuron-glia studies, a variety of human brain imaging investigations, and psychometric assessments.

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“…Therefore, even in normal conditions, microglia have been revealed to have some crucial roles in the homeostasis of synaptic conditions and in brain development. Moreover, we have recently reported that human social activities such as decision-making are modulated by minocycline not only in psychiatric patients but also in healthy persons (Kato et al, 2012; Watabe et al, 2012). Our human neuroeconomics studies have implied the possibility that brain development including neuron-microglia network establishment may formulate personality, and personality-oriented behaviors may be modulated by microglia (Kato et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, we have recently reported that human social activities such as decision-making are modulated by minocycline not only in psychiatric patients but also in healthy persons (Kato et al, 2012; Watabe et al, 2012). Our human neuroeconomics studies have implied the possibility that brain development including neuron-microglia network establishment may formulate personality, and personality-oriented behaviors may be modulated by microglia (Kato et al, 2012). Thus, we suppose that microglia could be one of the crucial players in human mental development during early stages, and also in various social/mental activities after developmental stages including under healthy and pathological conditions beyond the neuron-synapse doctrine.…”

Section: Introductionmentioning

confidence: 99%

Missing and Possible Link between Neuroendocrine Factors, Neuropsychiatric Disorders, and Microglia

Kato¹,

Hayakawa²,

Monji³

et al. 2013

Front. Integr. Neurosci.

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Endocrine systems have long been suggested to be one of the important factors in neuropsychiatric disorders, while the underlying mechanisms have not been well understood. Traditionally, neuropsychiatric disorders have been mainly considered the consequence of abnormal conditions in neural circuitry. Beyond the neuronal doctrine, microglia, one of the glial cells with inflammatory/immunological functions in the central nervous system (CNS), have recently been suggested to play important roles in neuropsychiatric disorders. However, the crosstalk between neuroendocrine factors, neuropsychiatric disorders, and microglia has been unsolved. Therefore, we herein introduce and discuss a missing and possible link between these three factors; especially highlighting the following hormones; (1) Hypothalamic-Pituitary-Adrenal (HPA) axis-related hormones such as corticotropin-releasing hormone (CRH) and glucocorticoids, (2) sex-related hormones such as estrogen and progesterone, and (3) oxytocin. A growing body of evidence has suggested that these hormones have a direct effect on microglia. We hypothesize that hormone-induced microglial activation and the following microglia-derived mediators may lead to maladaptive neuronal networks including synaptic dysfunctions, causing neuropsychiatric disorders. Future investigations to clarify the correlation between neuroendocrine factors and microglia may contribute to a novel understanding of the pathophysiology of neuropsychiatric disorders.

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Minocycline Modulates Human Social Decision-Making: Possible Impact of Microglia on Personality-Oriented Social Behaviors

Cited by 32 publications

References 56 publications

Neurotransmitters, Psychotropic Drugs and Microglia: Clinical Implications for Psychiatry

Neurotransmitters, Psychotropic Drugs and Microglia: Clinical Implications for Psychiatry

Neuron-Glia Interaction as a Possible Glue to Translate the Mind-Brain Gap: A Novel Multi-Dimensional Approach Toward Psychology and Psychiatry (R1)

Missing and Possible Link between Neuroendocrine Factors, Neuropsychiatric Disorders, and Microglia

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