Minocycline as a treatment for schizophrenia: is the discussion truly finished?

Kishimoto, Toshifumi; Horigome, Toshiro; Takamiya, Akihiro

doi:10.1016/s2215-0366(18)30389-4

Cited by 13 publications

(9 citation statements)

References 12 publications

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“…These opposing results do not necessarily mean that minocycline has no beneficial effects. The point in time when minocycline is administered could be a critical aspect, as previously discussed by Kishimoto and colleagues [ 154 ]. Furthermore, the additive treatment with minocycline might be useful for a subgroup of schizophrenia patients that clearly show a rise of inflammatory pathways.…”

Section: Inflammatory Processes Contribute To Hippocampal Abnormalitiesmentioning

confidence: 99%

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

Wegrzyn

Juckel

Faissner

2022

IJMS

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Schizophrenia is a grave neuropsychiatric disease which frequently onsets between the end of adolescence and the beginning of adulthood. It is characterized by a variety of neuropsychiatric abnormalities which are categorized into positive, negative and cognitive symptoms. Most therapeutical strategies address the positive symptoms by antagonizing D2-dopamine-receptors (DR). However, negative and cognitive symptoms persist and highly impair the life quality of patients due to their disabling effects. Interestingly, hippocampal deviations are a hallmark of schizophrenia and can be observed in early as well as advanced phases of the disease progression. These alterations are commonly accompanied by a rise in neuronal activity. Therefore, hippocampal formation plays an important role in the manifestation of schizophrenia. Furthermore, studies with animal models revealed a link between environmental risk factors and morphological as well as electrophysiological abnormalities in the hippocampus. Here, we review recent findings on structural and functional hippocampal abnormalities in schizophrenic patients and in schizophrenia animal models, and we give an overview on current experimental approaches that especially target the hippocampus. A better understanding of hippocampal aberrations in schizophrenia might clarify their impact on the manifestation and on the outcome of this severe disease.

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Section: Inflammatory Processes Contribute To Hippocampal Abnormalitiesmentioning

confidence: 99%

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

Wegrzyn

Juckel

Faissner

2022

IJMS

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“…Minocycline has recently shown promising results as an adjunct drug to treat depression (Emadi-Kouchak et al, 2016), bipolar disorder (Savitz et al, 2018), and schizophrenia (Zhang et al, 2018) and even to delay or prevent the incidence of schizophrenia (Sellgren et al, 2019). However, in the absence of mechanistic insights, its therapeutic potential remains controversial (Deakin et al, 2018;Kishimoto et al, 2018).…”

Section: Transient Minocycline Administration Rescues Prelimbic Deficits In Dual-hit Ge Micementioning

confidence: 99%

Resolving and Rescuing Developmental Miswiring in a Mouse Model of Cognitive Impairment

Chini

Pöpplau

Lindemann

et al. 2020

Neuron

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Cognitive deficits, core features of mental illness, largely result from dysfunction of prefrontal networks. This dysfunction emerges during early development, before a detectable behavioral readout, yet the cellular elements controlling the abnormal maturation are still unknown. Here, we address this open question by combining in vivo electrophysiology, optogenetics, neuroanatomy, and behavioral assays during development in mice mimicking the dual genetic-environmental etiology of psychiatric disorders. We report that pyramidal neurons in superficial layers of the prefrontal cortex are key elements causing disorganized oscillatory entrainment of local circuits in beta-gamma frequencies. Their abnormal firing rate and timing relate to sparser dendritic arborization and lower spine density. Administration of minocycline during the first postnatal week, potentially acting via microglial cells, rescues the neuronal deficits and restores pre-juvenile cognitive abilities. Elucidation of the cellular substrate of developmental miswiring causing later cognitive deficits opens new perspectives for identification of neurobiological targets amenable to therapies.

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“…However, and related to the main aim of this paper, the trials did not enrich their sample for patients with elevated measures of inflammation. It can not be ruled out that the negative and contrasting findings in the minocycline literature are caused by applying the minocycline to an unselected sample (131). Also the results for miscellaneous drugs are summarized in Table 1.…”

Section: Drug Studies To Treat Immune Dysregulation or Inflammation Imentioning

confidence: 99%

Constructing the Immune Signature of Schizophrenia for Clinical Use and Research; An Integrative Review Translating Descriptives Into Diagnostics

et al. 2019

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Schizophrenia is considered a syndrome comprised by several disease phenotypes, covering a range of underlying pathologies. One of these disease mechanisms seems to involve immune dysregulation and neuroinflammation. While the current dopamine receptor-blocking antipsychotic drugs decrease psychotic symptoms and prevent relapse in the majority of patients with schizophrenia, there is a huge need to explore new treatment options that target other pathophysiological pathways. Such studies should aim at identifying robust biomarkers in order to diagnose and monitor the immune biophenotype in schizophrenia and develop better selection procedures for clinical trials with anti-inflammatory and immune-modulating drugs. In this focused review, we describe available methods to assess inflammatory status and immune disturbances in vivo. We also outline findings of immune disturbances and signs of inflammation at cellular, protein, and brain imaging levels in patients with schizophrenia. Furthermore, we summarize the results from studies with anti-inflammatory or other immune-modulating drugs, highlighting how such studies have dealt with participant selection. Finally, we propose a strategy to construct an immune signature that may be helpful in selecting and monitoring participants in studies with immune modulating drugs and also applicable in regular clinical work.

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Minocycline as a treatment for schizophrenia: is the discussion truly finished?

Cited by 13 publications

References 12 publications

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

Resolving and Rescuing Developmental Miswiring in a Mouse Model of Cognitive Impairment

Constructing the Immune Signature of Schizophrenia for Clinical Use and Research; An Integrative Review Translating Descriptives Into Diagnostics

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