Deconstructing depression and negative symptoms of schizophrenia; differential and longitudinal immune correlates, and response to minocycline treatment

Krynicki, Carl R; Dazzan, Paola; Pariante, Carmine M.; Barnes, Nicholas M.; Vincent, Rachel; Roberts, AM; Giordano, Annalisa; Watson, Andrew; Suckling, John; Barnes, Thomas R. E.; Husain, Nusrat; Jones, Peter; Joyce, Eileen M.; Lawrie, Stephen M.; Lewis, Shôn; Deakin, Bill; Upthegrove, Rachel

doi:10.1016/j.bbi.2020.10.026

Cited by 32 publications

(23 citation statements)

References 53 publications

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“…A recent analysis of the inflammatory response to an induced microglia-like phenotype (iMG) has shown that cells from patients with schizophrenia have a stronger response to lipopolysaccharide, with TNF-α protein secretion most prominently observed [ 16 ]. TNF-α may be an indicator of the immune dysfunction associated with negative symptoms of schizophrenia [ 17 ]. Brain TNF-α is the most promising pharmacological target for the treatment of neuroinflammation that is known to be associated with schizophrenia [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Relationship between TNF-α levels and psychiatric symptoms in first-episode drug-naïve patients with schizophrenia before and after risperidone treatment and in chronic patients

Lin

Chen

et al. 2021

BMC Psychiatry

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Background The influence of antipsychotic drugs on tumor necrosis factor-α (TNF-α) levels is unclear, and there is no consensus on the association between TNF-α and psychotic symptoms. This study aimed to investigate the differences in TNF-α levels and clinical correlations in first-episode drug-naïve (FEDN) patients with schizophrenia before and after treatment and in chronic patients. Methods A total of 103 (51 FEDN and 52 chronic) patients and 114 healthy controls were recruited. Demographic and clinical data, including TNF-α levels, were recorded. We used the Positive and Negative Syndrome Scale (PANSS) to measure the psychopathology of all patients. Results TNF-α levels before treatment were significantly higher in FEDN patients than in chronic patients and healthy controls. No significant sex differences were found in the TNF-α levels of patients with schizophrenia. The TNF-α levels before treatment were significantly positively related to changes in PANSS negative symptoms in FEDN patients. The TNF-α levels in chronic patients were significantly negatively correlated with the general psychopathology subscales and PANSS total scores. Conclusions Increased TNF-α levels in FEDN patients and their correlation with psychopathology indicate that inflammatory cytokines may play a crucial role in the etiopathogenesis of schizophrenia, and inflammation-directed therapy may, therefore, improve negative symptoms.

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Section: Introductionmentioning

confidence: 99%

Relationship between TNF-α levels and psychiatric symptoms in first-episode drug-naïve patients with schizophrenia before and after risperidone treatment and in chronic patients

Lin

Chen

et al. 2021

BMC Psychiatry

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“…It is also worth noting that minocycline efficacy might be diagnosis-specific, considering that results about bipolar depression and also negative symptoms of schizophrenia are more conflicting. In particular, a recent, large clinical trial conducted in patients with schizophrenia ( Krynicki et al., 2020 ) found no evidence of an effect of minocycline on symptoms domains, particularly on depressive and negative symptoms. A possible interpretation is that the mechanisms underlying negative symptoms and comorbid depression in psychosis might be very different from those present in MDD and targeted by minocycline.…”

Section: Discussionmentioning

confidence: 99%

“…However, in a third and larger RCT in patients with early schizophrenia (207 randomized patients), minocycline was ineffective in improving any symptom dimension, even in those with increased baseline markers of peripheral inflammation. Furthermore, minocycline administration was not associated with changes in neuroimaging correlates of schizophrenia and in glutamate neurotransmission ( Deakin et al., 2018 ) ( Krynicki et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Minocycline in Major Depressive Disorder: And overview with considerations on treatment-resistance and comparisons with other psychiatric disorders

Nettis

2021

Brain, Behavior, & Immunity - Health

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Evidence on the link between the immune system and Major Depressive Disorder (MDD) has led to explore antidepressant properties of anti-inflammatory drugs. Among these, minocycline has been identified as a potential novel treatment for MDD, in particular for treatment-resistant depression. The aim of the current paper is to review current pre-clinical and clinical evidence on the antidepressant efficacy of minocycline. The review includes considerations on the role of both peripheral and central inflammation in the response to minocycline and comparisons of minocycline efficacy across different psychiatric disorders (i.e., unipolar depression, bipolar depression, and schizophrenia).

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“…This indicates that further investigation is required to test the therapeutic potential of targeting the immune system specifically in patients with depression, such as the Insight study, a proof-of-concept experimental medicine trial of tocilizumab 27 . Emerging evidence has also demonstrated that increased inflammation may identify the phenotypic profile of patients more likely to benefit from anti-inflammatory augmentation across depression and psychosis 28,29 . This highlights how, when testing an immune-modulatory drug in a complex disease like depression (or dementia), it is essential to first demonstrate that inflammation is occurring and stratify inflammatory patients to the therapy.…”

Section: Tools/technology Developmentmentioning

confidence: 99%

Research priorities for neuroimmunology: identifying the key research questions to be addressed by 2030

et al. 2021

Self Cite

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Neuroimmunology in the broadest sense is the study of interactions between the nervous and the immune systems. These interactions play important roles in health from supporting neural development, homeostasis and plasticity to modifying behaviour. Neuroimmunology is increasingly recognised as a field with the potential to deliver a significant positive impact on human health and treatment for neurological and psychiatric disorders. Yet, translation to the clinic is hindered by fundamental knowledge gaps on the underlying mechanisms of action or the optimal timing of an intervention, and a lack of appropriate tools to visualise and modulate both systems. Here we propose ten key disease-agnostic research questions that, if addressed, could lead to significant progress within neuroimmunology in the short to medium term. We also discuss four cross-cutting themes to be considered when addressing each question: i) bi-directionality of neuroimmune interactions; ii) the biological context in which the questions are addressed (e.g. health vs disease vs across the lifespan); iii) tools and technologies required to fully answer the questions; and iv) translation into the clinic. We acknowledge that these ten questions cannot represent the full breadth of gaps in our understanding; rather they focus on areas which, if addressed, may have the most broad and immediate impacts. By defining these neuroimmunology priorities, we hope to unite existing and future research teams, who can make meaningful progress through a collaborative and cross-disciplinary effort.

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Deconstructing depression and negative symptoms of schizophrenia; differential and longitudinal immune correlates, and response to minocycline treatment

Cited by 32 publications

References 53 publications

Relationship between TNF-α levels and psychiatric symptoms in first-episode drug-naïve patients with schizophrenia before and after risperidone treatment and in chronic patients

Relationship between TNF-α levels and psychiatric symptoms in first-episode drug-naïve patients with schizophrenia before and after risperidone treatment and in chronic patients

Minocycline in Major Depressive Disorder: And overview with considerations on treatment-resistance and comparisons with other psychiatric disorders

Research priorities for neuroimmunology: identifying the key research questions to be addressed by 2030

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