Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs—A Review

Messina, A.; Concerto, Carmen; Rodolico, Alessandro; Petralia, Antonino; Caraci, Filippo; Signorelli, Maria Salvina

doi:10.3390/brainsci13060957

Cited by 16 publications

(7 citation statements)

References 123 publications

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“…Interestingly, other anti-inflammatory medications, such as celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline, did not have a significant impact on SCZ symptoms in a recent meta-analysis, highlighting the presence of inflammatory-pathway-specific abnormalities in SCZ development. Collectively, these findings support the emerging importance of immune-related dysfunction as a targetable pathology of SCZ [ 196 ]. However, additional trials are required to confirm these findings as the effectiveness of selected therapies, including anti-IL-6 and anti-CD20 antibodies as well as prednisolone, has been questioned in some clinical studies [ 197 , 198 , 199 ].…”

Section: Implications For Mechanistic Studies and Therapeutic Develop...supporting

confidence: 69%

Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings

Nguyen,

Amerio,

Aguglia

et al. 2023

Cells

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Schizophrenia is a complex psychiatric condition that may involve immune system dysregulation. Since most putative disease mechanisms in schizophrenia have been derived from genetic association studies and fluid-based molecular analyses, this review aims to summarize the emerging evidence on clinical correlates to immune system dysfunction in this psychiatric disorder. We conclude this review by attempting to develop a unifying hypothesis regarding the relative contributions of microglia and various immune cell populations to the development of schizophrenia. This may provide important translational insights that can become useful for addressing the multifaceted clinical presentation of schizophrenia.

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Section: Implications For Mechanistic Studies and Therapeutic Develop...supporting

confidence: 69%

Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings

Nguyen,

Amerio,

Aguglia

et al. 2023

Cells

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“…Early detection and prompt treatment of catatonic symptoms is critical to avoid chronicity [53]. Thus, psychosocial interventions, cognitive remediation, and pharmacological approaches, purposeful to treat the negative symptoms and underlying in ammation could help to nd an answer to unmet needs still in the treatment of schizophrenia [7,54].…”

Section: Discussionmentioning

confidence: 99%

Catatonia-like behavior and immune activation: a crosstalk between psychopathology and pathology in schizophrenia

Messina

Caraci

Aguglia

et al. 2023

Preprint

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Background: in Kalhbaum's first description of catatonia, symptoms of the affective domain, such as blunted affect, were included in addition to motor symptoms. Recently some authors proposed to revisit the concept of catatonia by including symptoms such as blunted affect and psychomotor slowing. This study aimed to investigate the association between catatonic-like behavior (CLB) (emotional withdrawal, blunted affect, and psychomotor slowing) and inflammatory markers, such as neutrophil/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR) in patients diagnosed with schizophrenia. Method: a sample of 25 patients with schizophrenia (10 females, 15 males) was recruited, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of emotional withdrawal, blunted affect, and psychomotor slowing. Findings: the correlation analysis (Spearman r) revealed a robust direct association between blunted affect and psychomotor slowing (r=0.79, P=0.00), and a significant direct correlation between CLB (emotional withdrawal, r=0.51, P=0.05; blunted affect r=0.58, P=0.05; motor retardation, r=0.56, P=0.05) and LMR (r=0.53, P=0.05). In addition, patients with a duration of illness (DOI) older than five years had a higher presence of CLB and a higher LMR than patients with a more recent diagnosis of the disease. Likely, patients with positive symptoms and in the prodromal and active stages of the disease have a different immune profile than patients in the residual stage and with a predominance of negative symptoms. Conclusions: psychomotor slowing and blunted affect are two significantly related features, representing the two-faced Janus of immobility. Furthermore, aggregating them in CLB is more predominant the longer the duration of schizophrenia and is associated with different a specific pattern of immune activation.

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“…Minocycline is a pharmacological agent with antibacterial characteristics and the ability to reduce inflammation. Several clinical investigations have shown that the adjunctive use of minocycline with antipsychotic therapies may enhance symptomatology in individuals with schizophrenia [ 56 ]. Six randomized controlled trials (RCTs) were selected for inclusion in a review.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, psychosocial interventions, cognitive remediation, clinical and pharmacological approaches, purposeful to treat the negative symptoms and underlying inflammation could help to find an answer to unmet needs still in the treatment of schizophrenia [ 7 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Catatonia-like behavior and immune activation: a crosstalk between psychopathology and pathology in schizophrenia

Messina,

Caraci,

Aguglia

et al. 2023

Ann Gen Psychiatry

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Background In Kalhbaum's first characterization of catatonia, the emotional symptoms, such as decreased or restricted expression of feelings and emotions, which is described as blunted affect, are related to the motor symptoms. In later years, the affective domain was excluded from the concept of catatonia and was not included among the diagnostic criteria in the various Diagnostic Statistical Manual (DSM) versions. In recent times, some authors have proposed the proposition of reevaluating the notion of catatonia through the reintroduction of the affective domain. The objective of this study was to examine the correlation between catatonic-like behavior (CLB), such as emotional withdrawal, blunted affect, and psychomotor slowing, and inflammatory markers, namely the neutrophil/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR), in individuals diagnosed with schizophrenia. Method A sample of 25 patients with schizophrenia (10 females, 15 males) was recruited, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of emotional withdrawal, blunted affect, and psychomotor slowing. Findings: The correlation analysis (Spearman ρ) revealed a robust direct association between blunted affect and psychomotor slowing (ρ = 0.79, P = 0.001), and a significant direct correlation between CLB (emotional withdrawal, ρ = 0.51, P = 0.05; blunted affect ρ = 0.58, P = 0.05; motor retardation, ρ = 0.56, P = 0.05) and LMR (ρ = 0.53, P = 0.05). In addition, patients with a duration of illness (DOI) older than five years had a higher presence of CLB and a higher LMR than patients with a more recent diagnosis of the disease. Likely, patients with positive symptoms and in the prodromal and active stages of the disease have a different immune profile than patients in the residual stage and with a predominance of negative symptoms. Conclusions Psychomotor slowing and blunted affect are two significantly related features, representing the two-faced Janus of immobility. Furthermore, aggregating them in CLB is more predominant the longer the duration of schizophrenia and is associated with different a specific pattern of immune activation.

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Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs—A Review

Cited by 16 publications

References 123 publications

Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings

Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings

Catatonia-like behavior and immune activation: a crosstalk between psychopathology and pathology in schizophrenia

Catatonia-like behavior and immune activation: a crosstalk between psychopathology and pathology in schizophrenia

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