Publications by authors named "Angelos Halaris"

Interleukin-8 (IL-8/CXCL8), an essential CXC chemokine, significantly influences psychoneuroimmunological processes and affects neurological and psychiatric health. It exerts a profound effect on immune cell activation and brain function, suggesting potential roles in both neuroprotection and neuroinflammation. IL-8 production is stimulated by several factors, including reactive oxygen species (ROS) known to promote inflammation and disease progression.

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Objective: Autonomic dysregulation is common in many medical conditions and can have a widespread, negative impact on multiple bodily systems, leading to poorer health outcomes. Thus, addressing autonomic dysregulation as part of a comprehensive treatment plan is important. The goal of this study was to gain a better understanding of the physiological benefits of a mindfulness-based intervention (MBI) for a population with medical conditions, using validated, objective measures of autonomic functioning.

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: in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory analysis of the systemic inflammatory response index (SIRI = absolute neutrophils × absolute monocytes/absolute lymphocytes) in relation to other biomarkers and clinical outcomes after escitalopram (ESC), combined with the COX-2 inhibitor, celecoxib (CBX), versus placebo. : Baseline measures of SIRI were compared between TRBDD and healthy controls (HC), and correlated with blood-based inflammatory cytokines, kynurenines, and growth factors.

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Brain-Derived Neurotrophic Factor (BDNF) is crucial for various aspects of neuronal development and function, including synaptic plasticity, neurotransmitter release, and supporting neuronal differentiation, growth, and survival. It is involved in the formation and preservation of dopaminergic, serotonergic, GABAergic, and cholinergic neurons, facilitating efficient stimulus transmission within the synaptic system and contributing to learning, memory, and overall cognition. Furthermore, BDNF demonstrates involvement in neuroinflammation and showcases neuroprotective effects.

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It is well-established that cardiovascular disease and depression are highly comorbid. This study aimed to assess the possible role of the NOD-like receptor protein 3 (NLRP3) inflammasome pathway and the high-sensitivity C-reactive protein (CRP) in patients with incident myocardial infarction in the presence or absence of depression. Sixty-eight consecutive patients with incident ST-elevation myocardial infarction and twenty healthy subjects were included.

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(1) Background: Inflammation is associated with depressive illness and treatment resistance. This study assessed a novel inflammatory index, the Systemic Immune-Inflammation Index (SII), in patients diagnosed with treatment-resistant bipolar depression (TRBDD) before and after treatment with escitalopram (ESC) and celecoxib (CBX) add-on or ESC and placebo (PBO), and compared them to healthy control (HC) subjects. (2) Methods: This is a secondary biological analysis from a double-blind randomized placebo-controlled trial of CBX augmentation in TRBDD.

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Background: Affective illness has been associated with a proinflammatory state, and it is generally accepted that the immune system plays a key role in the pathophysiology of mood disorders. Since inflammatory biomarkers are elevated in bipolar disorder, anti-inflammatory combination therapies may enhance response and reverse treatment resistance.

Purpose: In the present study we investigated the possible impact of single nucleotide polymorphisms (SNPs) within the CRP gene on CRP blood levels, treatment response and level-of-stress perception in our cohort of treatment-resistant bipolar-depressed patients receiving escitalopram and celecoxib, or escitalopram and placebo, as previously reported (Halaris et al.

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The glutamatergic system is the primary excitatory pathway within the CNS and is responsible for cognition, memory, learning, emotion, and mood. Because of its significant importance in widespread nervous system function, it is tightly regulated through multiple mechanisms, such as glutamate recycling, microglial interactions, and inflammatory pathways. Imbalance within the glutamatergic system has been implicated in a wide range of pathological conditions including neurodegenerative conditions, neuromuscular conditions, and mood disorders including depression.

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: Inflammation plays a pivotal role in the etiopathology of Major Depressive Disorder (MDD), at least in a subset of patients. It is crucial to first establish which specific inflammatory biomarkers are of clinical utility. Anti-cardiolipin antibody (aCL IgM) is an inflammatory marker that has the potential to be such a candidate but there are insufficient studies to confirm this potential.

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Esketamine is a novel treatment for treatment resistant depression (TRD) and was approved by the FDA in early 2019. It antagonizes the NMDA receptor providing rapid improvement in symptoms with a complex mechanism of action primarily mediated through glutamatergic activation. Significant barriers exist to widespread use of esketamine including durability of response, particularly in the maintenance phase.

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Article Synopsis
  • The study explored the role of oxidative stress in neurodegeneration, specifically looking at antioxidant enzyme gene expressions in patients with depressive disorders compared to healthy controls.
  • Researchers found that protein levels of PON2 and PON3 were significantly higher in depressed patients, while MPO levels were significantly lower, suggesting a complex relationship between these enzymes and depression.
  • However, the mRNA expressions of PON genes were not significantly different between groups, leading to the conclusion that these enzymes may not be reliable biomarkers for depression without further research.
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(1) Background: Only 60-70% of depressed patients respond to standard antidepressant treatments. Hence, it is essential to search for new, effective and safe therapies for unmet clinical needs of treatment-resistant depression (TRD). Agents targeting the components of the JAK-STAT signaling pathway have been shown to be relevant in immunology and are commonly used in the treatment of many hematological, rheumatological and dermatological diseases.

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Objective: The present study aimed at exploring the potential utility of autonomic regulation as a useful marker in the diagnostic differentiation between unipolar and bipolar depression.

Method: Respiratory sinus arrhythmia (RSA), low-frequency (LF) of heart rate variability, and systolic blood pressure (SBP) were assessed in patients with bipolar depression (31) and major depressive disorder (MDD=32), and in healthy controls (HCs=32). Since bipolar depressed subjects were maintained on specific medications to manage manic/hypomanic symptoms, we explored whether mood stabilizers (atypical antipsychotics and anticonvulsants or their combinations) could independently affect the physiological parameters.

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Aim: To determine the efficacy and safety of vitamin D supplementation in reducing depressive symptoms in women with type 2 diabetes (T2D), depression, and low vitamin D.

Methods: In this double-blind randomized active comparator-controlled trial, women with significant depressive symptoms as assessed by the Center for Epidemiologic Studies Depression (CES-D) scale received weekly oral vitamin D supplementation (50,000 IU) or an active comparator (5,000 IU) for 6 months. Assessments of vitamin D, 25-hydroxyvitamin D [25 (OH) D], and depression were measured at baseline, 3 months, and 6 months.

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Pharmacogenomic (PGx) testing is being increasingly recognized by clinicians as an essential tool to guide medication decisions for treatment of psychiatric illnesses. Extensive implementation of PGx testing, however, varies by setting and location. In this retrospective study, we reviewed charts from 592 patients diagnosed with a psychiatric disorder at the Loyola University Medical Center, for whom PGx testing was performed.

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Objectives: Serum or plasma levels of C-reactive protein (CRP) and high-sensitivity CRP (CRP) are widely used clinical markers of inflammation in other branches of medicine, whereas its clinical use in psychiatry has been limited to research studies. We aimed to assess the possibility of using CRP/CRP in psychiatric practice. This is a review and evaluation of various lines of evidence supporting the concept of CRP as a biomarker for psychiatric disorders in certain conditions.

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Article Synopsis
  • The coronavirus pandemic has negatively affected both physical and mental health worldwide, regardless of different country responses.
  • Mental health impacts can be categorized into those stemming from preventive measures like isolation and remote work, and those caused by the virus's direct effects on the nervous system.
  • The review focuses on how COVID-19 has influenced public mental health, examining social restrictions and comparing the psychological effects in countries like the USA, Australia, Poland, Taiwan, and Thailand.
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Background: Neuroinflammation plays a role in the pathophysiology of Bipolar Disorder Depression (BDD) and altered levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1, aka CCL2) have been reported. This study reports specifically on MCP-1 levels, as a potential marker of BDD and/or treatment response in patients receiving combination treatment with the cyclooxygenase-2 inhibitor, celecoxib (CBX).

Methods: In this randomized, 10-week, double-blind, two-arm, placebo-controlled study, 47 patients with treatment resistant BDD received either escitalopram (ESC) + CBX, or ESC + placebo (PBO).

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Background: Vascular Endothelial Growth Factor (VEGF) has been implicated in the neurotrophic model of depression. We explored the potential role of VEGF in the pathophysiology of bipolar depression and potential utility as a diagnostic or outcome predictive biomarker.

Methods: In a double-blind study, treatment-resistant bipolar depressed patients received Escitalopram and were randomized to receive add-on Celecoxib (26 participants) or Placebo (21 participants).

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Background: Adjunctive inflammatory modulation improved remission rates in treatment-resistant bipolar depression (TRBDD), but reliable biomarkers must be established to characterize the biosignature of TRBDD and the mechanisms underlying treatment response. In this molecular profiling study, we describe TRBDD and treatment response from the standpoint of interleukin-1 Beta (IL-1β) and KYN/TRP.

Methods: 47 TRBDD patients with moderately severe HAMD-17 scores were randomized to receive either escitalopram (ESC) (10 mg-40 mg daily dose range) + celecoxib (CBX) (200 mg twice daily), or ESC (10 mg-40 mg daily dose range) + placebo (PBO) (twice daily).

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Background: Grand rounds is a formal meeting at which physicians and trainees discuss excellence in medical care. Residents should participate in scholarly activity per Accreditation Council for Graduate Medical Education (ACGME). Consultation-Liaison (CL) psychiatry focuses on caring for patients presenting with psychiatric complications in general hospital.

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There is increasing recognition in the neurological and psychiatric literature of patients with so-called isolated psychotic presentations (ie, with no, or minimal, neurological features) who have tested positive for neuronal autoantibodies (principally N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies. Although these individuals are sometimes described as having atypical, mild, or attenuated forms of autoimmune encephalitis, some authors feel that that these cases are sufficiently different from typical autoimmune encephalitis to establish a new category of so-called autoimmune psychosis. We briefly review the background, discuss the existing evidence for a form of autoimmune psychosis, and propose a novel, conservative approach to the recognition of possible, probable, and definite autoimmune psychoses for use in psychiatric practice.

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