The Impact of Mindfulness-Based Interventions on Objective Physiological Measures of Autonomic Function for Individuals With Medical Conditions: A Review of the Evidence.

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. METHODS: We conducted a review of the literature and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols. Studies were included if a) participants were diagnosed with a medical condition, b) an MBI was used, and c) objective pre/post measurements of autonomic nervous system function were collected. Medical conditions were included as a category for this review when a minimum of three articles met the criteria for inclusion. RESULTS: Ten articles met the criteria and included oncology, cardiac, and chronic pain conditions. Clinical recommendations were made based on the Clinical Practice Guideline Process Manual, 2017 Edition by the American Academy of Neurology. CONCLUSIONS: Based on level of evidence, only oncology met the criteria for "possibly effective." However, there was some evidence of the benefit of MBIs for all three medical conditions, based on individual study findings.

The Glutamatergic System in Treatment-Resistant Depression and Comparative Effectiveness of Ketamine and Esketamine: Role of Inflammation?

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. Major depressive disorder (MDD) is the most common mood disorder worldwide, has a high prevalence rate, and afflicts approximately 280 million people. While there are numerous treatments for the disease, 30-40% of patients are unresponsive to treatment and deemed treatment resistant; approximately another third experience only partial improvement (World Health Organization, Depression fact sheet [Internet], 2020). Esketamine, the S-enantiomer of ketamine, was approved by the Food and Drug Administration for treatment-resistant depression (TRD) in 2019 and has offered new hope to patients. It is the first treatment targeting the glutamatergic system through a complex mechanism. Numerous studies have implicated imbalance in the glutamatergic system in depression and treatment resistance. Esketamine and ketamine principally work through inhibition of the NMDA receptor, though more recent studies have implicated numerous other mechanisms mediating the antidepressant efficacy of these agents. These mechanisms include increase in brain-derived neurotrophic factor (BDNF), activation of mammalian target of the rapamycin complex (mTORC), and reduction in inflammation. Esketamine and ketamine have been shown to decrease inflammation in numerous ways principally through reducing pro-inflammatory cytokines (e.g., TNF-α, IL-6) (Loix et al., Acta Anaesthesiol Belg 62(1):47-58, 2011; Chen et al., Psychiatry Res 269:207-11, 2018; Kopra et al., J Psychopharmacol 35(8):934-45, 2021). This anti-inflammatory effect has also been shown to be involved in the antidepressive properties of both ketamine and esketamine (Chen et al., Psychiatry Res 269:207-11, 2018; Kopra et al., J Psychopharmacol 35(8):934-45, 2021).

A Review of the Global Impact of the COVID-19 Pandemic on Public Mental Health, with a Comparison Between the USA, Australia, and Poland with Taiwan and Thailand.

Coronavirus may have a negative impact not only on physical, but also on mental wellbeing. Despite the different approaches of countries to stop the spread of the virus and different infection rates, the dynamically developing pandemic has already affected the entire world. The consequences of the coronavirus for our mental health can be divided into those related to strategies for the prevention of infection, like isolation, quarantine, limitation of social contacts, and remote work, and those related to the direct impact of infection on our nervous system. This review aims to highlight the global effects of the Coronavirus Disease 2019 (COVID-19) pandemic on public mental health following social restrictions, to identify how infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have direct neurophysiological effects and to compare the impact on public mental health between the USA, Australia, and Poland with Taiwan and Thailand.

Effects of adjunctive inflammatory modulation on IL-1ß in treatment resistant bipolar depression.

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-1ß) 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). Plasma cytokine levels were measured in both treatment arms at baseline and week 8, and in a healthy control (HC) group of subjects (N = 43) once. A linear mixed model (LMM) was applied to evaluate whether clinical outcome is related to CBX and changes to biomarkers throughout treatment. A binary logistic regression model was formulated from this series to predict both the primary outcome of treatment response to CBX, and the secondary outcome of diagnosis of TRBDD using age, BMI, gender, and IL-1ß at baseline. RESULTS: Patients receiving ESC + CBX had 4.278 greater odds of responding (p = 0.021) with NNT = 3, and 15.300 times more likely to remit (p < 0.001) with NNT = 2, compared with ESC + PBO patients. Patient BMI (p = 0.003), baseline IL-1ß (p = 0.004), and baseline KYN/TRP (p = 0.001) were most predictive of TRBDD diagnosis. By Week 8, responders showed a downtrend in IL-1ß compared to non-responders in the ESC + CBX treatment arm. However, there was no statistical difference in the IL-1ß or KYN/TRP change after treatment between placebo and ESC + CBX group responders/non-responders (p = 0.239, and p = 0.146, respectively). While baseline IL-1ß was elevated in TRBDD compared to HC (p < 0.001), there was no difference in IL-1ß between treatment responders at Week 8 compared to HC (p = 0.067). CONCLUSIONS: Elevated IL-1ß and low KYN/TRP at baseline are components of the TRBDD molecular signature. CBX but not baseline IL-1ß or KYN/TRP predict treatment response. Change in IL-1ß and KYN/TRP did not predict treatment response.

Shared neurobiological pathways between type 2 diabetes and depressive symptoms: a review of morphological and neurocognitive findings.

Type 2 diabetes (T2D) patients are twice as likely to experience depressive symptoms than people without T2D, resulting in greater economic burden, worse clinical outcomes, and reduced quality of life. Several overlapping pathophysiological processes including hypothalamic-pituitary-adrenal axis hyperactivity, sympathetic nervous system activation, and elevated pro-inflammatory biomarkers are recognized as playing a role between T2D and depressive symptoms. However, other neurobiological mechanisms that may help to further link these comorbidities have not been extensively reviewed. Reduced neuroplasticity in brain regions sensitive to stress (e.g., hippocampus) may be associated with T2D and depressive symptoms. T2D patients demonstrate reduced neuroplasticity including morphological/volumetric abnormalities and subsequent neurocognitive deficits, similar to those reported by patients with depressive symptoms. This review aims to summarize recent studies on morphological/volumetric abnormalities in T2D and correlated neurocognitive deficits. Modifying factors that contribute to reduced neuroplasticity will also be discussed. Integrating reduced neuroplasticity with other biological correlates of T2D and depressive symptoms could enhance future therapeutic interventions and further disentangle the bidirectional associations between these comorbidities.

IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions.

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. Additionally, CXCL8 gene polymorphisms can alter IL-8 production, leading to potential differences in disease susceptibility, progression, and severity across populations. IL-8 levels vary among neuropsychiatric conditions, demonstrating sensitivity to psychosocial stressors and disease severity. IL-8 can be detected in blood circulation, cerebrospinal fluid (CSF), and urine, making it a promising candidate for a broad-spectrum biomarker. This review highlights the need for further research on the diverse effects of IL-8 and the associated implications for personalized medicine. A thorough understanding of its complex role could lead to the development of more effective and personalized treatment strategies for neuropsychiatric conditions.

Inflammation, heart disease, and depression.

Morbidity and mortality of cardiovascular disease is exceedingly high worldwide. Depressive illness afflicts a significant portion of the population worldwide. Epidemiological studies have confirmed the high co-morbidity between these two entities and the co-morbidity is bidirectional. Systems that contribute to this co-morbidity include the central and autonomic nervous systems, the neuroendocrine, immune, vascular and hematologic systems. Specific pathophysiologic factors include imbalance between the sympathetic and the parasympathetic systems, sympathoadrenal activation, hypothalamic-pituitary-adrenal axis activation, immune system dysregulation with release of pro-inflammatory cytokines and chemokines, platelet activation and hypercoaguability. Inflammation occurs in cardiac and cardiovascular pathology independent of the presence or absence of depression and in depression. Inflammation is closely associated with endothelial dysfunction which is a preamble to atherosclerosis and atherothrombosis. A likely common instigator underlying this co-morbidity is mental stress leading to sustained sympathetic overdrive and diminished vagal tone. Diminished vagal tone contributes to a pro-inflammatory status which affects neurotransmitter regulation, specifically serotonergic transmission. Stress hormones and certain pro-inflammatory substances released by macrophages and microglia upregulate the rate-limiting enzymes in the metabolic pathway of tryptophan. This results in a shunt in tryprophan metabolism away from serotonin formation and down the kynurenine pathway with resulting formation of neurotoxic metabolites.

Associations of BDNF/BDNF-AS SNPs with Depression, Schizophrenia, and Bipolar Disorder.

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. In contrast, BDNF antisense RNA (BDNF-AS) is linked to the regulation and control of BDNF, facilitating its suppression and contributing to neurotoxicity, apoptosis, and decreased cell viability. This review article aims to comprehensively overview the significance of single nucleotide polymorphisms (SNPs) in BDNF/BDNF-AS genes within psychiatric conditions, with a specific focus on their associations with depression, schizophrenia, and bipolar disorder. The independent influence of each BDNF/BDNF-AS gene variation, as well as the interplay between SNPs and their linkage disequilibrium, environmental factors, including early-life experiences, and interactions with other genes, lead to alterations in brain architecture and function, shaping vulnerability to mental health disorders. The potential translational applications of BDNF/BDNF-AS polymorphism knowledge can revolutionize personalized medicine, predict disease susceptibility, treatment outcomes, and guide the selection of interventions tailored to individual patients.

Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients.

Background: 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. Methods: Baseline measures of SIRI were compared between TRBDD and healthy controls (HC), and correlated with blood-based inflammatory cytokines, kynurenines, and growth factors. Post-treatment Hamilton Depression Rating Scale 17 (HAMD-17) total scores (clinical outcome) were modelled according to SIRI adjusting for demographics (including relevant interactions with SIRI), baseline depression, treatment arm, and treatment timepoint using multiple linear regression and robust linear mixed effects models. Results: Baseline SIRI did not distinguish TRBDD from HC groups. Baseline SIRI was significantly correlated with lower baseline MCP-1. The relationship between SIRI and HAMD-17 was significant at treatment week 8, in contrast to baseline. Finally, baseline SIRI predicted elevated post-treatment HAMD-17 scores, amongst patients with elevated depression scores at baseline. Significance: High pre-treatment SIRI may predict poorer depressive outcomes amongst TRBDD patients with baseline elevated depression.

Utilizing the Systemic Immune-Inflammation Index and Blood-Based Biomarkers in Association with Treatment Responsiveness amongst Patients with Treatment-Resistant Bipolar Depression.

(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. Our subsample with available complete blood count (CBC) data included 52 TRBDD subjects, randomized into an ESC + CBX, (n = 29), an ESC + PBO arm (n = 23), and an HC group (n = 32). SII was calculated from the CBC with differential (SII = platelets x neutrophils/lymphocytes) at baseline and end of treatment (8 weeks). Blood inflammation biomarkers, growth factors, and kynurenine metabolites were determined at both timepoints. Depressive symptom severity was the primary outcome, using the HAMD-17 rating scale score to quantitate treatment response and remission rates. (3) Results: Baseline SII did not discriminate TRBDD from HC, nor was it associated with HAMD-17 score at any timepoint, although it was significantly associated with lower baseline VEGF (p = 0.011) and higher week 8 levels of IL1-ß (p = 0.03) and CRP (p = 0.048). Post-treatment HAMD-17 was not independently predicted using baseline SII unless an interaction with age was present (p = 0.003 was included), even after relevant adjustments. A similar effect was seen with baseline neutrophils. (4) Conclusions: While SII was not an independent predictor of treatment outcome, elevated baseline SII was a predictor of poor treatment response amongst older patients with TRBDD.

Single nucleotide polymorphisms in C-reactive protein (CRP) predict response to adjunctive celecoxib treatment of resistant bipolar depression.

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., 2020). Methods: Study design, clinical findings, and CRP blood levels have been reported previously (Halaris et al., 2020; Edberg et al., 2018). In this follow-up study we extracted DNA from blood cells collected at baseline. Genome-wide genotyping was performed for all subjects using the Infinium Multi-Ethnic Global-8 v1.0 Kit. Based on reports in the literature indicating possible associations with psychiatric conditions, ten previously reported CRP gene polymorphisms were evaluated in a preliminary analysis. We focused on rs3093059 and rs3093077 were in complete LD. Carriers were defined as those possessing at least one C allele for rs3093059, or at least one G allele for rs3093077. Additionally, we determined blood levels of the medications administered. Results: Non-carriers of rs3093059 and rs3093077 had significantly lower baseline CRP blood levels than carriers (p = 0.03). Increased rates of HAM-D17 response (p = 0.21) and remission (p = 0.13) and lower PSS-14 scores (p = 0.13) were observed in non-carriers among subjects receiving celecoxib but they did not reach statistical significance. When examining all subjects, nominally significant associations between carrier-status and remission (p = 0.04) and PSS-14 scores (p = 0.04) were observed after correcting for treatment arm. Non-carriers receiving celecoxib had the highest rates of response and remission, and the lowest stress scores. Conclusions: Carriers of the CRP SNPs may have higher baseline CRP levels, although non-carriers appear to benefit more from celecoxib co-therapy. Determination of the carrier status in conjunction with pretreatment blood CRP level measurement may contribute to personalized psychiatric practice, but replication of the present findings is needed.

The Possible Role of NLRP3 Inflammasome in Depression and Myocardial Infarction Comorbidity.

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 (hsCRP) 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. The patients were assessed using the Structured Clinical Interview for DSM-5 Disorders-Clinician Version during their 1-4-day-long hospitalization and were divided into two groups: with and without comorbid depression. Blood samples for the determination of NLRP3, interleukin-18 (IL-18), interleukin-1ß (IL-1ß), and hsCRP levels were analyzed using ELISA. NLRP3, IL-1ß, IL-18, and hsCRP levels were significantly higher in myocardial infarction patients compared to the healthy group (p = 0.02, p < 0.001, p < 0.001, and p < 0.001, respectively). No significant difference was found between the myocardial groups with and without depression. However, in the logistic regression analysis, the NLRP3 variable in myocardial infarction patients was found to have a significant contribution to the likelihood of depression (p = 0.015, OR = 1.72, and CI = 1.11-2.66). The likelihood of depression is associated with increasing NLRP3 levels in myocardial infarction patients. However, this potential role should be further explored in a larger sample.

Adjunctive dopaminergic enhancement of esketamine in treatment-resistant depression.

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. Since it must be administered in combination with an oral antidepressant, investigating appropriate treatments to be given concomitantly may further improve outcomes and response duration. Specifically, due to dysfunction in dopaminergic pathways in many patients with MDD and TRD, addition of a prodopaminergic agent, such as bupropion, may provide additional benefit and durability of response. Historically, the addition of a dopaminergic agent to traditional treatment (e.g., SSRI, SNRI) has been shown to improve response in TRD. While we have anecdotal evidence to support adjunctive dopaminergic enhancement of esketamine response, robust data are limited. There are case reports that exhibit efficacy with the use of a MAO-I in combination with ketamine supporting at least in part a dopaminergic component. Additionally, there is mechanistic rationale for the use of dopaminergic agents with a NMDA antagonist. This includes co-localization of NMDA and dopamine receptors as well as increased glutamatergic signaling due to dopamine-induced phosphorylation of AMPAR. Recently, AXS-05, an oral combination of dextromethorphan and bupropion, has shown promise in both MDD and TRD clinical trials highlighting the potential validity of this mechanism. This paper describes how dopaminergic enhancement may increase efficacy and durability of response with esketamine, encouraging further research into this treatment option.

C-reactive protein as a potential biomarker in psychiatric practice: Are we there yet?

OBJECTIVES: Serum or plasma levels of C-reactive protein (CRP) and high-sensitivity CRP (hsCRP) 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/hsCRP 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. METHODS: We searched the literature for studies which assessed CRP/hsCRP levels in various psychiatric disorders. RESULTS: The accumulating evidence from large studies and meta-analyses allows us to understand the role of CRP in major psychiatric disorders and increase our understanding of specific symptoms and subtypes of disorders. CRP may be considered a 'psychiatric biomarker' which can alert clinicians about neuroinflammation, adverse effects of medications, cardiometabolic status, co-morbidities, and may also predict clinical outcomes and guide optimal treatment.selection. CONCLUSION: Although the underlying pathophysiological role of CRP and hsCRP is still elusive and the association between CRP and psychiatric disorders is inconsistent, CRP holds promise to become a psychiatric biomarker.

Cardiolipin Antibody: A Potential Biomarker for Depression.

Background: 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. Objective: To investigate the baseline titer level and the longitudinal progression of plasma titers of aCL IgM in MDD subjects receiving antidepressant therapy in comparison to healthy control (HC) subjects; to determine if changes in aCL IgM plasma titers correlate to changes in depressive symptoms; and, to ascertain if baseline aCL IgM plasma titers could predict treatment response. Methods: Forty-eight medically healthy outpatients diagnosed with MDD were enrolled in one of two groups in two sequentially conducted clinical trials. In Group-E, patients received a 12-week regimen of escitalopram (n = 20). Those in Group-Q received a 12-week regimen of quetiapine (n = 28). The main outcome measure was plasma aCL IgM titers, the Hamilton Rating Scale for Depression (HAM-D17) and the Hamilton Rating Scale for Anxiety (HAM-A). There were 16 HC subjects. Results: When Group-Q and Group-E participants were grouped together (n = 48), MDD subjects had an elevated baseline aCL IgM (19.9 µg/mL) compared to HC subjects (8.32 µg/mL) (p = 0.006). aCL IgM correlated significantly with HAM-D17 scores at baseline in MDD subjects (p = 0.0185, r = 0.296). Examining the individual groups, Group-Q MDD patients had a significantly elevated baseline aCL IgM (p = 0.008) while Group-E's MDD patients did not. On the other hand, only Group-E MDD patients showed a significant correlation at baseline between aCL IgM and HAM-A score (p = 0.0392, r = 0.4327); they also showed a significant inverse correlation between week 12 HAMD-17 Item #10 (Anxiety, Psychic) and week 12 aCL IgM titer (p = 0.0268, r = -0.5516). Conclusions: MDD patients had significantly higher plasma titers of aCL IgM when compared to HC subjects. Moreover, at baseline, the higher the aCL IgM titer, the higher the depression severity, as measured by HAMD-17 score. However, this study did not demonstrate that aCL IgM titers changed significantly throughout a 12-week course of antidepressant treatment and revealed no correlation between changes in depressive symptoms and changes in aCL IgM titers. Baseline aCL IgM could not predict treatment response. We conclude that, despite lacking predictive ability as regards treatment response, plasma titers of aCL IgM have a diagnostic potential in MDD that necessitates further exploration.

Expression of PON1, PON2, PON3 and MPO Genes in Patients with Depressive Disorders.

Background: Taking into account the role of oxidative stress in neurodegeneration, we sought to evaluate the expression of genes for select enzymes with antioxidant properties (paraoxonases PON1, PON2 and PON3 and myeloperoxidase MPO) at the mRNA and protein levels in patients with depressive disorders. We further sought to determine the impact of oxidative stress in the etiopathogenesis of this group of mood disorders. Methods: A total of 290 subjects (190 depressed patients, 100 healthy controls) took part in the study. Sociodemographic and clinical data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Venous blood was collected. RT-PCR was used to assess gene expression at the mRNA level, while enzyme-linked immunosorbent assay (ELISA) was used to assess gene expression at the protein level. Results: The expression of the PON2 and PON3 genes at the protein level was significantly higher in depressive patients than in healthy controls. mRNA expression of the PON1, PON2 and PON3 genes was slightly higher in patients with depressive disorders than in the control group, however, this relationship was not statistically significant. On the other hand, the expression of the MPO gene at both mRNA and protein levels was significantly lower in patients with depressive disorder than in the control group. Conclusions: Our results are not in agreement with many studies on enzymes involved in maintaining oxidative balance. Our findings may not support the utility of paraoxonases (PON) or myeloperoxidase (MPO) as promising biomarker candidates of depression pending larger and well controlled studies.

Autonomic Measures in Differentiating Depressive Disorders: A Potential AID.

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. Results: When the autonomic measures were analyzed by a multivariate analysis of variance (MANCOVA), after controlling for BMI, the combination of variables (RSA, LF, SBP) discriminated patients with bipolar depression and MDD from HC (F(6, 178)=3.036, p=0.007, Λ=0.823, partial η2=0.093). In any case, we cannot exclude that mood stabilizers might have affected SBP values in the bipolar group. To deconstruct this multivariate effect, pairwise ANOVAs and discriminant analyses contrasted groups and documented that RSA was the primary variable distinguishing the groups. Discriminant function analyses showed that RSA had a significant discriminating weight between bipolar depressed patients and HC subjects (p<0.0005). By contrast, RSA showed a trend towards the statistical significance in discriminating between bipolar depression and MDD patients (p=0.06). Conclusions: The assessment of RSA and SBP in outpatient settings might be helpful in the differential diagnosis of affective disorders.

Is the JAK-STAT Signaling Pathway Involved in the Pathogenesis of Depression?

(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. The aim of this study was to investigate the role of elements of the JAK-STAT signaling pathway in the etiopathogenesis of depressive disorders. (2) Methods: A total of 290 subjects took part in the study (190 depressed patients, 100 healthy controls). Sociodemographic data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). The gene expression at the mRNA protein levels of JAK (JAK1-JAK3) and STAT (STAT1-STAT5) was assessed by using RT-PCR and ELISA. (3) Results: Increased expression of JAK3 and decreased expression of STAT1 were observed in the group of depressed patients. (4) Conclusions: Further studies are necessary to determine whether moderation of the JAK-STAT signaling pathways is involved in the treatment of depression.