Processes In Psychiatric Disorders Research Articles

The Link between Social Anxiety and Peripheral Inflammatory Markers in Patients with Schizophrenia Diagnoses

Background: It exist increasing studies on the inflammatory process in psychiatric disorders, in which inflammation in schizophrenia (SZ) is questioned. Objective: assess the association between social anxiety (SA) and inflammation in patients with SZ, measuring primarily the neutrophil-to-lymphocyteratio (NLR) and secondarily the systemic immune-inflammation index (SII), monocyte-to-lymphocyteratio (MLR) and platelet-lymphocyte ratio (PLR). Methods: Across-sectional study. Results: Of the 82 patients who met the inclusion criteria, 59 patients had SA and observed a significant alteration in inflammation markers in patients with SZ, especially NLR

Four attachment-based categories of emotion regulation in adolescent psychic troubles.

Emotion regulation is altered in many psychiatric disorders in adolescence, but the understanding of mechanisms that underlie this alteration is still poor. The PERCEPT study explores alexithymia, empathy, facial emotion recognition (FER) and defence mechanisms in a sample of adolescents in psychiatric care (n = 61, 74% of girls, mean age = 15.03 y.o.), in relation with participants' attachment styles. Results revealed correlations between attachment dimensions and all of the emotion regulation variables, suggesting that attachment modalities have functional links with emotional regulation at its different levels: FER accuracy was inversely correlated with avoidant attachment, while affective empathy, difficulty in identifying feelings (alexithymia) and immature as well as neurotic defence mechanisms were positively correlated with anxious attachment. Moreover, attachment categories delineated distinct emotional perception profiles. In particular, preoccupied attachment included adolescents with the highest levels of facial emotion perception (sensitivity and accuracy) and of affective empathy, whereas detached attachment included adolescents with the lowest levels of these variables. Neurotic defence mechanisms and difficulty to identify feelings were correlated with preoccupied attachment; immature defence mechanisms and difficulty to describe feelings to others characterized fearful attachment. These results suggest that attachment categories underlie emotion regulation processes in psychiatric disorders in adolescence. Theoretical and clinical implications are discussed.

A Reflection Upon the Contribution of Retinal and Cortical Electrophysiology to Time of Information Processing in Psychiatric Disorders.

A Reflection Upon the Contribution of Retinal and Cortical Electrophysiology to Time of Information Processing in Psychiatric Disorders.

Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology

Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called “cytokine storm”. Both pro-inflammatory factors and viruses may cross the blood–brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson’s and Alzheimer’s disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.

The Possible Role of Telomere Length and Chemokines in the Aging Process: A Transdiagnostic Review in Psychiatry

Background:Psychiatric disorders are common, reaching a worldwide prevalence of 29.2%. They are associated with a high risk of premature death and with accelerated aging in clinical, molecular and neuroimaging studies. Recently, there is strong evidence suggesting a possible role of telomere length and chemokines in aging processes in psychiatric disorders.Objective:We aimed to review the literature on telomere length and chemokines and its association with early aging in mental illnesses on a transdiagnostic approach.Results:The review highlights the association between psychiatric disorders and early aging. Several independent studies have reported shorter telomere length and dysregulations on levels of circulating chemokines in schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorders, suggesting a complex interaction between these markers in a transdiagnostic level. However, studies have investigated the inflammatory markers and telomere shortening separately and associated with a particular diagnosis, rather than as a transdiagnostic biological feature.Conclusion:There is consistent evidence supporting the relationship between accelerated aging, telomere length, and chemokines in mental disorders, but they have been studied individually. Thus, more research is needed to improve the knowledge of accelerated senescence and its biomarkers in psychiatry, not only individually in each diagnosis, but also based on a transdiagnostic perspective. Moreover, further research should try to elucidate how the intricate association between the chemokines and telomeres together may contribute to the aging process in psychiatric disorders.

Delay Discounting as a Transdiagnostic Process in Psychiatric Disorders

Delay discounting is a behavioral economic index of impulsive preferences for smaller-immediate or larger-delayed rewards that is argued to be a transdiagnostic process across health conditions. Studies suggest some psychiatric disorders are associated with differences in discounting compared with controls, but null findings have also been reported. To conduct a meta-analysis of the published literature on delay discounting in people with psychiatric disorders. PubMed, MEDLINE, PsycInfo, Embase, and Web of Science databases were searched through December 10, 2018. The psychiatric keywords used were based on DSM-IV or DSM-5 diagnostic categories. Collected data were analyzed from December 10, 2018, through June 1, 2019. Following a preregistered Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol, 2 independent raters reviewed titles, abstracts, and full-text articles. English-language articles comparing monetary delay discounting between participants with psychiatric disorders and controls were included. Hedges g effect sizes were computed and random-effects models were used for all analyses. Heterogeneity statistics, one-study-removed analyses, and publication bias indices were also examined. Categorical comparisons of delay discounting between a psychiatric group and a control group. The sample included 57 effect sizes from 43 studies across 8 diagnostic categories. Significantly steeper discounting for individuals with a psychiatric disorder compared with controls was observed for major depressive disorder (Hedges g = 0.37; P = .002; k = 7), schizophrenia (Hedges g = 0.46; P = .004; k = 12), borderline personality disorder (Hedges g = 0.60; P < .001; k = 8), bipolar disorder (Hedges g = 0.68; P < .001; k = 4), bulimia nervosa (Hedges g = 0.41; P = .001; k = 4), and binge-eating disorder (Hedges g = 0.34; P = .001; k = 7). In contrast, anorexia nervosa exhibited statistically significantly shallower discounting (Hedges g = -0.30; P < .001; k = 10). Modest evidence of publication bias was indicated by a statistically significant Egger test for schizophrenia and at the aggregate level across studies. Results of this study appear to provide empirical support for delay discounting as a transdiagnostic process across most of the psychiatric disorders examined; the literature search also revealed limited studies in some disorders, notably posttraumatic stress disorder, which is a priority area for research.

Action-associated modulation of visual event-related potentials evoked by abstract and ecological stimuli.

This study investigated the influence of action-associated predictive processes on visual ERPs. In two experiments, we sought evidence for sensory attenuation (SA) indexed by ERP amplitude reductions for self-induced stimuli when compared to passive viewing of the same images. We assessed if SA is (a) present for both ecological and abstract stimuli (pictures depicting hands or checkerboards), (b) modulated by the degree of stimulus predictability (certain or uncertain action-effect contingencies), and (c) sensitive to laterality of hand movements (dominant or subdominant hand actions). We found reduced occipital responses in the early 77-90ms time interval (C1 component), irrespective of stimulus type, predictability, or the laterality of hand movements. However, the subsequent P1 component was increased (rather than reduced) for all action-associated stimuli. In addition, this P1 effect was influenced by the degree of stimulus predictability for ecological stimuli only. Finally, the posterior N1 component was not modulated by self-initiated actions. Overall, our findings indicate that movement-related predictive processes attenuate early visual responses. Moreover, we propose that amplitude modulations in the P1 time range reflect the interaction between expectation-based SA and attention-associated amplitude enhancements. These results can have implications for assessing the influence of action-associated predictions on visual processing in psychiatric disorders characterized by aberrant sensory predictions and alterations in hemispheric asymmetry, such as schizophrenia.

Cognitive impairment in first-episode drug-naïve patients with schizophrenia: Relationships with serum concentrations of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor

ObjectivesEvidence suggests that brain-derived neurotrophic factor (BDNF) and glial cell line -derived neurotrophic factor (GDNF) are important in the regulation of synaptic plasticity, which plays a key role in the cognitive processes in psychiatric disorders. Our work aimed at exploring the associations between serum BDNF and GDNF levels and cognitive functions in first-episode drug-naïve (FEDN) patients with schizophrenia. MethodsThe BDNF and GDNF levels of 58 FEDN patients and 55 age- and sex-matched healthy controls were measured and test subjects were examined using several neurocognitive tests including the verbal fluency test (VFT), the trail making test (TMT), the digit span test (DST), and the Stroop test. ResultsPatients performed significantly worse than controls in nearly all neurocognitive performances except the forward subscale part of the DST. BDNF levels were inversely correlated to TMT-part B scores and positively correlated to VFT-action in the FEDN group. GDNF levels showed a positive correlation with VFT-action scores and a negative correlation with TMT-part B scores of these patients. ConclusionCurrent data suggests that cognitive dysfunction widely exists in the early stages of schizophrenia. BDNF and GDNF may be jointly contributed to the pathological mechanisms involved in cognitive impairment in FEDN patients with schizophrenia.

Event-Related Potentials of Bottom-Up and Top-Down Processing of Emotional Faces.

Introduction:Emotional stimulus is processed automatically in a bottom-up way or can be processed voluntarily in a top-down way. Imaging studies have indicated that bottom-up and top-down processing are mediated through different neural systems. However, temporal differentiation of top-down versus bottom-up processing of facial emotional expressions has remained to be clarified. The present study aimed to explore the time course of these processes as indexed by the emotion-specific P100 and late positive potential (LPP) event-related potential (ERP) components in a group of healthy women.Methods:Fourteen female students of Alzahra University, Tehran, Iran aged 18–30 years, voluntarily participated in the study. The subjects completed 2 overt and covert emotional tasks during ERP acquisition.Results:The results indicated that fearful expressions significantly produced greater P100 amplitude compared to other expressions. Moreover, the P100 findings showed an interaction between emotion and processing conditions. Further analysis indicated that within the overt condition, fearful expressions elicited more P100 amplitude compared to other emotional expressions. Also, overt conditions created significantly more LPP latencies and amplitudes compared to covert conditions.Conclusion:Based on the results, early perceptual processing of fearful face expressions is enhanced in top-down way compared to bottom-up way. It also suggests that P100 may reflect an attentional bias toward fearful emotions. However, no such differentiation was observed within later processing stages of face expressions, as indexed by the ERP LPP component, in a top-down versus bottom-up way. Overall, this study provides a basis for further exploring of bottom-up and top-down processes underlying emotion and may be typically helpful for investigating the temporal characteristics associated with impaired emotional processing in psychiatric disorders.

Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders.

Preclinical Research Mitochondria are cell organelles crucial to the production of cellular energy. Several lines of evidence have indicated that mitochondrial dysfunction could be related to the pathophysiology of CNS diseases including bipolar disorder, major depressive disorder, and schizophrenia. These changes include impaired energy metabolism in the brain, co-morbidity with mitochondrial diseases, the effects of psychotropics on mitochondrial function, increased mitochondrial DNA (mtDNA) deletion in the brain, and association with mtDNA polymorphisms. Additionally, psychotropic drug treatments can alter energy metabolism and may affect mitochondrial processes. This review focuses on recent findings regarding the effects of antidepressants on mitochondrial processes in psychiatric disorders. Drug Dev Res 77 : 400-406, 2016. © 2016 Wiley Periodicals, Inc.

Effects of serotonin 2A/1A receptor stimulation on social exclusion processing

Social ties are crucial for physical and mental health. However, psychiatric patients frequently encounter social rejection. Moreover, an increased reactivity to social exclusion influences the development, progression, and treatment of various psychiatric disorders. Nevertheless, the neuromodulatory substrates of rejection experiences are largely unknown. The preferential serotonin (5-HT) 2A/1A receptor agonist, psilocybin (Psi), reduces the processing of negative stimuli, but whether 5-HT2A/1A receptor stimulation modulates the processing of negative social interactions remains unclear. Therefore, this double-blind, randomized, counterbalanced, cross-over study assessed the neural response to social exclusion after the acute administration of Psi (0.215 mg/kg) or placebo (Pla) in 21 healthy volunteers by using functional magnetic resonance imaging (fMRI) and resting-state magnetic resonance spectroscopy (MRS). Participants reported a reduced feeling of social exclusion after Psi vs. Pla administration, and the neural response to social exclusion was decreased in the dorsal anterior cingulate cortex (dACC) and the middle frontal gyrus, key regions for social pain processing. The reduced neural response in the dACC was significantly correlated with Psi-induced changes in self-processing and decreased aspartate (Asp) content. In conclusion, 5-HT2A/1A receptor stimulation with psilocybin seems to reduce social pain processing in association with changes in self-experience. These findings may be relevant to the normalization of negative social interaction processing in psychiatric disorders characterized by increased rejection sensitivity. The current results also emphasize the importance of 5-HT2A/1A receptor subtypes and the Asp system in the control of social functioning, and as prospective targets in the treatment of sociocognitive impairments in psychiatric illnesses.

Epigenetics and depressive disorders: a review of current progress and future directions.

Several broad lines of evidence support the involvement of epigenetic processes in neurodevelopment and psychiatric disorders. Epigenetic disruption also provides a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes. A review of the literature was performed with keywords 'depression', 'depressive disorder' or 'antidepressants' and 'DNA methylation', or 'epigenetics' in humans. Citations were limited to those written in English and published prior to July 2014. We present a summary of results to date. Most studies have focused on DNA methylation in various CNS or peripheral tissue, with almost universally small sample sizes. Although seven epigenome-wide association studies have now been reported, the majority of studies have used a candidate-gene approach. Three genes (SLC6A4, BDNF, NR3C1) have been investigated in more than one study, but replication of findings is generally lacking. Recent evidence provides insights to epigenetic processes in psychiatric disorders; however, replication is lacking and care must be taken in the interpretation of current findings. This applies to epigenetic epidemiology generally, which is subject to various limitations that no single approach can address in isolation. Due to limited focus of most depression studies to date, placing the findings within the broader context of mood disorder pathophysiology may prove challenging. However, identifying peripheral biomarkers for depressive disorder remains a tantalising possibility, especially given the potential for carefully-designed longitudinal studies with multiple biospecimens and ongoing advances in epigenetic technologies.

A Functional MRI Index of Spatial Context Effects in Vision

Coordination of brain activity, in the form of modulation of feedforward activity by stored information and expectations, occurs across domains of perception and cognition. A reliable and compelling example of this is size contrast in vision. This paper builds on a prior study to show that in healthy humans, the spread of activation in striate and extrastriate visual cortex during a context-modulated size perception task is dependent on the perceived size of the target image, not on the physical size of the retinal image. These data provide further evidence that early regions in visual cortex are modulated by top-down influences, and provide a framework for investigating visual context processing in psychiatric disorders where reduced sensitivity to visual contextual effects has been demonstrated in behavioral tasks.

Insomnia as a transdiagnostic process in psychiatric disorders.

Insomnia is a major public health concern, and is highly comorbid with a broad range of psychiatric disorders. Although insomnia has historically been considered a symptom of other disorders, this perspective has shifted. Epidemiological and experimental studies suggest that insomnia is related to the onset and course of several psychiatric disorders. Furthermore, several randomized controlled trials show that cognitive behavioral therapy for insomnia delivered to individuals who meet diagnostic criteria for insomnia and another psychiatric disorder improves the insomnia as well as the symptoms of the comorbid psychiatric disorder. Taken together, these results encompassing a range of methodologies have provided encouraging evidence and point toward insomnia as a transdiagnostic process in psychiatric disorders.

Neural substrates for altered reward prediction and decision making process in psychiatric disorders with serotonergic dysfunction

Neural substrates for altered reward prediction and decision making process in psychiatric disorders with serotonergic dysfunction

Using optogenetics to translate the “inflammatory dialogue” between heart and brain in the context of stress

Inflammatory processes are an integral part of the stress response and are likely to result from a programmed adaptation that is vital to the organism's survival and well-being. The whole inflammatory response is mediated by largely overlapping circuits in the limbic forebrain, hypothalamus and brainstem, but is also under the control of the neuroendocrine and autonomic nervous systems. Genetically predisposed individuals who fail to tune the respective contributions of the two systems in accordance with stressor modality and intensity after adverse experiences can be at risk for stress-related psychiatric disorders and cardiovascular diseases. Altered glucocorticoid (GC) homeostasis due to GC resistance leads to the failure of neural and negative feedback regulation of the hypothalamic-pituitary-adrenal axis during chronic inflammation, and this might be the mechanism underlying the ensuing brain and heart diseases and the high prevalence of co-morbidity between the two systems. By the combined use of light and genetically-encoded light-sensitive proteins, optogenetics allows cell-type-specific, fast (millisecond-scale) control of precisely defined events in biological systems. This method is an important breakthrough to explore the causality between neural activity patterns and behavioral profiles relevant to anxiety, depression, autism and schizophrenia. Optogenetics also helps to understand the "inflammatory dialogue", the inflammatory processes in psychiatric disorders and cardiovascular diseases, shared by heart and brain in the context of stress.

Soluble cytokine receptors (sIL-2Rα, sIL-2Rβ) induce subunit-specific behavioral responses and accumulate in the cerebral cortex and basal forebrain.

Soluble cytokine receptors are normal constituents of body fluids that regulate peripheral cytokine and lymphoid activity. Levels of soluble IL-2 receptors (sIL-2R) are elevated in psychiatric disorders linked with autoimmune processes, including ones in which repetitive stereotypic behaviors and motor disturbances are present. However, there is no evidence that sIL-2Rs (or any peripheral soluble receptor) induce such behavioral changes, or that they localize in relevant brain regions. Here, we determined in male Balb/c mice the effects of single peripheral injections of sIL-2Rα or sIL-2Rβ (0–2 µg/male Balb/c mouse; s.c.) on novelty-induced ambulatory activity and stereotypic motor behaviors. We discovered that sIL-2Rα increased the incidence of in-place stereotypic motor behaviors, including head up head bobbing, rearing/sniffing, turning, and grooming behavior. A wider spectrum of behavioral changes was evident in sIL-2Rβ-treated mice, including increases in vertical and horizontal ambulatory activity and stereotypic motor movements. To our knowledge, this is the first demonstration that soluble receptors induce such behavioral disturbances. In contrast, soluble IL-1 Type-1 receptors (0–4 µg, s.c.) didn't appreciably affect these behaviors. We further demonstrated that sIL-2Rα and sIL-2Rβ induced marked increases in c-Fos in caudate-putamen, nucleus accumbens and prefrontal cortex. Anatomical specificity was supported by the presence of increased activity in lateral caudate in sIL-2Rα treated mice, while sIL-2Rβ treated mice induced greater c-Fos activity in prepyriform cortex. Moreover, injected sIL-2Rs were widely distributed in regions that showed increased c-Fos expression. Thus, sIL-2Rα and sIL-2Rβ induce marked subunit- and soluble cytokine receptor-specific behavioral disturbances, which included increases in the expression of ambulatory activity and stereotypic motor behaviors, while inducing increased neuronal activity localized to cortex and striatum. These findings suggest that sIL-2Rs act as novel immune-to- brain messengers and raise the possibility that they contribute to the disease process in psychiatric disorders in which marked increases in these receptors have been reported.

Schmerzverarbeitung bei Borderline-Persönlichkeitsstörung, Fibromyalgie und Posttraumatischer Belastungsstörung

The authors review relevant experimental studies on pain perception and processing in psychiatric disorders with traumatic stress as an etiological factor. In borderline personality disorder, post-traumatic stress disorder, and fibromyalgia neurophysiological and neuropsychological patterns of pain processing appear to be different. Experimental studies in borderline patients show a desensitization of pain thresholds whereas patients with fibromyalgia show an opposite pattern, which could be explained by a central augmentation of pain processing. Furthermore, the authors outline methods to assess pain perception (peripheral and central) and describe the neurobiological mechanisms of pain processing, particularly the distinction between the sensory-discriminative lateral system and the affective-motivational medial system. Finally, suggestions for further research and implications for therapy are proposed.

GABA-based therapeutic approaches: GABAA receptor subtype functions

It is increasingly being appreciated that GABAA receptor subtypes, through their specific regional, cellular and subcellular localization, are linked to distinct neuronal circuits and consequently serve distinct functions. GABAA receptor subtype-selective drugs are therefore expected to provide novel pharmacological profiles. Receptors containing the alpha1 subunit mediate sedation and serve as targets for sedative hypnotics. Agonists selective for alpha2- and/or alpha3-containing GABAA receptors have been shown to provide anxiolysis without sedation in preclinical models, whereas inverse agonists selective for alpha5-containing GABAA receptors provide memory enhancement. Agonists selective for alpha3-containing GABAA receptors might be suitable for the treatment of deficits in sensorimotor processing in psychiatric disorders. Thus, a new pharmacology based on GABAA receptor subtype-specific actions is emerging.

Effects of dopaminergic and serotonergic manipulation on emotional processing: A pharmacological fMRI study

Recent neuroimaging studies have demonstrated abnormal central emotional processing in psychiatric disorders. The dopamine (DA) systems and serotonin (5-HT) systems are the main target of psychopharmacotherapy. DA D 2 receptor antagonists and selective serotonin reuptake inhibitors (SSRIs) are widely used in psychiatric practice. Investigating the effects of these drugs on emotional processing should lead to a better understanding of the pathophysiology and pharmacotherapy of neuropsychiatric disorders. We aimed to examine effects of dopaminergic and serotonergic manipulation on neural responses to unpleasant pictures in healthy volunteers using pharmacological fMRI. Thirteen healthy male subjects participated in a single-blind, randomized, placebo-controlled design study. Each subject participated in three fMRI sessions. In each session, participants were orally administered either 25 mg of sultopride or 50 mg of fluvoxamine or placebo prior to scanning, and neural responses to unpleasant and neutral pictures were recorded. Despite no significant differences being found in the subjective ratings of affective pictures across three sessions, compared to placebo, acute treatments of DA D 2 receptor antagonists and SSRIs commonly attenuated the amygdala activity, although both treatments had slightly different modulatory effects on other components of the neural circuit of emotional processing. This study has shown that even acute treatment of drugs that manipulate neurotransmitter systems could affect brain activation associated with emotional processing in human brain. At the same time, our findings suggest that pharmacological fMRI could be a powerful tool for investigating the neurophysiological properties of drugs targeting neuropsychiatric disorders.