Psychiatric comorbidities in children and adolescents with chronic urticaria.

BACKGROUND: Chronic urticaria (CU) has been shown to impact patients' quality of life negatively and may coexist with psychiatric disorders. We systematically reviewed the published evidence of comorbid psychiatric disorders in children and adolescents with CU. METHODS: A systematic review of studies published until February 2022 in PubMed, Google Scholar, and Scopus was performed. An a priori set of inclusion criteria was predefined for the studies to be included: (1) clear distinction between urticaria and other allergies; (2) precise distinction between acute and CU; (3) participants younger than 18 years old, exclusively; (4) use of appropriate standardized questionnaires, psychometric tools, and standard diagnostic nomenclature for the mental health and behavioral disorders diagnosis; and (5) manuscripts written or published in the English language. RESULTS: Our search identified 582 potentially relevant papers. Only eight of them satisfied the inclusion criteria. Quantitative meta-analysis was not deemed appropriate, given the lack of relevant randomized control trials, the small number of relevant shortlisted, the small sample size of the patients included in each study, and the remarkable heterogeneity of the studies' protocols. CONCLUSIONS: The included studies suggest an increased incidence of psychopathology among children and adolescents with CU as opposed to healthy age-matched individuals, but the data are scarce. Further research is required to clarify whether psychopathology is just a comorbid entity, the cause, or the consequence of CU. Meanwhile an interdisciplinary collaboration between allergists/dermatologists and psychiatrists is expected to substantially minimize CU burden and improve patients' quality of life.

Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression: The FOUR-D Randomized Noninferiority Clinical Trial.

Importance: Treatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in TRD. Theta burst stimulation (TBS), a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right continuous TBS for only 4 minutes. Objective: To establish the effectiveness and tolerability of TBS compared with standard rTMS in older adults with TRD. Design, Setting, and Participants: In this randomized noninferiority trial with open treatment and blinded assessors, recruitment occurred between December 2016 and March 2020. The trial was conducted at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada and included outpatients 60 years and older with a diagnosis of depression, moderate severity, and nonresponse to 1 or more antidepressant trial of adequate dosage and duration or intolerance of 2 or more trials. Interventions: Participants were randomized to receive a course of 4 to 6 weeks of either bilateral standard rTMS or TBS. Main Outcomes and Measures: The primary outcome measure was change in Montgomery-Åsberg Depression Rating Scale; secondary outcome measures included the 17-item Hamilton Rating Scale for Depression, Quick Inventory of Depressive Symptomatology (16-item) (self-report), and dropout rates. A noninferiority margin of 2.75 points was used for the primary outcome. All participants who attained the primary completion point of 4 weeks were analyzed. Results: A total of 87 participants (mean [SD] age, 67.1 [6.7] years; 47 [54.0%] female) were randomized to standard bilateral rTMS and 85 (mean [SD] age, 66.3 [5.3] years; 45 [52.9%] female) to TBS, of whom 85 (98%) and 79 (93%) were assessed for the primary outcome, respectively, whereas tolerability was assessed in all randomized participants. In the rTMS group, 4 (4.6%) were American Indian, reported other, or preferred not to answer; 5 (5.8%) were Asian; and 78 (89.7%) were White. In the TBS group, 6 (7.1%) were Asian, 2 (2.4%) were Black or reported other, and 77 (90.3%) were White. Mean (SD) Montgomery-Åsberg Depression Rating Scale total scores improved from 25.6 (4.0) to 17.3 (8.9) for rTMS and 25.7 (4.7) to 15.8 (9.1) for TBS (adjusted difference, 1.55; lower 95% CI -0.67), establishing noninferiority for TBS. The all-cause dropout rates were relatively similar between groups (rTMS: 2 of 87 [2.3%]; TBS: 6 of 85 [7.1%]; P = .14; χ2 = 2.2). Conclusions and Relevance: In older adults with TRD, bilateral TBS compared with standard bilateral rTMS achieved noninferior reduction in depression symptoms. Both treatments had low and similar dropout rates. Using TBS rather than rTMS could increase access to treatment several-fold for older adults with TRD. Trial Registration: ClinicalTrials.gov Identifier: NCT02998580.

Further Understanding of Neuro-Immune Interactions in Allergy: Implications in Pathophysiology and Role in Disease Progression.

The complicated interaction between the central and the autonomic (sympathetic, parasympathetic, and enteric) nervous systems on the one hand and the immune system and its components, on the other hand, seems to substantially contribute to allergy pathophysiology, uncovering an under-recognized association that could have diagnostic and therapeutic potentials. Neurons connect directly with and regulate the function of many immune cells, including mast cells, the cells that have a leading role in allergic disorders. Proinflammatory mediators such as cytokines, neurotrophins, chemokines, and neuropeptides are released by immune cells, which stimulate sensory neurons. The release of neurotransmitters and neuropeptides caused by the activation of these neurons directly impacts the functional activity of immune cells and vice versa, playing a decisive role in this communication. Successful application of Pavlovian conditioning in allergic disorders supports the existence of a psychoneuroimmunological interplay in classical allergic hypersensitivity reactions. Activation of neuronal homeostatic reflexes, like sneezing in allergic rhinitis, coughing in allergic asthma, and vomiting in food allergy, offers additional evidence of a neuroimmunological interaction that aims to maintain homeostasis. Dysregulation of this interaction may cause overstimulation of the immune system that will produce profound symptoms and exaggerated hemodynamic responses that will lead to severe allergic pathophysiological events, including anaphylaxis. In this article, we have systematically reviewed and discussed the evidence regarding the role of the neuro-immune interactions in common allergic clinical modalities like allergic rhinitis, chronic rhinosinusitis, allergic asthma, food allergy, atopic dermatitis, and urticaria. It is essential to understand unknown - to most of the immunology and allergy experts - neurological networks that not only physiologically cooperate with the immune system to regulate homeostasis but also pathogenetically interact with more or less known immunological pathways, contribute to what is known as neuroimmunological inflammation, and shift homeostasis to instability and disease clinical expression. This understanding will provide recognition of new allergic phenotypes/endotypes and directions to focus on specialized treatments, as the era of personalized patient-centered medicine, is hastening apace.

Repetitive transcranial magnetic stimulation in patients with borderline personality disorder: A systematic review.

The literature on the application of repetitive transcranial magnetic stimulation (rTMS) in Borderline Personality Disorder (BPD) is unclear, even though its neuromodulatory effects on underlying neural circuitry involved in BPD symptoms suggest that it could be a potential treatment option. We sought to review the evidence on rTMS as a treatment option in BPD. PubMed (for Medline database), Google Scholar, and Scopus were systematically searched following the PRISMA guidelines for studies of any design examining the application of the rTMS treatment in adult patients with precise and primary diagnosis of BPD written in the English language. The systematic review has been registered on PROSPERO (CRD42020215927). Forty one records were screened, and eight fulfilled inclusion criteria (total of 63 patients). The existing studies suggest that rTMS is a well-tolerated treatment in patients with BPD. Double-blind randomized controlled studies are necessary to help elucidate the effects of rTMS in the different symptoms in BPD and establish efficacy and the best cortical targets and stimulation protocols. Longitudinal studies that combine evidenced based psychotherapy with rTMS may be a future line of investigation that could potentially improve outcomes for this population.

The Vision of Blindness-Sight Versus Insight: A Case Report and Literature Review of Self-enucleation (Oedipism).

Self-enucleation or "Oedipism" is a rare ophthalmic and psychiatric emergency. Given the severity of its consequences, it requires proper medical management and that clinicians understand and be aware of the psychiatric presentation. Important clinical considerations include identification of various etiologies leading to self-enucleation, awareness of possible complications, and provision of appropriate care. We present a case of bilateral self-enucleation by a young male patient in the context of his first episode of psychosis and review the literature on this clinical entity. Ocular damage interferes significantly with activities of daily living and is associated with decreased quality of life so that identifying risk factors is of major importance to prevent this dangerous behavior.

Accelerated Intermittent Theta Burst Stimulation in Late-Life Depression: A Possible Option for Older Depressed Adults in Need of ECT During the COVID-19 Pandemic.

OBJECTIVE: Electroconvulsive therapy (ECT) is an essential psychiatric service with an important role in treating older adults with severe or treatment-resistant depression. During the COVID-19 pandemic, ECT services have be constrained by infection control measures. We report a case of a 66-year-old female patient with a severe major depressive episode who had previously responded to right unilateral ECT and was treated with two modified accelerated intermittent theta-burst stimulation (aiTBS) protocols. METHODS: The two aiTBS courses consisted of eight daily sessions over five consecutive days, followed by gradual tapering, using 1,800 pulses per session pre-COVID-19 (first course), and 600 pulses per session during the pandemic (second course). RESULTS: Moderate to severe baseline depressive symptoms reached remission levels after both courses. CONCLUSION: The 600-pulses aiTBS treatment protocol reported here warrants further study and evaluation, but may be a potential option in cases where older adults with severe depressive symptoms cannot access ECT during the COVID-19 pandemic.

"A systematic review of non-invasive neurostimulation for the treatment of depression during pregnancy".

BACKGROUND: Antidepressant use in pregnancy is associated with high levels of decision-making difficulty for patients, and psychotherapy may not be effective for severe symptoms. Alternative treatment options are needed. We conducted a systematic review of the clinical effects and tolerability of non-invasive neurostimulation: repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), trigeminal nerve stimulation (TNS), and transcutaneous vagus nerve stimulation (tVNS) for the treatment of antenatal depression. METHODS: We searched PubMed, Google Scholar and Scopus for published articles in English (1990 to June 2019). Two reviewers reviewed full-text articles, assessed quality, and extracted data on maternal psychiatric, pregnancy and neonatal outcomes. RESULTS: Of 565 articles, 21 met inclusion criteria: two RCTs (1 rTMS; 1 tDCS), four open-label studies (3 rTMS; 1 tDCS), three case series (3 rTMS), and twelve case reports (9 rTMS; 1 tDCS; 1 tACS; 1 TNS). In all but one published study (1 rTMS), non-invasive neurostimulation resulted in either response or remission of antenatal depression. Minor maternal side effects were reported in rTMS and tDCS studies, but not in other modalities. Fetal adverse effects were not reported in any intervention. A small proportion of participants dropped out of treatment (rTMS, tDCS). LIMITATIONS: Very few randomized trials have been conducted and there is significant heterogeneity in the parameters of the modalities that have been studied. CONCLUSIONS: Non-invasive neurostimulation holds promise as a potentially effective and feasible alternative treatment for antenatal depression. Strategies to enhance recruitment of pregnant women into non-invasive neurostimulation trials that have longitudinal follow-up are needed.

Psychological Stress and Chronic Urticaria: A Neuro-immuno-cutaneous Crosstalk. A Systematic Review of the Existing Evidence.

PURPOSE: It has been observed that certain patients with chronic spontaneous or idiopathic urticaria (CSU/CIU) have a personal history of a significant stressor before urticaria onset, while the prevalence of any psychopathology among these patients is significantly higher than in healthy individuals. Research has confirmed that skin is both an immediate stress perceiver and a target of stress responses. These complex interactions between stress, skin, and the nervous system may contribute to the onset of chronic urticaria. This systematic review investigated the association between CSU/CIU and neuroimmune inflammation with or without evidence of co-existing psychological stress from in vivo and ex vivo studies in human beings. METHODS: PubMed and Scopus were searched to September 2019 for reports in human beings describing neuroimmune inflammation, stress, and CSU/CIU. A comprehensive search strategy was used that included all the relevant synonyms for the central concept. FINDINGS: A total of 674 potentially relevant articles were identified. Only 13 satisfied the predefined inclusion criteria and were included in the systematic review. Five of these 13 studies evaluated the correlation between CSU/CIU, stress, and neuro-immune-cutaneous factors, while the remaining 8 focused on the association between CSU/CIU and these factors without examining any evidence of stress. IMPLICATIONS: The complex neuro-immune-cutaneous model that involves numerous neuropeptides and neurokinins, inflammatory mediators and cells, hypothalamic-pituitary-adrenal axis hormones, and the skin may better explain the underlying pathophysiological mechanisms involved in the onset of urticaria. In addition, the elevated psychological stress level that has been closely related to CSU/CIU could be attributed to the imbalance or irregularity of this neuro-immune-cutaneous circuit. It is still unclear and must be further investigated whether any psychological stress results in or triggers CSU/CIU onset on top of a preexisting neuroimmune dysregulation. Nevertheless, new psycho-phenotypic or neuro-endotypic CSU/CIU subsets should be considered as the era of personalized treatment strategies emerges. A better understanding of CSU/CIU pathophysiology and consideration of the patient as a whole is vital for identifying targets for new potential treatment options.

Psychiatric comorbidity in chronic urticaria patients: a systematic review and meta-analysis.

BACKGROUND: Dermatological illness can affect the quality of life and may coexist with psychiatric disorders. OBJECTIVE: The aim of this review was to systematically evaluate the published evidence of any psychiatric disorders that may coexist with chronic urticaria (CU) and any effect psychiatric interventions may have on CU. METHODS: Following the Cochrane guidance, we conducted a systematic literature search using web-based search engines provided by PubMed (for Medline database), Google Scholar and Scopus for studies that have investigated the existence of psychiatric comorbidity in patients with CU. To be included, a study had to possess features, such as: (1) distinction between chronic urticaria and allergic conditions, (2) direct collection of diagnostic psychiatric data by using clinical interview and standardized questionnaires, (3) International Classification of Disorders criteria or the Diagnostic and Statistical Manual of Mental Disorders criteria for the diagnosis of mental disorders, and (4) manuscripts written or published in the English language. Unpublished research and research in progress were not included. All the eligible studies were scrutinized for any reported psychiatric interventions that had any effect on CU. The systematic review has been registered on PROSPERO (registration number CRD42019122811) and was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). RESULTS: Twenty-five studies were identified. Almost one out of three CU patients have at least one underlying psychiatric disorder. None of the studies clarified whether the psychiatric disorders pre-existed the CU onset, and no association was found between CU severity and duration, and psychological functioning. Only one case report and two case series mentioned that treatment of psychiatric disorders with either anti-depressants, anti-anxiety drugs or psychological interventions might result in improvement of urticaria. CONCLUSIONS: Patients with CU frequently experience psychiatric disorders. This highlights the need for a multidisciplinary therapeutic approach involving prompt recognition and management of any potential psychiatric disorder in addition to urticaria treatment. Further studies are needed to assess whether psychiatric disorders coexist with CU independently or follow urticaria onset and whether any psychological or psychiatric intervention may help in CU control.