Publications

Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers

The gut-brain barrier in major depression

Major Differences in Neurooxidative and Neuronitrosative Stress Pathways Between Major Depressive Disorder and Types I and II Bipolar Disorder

Late or Delayed Induced or Spontaneous Puberty in Girls with Turner Syndrome Treated with Growth Hormone Does Not Affect Final Height

Although it has been well established that GH treatment increases final height (FH) in girls with Turner syndrome (TS), the optimal ages to start GH therapy and introduce estrogens for pubertal induction have not been defined.We evaluated retrospectively the influence of the age at onset of GH treatment and age at onset of puberty on FH of 186 adult TS women treated during childhood with GH.Puberty started spontaneously in 38 patients, and it was induced in 148 girls with ethinyl estradiol (mean ± SD starting dose, 66 ± 32 ng/kg•d).Patients with spontaneous or induced puberty were divided into quartiles on the basis of age at initiation of GH treatment (3-10, 10-12, 12-14, and 14-19 yr).FH was 151.7 ± 6.0 cm; there were no FH differences between patients with induced or spontaneous puberty, nor were there differences between the age quartiles.Puberty started earlier in the girls with spontaneous puberty than in those with induced puberty (12.4 ± 1.3 yr vs. 14.5 ± 1.9 yr; P < 0.0001).The age at onset of puberty was not related to FH. Pubertal growth was 15.4 ± 4.6 cm in the girls with spontaneous puberty and 8.6 ± 4.3 cm in the girls with induced puberty (P < 0.0001).We conclude that GH treatment results in a significant increase in FH in most TS girls.Under the conditions of GH treatment and induction of puberty that we have used, the age at start of GH treatment was not related to FH; in addition, late or delayed induced or spontaneous puberty did not affect FH.

Cell Death Pathways: a Novel Therapeutic Approach for Neuroscientists

In the first part, the following mechanisms involved in different forms of cell death are considered, with a view to identifying potential therapeutic targets: tumour necrosis factor receptors (TNFRs) and their engagement by tumour necrosis factor-alpha (TNF-α); poly [ADP-ribose] polymerase (PARP)-1 cleavage; the apoptosis signalling kinase (ASK)-c-Jun N-terminal kinase (JNK) axis; lysosomal permeability; activation of programmed necrotic cell death; oxidative stress, caspase-3 inhibition and parthanatos; activation of inflammasomes by reactive oxygen species and the development of pyroptosis; oxidative stress, calcium dyshomeostasis and iron in the development of lysosomal-mediated necrosis and lysosomal membrane permeability; and oxidative stress, lipid peroxidation, iron dyshomeostasis and ferroptosis. In the second part, there is a consideration of the role of lethal and sub-lethal activation of these pathways in the pathogenesis and pathophysiology of neurodegenerative and neuroprogressive disorders, with particular reference to the TNF-α-TNFR signalling axis; dysregulation of ASK-1-JNK signalling; prolonged or chronic PARP-1 activation; the role of pyroptosis and chronic inflammasome activation; and the roles of lysosomal permeabilisation, necroptosis and ferroptosis. Finally, it is suggested that, in addition to targeting oxidative stress and inflammatory processes generally, neuropsychiatric disorders may respond to therapeutic targeting of TNF-α, PARP-1, the Nod-like receptor NLRP3 inflammasome and the necrosomal molecular switch receptor-interacting protein kinase-3, since their widespread activation can drive and/or exacerbate peripheral inflammation and neuroinflammation even in the absence of cell death. To this end, the use is proposed of a combination of the tetracycline derivative minocycline and N-acetylcysteine as adjunctive treatment for a range of neuropsychiatric disorders.

Immune Aberrations in Obsessive-Compulsive Disorder: a Systematic Review and Meta-analysis

Brain antioxidant effect of mirtazapine and reversal of sedation by its combination with alpha-lipoic acid in a model of depression induced by corticosterone

International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder

Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω–3 polyunsaturated fatty acids (n–3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n–3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n–3 PUFAs in depression treatment; (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA &gt;2) are considered effective, and the recommended dosages should be 1–2 g of net EPA daily, from either pure EPA or an EPA/DHA (&gt;2:1) formula; (3) the quality of n–3 PUFAs may affect therapeutic activity; and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n–3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.

Seasonal variation in postdexamethasone cortisol values in depressed inpatients

Herpes Viruses, Cytokines, and Altered Hemostasis in Vital Exhaustion

Objective Infections with herpes viruses have been implicated in the pathogenesis of atherosclerosis. We tested the hypothesis that vital exhaustion (VE) is associated with multiple herpesvirus infections, such as herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus, and with an increase in pathogen burden (ie, the aggregated seropositivity to immunoglobulin G antibodies for herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus). In addition, we examined the association of VE and pathogen burden with measures of hemostasis and inflammation. Methods Blood samples were drawn from 29 men with VE and 30 male control subjects, all healthy and nonsmokers, to assess serological evidence of infection and measures of hemostasis and inflammation. Results VE is associated with a relatively high pathogen burden, altered hemostasis, and higher levels of cytokines, such as interleukin-6. Across all subjects, a relatively high pathogen burden was also associated with altered hemostasis but not with increased cytokine levels. The interaction of VE with pathogen burden revealed significant linear increases in measures of hemostasis and inflammation. Finally, immunoglobulin G antibody titer levels of individual herpesvirus infections were not associated with hemostatic measures or with cytokines. Conclusions We conclude that stress-related alterations in hemostasis and inflammation are not necessarily linked to one particular herpesvirus infection but rather to an increase in aggregated seropositivity to herpesvirus infections.

De gedaalde natural killer cell activiteit tijdens een depresssieve episode is geen kenmerk van meegemaakte levensgebeurtenissen

Summary Recently, some investigators have reported blunted natural killer cell activity (NKCA) in patients with major depression. In addition, there were some reports on negative relationships between NKCA and the occurence of negative life events. In order to replicate the above findings, the present study investigates NKCA and negative life events in 11 normal and 35 unipolar (minor, simple major, melancholic) depressed subjects. NKCA has been determined by all subjects. They completed the Questionnaire on Recently Experienced Events with scores on number and impact factor of events related to a) illness, b) working conditions, c) social relationships, d) housing problems, e) loss of possession. Depressed subjects reported higher scores on number and/or impact factor of events related to illness, social relationships and housing problems. In our investigation NKCA was significantly blunted in depressed subjects and, particularly in melancholies. So NKCA is negative correlated to the severity of depression. We were unable to detect any significant relationship between NKCA, and life events ( number of impact factors ), Our results do not corroborate the thesis that life events may affect immune function, as assessed by NKCA.

Validation of the Thai version of the short Boston Naming Test (T-BNT) in patients with Alzheimer’s dementia and mild cognitive impairment: clinical and biomarker correlates.

Objectives: Impairments in the Boston Naming Test (BNT), which measures confrontational word retrieval, frequently accompanies Alzheimer's dementia (AD) and may predict a more rapid progression of illness. This study aims to validate the Thai version of the 15-item BNT (T-BNT) in participants with AD and amnestic mild cognitive impairment (aMCI) and to externally validate the T-BNT using clinical and biomarker measurements.Methods: This cross-sectional study recruited patients with AD, diagnosed according to NINCDS-ADRDA criteria (n = 60), aMCI, diagnosed using the Petersen criteria (n = 60), and healthy controls (n = 62). We examined the internal consistency, concurrent and discriminant reliability of the T-BNT. We also assessed the Mini Mental State Examination (MMSE), the Verbal Fluency Test (VFT) and the Word List Memory (WLM) tests and measured apolipoprotein E polymorphism and serum levels of folic acid, high-density lipoprotein cholesterol (HDL) and triglycerides.Results: This study validated a 10-item T-BNT (10T-BNT), which yielded good internal consistency (0.92), a one-factor unidimensional structure, and adequate concurrent and discriminant validity. Lower scores on the 10T-BNT highly significantly predict AD, but not aMCI, and are positively associated with VFT and WLM test scores. Furthermore, lowered 10T-BNT scores are significantly associated with the ApoE4 allele, lower folate levels and an increased triglyceride/HDL-cholesterol ratio.Conclusions: This study validated the 10T-BNT and the total score on this scale is strongly associated with AD, impairments in semantic and episodic memory and biomarkers, which are known to modify memory via different mechanisms.

Omics-based depression and inflammation research

Omics-based depression and inflammation research Michael Maes, Cristiano Noto, Elisa Brietzke Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. IMPACT Research Center, Deakin University, Geelong, Australia. Graduate Program in Health Sciences, Health Sciences Center, Universidade Estadual de Londrina, Londrina, PR, Brazil. Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, SP, Brazil.

Inflammation markers in relation to cognition in a healthy aging population

Effects of Trazodone and Fluoxetine in the Treatment of Major Depression

It has been suggested that (1) the clinical efficacy of the heterocyclic antidepressant trazodone in depression may, in part, be attributed to its metabolite meta-chlorophenylpiperazine (mCPP); and (2) the enhancement of the efficacy of trazodone by the addition of fluoxetine, a selective serotonin reuptake inhibitor, may, in part, be ascribed to fluoxetine-induced plasma concentrations of trazodone. After a washout period of 10 days, 27 inpatients with major depression were treated with trazodone 100 mg/day (orally). One week later (T0), fluoxetine 20 mg/day, placebo, or pindolol 7.5 mg/day was added. Plasma concentrations of mCPP and trazodone were determined at T0 and 2 and 4 weeks later. Although placebo and pindolol had no significant effect on the plasma concentrations of mCPP and trazodone, there was a significant increase of the concentrations of these compounds associated with the combination of trazodone + fluoxetine. The results suggest that fluoxetine-induced increases in plasma mCPP and trazodone concentrations contribute to the clinical efficacy of the combination of fluoxetine + trazodone. It is suggested that desensitization of 5-HT2C receptor function by mCPP as well as fluoxetine may contribute to the antidepressant effects of this combination. (J Clin Psychopharmacol 1997;17:358-364).

‘Distant socializing,’ not ‘social distancing’ as a public health strategy for COVID-19

Social distancing, also referred to as physical distancing, means creating a safe distance of at least two meters (six feet) between yourself and others. This is a term popularized during the COVID-19 pandemic, as it is one of the most important measures to prevent the spread of this virus. However, the term 'social distancing' can be misleading, as it may imply that individuals should stop socializing. However, socializing in a safe context (i.e. over the phone, video-chat, etc.) is especially important during this time of crisis. Therefore, in this narrative review, we suggest the term 'distant socializing' as more apt expression, to promote physical distancing measures while also highlighting the importance of maintaining social bonds. Further, articles discussing the practice, implementation, measurement, and mental health effects of physical distancing are reviewed. Physical distancing is associated with psychiatric symptoms (such as anxiety and depression), suicidal ideation, and domestic violence. Further, unemployment and job insecurity have significantly increased during COVID-19, which may exacerbate these negative mental health effects. Governments, medical institutions, and public health bodies should therefore consider increasing mental health resources both during and after the pandemic, with a specific focus on frontline workers, COVID-19 survivors, and marginalized communities.

Effective Connectivity between Major Nodes of the Limbic System, Salience and Frontoparietal Networks Differentiates Schizophrenia and Mood Disorders from Healthy Controls

This study was conducted to examine whether there are quantitative or qualitative differences in the connectome between psychiatric patients and healthy controls and to delineate the connectome features of major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BD), as well as the severity of these disorders. Toward this end, we performed an effective connectivity analysis of resting state functional MRI data in these three patient groups and healthy controls. We used spectral Dynamic Causal Modeling (spDCM), and the derived connectome features were further subjected to machine learning. The results outlined a model of five connections, which discriminated patients from controls, comprising major nodes of the limbic system (amygdala (AMY), hippocampus (HPC) and anterior cingulate cortex (ACC)), the salience network (anterior insula (AI), and the frontoparietal and dorsal attention network (middle frontal gyrus (MFG), corresponding to the dorsolateral prefrontal cortex, and frontal eye field (FEF)). Notably, the alterations in the self-inhibitory connection of the anterior insula emerged as a feature of both mood disorders and SCZ. Moreover, four out of the five connectome features that discriminate mental illness from controls are features of mood disorders (both MDD and BD), namely the MFG→FEF, HPC→FEF, AI→AMY, and MFG→AMY connections, whereas one connection is a feature of SCZ, namely the AMY→SPL connectivity. A large part of the variance in the severity of depression (31.6%) and SCZ (40.6%) was explained by connectivity features. In conclusion, dysfunctions in the self-regulation of the salience network may underpin major mental disorders, while other key connectome features shape differences between mood disorders and SCZ, and can be used as potential imaging biomarkers.

Construction of a short version of the Montreal Cognitive Assessment (MoCA) rating scale using Partial Least Squares analysis

Abstract Background The Montreal Cognitive Assessment (MoCA) rating scale is frequently used to assess cognitive impairments in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Objectives The aims of this study are to a) evaluate the construct validity of the MoCA and its subdomains or whether the MoCA can be improved by feature reduction, and b) develop a short version of the MoCA (MoCA-Brief). Methods We recruited 181 participants, divided into 60 healthy controls, 61 aMCI, and 60 AD patients. Results The construct reliability of the original MoCA was not optimal and could be improved by deleting one subdomain (Naming) and five items, namely Clock Circle, Lion, Digit Forward, Repeat 2 nd Sentence, and Place, which showed inadequate loadings on the extracted latent vectors. To construct the MoCA-Brief, the reduced model underwent further reduction and feature selection based on model quality data of the outer models. We produced a MoCA-Brief rating scale comprising five items, namely Clock Time, Subtract 7, Fluency, Month, and Year. The first latent vector extracted from these five indicators showed adequate construct validity with an Average Variance Extracted of 0.599, composite reliability of 0.822, Cronbach’s alpha of 0.832 and rho_A of 0.833. The MoCA-Brief factor score showed a strong correlation with the total MoCA score (r=0.98, p&lt;0.001) and shows adequate concurrent, test-retest, and inter-rater validity. Conclusion The construct validity of the MoCA may be improved by deleting five items. The new MoCA-Brief rating scale deserves validation in independent samples and especially in other countries.