Fetal Sex as Moderating Factor for the Relationship Between Maternal Childhood Trauma and Salivary Kynurenic Acid and Tryptophan in Pregnancy: A Pilot Study.

Traumatic experiences and fetal development influence tryptophan (TRP) and its neuroactive byproduct, kynurenic acid (KYNA). Maternal TRP metabolite levels during pregnancy vary by fetal sex, with higher concentrations in mothers carrying male fetuses. This pilot study aimed to explore the relationship between offspring sex, maternal childhood trauma, and maternal salivary KYNA and TRP levels during pregnancy. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine KYNA and TRP levels in maternal saliva samples collected from 35 late-pregnancy participants. Maternal childhood trauma was assessed using the Childhood Trauma Questionnaire, including subscales for emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. Among mothers pregnant with boys, salivary KYNA significantly correlated with physical and emotional neglect, and salivary TRP with emotional neglect. No significant correlations were found in mothers who delivered female offspring. Significant associations of childhood trauma and offspring sex were found for salivary KYNA but not TRP concentrations. Mothers with higher trauma levels who delivered boys exhibited higher levels of salivary KYNA compared to those with lower trauma levels. Moreover, mothers with higher trauma levels who delivered boys had higher salivary KYNA levels than those with higher trauma levels who delivered girls. This pilot study provides evidence of an association between maternal childhood trauma and TRP metabolism, measured in saliva, especially in mothers pregnant with boys. However, longitudinal studies with larger sample sizes are required to confirm these results.

Different Kynurenine Pathway Dysregulation in Systemic Sclerosis in Men and Women.

Systemic sclerosis (SSc), a predominantly female-affected systemic autoimmune disease, requires tailored treatment strategies contingent on organ involvement and symptom severity. Given SSc's inflammatory nature, the involvement of the kynurenine pathway (KP) in its pathophysiology is underexplored. Our study aimed to investigate sex-related differences in KP activation among SSc patients and assess the impact of angiotensin-converting enzyme (ACE) inhibitors and estimated glomerular filtration rate (eGFR) on KP metabolite concentrations. We enrolled 48 SSc patients and 53 healthy controls, quantifying KP metabolites (tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA)) in serum via high-performance liquid chromatography. Separate multivariate analyses of covariance (MANCOVAs) for women and men were performed to ascertain mean differences between patients and healthy controls while correcting for age. For our secondary objective, we conducted a MANCOVA to explore disparities in ACE inhibitor users and non-users among patients, with BMI correction. Our findings revealed decreased TRP concentrations but increased KYNA/TRP ratio and KYN/TRP ratio in both male and female SSc patients compared to their respective controls. Unlike women, SSc males exhibited higher KYN concentrations and decreased KYNA/KYN ratio relative to their controls. Additionally, SSc patients using ACE inhibitors had higher serum KYNA levels than non-users. Notably, we established a significant correlation between eGFR and KYNA in SSc patients. These results indicate differential KP activation in male and female SSc patients, with males demonstrating heightened KP activation. While ACE inhibitors may influence the KP in SSc patients, further research is necessary to comprehensively understand their impact on symptoms and prognosis in the context of these KP alterations.

Stress during pregnancy and fetal serum BDNF in cord blood at birth.

INTRODUCTION: Adverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth. Brain-derived neurotrophic factor (BDNF) is essential for neurodevelopment. Short-term higher levels of BDNF in mice upon stressors associate with lower BDNF later in life, which itself associates with depression in animals and humans. Stress including glucocorticoids may impact BDNF, but there is a lack of data at birth. This study investigated if stress near term associates with fetal BDNF at birth in humans. METHODS: Pregnant women near term who underwent primary cesarean sections (at 38.80±0.64 weeks), were included in this study (n=41). Stress at the end of pregnancy was assessed before the cesarean section by determining maternal depressive symptoms (EDPS), maternal state and trait anxiety (STAI-S and STAI-T), maternal prenatal distress (PDQ), stress over the past month (PSS), prenatal attachment to the offspring (PAI), maternal social support (F-Sozu), maternal early life stress (CTQ), socioeconomic status, and the glucocorticoids cortisol and cortisone (n=40) in amniotic fluid at birth. The association with fetal BDNF was analyzed. Cord blood serum of n=34 newborns at birth was analyzed for BDNF and newborn anthropometrics (weight, length and head circumference per gestational age at birth) were assessed. The association of fetal BDNF with anthropometrics at birth was analyzed. RESULTS: After a BDNF-outlier (>3 SD) was removed, higher fetal BDNF associated significantly with maternal depressive symptoms (r=0.398, p=0.022), with lower socioeconomic status as assessed by the average number of people per room in the household (r=0.526, p=0.002) and with borderline significance with net income per person in the household (r=-0.313, p=0.087) in the bivariate analyses. In multivariable analysis, BDNF stayed positively associated with maternal depressive symptoms (ß=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (ß=-0.562, 95% CI [-914.511, -60.523], p=0.027) when controlling for maternal age, maternal pre-pregnancy BMI, fetal sex and gestational age. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed in bivariate analyses or in multivariable analyses when controlling for maternal BMI and fetal sex. CONCLUSION: Maternal depressive symptoms and lower socioeconomic status associated with higher fetal BDNF when controlling for confounders. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed. Further studies should investigate how early altered BDNF associate with the development and possibly psychopathology of the offspring.

Cross-cultural validation of the COVID-19 peritraumatic distress index (CPDI) among Spanish and Peruvian populations.

The COVID-19 pandemic has had a significant psychological impact worldwide. The COVID-19 Peritraumatic Distress Index (CPDI) is widely used to assess psychological stress during the COVID-19 pandemic. Although CPDI has been validated in Peru and Spain, no cross-cultural validation studies have been conducted. As an exploratory aim, differences in CPDI factorial scores between the most prevalent medical conditions in the two samples (arterial hypertension, respiratory diseases and anxious-depressive disorders) from a general population of Peru and Spain were investigated. We conducted secondary data analysis with data from Peru and Spain to validate the CPDI in a cross-cultural context. Exploratory factor analysis (EFA) and multigroup confirmatory factor analysis (MGCFA) were performed to evaluate the factor structure and measurement invariance of the CPDI across cultural contexts. Concerning the exploratory analysis, we performed a U-Mann-Whitney test to evaluate differences in the factorial scores in the two samples. This study revealed a two-factor solution (stress and rumination/information) for the CPDI that included 21 of the 24 original items, and consistent with previous studies. The MGCFA demonstrated measurement invariance across cultural contexts (scalar invariance), indicating that the CPDI construct has the same meaning across both groups, regardless of cultural context and language variations of Spanish. Patients with anxious-depressive disorders showed higher CPDI factorial scores for both factors, whereas patients with respiratory diseases were only associated with the stress factor. This study provides evidence for the cross-cultural validity of the CPDI, highlighting its utility as a reliable instrument for assessing psychological stress in the context of COVID-19 across different cultures. These findings have important implications for developing and validating measures to assess psychological distress in different cultural contexts.

Reduced urine pregnenolone concentration after clinical response in patients with depression: An open-label short-term prospective study.

BACKGROUND: Identifying biological alterations in patients with depression, particularly those that differ between responders and non-responders, is of interest to clinical practice. Biomarker candidates involve neuroactive steroids, including pregnenolone (PREG) and allopregnanolone (ALLO). However, alterations in PREG and ALLO associated with treatment response are understudied. This study's main aim was to evaluate the effects of antidepressant treatment, clinical response, and treatment duration on PREG and ALLO in depression. MATERIALS AND METHODS: In a 4-week, open-label trial, participants were allocated randomly to the venlafaxine (n = 27) or mirtazapine (n = 30) group. Urine concentrations of PREG and ALLO were assessed through gas chromatography-mass spectrometry. Participants collected night urine between 10:30 p.m. and 8:00 a.m. Two primary outcomes were analyzed. Firstly, the effect of treatment (mirtazapine or venlafaxine), clinical response (operationalized through the Hamilton Depression Rating Scale), and time (baseline compared to 28 days) on the urine concentrations of PREG or ALLO in depression. Finally, the effect of clinical response and time on the urine concentration of PREG or ALLO, independently of the antidepressant given (mirtazapine or venlafaxine). Linear mixed models were carried out. RESULTS: There was no significant difference in PREG and ALLO concentrations between baseline and 28 days in responders and non-responders when investigating the venlafaxine or the mirtazapine group. However, we found a significant reduction of urine PREG concentration after 28 days of treatment in responders who received either venlafaxine or mirtazapine (estimate = -0.56; p = 0.016; 95CI [-1.003; -0.115]; Cohen's d = -0.61). CONCLUSIONS: Our main results indicate that responders in depression show reduced urinary PREG concentrations after 4-weeks of therapy, independently of the antidepressant used. More studies are needed to confirm these findings.

LC-MS/MS-based quantification of tryptophan, kynurenine, and kynurenic acid in human placental, fetal membranes, and umbilical cord samples.

Tryptophan breakdown metabolites formed along the kynurenine pathway play a significant role in pregnancy and fetal development. To understand their involvement, it is crucial to quantify the levels of tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA) in relevant biological samples such as the placenta, fetal membranes, and umbilical cord. This study used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine TRP, KYN, and KYNA levels. The LC-MS/MS method was optimized for high sensitivity and specificity, demonstrating good reproducibility with a precision of < 10% CV and an accuracy of 85-115%. The lower limit of quantification for both TRP and KYN was 0.5 µg/ml, while for KYNA, it was 0.5 ng/mL. The method exhibited linearity within the examined range of concentrations in the homogenate, ranging from 0.5 to 30 µg/ml for TRP and KYN and from 0.5 to 25 ng/ml for KYNA. Using this method, we found significant differences in the concentrations of these substances in investigated maternal-fetal compartments. Placenta samples exhibited higher KYN and lower KYNA concentrations than the umbilical cord and fetal membrane, indicating a potentially important role for kynurenines in late pregnancy. Collectively, this finding may facilitate further research and provide inside into the involvement of the kynurenine pathway of TRP metabolism in fetal development.

Effects of left anodal transcranial direct current stimulation on hypothalamic-pituitary-adrenal axis activity in depression: a randomized controlled pilot trial.

The main objective of this study was to evaluate the effect of left anodal transcranial direct current stimulation (tDCS) on hypothalamic-pituitary-adrenal axis (HPAA) activity in individuals with depression. We conducted a 3-week, randomized, triple-blind pilot trial with 47 participants (dropout rate: 14.89%) randomly assigned to either the tDCS or control group (sham stimulation). Salivary cortisol was used as an HPAA activity marker since cortisol is the effector hormone of the HPAA. The primary outcome was the effect of tDCS on the diurnal cortisol pattern (DCP and area under the curve with respect to ground -AUCg-). Secondary outcomes included tDCS effects on cortisol awakening response (CAR) and cortisol decline (CD), as well as the variation of cortisol concentrations between the initiation of tDCS and 2 weeks later. Intention-to-treat and per-protocol analyses were conducted. Our primary outcome showed an absent effect of tDCS on DCP and AUCg. Additionally, tDCS had an absent effect on CAR, CD, and cortisol concentration variation before-after stimulation. Our pilot study suggests that anodal tDCS showed an absent effect on HPAA activity in individuals with depression. More studies are needed to confirm these findings.

Improvement of depressive symptoms, after a suicide attempt, with dextromethorphan/bupropion combination treatment in a patient with treatment-resistant depression and psychiatric comorbidities.

We admitted a 42-year-old patient with severe treatment-resistant depression and with psychiatric comorbidities. The patient attempted suicide 5 weeks after admission. Subsequently, we initiated dextromethorphan/bupropion based on prior evidence. As a result, the patient demonstrated an improvement in mood symptoms and a reduction in suicide risk, leading to her discharge.

Fractional anisotropy and peripheral cytokine concentrations in outpatients with depressive episode: a diffusion tensor imaging observational study.

Over the past few years, evidence of a positive relationship between inflammation and depression has grown steadily. The aim of the current study was to investigate whether such depression-related inflammation could also be associated with altered microstructural changes in the white matter. FA and serum cytokines (IL-1ß, IL-6, TNF-α, and IFN-γ) were measured in 25 patients with depression (DE) and 24 healthy controls (HC). Diffusion tensor imaging was performed. Fractional anisotropy (FA) was calculated using the FSL pipeline for Tract-Based Spatial Statistics (TBSS). Both voxelwise and mean whole-brain FA were analyzed using general linear models (GLM). Higher concentrations of IL-1ß were associated with lower whole-brain fractional anisotropy, particularly in people with depression (ρ = - 0.67; p < 0.001). TNF-α shared some variance with IL-1ß and also showed a negative relationship between TNF-α concentrations and FA in depression (F1,46 = 11.13, p = 0.002, η2p = 0.21). In detail, the voxelwise analysis showed that the regression slopes of IL-1ß on FA were more negative in the DE group than in the HC group, mainly in the corpus callosum (cluster statistics: genu corpus callosum, p = 0.022; splenium of corpus callosum, p = 0.047). Similar effects were not found for the other remaining cytokines. This study clearly demonstrated an association between peripherally measured IL-1ß and white matter integrity in depression as assessed by DTI. The results suggest that microstructural changes in the corpus callosum are associated with increased peripheral IL-1ß concentrations in depression.

[Medical conditions, symptoms of anxiety, and depression during the COVID-19 pandemic in a population sample of Lima, Peru]. / Condiciones médicas, síntomas de ansiedad y depresión durante la pandemia por COVID-19 en una muestra poblacional de Lima, Perú.

Introduction: This study aims to determine differences between the number of underlying medical conditions, depression, and anxiety, when controlling for the covariates of age, sex, and completed education.Methods: Participants (n=484) indicated the number of medical conditions present during the survey, also including the PHQ-9 and GAD-7, to assess depression and anxiety, respectively.Results: Differences were found between groups of medical conditions and the combined values of PHQ-9 and GAD-7 after controlling for the covariates mentioned above (F4,954=5.78; Wilks' Λ=0.95; P<0.0005). The univariate tests showed differences for PHQ-9 (F2,478=8.70; P<0.0005) and GAD-7 (F2,478=11.16; P<0.0005) between the 3 groups. Finally, post-hoc analysis showed differences between participants with one medical condition and with no medical condition (PHQ-9: MD=1.82; 95%CI, 0.25-3.40; GAD-7: MD=1.73; 95%CI, 0.55-2.91), and between participants with more than one medical condition and participants with no medical condition (PHQ-9: MD=3.10; 95%CI, 1.11-5.10; GAD-7: MD=2.46; 95%CI, 0.97-3.95).Conclusions: Our results suggest that people who had a medical condition during the COVID-19 pandemic were more prone to developing severe symptoms of anxiety and depression.

Content validation using Aiken methodology through expert judgment of the first Spanish version of the Eppendorf Schizophrenia Inventory (ESI) in Peru: A brief qualitative report.

BACKGROUND: The main objective of this study was the validation through the expert judgment of the first Spanish version of the Eppendorf Schizophrenia Inventory (ESI-Sp). MATERIALS AND METHODS: A translation and cultural adaptation procedure as a first stage was carried out, which was evaluated by four psychiatrists with clinical experience. In a second stage, we recruited a group of clinical psychiatrists to evaluate the translated instrument by judging the items' clarity and relevance. Content validity was performed using the Aiken methodology (Aiken's V). RESULTS: For the first stage, we did not find any items that needed alteration during translation and adaptation. Concerning the raters' stage, 30 clinical psychiatrists (47.07±13.62 years) completed the rating of the ESI-Sp. Of them, the majority worked in an institute (10/30; 33.33%) and had "15 or more" years of experience (12/30; 40.00%). The null hypothesis was rejected for all items and demonstrated the content validity of each item. Similar results were found for the factors of the ESI. Finally, the total Aiken's V for the ESI did not include the values of the null hypothesis in the confidence intervals (V=0.78; CI95 [0.70; 0.85]), demonstrating content validity. CONCLUSIONS: ESI-Sp is a valid and representative instrument to determine subjective experiences in patients with a high risk of schizophrenia. The construct validation of the ESI-Sp is pending, which our research group will carry out after this first step.

Emotional Impact on Health Personnel, Medical Students, and General Population Samples During the COVID-19 Pandemic in Lima, Peru.

BACKGROUND: The aim of the study is to compare the emotional effects of COVID-19 among three different groups, namely: health personnel, medical students, and a sample of the general population. METHODS: 375 participants were recruited for this study, of which 125 were medical students (preclinical studies, 59; clinical studies, 66), 125 were health personnel (COVID-19 frontline personnel, 59; personnel not related with COVID-19, 66), and 125 belonged to the general population. The PHQ-9, GAD-7, and CPDI scales were used to assess the emotional impact. A multinomial logistic regression was performed to measure differences between groups, considering potential confounding factors. RESULTS: Regarding CPDI values, all other groups showed reduced values compared to COVID-19 frontline personnel. However, the general population, preclinical and clinical medical students showed increased PHQ-9 values compared to COVID-19 frontline personnel. Finally, confounding factors, gender and age correlated negatively with higher CPDI and PHQ-9 scores. CONCLUSIONS: Being frontline personnel is associated with increased COVID-19-related stress. Depression is associated, however, with other groups not directly involved with the treatment of COVID-19 patients. Female gender and younger age correlated with COVID-19-related depression and stress.

Emotional Impact on Health Personnel, Medical Students, and General Population Samples During the COVID-19 Pandemic in Lima, Peru / Impacto emocional en personal de salud, estudiantes de Medicina y población general durante la pandemia de COVID-19 en Lima, Perú

ABSTRACT Background: The aim of the study is to compare the emotional effects of COVID-19 among three different groups, namely: health personnel, medical students, and a sample of the general population. Methods: 375 participants were recruited for this study, of which 125 were medical students (preclinical studies, 59; clinical studies, 66), 125 were health personnel (COVID-19 frontline personnel, 59; personnel not related with COVID-19, 66), and 125 belonged to the general population. The PHQ-9, GAD-7, and CPDI scales were used to assess the emotional impact. A multinomial logistic regression was performed to measure differences between groups, considering potential confounding factors. Results: Regarding CPDI values, all other groups showed reduced values compared to COVID-19 frontline personnel. However, the general population, preclinical and clinical medical students showed increased PHQ-9 values compared to COVID-19 frontline personnel. Finally, confounding factors, gender and age correlated negatively with higher CPDI and PHQ-9 scores. Conclusions: Being frontline personnel is associated with increased COVID-19-related stress. Depression is associated, however, with other groups not directly involved with the treatment of COVID-19 patients. Female gender and younger age correlated with COVID-19-related depression and stress.

RESUMEN Introducción: El objetivo del estudio es comparar los efectos emocionales de la COVID-19 entre 3 grupos diferentes, a saber: personal de salud, estudiantes de Medicina y una muestra de la población general. Métodos: Se incluyó a 375 participantes en este estudio, de los que 125 eran estudiantes de Medicina (estudios preclínicos, 59; estudios clínicos, 66), 125 eran personal de salud (personal de primera línea contra la COVID-19, 59; personal no relacionado con la COVID-19, 66) y 125 pertenecían a la población general. Las escalas PHQ-9, GAD-7 y CPDI se utilizaron para evaluar el impacto emocional. Se realizó una regresión logística multinomial para medir las diferencias entre grupos, considerando posibles factores de confusión. Resultados: Con respecto a los valores del CPDI, todos los demás grupos mostraron valores reducidos en comparación con el personal de primera línea contra la COVID-19. Sin embargo, la población general y los estudiantes de Medicina preclínica y clínica mostraron un aumento de los valores del PHQ-9 en comparación con el personal en primera línea. Por último, los factores de confusión, sexo y edad se correlacionaron negativamente con puntuaciones más altas del CPDI y el PHQ-9. Conclusiones: Ser personal de primera línea se asocia con más estrés relacionado con la COVID-19. Sin embargo, la depresión está asociada con otros grupos que no están directamente involucrados en el tratamiento de los pacientes con COVID-19. Las mujeres y los participantes más jóvenes se correlacionaron con la depresión y el estrés relacionados con la COVID-19.

Emotional Impact on Health Personnel, Medical Students, and General Population Samples During the COVID-19 Pandemic in Lima, Peru.

Background: The aim of the study is to compare the emotional effects of COVID-19 among three different groups, namely: health personnel, medical students, and a sample of the general population. Methods: 375 participants were recruited for this study, of which 125 were medical students (preclinical studies, 59; clinical studies, 66), 125 were health personnel (COVID-19 frontline personnel, 59; personnel not related with COVID-19, 66), and 125 belonged to the general population. The PHQ-9, GAD-7, and CPDI scales were used to assess the emotional impact. A multinomial logistic regression was performed to measure differences between groups, considering potential confounding factors. Results: Regarding CPDI values, all other groups showed reduced values compared to COVID-19 frontline personnel. However, the general population, preclinical and clinical medical students showed increased PHQ-9 values compared to COVID-19 frontline personnel. Finally, confounding factors, gender and age correlated negatively with higher CPDI and PHQ-9 scores. Conclusions: Being frontline personnel is associated with increased COVID-19-related stress. Depression is associated, however, with other groups not directly involved with the treatment of COVID-19 patients. Female gender and younger age correlated with COVID-19-related depression and stress.

Introducción: El objetivo del estudio es comparar los efectos emocionales de la COVID-19 entre 3 grupos diferentes, a saber: personal de salud, estudiantes de Medicina y una muestra de la población general. Métodos: Se incluyó a 375 participantes en este estudio, de los que 125 eran estudiantes de Medicina (estudios preclínicos, 59; estudios clínicos, 66), 125 eran personal de salud (personal de primera línea contra la COVID-19, 59; personal no relacionado con la COVID-19, 66) y 125 pertenecían a la población general. Las escalas PHQ-9, GAD-7 y CPDI se utilizaron para evaluar el impacto emocional. Se realizó una regresión logística multinomial para medir las diferencias entre grupos, considerando posibles factores de confusión. Resultados: Con respecto a los valores del CPDI, todos los demás grupos mostraron valores reducidos en comparación con el personal de primera línea contra la COVID-19. Sin embargo, la población general y los estudiantes de Medicina preclínica y clínica mostraron un aumento de los valores del PHQ-9 en comparación con el personal en primera línea. Por último, los factores de confusión, sexo y edad se correlacionaron negativamente con puntuaciones más altas del CPDI y el PHQ-9. Conclusiones: Ser personal de primera línea se asocia con más estrés relacionado con la COVID-19. Sin embargo, la depresión está asociada con otros grupos que no están directamente involucrados en el tratamiento de los pacientes con COVID-19. Las mujeres y los participantes más jóvenes se correlacionaron con la depresión y el estrés relacionados con la COVID-19.

Validación por expertos del Índice de Distrés Peri-traumático relacionado con la Enfermedad por Coronavirus 2019 para su uso en el Perú / Expert validation of the COVID-2019 Peri-traumatic Distress Index for use in Peru

RESUMEN Objetivo: Efectuar una validación de contenido por expertos del Índice de Distrés Peri-traumático relacionado a COVID-19 (CPDI) para su uso en el Perú. Material y Métodos: El CPDI fue traducido al castellano y luego adaptado en una primera ronda de expertos. En una segunda ronda (n = 13), se evaluó la validez del contenido mediante el uso de la V de Aiken (V). Se calculó la V para cada ítem, así como para el instrumento en su conjunto (VTOT). Resultados : De los 24 ítems originales, solo un ítem (S7) presentó valores no significativos para validez de contenido, razón por la que fue eliminado. La escala con 23 ítems no presentó alteraciones en el cálculo de la VTOT. Conclusiones : Sobre la base de su validez de contenido, el CPDI en castellano es adecuado para su aplicación en la población peruana. Quedan por definirse las características psicométricas así como la modificación propuesta del instrumento, mediante estudios cuantitativos en torno a la validez del constructo.

SUMMARY Objectives : To perform an expert validation study of COVID-19 Peritraumatic Distress Index (CPDI) for its eventual use in Perú. Material and Methods: In a first round by experts, the CPDI was translated into Spanish and then adapted. In a second round, (n = 13), the content validity was evaluated by using Aiken's V (V). The V was calculated for each item, as well as for the whole instrument (VTOT). Results : Of the 24 original items, only one (S7) presented non-significant values for content validity, reason for which it was removed. The final 23-items scale did not present any alterations for the VTOT calculation. Conclusions : On the basis of its adequate content validity, the Spanish version of CPDI is suitable for its application in the Peruvian population. The psychometric characteristics of the instrument, as well as its proposed modification remain to be defined through quantitative studies of the construct validity.

Pro-inflammatory markers and fatigue in patients with depression: A case-control study.

The aim of this work was to investigate differences between depressed subjects (PG) and non-depressed healthy control participants (HCG) with regard to fatigue dimensions and inflammation. For this purpose, 43 participants in the PG and 51 participants in the HCG were included in the study. IL-6, IL-1ß, TNF-α, IFN-γ, and CRP were assessed in venous blood samples. Fatigue and depression were assessed using the FIS-D and BDI-FS questionnaires. Main results showed higher BDI-FS values in PG. Moreover, PG showed mean differences for fatigue dimensions when compared to the HCG. For the pro-inflammatory markers, a moderate group effect was found between PG and HCG which was mainly caused by IL-6. Correlations between TNF-α and BDI-FS, TNF-α and cognitive fatigue, TNF-α and psychosocial fatigue were found within the PG. In the HCG, correlations were found between IL-6, TNF-α and somatic fatigue, as well as IL-6 and cognitive fatigue. Significant correlations were found between the psychological variables in both groups. All results were controlled for the confounding variables gender, age, BMI and multiple comparisons. These results suggest the presence of inflammation in both depression and fatigue. However, each correlates with different pro-inflammatory parameters, suggesting a biological heterogeneity.

Translation, adaptation and expert validation of the COVID-19 Peri-traumatic Distress Index (CPDI) for its use in Peru. / Traducción, adaptación y validación por expertos del Indice de Distrés Peri-traumatico relacionado a la enfermedad por coronavirus 2019 (CPDI) para su uso en el Perú. / Tradução, adaptação e validação por especialistas do Índice de Estresse Peri-traumático de 2019 relacionado à doença de coronavírus (CPDI) para uso no Peru.

In order to have an instrument that measures emotional impact related to COVID-19 in Peru, a validation study for COVID-19 Peri-traumatic distress index (CPDI) was done. The CPDI was translated into Spanish and then adapted in a first round of experts. In a second round of experts (n = 13), the validity of the content and the reliability of the CPDI were evaluated. Of the 24 original items, only one item (S7) presented non-significant values for content validity and then it was removed. The reliability values of the original CPDI (24 items) and the modified CPDI (23 items) remained unchanged. In conclusion, the CPDI in Spanish presents adequate content validity and reliability, being suitable for its application in Peru. Finally, the modification of the CPDI did not alter its characteristics. Therefore, it is suggested to use the modified CPDI version for a better assessment.

Para disponer de un instrumento que mida impacto emocional relacionado a COVID-19, se procedió a la validación del indice de distrés peri-traumático relacionado a COVID-19 (CPDI) para su uso en el Perú. El CPDI fue traducido al castellano y luego adaptado en una primera ronda de expertos. En una segunda ronda de expertos (n = 13), se evaluó la validez del contenido y la fiabilidad del CPDI. De los 24 items originales, solo un ítem (S7) presentó valores no significativos para validez de contenido y se eliminó el ítem. Los valores de fiabilidad del CPDI original (24 items) y del modificado (23 items) permanecieron invariables. En conclusión, el CPDI en castellano presenta adecuadas validez de contenido y fiabilidad, por lo que se puede aplicar en el Perú. Finalmente, la modificación del CPDI no alteró sus caracteristicas por lo que se sugiere usar la versión modificada para una mejor evaluación.

Para ter um instrumento que mensure o impacto emocional relacionado ao COVID-19, o índice de sofrimento peri-traumático relacionado ao COVID-19 (CPDI) foi validado para uso no Peru. O CPDI foi traduzido para o espanhol e depois adaptado em uma primeira rodada de especialistas. Em uma segunda rodada de especialistas (n = 13), a validade do conteúdo e a confiabilidade do CPDI foram avaliadas. Dos 24 itens originais, apenas um item (S7) apresentou valores não significativos para a validade do conteúdo e o item foi removido. Os valores de confiabilidade do CPDI original (24 itens) e do CPDI modificado (23 itens) permaneceram inalterados. Concluindo, o CPDI em espanhol apresenta validade e confiabilidade adequadas de conteúdo, podendo ser aplicado no Peru. Por fim, a modificação do CPDI não alterou suas características, portanto, sugere-se o uso da versão modificada para uma melhor avaliação.

Effects of inflammation on the kynurenine pathway in schizophrenia - a systematic review.

BACKGROUND: In the last decade, there has been growing evidence that an interaction exists between inflammation and the kynurenine pathway in schizophrenia. Additionally, many authors found microglial activation in cases of schizophrenia due to inflammatory mechanisms related mostly to an increase of pro-inflammatory cytokines. In order to gain new insights into the pathophysiology of schizophrenia, it is important to incorporate the latest published evidence concerning inflammatory mechanisms and kynurenine metabolism. This systematic review aims to collect reliable recent findings within the last decade supporting such a theory. METHODS: A structured search of electronic databases was conducted for publications between 2008 and 2018 to identify eligible studies investigating patients with schizophrenia/psychosis and the relationship between inflammation and kynurenine pathway. Applicable studies were systematically scored using the NIH Quality Assessment Tools. Two researchers independently extracted data on diagnosis (psychosis/schizophrenia), inflammation, and kynurenine/tryptophan metabolites. RESULTS: Ten eligible articles were identified where seven studies assessed blood samples and three assessed cerebrospinal fluid in schizophrenic patients. Of these articles: Four investigated the relationship between immunoglobulins and the kynurenine pathway and found correlations between IgA-mediated responses and levels of tryptophan metabolites (i.e., kynurenine pathway).Five examined the correlation between cytokines and kynurenine metabolites where three showed a relationship between elevated IL-6, TNF-α concentrations, and the kynurenine pathway.Only one study discovered correlations between IL-8 and the kynurenine pathway.Two studies showed correlations with lower concentrations of IL-4 and the kynurenine pathway.Moreover, this systematic review did not find a significant correlation between CRP (n = 1 study), IFN-γ (n = 3 studies), and the kynurenine pathway in schizophrenia. INTERPRETATION: These results emphasize how different inflammatory markers can unbalance the tryptophan/kynurenine pathway in schizophrenia. Several tryptophan/kynurenine pathway metabolites are produced which can, in turn, underlie different psychotic and cognitive symptoms via neurotransmission modulation. However, due to heterogeneity and the shortage of eligible articles, they do not robustly converge to the same findings. Hence, we recommend further studies with larger sample sizes to elucidate the possible interactions between the various markers, their blood vs. CSF ratios, and their correlation with schizophrenia symptoms.

Aspectos psico-espirituales medidos con la FACIT-Sp en pacientes con cáncer estadio IV / Psycho-spiritual elements evaluated by FACIT-Sp in stage IV cancer patients

Resumen Objetivo: Describir los diferentes elementos psico-espirituales en pacientes con cáncer aplicando la escala Functional Assessment of Chronic Illness Therapy - Spiritual Well Being, FACIT-Sp (Evaluación Funcional de Terapia de Enfermedades Crónicas y Bienestar Espiritual). Métodos: Aplicación de la escala a una muestra de pacientes (n =100) con diagnóstico de cáncer, estadio IV, del Servicio de Oncología del Hospital Nacional Arzobispo Loayza. El instrumento de 33 preguntas examina cinco áreas: bienestar social (SWB), bienestar emocional (EWB), bienestar funcional (FWB), sentido y paz (MP) y fe (F). Resultados: En la muestra estudiada, el aspecto más resaltante fue el relacionado con F (puntaje promedio=13,53 ± 3,05, correspondiente al 84,56% del puntaje máximo posible) y el más bajo fue el vinculado a FWB (puntaje promedio=15,79 ± 6,89, correspondiente al 56,39% del puntaje máximo posible). Conclusiones: De acuerdo a FACIT-Sp, el aspecto psico-espiritual más desarrollado en los pacientes de la muestra estudiada fue el relativo a la Fe y el menos desarrollado, el vinculado al área de Bienestar Funcional.

Summary Objective: To describe different psycho-spiritual elements in a sample of stage IV cancer patients from a public hospital in Lima, Peru, through the application of the Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being (FACIT-Sp) scale. Methods: Application of FACIT-Sp to a sample of patients (n = 100) diagnosed with stage IV cancer at the Oncology Service of the Hospital Nacional Arzobispo Loayza. The 33-question instrument, designed to evaluate psycho-spiritual elements, analyzes five areas: social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), meaning and peace (MP) and faith (F). Results: The most prominent aspect was F (average score=13.53 ± 3.05, corresponding to 84.56% of the maximum possible score), and the lowest was FWB (average score=15.79 ± 6.89, corresponding to 56.39% of the maximum possible score). Conclusions: According to FACIT-Sp, the most developed psycho-spiritual aspect among the participating patients was the one related to Faith, whereas the least developed, the one linked to the area of Functional Well-Being.

Fatiga: historia, neuroanatomía y caracteristicas psicopatológicas. Una revisión de la Literatura / Fatigue: history, neuroanatomy and psychopathology characteristics. A review of the Literature

Se examina el fenómeno clínico conocido como "fatiga", resumiendo los principales hallazgos vinculados a su definición y aspectos históricos, información epidemiológica, conceptos neuroanatómicos y descripción psicopatológica. Las correlaciones entre los distintos tipos de daño estructural y funcional son numerosas generando dudas en torno a la existencia del síntoma y planteándose entonces una redefinición. La búsqueda de mecanismos fisiopatológicos y objetivos terapéuticos evidencian también el interés de los investigadores. La fatiga causa una carga ingente en la salud global debido a la disfuncionalidad resultante, por lo que se sugiere una variedad de análisis psicométricos y categorización de los componentes conocidos a fin de dejar atrás todos los elementos de confusión encontrados previamente. Finalmente, se plantea la necesidad de que futuros estudios, luego de definir qué es lo que realmente está detrás de fatiga, identifiquen marcadores biológicos y busquen daños estructurales micro- o macroscópicos de forma tal que se pueda mejorar la calidad de vida de la población que la padece.

Clinical, historical and research aspects of the phenomenon known as "fatigue" are examined. A summary of the main findings regarding its history, epidemiological data, neuroanatomical and psychopathological descriptions, is presented. The correlations between the different types of structural and functional damage are numerous, which generates doubts about the symptom's existence and forces a redefinition. The search of a physio-pathological mechanisms and therapeutic targets are also evidence of the interest of investigators. Fatigue is cause of significant impact on global health due to the resulting dysfunctionality; such is the reason for the suggestions of using psychometric and factorial analyses and a categorization of its known components in order to leave behind all the confusing elements previously found. It is necessary that future studies, after defining its underlying processes, focus on identifying biological markers and micro- and macroscopic structural damages, so that the quality of life of affected populations can be improved.