Clinical, environmental, and molecular factors associated to the occurrence and persistence of posttraumatic stress disorder after an earthquake.

Post-traumatic stress disorder (PTSD) is a common and disabling condition with high incidence after an earthquake. The objective of the present study was to identify risk factors associated with the occurrence and persistence of PTSD. Individuals (18-65 years old) who experienced the earthquake of September 19th, 2017, attended the National Institute of Psychiatry (INPRFM) between October and November 2017 (baseline n = 68). Participants were followed 4-6 (first follow-up, n = 40) and 7-9 (second follow-up n = 41) months after the earthquake. Delay returning to normal activities, a negative emotional valence to a previous earthquake, comorbidity with depression, history of childhood maltreatment, and low expression of Glucocorticoid Receptor (GR) were associated with PTSD in the basal assessment. The earthquake-related variable associated with the persistence of PTSD at the second follow-up was that the earthquake had directly affected the participants, either because they were evicted, had damage to their homes, or suffered some injury. Comorbidity with dysthymia, history of childhood maltreatment, and higher severity of PTSD in the basal assessment were associated with persistent PTSD in the second follow-up. The lower expression of the FK506 binding protein 5 (FKBP5) in participants with persistent PTSD in the second follow-up was better explained by childhood physical abuse than with PTSD severity. These findings suggest that acute exposure to earthquake-related stressful situations is relevant for the initial risk of PTSD, while potential long-term stressful conditions are associated with its persistence. Likewise, molecular markers associated with hypothalamus-pituitary-adrenal-axis dysregulation were differentially associated with PTSD diagnosis at the different assessment times.

The cytokine profile of women with severe anxiety and depression during pregnancy.

BACKGROUND: Controversial findings regarding the association between pro-inflammatory cytokines and depression have been reported in pregnant subjects. Scarce data about anxiety and its relationships with cytokines are available in pregnant women. To understand the association between anxiety and cytokines during pregnancy, we conducted the present study in women with or without depression. METHODS: Women exhibiting severe depression (SD) and severe anxiety (SA) during the 3rd trimester of pregnancy (n = 139) and control subjects exhibiting neither depression nor anxiety (n = 40) were assessed through the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Serum cytokines were measured by a multiplex bead-based assay. Correlation tests were used to analyze the data and comparisons between groups were performed. A general linear model of analysis of variance was constructed using the group as a dependent variable, interleukin concentrations as independent variables, and HDRS/HARS scores and gestational weeks as covariables. RESULTS: The highest levels of Th1- (IL-6, TNF-α, IL-2, IFN-γ), Th17- (IL-17A, IL-22), and Th2- (IL-9, IL-10, and IL-13) related cytokines were observed in women with SD + SA. The SA group showed higher concentrations of Th1- (IL-6, TNF-α, IL-2, IFN-γ) and Th2- (IL-4, and IL-10) related cytokines than the controls. Positive correlations were found between HDRS and IL-2, IL-6, and TNF-α in the SA group (p < 0.03), and between HDRS and Th1- (IL-2, IL-6, TNF-α), Th2- (IL-9, IL-10, IL-13) and Th17- (IL-17A) cytokines (p < 0.05) in the SD + SA group. After controlling the correlation analysis by gestational weeks, the correlations that remained significant were: HDRS and IL-2, IL-6, IL-9, and IL-17A in the SD + SA group (p < 0.03). HARS scores correlated with IL-17A in the SA group and with IL-17A, IL-17F, and IL-2 in the SD + SA group (p < 0.02). The linear model of analysis of variance showed that HDRS and HARS scores influenced cytokine concentrations; only IL-6 and TNF-α could be explained by the group. CONCLUSIONS: We found that the cytokine profiles differ when comparing pregnant subjects exhibiting SA with comorbid SD against those showing only SA without depression.

Comparison of clinical and cognitive characteristics of a Mexican adult clinical population with and without ADHD / Comparación de las características clínicas y cognitivas de una población clínica adulta mexicana con y sin TDAH

Abstract Introduction Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting approximately 5% of the world population, with symptoms that may persist into adulthood. Despite the findings on the clinical course of this disorder, information regarding comorbidity patterns, psychosocial and executive functioning in adult life in those with and without ADHD in Latin American samples is scarce. Objective The aim of this study is to compare the comorbidity pattern, psychosocial, and executive functioning of adults with and without ADHD from a clinical sample. Method One hundred and fifty-one patients between 20 and 45 years, with screened positively on ASRS-V1.1, were invited to continue an evaluation process as part of clinical research program (PROMETEO): 1) K-SADS-PL Mx interview, 2) MINI-Plus interview, ASRS-V1-1 18 item version, BRIEF self-reported questionnaire, SCQA-ADHD, and 3) Individual case review by clinical expert in ADHD. Results Individuals in the ADHD group had a higher average of comorbid disorders (2.5 SD 1.1 vs. 1.3 SD 1.0 respectively, F = .439; t = -6.621; df = 149; p < .001), more likelihood of procrastinating (OR = 6.5; 95% CI[2.6, 16.2]; z = 4.0) and were more likely to present difficulties in both the behavior regulation index (OR = 104.9; 95% CI[31.8, 345.7]; z = 7.65) and the metacognitive index (OR = 94.79; 95% CI[29.10, 308.76]; z = 7.56) compared to the non-ADHD group, regardless of gender. Discussion and conclusions Our results indicate that the ADHD adult group presented with more comorbidity, and worse psychosocial and executive functioning than non-ADHD adults.

Resumen Introducción El trastorno por déficit de atención con hiperactividad (TDAH) es un trastorno del neurodesarrollo que afecta aproximadamente al 5% de la población mundial, persistiendo hasta la adultez. A pesar de los hallazgos acerca del curso clínico de este trastorno, la información es escasa con respecto a los patrones de comorbilidad, funcionamiento psicosocial y ejecutivo en la vida adulta entre aquellos con y sin TDAH en muestras latinoamericanas. Objetivo Comparar el patrón de comorbilidad, el funcionamiento psicosocial y ejecutivo de adultos con y sin TDAH de una muestra clínica. Método Ciento cincuenta y un pacientes entre 20 y 45 años, quienes inicialmente presentaron un tamizaje positivo del ASRS-V1.1, fueron evaluados dentro de un programa de investigación clínica (PROMETEO) con los siguientes instrumentos: 1) la entrevista K-SADS-PL-Mx, 2) la entrevista MINI-Plus, la version de 18 items del ASRS-V1-1, y los cuestionarios autoaplicados BRIEF y SCQA-ADHD y 3) Revisión de cada caso por un clínico experto en el diagnóstico de TDAH. Resultados El grupo de TDAH comparado con aquel sin TDAH presentó un mayor promedio de trastornos comórbidos (2.5 DE 1.1 vs 1.3 DE 1.0 respectivamente, F = .439; t = -6.621; gl = 149; p < .001), mayor probabilidad de procrastinar (OR = 6.5; 95% IC[2.6, 16.2]; z = 4.0), y mayor probabilidad de presentar dificultades tanto en el índice de regulación de la conducta (OR = 104.9; 95% IC[31.8, 345.7]; z = 7.65) como en el índice metacognitivo (OR = 94.79; 95% IC[29.10, 308.76]; z = 7.56) independientemente del sexo. Discusión y conclusión Nuestros resultados señalan que los adultos con TDAH presentan mayor comorbilidad y peor funcionamiento psicosocial y ejecutivo que los adultos sin TDAH.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.

Incidence of adverse cutaneous drug reactions in a Mexican sample: an exploratory study on their association to tumour necrosis factor alpha TNF2 allele.

BACKGROUND: Most adverse cutaneous drug reactions (ACDR) are mediated by delayed hypersensitivity (dh) with lymphocyte recruitment and inflammatory cytokines release, including tumour necrosis factor alpha (TNFalpha). Polymorphisms in the TNFalpha gene, such as the infrequent allele TNF2, predispose to certain inflammatory entities and enhance TNFalpha production. The incidence of the TNF2 allele is increased in British patients with severe ACDR, suggesting TNFalpha as a major contributor in the pathogenesis of ACDR. OBJECTIVE: We designed a prospective study to analyse the epidemiology of ACDR in a third-level Mexican hospital and explore the possibility of a relationship between the TNF2 allele and ACDR-dh. METHODS: A prospective study during 9 months allowed recognition of 34 ACDR-dh patients. The study included 33 paired patients, and 44 healthy volunteers. All subjects were genotyped for TNF2 by PCR DNA amplification and NcoI restriction endonuclease digestion. Results Incidence of ACDR was 0.95%. The TNF2 allele was detected in 9.9% of the sample population with no significant differences between healthy controls, and patients with or without ACDR-dh. Only 3 of the 34 ACDR-dh subjects presented severe reactions, with 1 having the TNF2 allele. Comorbidity analysis showed significance only with autoimmune thyroid disease, consistent with reports on Chinese and Tunisian patients. CONCLUSION: ACDR incidence and TNF2/TNFA heterozygosity were lower in Mexican than in Caucasian patients. ACDR-dh patients showed no increased frequency in the TNF2 allele.

Efficacy of metadoxine in the management of acute alcohol intoxication.

This randomized, open-label study evaluated the efficacy of 300 mg metadoxine (given intravenously) added to standard treatment compared with standard treatment alone in managing the physical and psychological signs of acute alcohol intoxication. Fifty-two acutely intoxicated patients were randomly assigned to one of two groups and followed during a 2-h period. Changes in clinical symptoms, degree of intoxication, and blood alcohol level were monitored. More patients receiving metadoxine in addition to standard therapy significantly improved by at least one degree of intoxication (one clinical category) compared with those receiving standard treatment alone (76.9% versus 42.3%, respectively). Metadoxine-treated patients also exhibited a significantly greater decrease in blood alcohol concentration compared with those receiving standard treatment alone (-105.4 +/- 61.5 mg/dl versus -60.1 +/- 38.6 mg/dl, respectively). Metadoxine improved the clinical signs of acute alcohol intoxication and accelerated alcohol clearance from the blood, thus supporting existing data. In contrast to previous data, these effects were concurrent but independent. No adverse effects were observed with metadoxine therapy.