Microbiota-gut-brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities.

Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic and depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is a complex picture of genetic and environmental factors implicated. Nowadays, gut microbiota is in the spotlight of new research related to this kind of psychiatric disorder, as it can be consistently related to several pathophysiological events observed in BD. In the context of the so-called microbiota-gut-brain (MGB) axis, it is shown to have a strong influence on host neuromodulation and endocrine functions (i.e., controlling the synthesis of neurotransmitters like serotonin or mediating the activation of the hypothalamic-pituitary-adrenal axis), as well as in modulation of host immune responses, critically regulating intestinal, systemic and brain inflammation (neuroinflammation). The present review aims to elucidate pathophysiological mechanisms derived from the MGB axis disruption and possible therapeutic approaches mainly focusing on gut microbiota in the complex network of BD. Understanding the mechanisms of gut microbiota and its bidirectional communication with the immune and other systems can shed light on the discovery of new therapies for improving the clinical management of these patients. Besides, the effect of psychiatric drugs on gut microbiota currently used in BD patients, together with new therapeutical approaches targeting this ecosystem (dietary patterns, probiotics, prebiotics, and other novelties) will also be contemplated.

Association of Prolactin, Oxytocin, and Homocysteine With the Clinical and Cognitive Features of a First Episode of Psychosis Over a 1-Year Follow-Up.

BACKGROUND: The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics. METHODS: We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features. RESULTS: At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients. CONCLUSION: This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind.

Negative symptoms in First-Episode Schizophrenia related to morphometric alterations in orbitofrontal and superior temporal cortex: the OPTiMiSE study.

BACKGROUND: Negative symptoms are one of the most incapacitating features of Schizophrenia but their pathophysiology remains unclear. They have been linked to alterations in grey matter in several brain regions, but findings have been inconsistent. This may reflect the investigation of relatively small patient samples, and the confounding effects of chronic illness and exposure to antipsychotic medication. We sought to address these issues by investigating concurrently grey matter volumes (GMV) and cortical thickness (CTh) in a large sample of antipsychotic-naïve or minimally treated patients with First-Episode Schizophrenia (FES). METHODS: T1-weighted structural MRI brain scans were acquired from 180 antipsychotic-naïve or minimally treated patients recruited as part of the OPTiMiSE study. The sample was stratified into subgroups with (N = 88) or without (N = 92) Prominent Negative Symptoms (PMN), based on PANSS ratings at presentation. Regional GMV and CTh in the two groups were compared using Voxel-Based Morphometry (VBM) and FreeSurfer (FS). Between-group differences were corrected for multiple comparisons via Family-Wise Error (FWE) and Monte Carlo z-field simulation respectively at p < 0.05 (2-tailed). RESULTS: The presence of PMN symptoms was associated with larger left inferior orbitofrontal volume (p = 0.03) and greater CTh in the left lateral orbitofrontal gyrus (p = 0.007), but reduced CTh in the left superior temporal gyrus (p = 0.009). CONCLUSIONS: The findings highlight the role of orbitofrontal and temporal cortices in the pathogenesis of negative symptoms of Schizophrenia. As they were evident in generally untreated FEP patients, the results are unlikely to be related to effects of previous treatment or illness chronicity.

Bioinformatic Approach of B and T Cell Epitopes of PLD and CP40 Proteins of Corynebacterium pseudotuberculosis ovis Mexican Isolate 2J-L towards a Peptide-Based Vaccine.

Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of Corynebacterium pseudotuberculosis biovar ovis, a causal agent of Caseous Lymphadenitis, have been evaluated in a murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of Corynebacterium pseudotuberculosis ovis. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of Corynebacterium pseudotuberculosis ovis Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico.

The Influence of Oxytocin and Prolactin During a First Episode of Psychosis: The Implication of Sex Differences, Clinical Features, and Cognitive Performance.

BACKGROUND: Approximately 3% of the population suffers a first episode of psychosis (FEP), and a high percentage of these patients subsequently relapse. Because the clinical course following a FEP is hard to predict, it is of interest to identify cognitive and biological markers that will help improve the diagnosis, treatment, and outcome of such events and to define new therapeutic targets. Here we analyzed the plasma oxytocin and prolactin levels during an FEP, assessing their correlation with clinical and cognitive features. METHODS: The oxytocin and prolactin in plasma was measured in 120 FEP patients and 106 healthy controls, all of whom were subjected to a clinical and neuropsychological assessment. Most patients were under antipsychotics. Statistical analyses aimed to identify factors associated with the FEP and to search for associations between the variables. This study is preliminary and exploratory because the P-values were not corrected for multiple comparisons. RESULTS: FEP patients had less oxytocin, more prolactin, and a poor premorbid IQ, and they performed worse in sustained attention. Male patients with higher prolactin levels experienced more severe psychotic symptoms and required higher doses of antipsychotics. Low oxytocin was associated with poor sustained attention in women, whereas low oxytocin and high prolactin in men correlated with better performance in sustained attention. CONCLUSION: Low oxytocin, high prolactin, and poor premorbid IQ and sustained attention are factors associated with an FEP, representing potential therapeutic targets in these patients. These biological factors and cognitive domains might play an important role during a FEP, which could help us to develop new strategies that improve the outcomes of this disorder and that should perhaps be gender specific.

Cultural adaptation to Spanish of the “Patient Satisfaction Survey” to assess satisfaction with electroconvulsive therapy (ECT).

The degree of satisfaction of patients and their relatives with electroconvulsive therapy (ECT) is considered an important treatment goal; however there is no scale in Spanish to quantify it. The aim of the study was to translate and adapt into Spanish the “Patient Satisfaction Survey” (PSS) for its use in patients and their relatives.

Trypanosoma cruzi co-infections with other vector borne diseases are frequent in dogs from the pacific coast of Ecuador.

Dogs are a reservoir for Chagas disease, caused by Trypanosoma cruzi (T. cruzi), and other companion vector-borne diseases, including ehrlichiosis (Ehrlichia canis and Ehrlichia ewingii), anaplasmosis (Anaplasma phagocytophilum and Anaplasma platys), dirofilariasis (Dirofilaria immitis) and Lyme disease (Borrelia burgdorferi). This study has two key objectives: 1) to determine seroreactivity against T. cruzi in dogs from the town of Colón, in Portoviejo city, in the central coast of Ecuador; and 2) to establish the coinfection frequency of other companion vector-borne diseases in dogs positive for T. cruzi. Antibodies against T. cruzi were detected using two enzyme-linked immunosorbent assays. Diagnostic consensus between ELISA tests was established using the Cohen's Kappa coefficient. Other haemoparasitic diseases were detected using the IDEXX SNAP® 4Dx® kit in dogs previously diagnosed as T. cruzi-seropositive. From 84 dogs sampled, 57.14% (48/84) tested positive for T. cruzi. Co-infection analysis of 25 dogs positive for T. cruzi revealed antibodies also against Ehrlichia spp. (48%), Anaplasma spp. (28%), and Dirofilaria immitis (12%). These results provide a novel perspective regarding the status of these pathogens which co-infect dogs in Colón. Since all these pathogens are zoonotic, our findings should warn regional health authorities to implement sanitary programs, to better prevent and control vectors associated to these pathogens. On the other hand, human and veterinarian doctors, should consider that patients with a cardiac infection condition could be suffering co-infections with two or more vector transmitted pathogens.

Diagnostic concordance between Primary Care and Mental Health.

To analyse the diagnostic concordance index between Primary Care and Mental Health.

Cannabis-induced psychosis: clinical characteristics and its differentiation from schizophrenia with and without cannabis use. / Psicosis inducida por cannabis: características clínicas y su diferenciación con la esquizofrenia con y sin consumo de cannabis asociado.

Cannabis use is considered an established risk factor for psychosis development. Differentiating between cannabis-induced disorders and schizophrenia is useful for prognostic and therapeutic purposes. Three inpatients groups were differentiated: cannabis-induced psychosis (CIP) (n = 69; mean age = 27.4, SD = 6.5; 82.6% males), schizophrenia with cannabis abuse or dependence (SZ + CB) (n = 57; mean age = 31.9, SD = 10.1; 94.7% males) and schizophrenia without cannabis abuse or dependence (SZ) (n = 181; mean age = 41.8, SD = 13.3; 54.1% males). The Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) scale was used to differentiate induced psychosis. The CIP group presented lower mean scores on the negative PANSS subscale (M = 12.9, SD = 5.9; F = 32.24, p < 0.001), fewer auditory hallucinations (60.3%; X² = 6.60, p = 0.037) and greater presence of mania (26.1% vs. 12.3%; X² = 32.58, p < 0.001) than the SZ + CB group. There were few clinical differences between patients with schizophrenia, regardless of previous cannabis use. The age of first admission due to psychosis was lower in both psychotic inpatients groups with cannabis use (M = 26.1, SD = 6.4 in CIP and M = 25.3, SD = 6.2 in SZ + CB; X² = 20.02, p < 0,001). A clinical pattern characteristic of cannabis-induced psychosis was not observed, but the precipitating role of cannabis in the appearance of psychotic symptoms was demonstrated, given the lower age of first admission due to psychosis in cannabis user groups.

El consumo de cannabis se considera un factor de riesgo establecido para el desarrollo de psicosis. Diferenciar los trastornos inducidos por cannabis de la esquizofrenia resulta útil desde el punto de vista pronóstico y terapéutico. Se diferenciaron tres grupos de pacientes hospitalizados: psicosis inducida por cannabis (PIC) (n = 69; Media de edad = 27,4, DE = 6,5; 82,6 % varones), esquizofrenia con abuso o dependencia de cannabis (EZ + CB) (n = 57; Media de edad = 31,9, DE = 10,1; 94,7% varones) y esquizofrenia sin abuso o dependencia de cannabis (EZ) (n = 181; Media de edad = 41,8, DE = 13,3; 54,1% varones). Se utilizó la escala Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) para la diferenciación de cuadros inducidos. El grupo PIC presentó puntaciones inferiores en la subescala PANSS negativa (M = 12,9, DE = 5,9; F = 32,24; p < 0,001), menos alucinaciones auditivas (60,3%; X²  = 6,60; p = 0,037) y mayor presencia de manía (26,1% vs. 12,3%; X² = 32,58; p < 0,001) en comparación con el grupo EZ + CB. Hubo pocas diferencias clínicas entre los pacientes con esquizofrenia, independientemente del consumo de cannabis. La edad del primer ingreso por psicosis fue menor en ambos grupos de psicóticos consumidores (M = 26,1, DE = 6,4 en PIC y M = 25,3, DE = 6,2 en EZ + CB; X² = 20,02; p < 0,001). No se observó un patrón clínico característico de las psicosis inducidas por cannabis, aunque sí se demostró el papel precipitante del cannabis en la aparición de psicosis, dada la menor edad de ingreso en los consumidores.

Mental Health in Elderly Spanish People in Times of COVID-19 Outbreak.

BACKGROUND: We aim to assess COVID-19 outbreak-related emotional symptoms, identify gender differences, and study the relationship between the emotional state and environmental features in the elderly. METHODS: We conducted a cross-sectional study starting on March 29 to April 5, 2020 based on a national online survey using snowball sampling techniques. Symptoms of anxiety (Hamilton Anxiety Scale), depression (Beck Depression Inventory) and acute stress (Acute Stress Disorder Inventory) were compared between people over and under 60 years old. Gender differences and the relationship of loneliness, regular exercise, economic losses and use of anxiolytics on the mental state were evaluated. RESULTS: One thousand six hundred thirty-nine (150 [9.2%] aged ≥60) participants completed the survey. The greater than or equal to 60 group showed lower mean (SD) BDI levels than the less than 60 group (3.02 [3.28] versus 4.30 [4.93]); and lower mean (SD) acute stress disorder inventory scores than the less than 60 group (3.68 [3.20] versus 4.45 [3.06]). There were no gender differences in any of the clinical measures. The presence of economic losses as well as the increase in the use of anxiolytics was significantly associated with higher emotional distress in the elderly compared to the younger group. CONCLUSIONS: Older people have shown less emotional distress, with no differences between men and women. Economic loss and substance use should be monitored to guarantee the emotional well-being of the elderly.

Progression of the functional deficit in a group of patients with bipolar disorder: a cluster analysis based on longitudinal data.

We aimed to examine the trajectory of psychosocial functioning in a sample of euthymic patients with bipolar disorder (BD) throughout a 5-year follow-up. Ninety-nine euthymic bipolar patients and 40 healthy controls (HC) were included. A neurocognitive assessment (17 neurocognitive measures grouped in 6 domains) was carried out at baseline. The split version of the Global Assessment of Functioning scale (GAF-F) and the Functioning Assessment Short Test (FAST) were used to examine psychosocial functioning at baseline (T1), and after a 5-year follow-up (T2). The statistical analysis was performed through repeated measures ANOVA and hierarchical cluster analysis based on the GAF-F and the FAST scores at T1 and T2. Eighty-seven patients (87.9%) were evaluated at T2. The cluster analysis identified two groups of patients. The first group included 44 patients (50.6%) who did not show a progression of the functional impairment (BD-NPI). The second cluster, which included 43 patients (49.4%), was characterized by a progression of the functional impairment (BD-PI). The BD-PI had a higher number of relapses and a higher number of hospitalizations during the follow-up period, as well as worse neurocognitive functioning than the BD-NPI. The repeated measures ANOVA confirmed that the psychosocial performance of BD-NPI is stable while there was a progression of the functional deterioration in BD-PI. The trajectory of the psychosocial functioning of patients with BD is not homogeneous. Our results suggest that in at least one subset of patients with BD, which might account for half of the patients, the disease has a progressive course.

Climbing the ladder of decline: Income and acculturation associated with chronic inflammation among Mexican immigrants.

OBJECTIVES: Financial hardship and immigrant status are often associated with poorer health as immigrant groups acculturate to life in the US. Known as the Latino health paradox, studies have shown that Latino/a immigrants in particular often experience declines in health the more they embrace ways of life considered "dominant" by US society. At present, critical biological pathways linking socioeconomic and acculturative processes remain to be better explained. The present study investigates associations among financial strain, acculturation, and chronic inflammation. METHODS: In our study of 129 Mexican-born immigrants living in the US, we used Pearson's correlations and multiple regression analyses to investigate links among income-to-poverty ratio (an indicator of financial strain), English language engagement (acculturation), and C-reactive protein (CRP), a measure of systemic inflammation. RESULTS: Results showed that for men, but not women, acculturation as defined by English language engagement moderated the association between an income-to-poverty ratio and CRP levels. CONCLUSIONS: Consistent with the Latino health paradox, more acculturated men with relatively higher income levels (compared with the study sample) had significantly higher levels of CRP.

Schoolbag weight carriage in Portuguese children and adolescents: a cross-sectional study comparing possible influencing factors.

BACKGROUND: Schoolbags and the consequences of carrying them, particularly those associated with overload, are often studied as a health concern. Modifications in gait and posture were reported when children carried loads that corresponded to more than 10% of their body weight (BW). The aims of this study were to verify the load that is carried by Portuguese students and how it is influenced by factors such as school grade, school schedule, lunch site, physical education, sex and body mass index (BMI). Acquiring a more specific knowledge of the Portuguese context and understanding the influence of these factors may allow us to generate proposals to control them in ways that benefit students. METHODS: The load carried by students in the 5th grade (10.6 ± 0.4 years) and 9th grade (14.7 ± 0.6 years) were weighed with a luggage scale on all days of the week, resulting in 680 evaluations. Data related to the school day were also collected, such as the student's lunch site, how he or she got to school and his or her school schedule for that day. Individual height and weight were also assessed. RESULTS: The 5th grade students carried greater loads than the 9th grade students, resulting in a substantial difference relative to their BW. The school loads of the 5th grade students were mostly greater than 10% of their BWs. Girls tended to carry heavier loads than boys, and overweight students also tended to carry heavier loads. Students who could eat lunch at home carried less weight, and on physical education days, the total load carried increased, but the backpacks of the 5th grade students were lighter. CONCLUSIONS: The results of the current study describe excessive schoolbag weight among Portuguese students and expound on some of the factors that influence it, which can help researchers and professionals design a solution to decrease children's schoolbag loads.

Digital Technology for Internet Access by Patients With Early-Stage Schizophrenia in Spain: Multicenter Research Study.

BACKGROUND: Digital technology and social networks are part of everyday life in the current internet age, especially among young people. To date, few studies have been published worldwide on the pattern of use of digital technology devices and applications in patients with early-stage schizophrenia and even fewer comparing them with healthy participants (not using data from general population surveys) from the same demographic areas. In Spain, no such study has been carried out. OBJECTIVE: The aim of this study was to analyze how patients with early-stage schizophrenia use internet and social networks compared with healthy participants matched by age and gender and also to examine which devices are utilized to access internet resources. METHODS: A cross-sectional, multicentric study was carried out through a semistructured interview asking about the use of digital technology devices and internet. The sample comprised 90 patients and 90 healthy participants. The semistructured interview was conducted on 30 outpatients and 30 healthy subjects in each of the 3 different cities (Madrid, Alicante, and Cuenca). Student t test was used for continuous variables and chi-square test for categorical variables. In the case of ordinal variables, nonparametric Mann-Whitney U and Kruskal-Wallis H tests for independent samples were performed to compare groups. RESULTS: The results indicated that a large proportion of patients with early-stage schizophrenia have access to different digital devices and use them frequently. In addition, both groups coincide in the order of preference and the purpose for which they use the devices. However, a lower frequency of use of most digital technology devices was detected in patients compared with healthy participants. In the case of some devices, this was due to the impossibility of access and not a lack of interest. CONCLUSIONS: To our knowledge, this is the first study to analyze patterns of internet access and use of digital technology devices and applications in Spanish patients with early-stage schizophrenia compared with healthy participants from the same demographic areas. The results on significant access and use of digital technology and internet shown in this cross-sectional study will allow enhanced and more efficient treatment strategies to be planned, utilizing digital technology devices, for patients with early-stage schizophrenia.

Effects of Suspension Versus Traditional Resistance Training on Explosive Strength in Elementary School-Aged Boys.

PURPOSE: The aim of this study was to determine the effects of an 8-week program of resistance training (RT) or suspension training (ST) on explosive strength in prepubescent boys. METHODS: Fifty-seven boys aged 10-11 years were assigned to 2 training groups, RT or ST or a control group (no training program). Boys trained twice weekly for 8 weeks. RESULTS: A significant interaction was reported with a large (P < .001, ηp2=.463), medium (P < .001, ηp2=.395), and small effect sized (P ≤ .001, ηp2=.218) in the 1-kg ball throw, 3-kg ball throw, and time-at-20-m test, respectively. There was no significant interaction in the countermovement vertical jump or the standing long jump. Changes from preintervention to postintervention for the 1-kg ball throw were 5.94% and 5.82% for the ST and RT, respectively, and 8.82% and 8.14% in the 3-kg ball throw for the ST and RT, respectively. The improvement in the 20-m sprint was 1.19% for the ST and 2.33% for the RT. CONCLUSION: Traditional RT and ST seem to be effective methods for improving explosive strength in prepubescent boys. ST could be considered as an alternative modality to optimize explosive strength training in school-based programs.

Isolation and molecular characterization of Corynebacterium pseudotuberculosis from sheep and goats in Mexico.

The pathogenic bacteria of Corynebacterium pseudotuberculosis caused a chronic contagious infectious disease of the caseous lymphadenitis or pseudotuberculosis. Globally, isolates obtained from different injuries that affect sheep and goats, have been identified by fully or partially gene sequencing. However, in Mexico there is no complete study to identify by molecular and phylogenetic techniques the circulating isolates as well as its virulence factors. Therefore, in the present study we reported the identification of 57 isolates of C. pseudotuberculosis by bacteriological tests and the amplification of 16S rRNA, rpoB and pld genes, as well as, genes involved in virulence and pathogenicity: Fag A, Fag B, Fag C, Fag D and hsp60. Phylogenetic analysis was performed based on the partial sequence of the rpoB gene. Genes involved in virulence and pathogenicity were identified in the 98.2% of the isolates. Regarding the phylogenetic analysis, were identified the species and subspecies to which they belong of all the tested isolates. The phenotypic and genotypic characterization will allow to establish preventive and prophylactic measures aimed to the creation of effective immunogens against Corynebacterium pseudotuberculosis.

Antibiotics susceptibility of quinolones against Salmonella spp. strains isolated and molecularly sequenced for gyrA gene.

Drug-resistant Salmonella is frequently detected in most parts of the world, and its rate of resistance has increased significantly in recent years. However, this study aimed to evaluate the minimum inhibitory concentration (MIC, determined with the Kirby-Bauer method) of quinolones in 86 Salmonella spp. strains isolated from pigs. Both the inside and outside of the QRDR region of strains were sequenced. The DNA sequence of the QRDR region of Salmonella spp. revealed the mutations S83F, D87N and S83Y. The region outside the QRDR showed a mutation in L582G. Forty-five isolates of Salmonella ssp. were categorized as quinolone-resistant; out of these, 16 corresponded to Salmonella enterica and isolates showed intermediate resistance (6.25%) to nalidixic acid. Three isolats (18.6%) were resistant to ampicillin; two (12.5%) were resistant to carbenicillin. Moreover, three (18.7%) isolates were resistant to gentamicin, nitrofurantoin and pefloxacin, and 8 (50%) were resistant to trimethoprim/sulfamethoxazole. Six percent of Salmonella spp. strains showed less resistance to antimicrobial agents compared to S. Thyphimurium (18%). The resistance to individual quinolones varied by serotypes. For S. anatum and S. Reading, it was 12.25%, and for S. choreaeaesuis, S. typhimurium monofasica, 6.25%. In contrast, S. agona, S. bredeney and S. london were sensitive to these antibiotics. In conclusion, quinolones have become the drugs of choice for the treatment of severe Salmonella infections. The study of mutations outside the QRDR region opens up new insights about the resistance of Salmonella to fluoroquinolones.