Inflammatory blood cells and ratios at remission for psychosis relapse prediction: A three-year follow-up of a cohort of first episodes of schizophrenia.

BACKGROUND: The clinical course following a first episode of schizophrenia (FES) is often characterized by recurrent relapses, resulting in unfavorable clinical and functional outcomes. Inflammatory dysregulation has been implicated in relapse risk; however, the predictive value of inflammatory blood cells in clinically remitted patients after a FES has not been previously explored. METHODS: In this study, we closely monitored 111 patients in remission after a FES until relapse or a three-year follow-up endpoint. The participants were recruited from the multicenter 2EPS Project. Data on inflammatory blood cells and ratios were collected at baseline and at the time of relapse or after three years of follow-up. RESULTS: Monocyte counts (OR = 1.91; 95 % CI = 1.07-3.18; p = 0.009) and basophil counts (OR = 1.09; 95 % CI = 1.01-1.12; p = 0.005) at baseline were associated with an increased risk of relapse, while the platelet-lymphocyte ratio (OR = 0.98; 95 % CI = 0.97-0.99; p = 0.019) was identified as a protective factor. However, after adjusting for cannabis and tobacco use during the follow-up, only monocyte counts (OR = 1.73; 95 % CI = 1.03-2.29; p = 0.027) and basophil counts (OR = 1.08; 95 % CI = 1.01-1.14; p = 0.008) remained statistically significant. ROC curve analysis indicated that the optimal cut-off values for discriminating relapsers were 0.52 × 10^9/L (AUC: 0.66) for monocytes and 0.025 × 10^9/L (AUC: 0.75) for basophils. When considering baseline inflammatory levels, no significant differences were observed in the inflammatory biomarkers at the endpoint between relapsers and non-relapsers. CONCLUSION: This study provides evidence that higher monocyte and basophil counts measured at remission after a FES are associated with an increased risk of relapse during a three-year follow-up period.

Association between neutrophil to lymphocyte ratio and inflammatory biomarkers in patients with a first episode of psychosis.

Neutrophil to lymphocyte ratio (NLR) has been proposed as an emerging marker of the immune system alterations in psychotic disorders. However, it is not entirely clear whether NLR elevation is a characteristic of the psychotic disorder itself, which inflammatory pathways activation is detecting, or which possible confounding variables could alter its interpretation. We aimed to analyze the relationship of NLR values with a panel of inflammatory and oxidative/nitrosative stress biomarkers and main potential confounding factors in a well-characterized cohort of 97 patients with a first episode of psychosis (FEP) and 77 matched healthy controls (HC). In the FEP group, NLR values presented a moderate, positive correlation with the pro-inflammatory mediator Prostaglandin E2 levels (r = 0.36, p < 0.001) and a small but significant, positive correlation with cannabis use (r = 0.25, p = 0.017). After controlling for cannabis use, the association between NLR and PGE2 remained significant (beta = 0.31, p = 0.012). In the HC group, NLR values negatively correlated with body mass index (BMI, r = -0.24, p = 0.035) and positively correlated with tobacco use (r = 0.25, p = 0.031). These findings support a relationship between the elevation of NLR values and an elevated expression of proinflammatory pathways related to stress response in patients with a FEP. In addition, our study highlights the importance of considering variables such as cannabis or tobacco consumption, and BMI when interpreting the results of studies aimed to establish a clinical use of NLR. These considerations may help future research to use NLR as a reliable biomarker to determine immune system status in this population.

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

Progressive loss of cortical gray matter in first episode psychosis patients with auditory hallucinations.

BACKGROUND: Previous longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. METHODS: A Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. RESULTS: At baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. CONCLUSIONS: Brain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients.

Identifying risk factors for predominant negative symptoms from early stages in schizophrenia: A longitudinal and sex-specific study in first-episode schizophrenia patients.

BACKGROUND: People with schizophrenia and predominant negative symptoms (PNS) present a different clinical and functional profile from those without such symptomatology. Few studies have examined the risk factors and the incidence of PNS in first-episode schizophrenia patients (FES) and differentiating by sex. This study aims to assess prevalence, demographic and clinical characteristics related to PNS from early stages and to study if there are sex-specific features in terms of developing PNS. METHODS: In a sample of 121 FES patients derived from a multicentre and naturalistic study, those who developed PNS at 12-months were identified. Environmental, clinical, functional, and cognitive ratings were examined longitudinally. Binary logistic regressions were applied to detect baseline risk factors for developing PNS at one-year follow-up. RESULTS: In the present FES cohort, 24.8% of the patients (n=30) developed PNS (20% of the women, 27.6% of the men). Compared to non-PNS (75.2%, n=91), at baseline, PNS group had more negative (t=-6.347; p<0.001) and depressive symptoms (t=-5.026; p<0.001), poorer premorbid adjustment (t=-2.791; p=0.006) and functional outcome (t=-2.649; p<0.001), more amotivation (t=-7.333; p<0.001), more expressivity alterations (t=-4.417; p<0.001), worse cognitive reserve (t=2.581; p<0.011), a lower estimated intelligent quotient (t=2.417; p=0.017), worse verbal memory (t=2.608; p=0.011), and worse fluency (t=2.614; p=0.010). Regressions showed that the premorbid adjustment was the main predictor of PNS in females (p=0.007; Exp(B)=1.106) while in males were a worse verbal memory performance (p=0.031; Exp(B)=0.989) and more alterations in the motivation domain (p=0.001; Exp(B)=1.607). CONCLUSIONS: A different baseline clinical profile and notable risk factors differences in the development of PNS between males and females were found. Results suggest that sex may be an important confounder in studies comparing schizophrenia patients with predominant and non-predominant negative symptomatology.

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.

The polygenic basis of relapse after a first episode of schizophrenia.

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11-0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse.

Hospital admissions due to suicide attempts during the COVID-19 pandemic, a 3-year longitudinal study.

The appearance of the SARS CoV-2 virus and the associated COVID-19 pandemic has been associated with the onset of mental disorders in healthy people and the worsening in those with pre-existing mental conditions. One of the areas that has raised the greatest concern is that of suicidality. Most of the published studies have been carried out cross-sectional or with small samples, without stratifying by age and gender. Thus, the aim of this longitudinal research is to study, in a large population sample of around 6,700,000 inhabitants belonging to the entire region of Madrid (Spain), the admissions in psychiatric hospitalization units due to suicidal attempts along 2019, 2020 and 2021. No clear increase in the number of admissions due to suicidality in the total population have been found. In addition, a higher prevalence in admissions among women is verified. Moreover, stratifying by age and gender, a striking and significant increase in hospital admissions due to suicidality has been observed in the group up to 17 years old, from September 2020 until the end of the study. These results highlight the special vulnerability of children and adolescents, specifically girls, and the need for preventive measures in the face of future pandemics.

Dramatic increase of suicidality in children and adolescents after COVID-19 pandemic start: A two-year longitudinal study.

The COVID-19 pandemic has impacted the mental health of the youngest, worsening their emotional well-being. The demand for care in psychiatric emergencies may indirectly reflect the mental health state of children and adolescents and the emotional consequences of the pandemic. Moreover, suicidality can be considered a marker of severity in this population group. Therefore, we have aimed to longitudinally describe the number of children and adolescents attended in the psychiatry emergency department due to suicidal ideation or attempts and, to explore differences in suicidality according to gender and age. A retrospective study was carried out in the University Hospital of San Juan, Alicante, Spain, from January 01, 2018 to December 31, 2021. A total of 138 participants under 18 years requesting psychiatric care due to suicidal ideation or attempts were included. The sample was composed by 35% of males and the mean age was 14.8 years old (SD = 2.2). The number of cases per year range from 10 in 2018 to 88 in 2021. Attendances were significantly higher between 2021 and the three previous years. Besides, the number of attentions registered in the last 9 months of 2021 equals those that occurred in the entire previous period. Most of the cases were girls and middle adolescents. Suicide ideation or attempts have skyrocketed in children and adolescents. This alarming increase presents a one-year lag peak from the COVID-19 outbreak and continues until the end of 2021. Girls and those over 12 years have been identified as risk groups to present suicidal ideation or attempts.

Women with psychotic episodes during pregnancy show increased markers of placental damage with Tenney-Parker changes.

Psychosis is a hazardous and functionally disruptive psychiatric condition which may affect women in pregnancy, entailing negative consequences for maternofetal well-being. The precise pathophysiological basis and consequences of a psychotic episode in pregnancy remain to be further elucidated. The placenta is a pivotal tissue with many functions in the gestational period, critically influencing the fate and development of pregnancy. Although detrimental alterations have been observed in women undergoing severe psychiatric disorders in pregnancy, there are little studies evaluating the consequences of suffering from a psychotic episode in the placental tissue In this work, we have evaluated the histopathological consequences of a first episode of psychosis in pregnancy (FE-PW; N=22) and compare them with healthy pregnant women (HC-PW; N=20) by using histological, immunohistochemical and gene expression techniques. Our results define that the placental tissue of FE-PW display an increase in the number of placental villi, bridges, syncytial knots and syncytial knots/villi. Besides, we have also observed an enhanced gene and protein expression in FE-PW of the hypoxic marker HIF-1α, together with the apoptotic markers BAX and Bcl-2. To our knowledge, this is the first study demonstrating significant histopathological changes in the placenta of women suffering a new-onset psychotic episode in pregnancy. Further studies should be aimed at deepening the knowledge about the pernicious effects of psychosis in the maternofetal tissues, as well as the potential implications of these alterations.

Neighborhood Vulnerability and Disability in First Episode of Psychosis: A Multilevel Study.

Objective: Neighborhood socioeconomic status seems to be related to functioning in patients with first episode of psychosis (FEP). The present study aimed to assess if neighborhood vulnerability and risk of social exclusion could predict functional outcomes in people with FEP after controlling for other key variables identified in previous literature.Methods: A total of 137 patients with FEP (DSM-IV-TR criteria) and 90 controls comprised the study sample from February 2013 to May 2019. Functioning was assessed with the WHO Disability Assessment Schedule. Neighborhood vulnerability was measured using a multidimensional socioeconomic deprivation index; data for the index were collected by the Madrid City Council and based on the participant's home address. Multilevel mixed-effects regression analyses were conducted to estimate the effects of neighborhood vulnerability on functioning.Results: Our results show that FEP patients could be more vulnerable to the effects of neighborhood-level characteristics than healthy controls (B = 1,570.173; z = 3.91; P < .001). In addition, our findings suggest that higher neighborhood vulnerability is related to greater functional disability in people with FEP, after controlling for other relevant confounders (B = 1,230.332; z = 2.59; P = .010).Conclusions: These results highlight the importance of incorporating contextual factors into assessment of patients with FEP, since psychosocial difficulties observed in these patients could be partially related to the quality of neighborhood social-related resources.

Failure of deactivation in bipolar disorder during performance of an fMRI adapted version of the Stroop task.

INTRODUCTION: Few studies have examined the functional brain correlates of the performance of the Stroop task in bipolar disorder (BD). It is also not known whether it is associated with failure of de-activation in the default mode network, as has been found in studies using other tasks. METHODS: Twenty-four BD patients and 48 age, sex and educationally estimated intellectual quotient (IQ) matched healthy subjects (HS) underwent a functional MRI during performance of the counting Stroop task. Task-related activations (incongruent versus congruent condition) and de-activations (incongruent versus fixation) were examined using whole-brain, voxel-based methodology. RESULTS: Both the BD patients and the HS showed activation in a cluster encompassing the left dorsolateral and ventrolateral prefrontal cortex and the rostral anterior cingulate cortex and supplementary motor area, with no differences between them. The BD patients, however, showed significant failure of de-activation in the medial frontal cortex and the posterior cingulate cortex/precuneus. CONCLUSIONS: The failure to find activation differences between BD patients and controls suggests that the 'regulative' component of cognitive control remains intact in the disorder, at least outside episodes of illness. The failure of de-activation found adds to evidence documenting trait-like default mode network dysfunction in the disorder.

Social Cognition Mediates the Impact of Processing Speed and Sustained Attention on Global Functioning in Schizophrenia.

BACKGROUND: Deficits in information processing, sustained attention and social cognition have important implications for the daily functioning of people with schizophrenia. The present study analyzed the relationship between processing speed, sustained attention, social cognition, and functioning in clinically stable people with schizophrenia. METHOD: Ninety people with schizophrenia and 100 healthy controls completed a battery of measures to assess clinical symptoms, processing speed, sustained attention, social cognition, and functioning. GLMMs and SEM were used to assess the relationships between these variables. RESULTS: People with schizophrenia had impaired performance in all cognitive outcomes compared to healthy controls. Processing speed and sustained attention, together in a latent variable, had a strong effect on functioning (Beta = 0.32; p <.05). However, social cognition had also a strong effect on functioning (Beta = 0.29; p <.001) in the mediation model, which exhibited better indices of fit than the model including neurocognition alone (e.g. RMSEAbasic = 0.131 and RMSEAmediator = 0.054). CONCLUSIONS: The mediating effect of social cognition on the relationship between processing speed, sustained attention, and functioning in people with schizophrenia suggests the importance of including both domains of neurocognition along with social cognition as treatment targets in rehabilitation interventions to optimize improvements in functioning in schizophrenia.

Cognitive versus emotional modulation within a Stroop paradigm in patients with schizophrenia.

BACKGROUND: Schizophrenia is a complex disorder involving deficits in both cognitive and emotional processes. Specifically, a marked deficit in cognitive control has been found, which seems to increase when dealing with emotional information. AIMS: With the aim of exploring the possible common links behind cognitive and emotional deficits, two versions of the emotional Stroop task were administered. METHOD: In the cognitive-emotional task, participants had to name the ink colour (while ignoring the meaning) of emotional words. In contrast, the emotional-emotional task consisted of emotional words superimposed on emotional faces, and the participants had to indicate the emotional valence of the faces. Fifty-eight participants (29 in-patients diagnosed with schizophrenia and 29 controls) took part in the study. RESULTS: Patients and controls showed similar response times in the cognitive-emotional task; however, patients were significantly slower than controls in the emotional-emotional task. This result supports the idea that patients show a more pronounced impairment in conflict modulation with emotional content. Besides, no significant correlations between the tasks and positive or negative symptoms were found. This would indicate that deficits are relatively independent of the clinical status of patients. However, a significant correlation between the emotional-emotional task and cognitive symptoms was found. CONCLUSIONS: These findings suggest a restricted capacity of patients with schizophrenia to deal with the attentional demands arising from emotional stimuli.

Emotional processing in patients with single brain damage in the right hemisphere.

BACKGROUND: The interest in the relationship between brain damage and social cognition has increased in recent years. The objectives of the present study were the following: (1) to evaluate and compare emotional facial recognition and subjective emotional experience in patients who have suffered a single ischemic stroke in the right hemisphere (RH) and in healthy people, (2) to analyze the relationship between both variables in both groups of subjects, and (3) to analyze the association between the cerebral location of the stroke and these two variables. METHODS: Emotional facial recognition and the subjective emotional experience of 41 patients who had suffered a single ischemic stroke in the RH and 45 volunteers without previous cerebrovascular pathology were evaluated. RESULTS: Brain damaged patients performed lower in facial emotional recognition and had a less intense subjective emotional response to social content stimuli compared to healthy subjects. Likewise, among patients with RH ischemic stroke, we observed negative associations between facial recognition of surprise and reactivity to unpleasant images, and positive associations between recognition of disgust and reactivity to pleasant images. Finally, patients with damage in the caudate nucleus of the RH presented a deficit in the recognition of happiness and sadness, and those with damage in the frontal lobe exhibited a deficit in the recognition of surprise, compared to those injured in other brain areas. CONCLUSIONS: Emotional facial recognition and subjective emotional experience are affected in patients who have suffered a single ischemic stroke in the RH. Professionals caring for stroke patients should improve their understanding of the general condition of affected persons and their environment, assess for risk of depression, and facilitate their adaptation to work, family, and social environments.

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.

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.