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.

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.

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.

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.

Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial.

BACKGROUND: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. METHODS: Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I ≤ 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using χ2-test or t-test, as per data type. RESULTS: Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore ≤2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]). CONCLUSIONS: PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced. TRIAL REGISTRATION: European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.

Elevated midline-parietal gamma band noise power in schizophrenia but not in bipolar patients.

Gamma oscillations are key in coordinating brain activity and seem to be altered in schizophrenia. In previous work, we studied the spatial distribution of a noise power measure (scalp-recorded electroencephalographic activity unlocked to stimuli) and found higher magnitudes in the gamma band related to symptoms and cognition in schizophrenia. In the current study, we sought to replicate those findings and to study its specificity for schizophrenia in a completely independent sample. A principal component analysis (PCA) was used to determine the factorial structure of gamma noise power acquired with an electroencephalographic recording during an odd-ball P300 paradigm in the 250- to 550-ms window in 70 patients with schizophrenia (16 patients with first episode), 45 bipolar patients and 65 healthy controls. Clinical and cognitive correlates of the resulting factors were also assessed. Three factors arose from the PCA. The first displayed a midline-parietal distribution (roughly corresponding to the default mode network), the second was centro-temporal and the third anterior-frontal. Schizophrenia but not bipolar patients showed higher gamma noise power loadings in the first factor in comparison with controls. Scores for this factor were significantly and directly associated with positive and total symptoms in patients and inversely associated with global cognition in all participants. The results of this study replicate those of our previous publication and suggest an elevated midline-parietal gamma noise power specific to schizophrenia. The gamma noise power measure seems to be a useful tool for studying background oscillatory activity during performance of cognitive tasks.

Sensory Gating Deficits in First-Episode Psychosis: Evidence From Neurophysiology, Psychophysiology, and Neuropsychology.

Sensory gating deficits are commonly found in patients with schizophrenia. However, there is still scarce research on this issue. Thirty-eight patients with first-episode psychosis (FEP) were compared to thirty-eight controls. A condition-test paradigm of event-related potentials (ERP), prepulse inhibition (PPI), and some specific tasks of the MATRICS Consensus Cognitive Battery (MCCB) were used (i.e., TMT, BACS-SC, and Fluency for processing speed and CPT-IP for attention and vigilance). The ERP components measured were P50, N1, and P2. The PPI intervals examined were 30, 60, and 120 msec. Regarding the MCCB, processing speed and attention/vigilance cognitive domains were selected. FEP patients showed significant deficits in N1 and P2 components, at 30 and 60 PPI levels and in all the MCCB subtests selected. We obtained significant relationships in N1 with PPI-60, and with one MCCB subtest for processing speed. In addition, this same subtest showed significant association with P2. Therefore, sensory gating functioning is widely impaired since the very early stages of schizophrenia.

Cannabis abuse effects on prepulse inhibition in patients with first episode psychosis in schizophrenia.

Deficits in prepulse inhibition (PPI) and cannabis abuse are consistently found in schizophrenia. The authors studied PPI deficits in first episode psychosis (FEP) with schizophrenia and cannabis abuse influence. Thirty-five patients with FEP and 22 control subjects were examined. Patients were divided into cannabis use disorder (CUD) (N=21) and non-CUD (N=14). Startle measures were as follows: PPI at 30, 60, and 120 msec. Patients with CUD and patients without CUD showed lower PPI at 30 msec than control subjects. At 60 msec, patients with CUD obtained higher %PPI than patients without CUD, and patients without CUD obtained lower levels than control subjects. These findings show that cannabis abuse may improve PPI in patients with FEP at some levels.

A five-year follow-up study of neurocognitive functioning in bipolar disorder.

OBJECTIVES: Cognitive dysfunction in bipolar disorder has been well-established in cross-sectional studies; however, there are few data regarding the longitudinal course of cognitive performance in bipolar disorder. The aim of this study was to examine the course of cognitive function in a sample of euthymic patients with bipolar disorder during a five-year follow-up period. METHODS: Eighty euthymic outpatients with a DSM-IV diagnosis of bipolar disorder and 40 healthy control comparison subjects were neuropsychologically assessed at baseline (T1) and then at follow-up of five years (T2). A neurocognitive battery including the main cognitive domains of speed of processing, working memory, attention, verbal memory, visual memory, and executive function was used to evaluate cognitive performance. RESULTS: Repeated-measures multivariate analyses showed that progression of cognitive dysfunction in patients was not different to that of control subjects in any of the six cognitive domains examined. Only a measure from the verbal memory domain, delayed free recall, worsened more in patients with bipolar disorder. Additionally, it was found that clinical course during the follow-up period did not influence the course of cognitive dysfunction. CONCLUSIONS: Cognitive dysfunction that is characteristic of bipolar disorder is persistent and stable over time. Only dysfunction in verbal recall was found to show a progressive course that cannot be explained by clinical or treatment variables.

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.

Public perception of psychiatry, psychology and mental health professionals: a 15-year analysis.

Background: X (previously known as "Twitter") serves as a platform for open discussions on mental health, providing an avenue for scrutinizing public perspectives regarding psychiatry, psychology and their associated professionals. Objective: To analyze the conversations happening on X about psychiatrists, psychologists, and their respective disciplines to understand how the public perception of these professionals and specialties has evolved over the last 15 years. Methods: We collected and analyzed all tweets posted in English or Spanish between 2007 and 2023 referring to psychiatry, psychology, neurology, mental health, psychiatrist, psychologist, or neurologist using advance topic modelling and sentiment analysis. Results: A total of 403,767 tweets were analyzed, 155,217 (38%) were in English and 248,550 (62%) in Spanish. Tweets about mental health and mental health professionals and disciplines showed a consistent volume between 2011 and 2016, followed by a gradual increase from 2016 through 2022. The proportion of tweets discussing mental health doubled from 2016 to 2022, increasing from 20% to 67% in Spanish and from 15% to 45% in English. Several differences were observed on the volume of tweets overtime depending on the language they were written. Users associated each term with varied topics, such as seeking for help and recommendation for therapy, self-help resources, medication and side effects, suicide prevention, mental health in times of crisis, among others. The number of tweets mentioning these topics increased by 5-10% from 2016 to 2022, indicating a growing interest among the population. Emotional analysis showed most of the topics were associated with fear and anger. Conclusion: The increasing trend in discussions about mental health and the related professionals and disciplines over time may signify an elevated collective awareness of mental health. Gaining insights into the topics around these matters and user's corresponding emotions towards them presents an opportunity to combat the stigma surrounding mental health more effectively.