Psychological Distress in Low-Income and Economically Marginalized Populations in India: Protective and Risk Factors.

Studies at the juncture of development economics and public health take on considerable responsibility in addressing inequality and related mental health distress. Mental healthcare in economically marginalized populations requires depicting the linkages between socioeconomic status and psychological distress. In the present work, a sequential mixed-methods design was used to study 190 people in such communities in India. Gender-dependent psychological distress was found according to the Kessler Psychological Distress Scale (K-10) with moderate distress in women (M = 26.30, SD = 9.15) and mild distress in men (M = 21.04, SD = 8.35). Regression analysis indicated that gender significantly predicted psychological distress, followed by age, marital status, and the level of education of the head of the family. The Interpretative Phenomenological Analysis of semi-structured interviews of the six women who scored the highest on the distress scale unveiled three master themes: (1) manifestation of psychological distress, (2) contextual challenges, and (3) sources of strength and resilience. Overall, participants reported a lack of resources, community violence, gender discrimination, and widespread substance use as major contributors to the ongoing distress. These findings can pave the way for future studies to expand beyond independent economic indicators and curate clinical interventions for culturally competent mental healthcare.

Resilience among involuntarily childless couples and individuals undergoing infertility treatment: a systematic review.

Infertility is regarded as a highly stressful and challenging experience. However, the response to this unexpected moment varies from one individual to the other. The review explores research that studies resilience in the context of infertility and its treatment. The purpose was to study the protective and risk factors associated with resilience and to identify psychosocial factors that could play a crucial role in resilience among infertile couples and individuals who are seeking infertility treatment. Four major databases (PubMed, Scopus, ScienceDirect, and Wiley Online Library) were searched with appropriate keywords. A total of 4101 articles were retrieved from the databases and after following various levels of screening 18 articles were finalized. These articles explored resilience and other psychosocial factors in couples/individuals seeking infertility treatment. The protective factors associated with resilience were quality of life, coping, social support, and posttraumatic growth. The risk factors associated with resilience were infertility-related stress, anxiety and depression. The unexpected diagnosis of infertility might be disturbing for many, still, it may not be extremely agonizing for some. Individuals who are encouraged to utilize their own resources and seek support are able to deal with stressors associated with infertility.

Seed amplification assay for the detection of pathologic alpha-synuclein aggregates in cerebrospinal fluid.

Misfolded alpha-synuclein (αSyn) aggregates are a hallmark event in Parkinson's disease (PD) and other synucleinopathies. Recently, αSyn seed amplification assays (αSyn-SAAs) have shown promise as a test for biochemical diagnosis of synucleinopathies. αSyn-SAAs use the intrinsic self-replicative nature of misfolded αSyn aggregates (seeds) to multiply them in vitro. In these assays, αSyn seeds circulating in biological fluids are amplified by a cyclical process that includes aggregate fragmentation into smaller self-propagating seeds, followed by elongation at the expense of recombinant αSyn (rec-αSyn). Amplification of the seeds allows detection by fluorescent dyes specific for amyloids, such as thioflavin T. Several αSyn-SAA reports have been published in the past under the names 'protein misfolding cyclic amplification' (αSyn-PMCA) and 'real-time quaking-induced conversion'. Here, we describe a protocol for αSyn-SAA, originally reported as αSyn-PMCA, which allows detection of αSyn aggregates in cerebrospinal fluid samples from patients affected by PD, dementia with Lewy bodies or multiple-system atrophy (MSA). Moreover, this αSyn-SAA can differentiate αSyn aggregates from patients with PD versus those from patients with MSA, even in retrospective samples from patients with pure autonomic failure who later developed PD or MSA. We also describe modifications to the original protocol introduced to develop an optimized version of the assay. The optimized version shortens the assay length, decreases the amount of rec-αSyn required and reduces the number of inconclusive results. The protocol has a hands-on time of ~2 h per 96-well plate and can be performed by personnel trained to perform basic experiments with specimens of human origin.

A longitudinal study of depression, anxiety, and stress among Indians during COVID-19 pandemic.

The COVID-19 has caused significant public health chaos. Whether infected or uninfected, people have reported significant mental health issues during the COVID-19 pandemic. The present study explored symptoms of depression, anxiety, and stress of uninfected people with the disease over three time periods. A total of 132 participants took part in all the three phases. Data at Time 1 and Time 2 were collected during the national lockdown with 1 month apart, while data at Time 3 were collected immediately once the lockdown was uplifted in India. Participants completed the Depression, Anxiety and Stress Scale-21 online. The results indicated that despite an increase in the average number of COVID-19 cases, depression, anxiety, and stress symptoms decreased over time with the lowest level once the lockdown was ended. These results suggest that the restrictions implemented during the national lockdown led to distress, and not an increase in COVID-19 cases per se.

Wellbeing and Problematic Smartphone Use: Serial Mediation of Mindfulness and Self-Compassion.

The relationship between wellbeing and Problematic Smartphone Use (PSU) has been explored in the past, however, the role of the potential mediators of this association is a relatively neglected area of research. Therefore, the current study examined mindfulness and self-compassion as mediators of the relationship between wellbeing and PSU in 220 university students. WHO-5 Wellbeing Index, Mindful Attention Awareness Scale- State, Self-Compassion Scale- Short form and Smartphone Addiction Scale- Short version were used for assessing wellbeing, mindfulness, self-compassion, and PSU respectively. Wellbeing had a direct and indirect effect on PSU. In addition, results supported a serial mediation model where wellbeing was found to influence PSU via mindfulness and self-compassion in a sequential manner. The results expanded the Compensatory Internet Use Theory (CIUT) to understand PSU and have implications for the management of PSU.

Uneven Implications of Lockdown Amid COVID-19 in India: From Harassment, Stigma, Crime, and Internally Displaced People to Stress and Coping Strategies in the Middle/Upper Class.

A content analysis of an English Newspaper, The Times of India (the world's largest newspaper by circulation) during the first national lockdown amid the COVID-19 pandemic identified nine different categories culled out from a total of 129 news categories reporting unprecedented COVID-19 stories. Half of them portrayed two sides of a coin: from daily wagers and migrant workers, including internally displaced people (23/129), harassment and stigma (4/129), and crime (3/129) to stressors and coping strategies for middle/upper class individuals (39/129). Reports evidenced increased vulnerability in the lower layers of Indian stratified society. Yet, two years later, the uneven implications on physical and mental health are scarcely studied by scientific researchers.

Individual and group level risk factors in preventive health and panic buying behaviors during COVID-19 pandemic in India.

The present research explored individual and group level risk factors in preventive health and panic buying behaviors during the COVID-19 pandemic in India. Perceived susceptibility, perceived severity, COVID-19 anxiety, and personal identity were considered individual-level risk factors. Group based identities such as family, religious groups, and identification with one's nation were considered as group level risk factors. Standardized scales have been used to measure all the constructs under study. Data were collected electronically from 305 Indian respondents. Hierarchical regression analysis in SPSS Version 22 was used to test the hypotheses. Results showed that personal identity and identification with the nation predicted preventive health behavior. Panic buying behavior was predicted by the location of the respondents (containment versus non-containment zones), perceived severity, and one's personal identity. The interplay of individual and social factors is reflective of both individual and collective agencies in the adoption of preventive health behaviors, while only individual-level factors led to panic buying behavior. The findings of this study have implications for curbing, managing, and reinforcing desirable and non-desirable behavior during the present pandemic as well as in the future as well.

Risk perception, social distancing, and distress during COVID-19 pandemic: Exploring the role of online counseling and perceived social support.

The study explored the relationship between social distancing and distress along with risk factors of social distancing. Further, online counseling/mental health services and perceived social support were tested as possible moderators between social distancing and distress. Valid and reliable measures were used to collect the data from 300 Indian respondents. Process use of social networking platforms was found to significantly explain social distancing. Online counseling/mental health services and perceived social support moderated the relationship between social distancing and distress. Only 16% of the respondents used online mental health services during the study period. Lack of awareness and acceptance of these services were major barriers.

Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-ß (Aß) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

Multiple system atrophy-associated oligodendroglial protein p25α stimulates formation of novel α-synuclein strain with enhanced neurodegenerative potential.

Pathology consisting of intracellular aggregates of alpha-Synuclein (α-Syn) spread through the nervous system in a variety of neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. The discovery of structurally distinct α-Syn polymorphs, so-called strains, supports a hypothesis where strain-specific structures are templated into aggregates formed by native α-Syn. These distinct strains are hypothesised to dictate the spreading of pathology in the tissue and the cellular impact of the aggregates, thereby contributing to the variety of clinical phenotypes. Here, we present evidence of a novel α-Syn strain induced by the multiple system atrophy-associated oligodendroglial protein p25α. Using an array of biophysical, biochemical, cellular, and in vivo analyses, we demonstrate that compared to α-Syn alone, a substoichiometric concentration of p25α redirects α-Syn aggregation into a unique α-Syn/p25α strain with a different structure and enhanced in vivo prodegenerative properties. The α-Syn/p25α strain induced larger inclusions in human dopaminergic neurons. In vivo, intramuscular injection of preformed fibrils (PFF) of the α-Syn/p25α strain compared to α-Syn PFF resulted in a shortened life span and a distinct anatomical distribution of inclusion pathology in the brain of a human A53T transgenic (line M83) mouse. Investigation of α-Syn aggregates in brain stem extracts of end-stage mice demonstrated that the more aggressive phenotype of the α-Syn/p25α strain was associated with an increased load of α-Syn aggregates based on a Förster resonance energy transfer immunoassay and a reduced α-Syn aggregate seeding activity based on a protein misfolding cyclic amplification assay. When injected unilaterally into the striata of wild-type mice, the α-Syn/p25α strain resulted in a more-pronounced motoric phenotype than α-Syn PFF and exhibited a "tropism" for nigro-striatal neurons compared to α-Syn PFF. Overall, our data support a hypothesis whereby oligodendroglial p25α is responsible for generating a highly prodegenerative α-Syn strain in multiple system atrophy.

Alpha-Synuclein Oligomers and Neurofilament Light Chain Predict Phenoconversion of Pure Autonomic Failure.

OBJECTIVE: To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NfL) in cerebrospinal fluid (CSF) of patients with pure autonomic failure (PAF) as markers of future phenoconversion to multiple system atrophy (MSA). METHODS: Well-characterized patients with PAF (n = 32) were enrolled between June 2016 and February 2019 at Mayo Clinic Rochester and followed prospectively with annual visits to determine future phenoconversion to MSA, Parkinson's disease (PD), or dementia with Lewy bodies (DLB). ELISA was utilized to measure NfL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF collected at baseline. RESULTS: Patients were followed for a median of 3.9 years. Five patients converted to MSA, 2 to PD, and 2 to DLB. NfL at baseline was elevated only in patients who later developed MSA, perfectly separating those from future PD and DLB converters as well as non-converters. ASyn-PMCA was positive in all but two cases (94%). The PMCA reaction was markedly different in five samples with maximum fluorescence and reaction kinetics previously described in MSA patients; all of these patients later developed MSA. INTERPRETATION: αSyn-PMCA is almost invariably positive in the CSF of patients with PAF establishing this condition as α-synucleinopathy. Both NfL and the magnitude and reaction kinetics of αSyn PMCA faithfully predict which PAF patients will eventually phenoconvert to MSA. This finding has important implications not only for prognostication, but also for future trials of disease modifying therapies, allowing for differentiation of MSA from Lewy body synucleinopathies before motor symptoms develop. ANN NEUROL 2021;89:1212-1220.

Generation of a humanized Aß expressing mouse demonstrating aspects of Alzheimer's disease-like pathology.

The majority of Alzheimer's disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aß under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aß sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Aß sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAß expression, rescues cognition and reduces the formation of PAS granules.

Depression, Anxiety and Stress Among Indians in Times of Covid-19 Lockdown.

Covid-19 has caused significant distress around the globe. Apart from the evident physical symptoms in infected cases, it has caused serious damage to public mental health. India, like other countries, implemented a nationwide lockdown to contain and curb the transmission of the virus. The current research is an attempt to explore psychological distress among people residing in India during the lockdown. Four hundred and three participants were asked to complete a questionnaire with questions around symptoms of depression, anxiety, stress, and family affluence. The results indicated that people who do not have enough supplies to sustain the lockdown were most affected, and family affluence was found to be negatively correlated with stress, anxiety, and depression. Among different professions, students and healthcare professionals were found to experience stress, anxiety, and depression more than others. Despite the current situation, stress, anxiety, and depression were found to be in normal ranges for mental health professionals highlighting their capabilities to remain normal in times of distress. Policymakers and other authorities may take the assistance of mental health professionals to help overcome psychological issues related to Covid-19.

Quality of Life in the COVID-19 Pandemic in India: Exploring the Role of Individual and Group Variables.

The role of individual variables (COVID-19 anxiety, perceived susceptibility, perceived severity, optimistic bias and personal identity) as predictors of quality of life (QoL) during the novel coronavirus or COVID-19 pandemic is explored. Impact of group related variables (identification to family, religious group and nation) on QoL is also examined. Sample comprised 305 male and female Indian respondents, aged 18 to 78 years. Standardized measures have been utilised to assess the constructs. Results revealed that QoL was significantly influenced by individual variables (COVID-19 anxiety and personal identity) and group variables (identification with family and nation). The effect of COVID-19 anxiety and personal identity as individual variables is over and above that of demographic variables on QoL. Group variables (family and national identification) significantly impacted QoL over and above the individual variables. Findings would indeed, aid in the rehabilitation and assistance of people to live in COVID-19 crisis, and thereafter.

Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer's disease.

Previous studies showed that injection of tissue extracts containing amyloid-ß (Aß) aggregates accelerate amyloid deposition in the brain of mouse models of Alzheimer's disease (AD) through prion-like mechanisms. In this study, we evaluated whether brain amyloidosis could be accelerated by blood infusions, procedures that have been shown to transmit prion diseases in animals and humans. Young transgenic mice infused with whole blood or plasma from old animals with extensive Aß deposition in their brains developed significantly higher levels brain amyloidosis and neuroinflammation compared to untreated animals or mice infused with wild type blood. Similarly, intra-venous injection of purified Aß aggregates accelerated amyloid pathology, supporting the concept that Aß seeds present in blood can reach the brain to promote neuropathological alterations in the brain of treated animals. However, an amyloid-enhancing effect of other factors present in the blood of donors cannot be discarded. Our results may help to understand the role of peripheral (amyloid-dependent or -independent) factors implicated in the development of AD and uncover new strategies for disease intervention.

Alpha-Synuclein Oligomers and Neurofilament Light Chain in Spinal Fluid Differentiate Multiple System Atrophy from Lewy Body Synucleinopathies.

OBJECTIVE: To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NFL) in cerebrospinal fluid (CSF) as markers of early multiple system atrophy (MSA) and to contrast findings with Lewy body synucleinopathies. METHODS: In a discovery cohort of well-characterized early MSA patients (n = 24) and matched healthy controls (CON, n = 14), we utilized enzyme-linked immunosorbent assay to measure NFL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF. We confirmed findings in a separate prospectively enrolled cohort of patients with early MSA (n = 38), Parkinson disease (PD, n = 16), and dementia with Lewy bodies (DLB, n = 13), and CON subjects (n = 15). RESULTS: In the discovery cohort, NFL was markedly elevated in MSA patients, with perfect separation from CON. αSyn-PMCA was nonreactive in all CON, whereas all MSA samples were positive. In the confirmatory cohort, NFL again perfectly separated MSA from CON, and was significantly lower in PD and DLB compared to MSA. PMCA was again nonreactive in all CON, and positive in all but 2 MSA cases. All PD and all but 2 DLB samples were also positive for αSyn aggregates but with markedly different reaction kinetics from MSA; aggregation occurred later, but maximum fluorescence was higher, allowing for perfect separation of reactive samples between MSA and Lewy body synucleinopathies. INTERPRETATION: NFL and αSyn oligomers in CSF faithfully differentiate early MSA not only from CON but also from Lewy body synucleinopathies. The findings support the role of these markers as diagnostic biomarkers, and have important implications for understanding pathophysiologic mechanisms underlying the synucleinopathies. ANN NEUROL 2020;88:503-512.

Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy.

Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of α-synuclein, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy1. Clinically, it is challenging to differentiate Parkinson's disease and multiple system atrophy, especially at the early stages of disease2. Aggregates of α-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of α-synuclein that can self-propagate and spread from cell to cell3-6. Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect α-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity7,8. Here we show that the α-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson's disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of α-synuclein-PMCA, and found that the characteristics of the α-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson's disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that α-synuclein aggregates that are associated with Parkinson's disease and multiple system atrophy correspond to different conformational strains of α-synuclein, which can be amplified and detected by α-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of α-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson's disease and multiple system atrophy.

Trauma and Post-traumatic Growth: Spirituality and Self-compassion as Mediators Among Parents Who Lost Their Young Children in a Protracted Conflict.

The purpose of the present study was to expand the knowledge on trauma and post-traumatic growth (PTG) by exploring this relationship in parents who lost their children in Kashmir (India). The main aim of the present study was to examine whether spirituality and self-compassion mediate the relationship between trauma and PTG. Data were collected from 80 parents in the age range of 35-80 years (Mean Age = 52.09). Traumatic Grief scale Prigerson et al. (in Am J Psychiatry 154:616-623, 1997), Daily Spirituality Scale (Underwood and Teresi, Ann Behav Med 24(1):22-33, 2002), Self-Compassion Scale (Raes et al., Clin Psychol Psychoth 18:250-255, 2011), and PTG Inventory (Tedeschi and Calhoun, J Trauma Stress 9(3):455-471, 1996) scales were used to measure trauma, spirituality, self-compassion, and PTG, respectively. Results of the study indicated the presence of average amount of spirituality and high amount of trauma among the participants. High level of self-compassion and post-traumatic growth was also found among the participants. The results showed that there is no significant direct relationship between trauma and PTG; however, both the indirect paths (trauma, spirituality, and PTG as well as trauma, self-compassion, and PTG) were found to be significant. The results of the present study supported serial mediation model of Trauma and PTG through spirituality and self-compassion. It implies that trauma would lead to spirituality which in turn would lead to self-compassion and which would finally result in PTG. The result provided another lens to see the relationship between trauma and PTG.

Smartphone addiction in students: A qualitative examination of the components model of addiction using face-to-face interviews.

BACKGROUND AND AIMS: Smartphone use has increased markedly over the past decade and recent research has demonstrated that a small minority of users experience problematic consequences, which in extreme cases have been contextualized as an addiction. To date, most research have been quantitative and survey-based. This study qualitatively examined the components model of addiction for both "addicted" and "non-addicted" users. METHODS: A screening tool comprising 10 dichotomous items was administered to 40 college students. Of these, six addicted and six non-addicted participants were identified on the basis of their score on the screening tool and were asked to participate in a semi-structured interview. The interview questions were based on the components model of addiction comprising six domains (i.e., salience, withdrawal, conflict, relapse and reinstatement, tolerance, and mood modification). Directed content analysis was used to analyze the transcribed data and subthemes as well as emerging themes for the study as a whole were established. RESULTS: There was some evidence of demarcation between smartphone addicts on the dimensions of salience, tolerance, withdrawal, and conflict. Mood modification was not much different in either group, and no participant reported relapse. CONCLUSIONS: The non-addicted group had much greater control over their smartphone usage than the addicted group on four (of six) aforementioned dimensions of behavioral addiction. Consequently, the main findings of this study provided good support for the components model of behavioral addiction.