Early Vulnerability Research Articles

A geography of early vulnerabilities and exploitation in the narratives of adolescent males in England

Purpose The victimisation and criminal involvement of young people in organised criminal groups is a recognised form of child criminal exploitation (CCE) in the UK. Three phases of exploitation were identified (peer influence, adult street-level gangs and organised criminal groups). This paper aims to consider the locations associated with three stages of criminal exploitation and considers implications for safeguarding. Design/methodology/approach The research uses narratives of adolescent males and those of adults reflecting on their experiences as adolescents who had been immersed in street gangs and organised crime from northern England. Method Narratives of criminal action approach, a thematic analysis and multidimensional scaling (smallest space analysis) were undertaken to explore key locations in the planning and commissioning of a crime with at least one other person. Findings The narratives revealed that local and regional geographic locations relate to the stages of CCE. They offer an insight into the process of CCE and identify locations that could be used as a risk indicator for police forces and safeguarding teams. A clear pathway from involvement with street-level gangs to direct contact with organised criminal groups was found. This transition was represented by a move from outdoor to indoor locations. Research limitations/implications Out of the 30 participants, 29 came from the same region in Northern England, spanning a period of 30 years. It is possible that the findings may be limited to this region, or that there have been changes to criminal structures and opportunities over this time. Originality/value Although drug selling and the movement of victims across the UK is central to CCE, comparatively little attention has been given to the locations where early exploitation takes place at a micro level. Practical implications for policing and safeguarding will be discussed.

The impact of subclinical psychotic symptoms on delay and effort discounting: Insights from behavioral, computational, and electrophysiological methods

BackgroundThe ability to value rewards is crucial for adaptive behavior and is influenced by the time and effort required to obtain them. Impairments in these computations have been observed in patients with schizophrenia and may be present in individuals with subclinical psychotic symptoms (PS). MethodsIn this study, we employed delay and effort-discounting tasks with food rewards in thirty-nine participants divided into high and low levels of PS. We investigated the underlying mechanisms of effort-discounting through computational modelling of dopamine prefrontal and subcortical circuits and the electrophysiological biomarker of both delay and effort-discounting alterations through resting-state frontal alpha asymmetry (FAA). ResultsResults revealed greater delay discounting in the High PS group compared to the Low PS group but no differences in the effort discounting task. However, in this task, the same levels of estimated dopamine release were associated with a lower willingness to exert effort for high-calorie food rewards in High PS participants compared to Low PS participants. Although there were no significant differences in FAA between the High PS and Low PS groups, FAA was significantly associated with the severity of participants' negative symptoms. ConclusionsOur study suggests that the dysfunction in temporal and effort cost computations, seen in patients with schizophrenia, may be present in individuals with subclinical PS. These findings provide valuable insight into the early vulnerability markers (behavioral, computational, and electrophysiological) for psychosis, which may aid in the development of preventive interventions. These findings are preliminary and warrant further investigation.

Entorhinal cortex vulnerability to human APP expression promotes hyperexcitability and tau pathology.

Preventative treatment for Alzheimer's Disease is of dire importance, and yet, cellular mechanisms underlying early regional vulnerability in Alzheimer's Disease remain unknown. In human patients with Alzheimer's Disease, one of the earliest observed pathophysiological correlates to cognitive decline is hyperexcitability. In mouse models, early hyperexcitability has been shown in the entorhinal cortex, the first cortical region impacted by Alzheimer's Disease. The origin of hyperexcitability in early-stage disease and why it preferentially emerges in specific regions is unclear. Using cortical-region and cell-type-specific proteomics coupled with ex vivo and in vivo electrophysiology, we uncovered differential susceptibility to human-specific amyloid precursor protein (hAPP) in a model of sporadic Alzheimer's. Unexpectedly, our findings reveal that early entorhinal hyperexcitability may result from intrinsic vulnerability of parvalbumin (PV) interneurons, rather than the suspected layer II excitatory neurons. This vulnerability of entorhinal PV interneurons is specific to hAPP, as it could not be recapitulated with increased murine APP expression. However, partial replication of the findings could be seen after introduction of a murine APP chimera containing a humanized amyloid-beta sequence. Surprisingly, neurons in the Somatosensory Cortex showed no such vulnerability to adult-onset hAPP expression. hAPP-induced hyperexcitability in entorhinal cortex could be ameliorated by enhancing PV interneuron excitability in vivo. Co-expression of human Tau with hAPP decreased circuit hyperexcitability, but at the expense of increased pathological tau species. This study suggests early disease interventions targeting non-excitatory cell types may protect regions with early vulnerability to pathological symptoms of Alzheimer's Disease and downstream cognitive decline.

Vulnerability of Spatial Pattern Separation in 5xFAD Alzheimer's Disease Mouse Model.

Alzheimer's disease (AD) is the most common cause of dementia and remains incurable. This age-related neurodegenerative disease is characterized by an early decline in episodic and spatial memory associated with progressive disruption of the hippocampal functioning. Recent clinical evidence suggests that impairment of the spatial pattern separation (SPS) function, which enables the encoding and storage of episodic spatial information, may be an indicator of the early stages of AD. The aim of our study was to characterize SPS performance at a prodromal stage in 5xFAD transgenic mouse model of AD. Behavioral performance of male wild-type (WT) and 5xFAD mice (n = 14 per group) was assessed from the age of 4 months in two validated paradigms of SPS function either based on spontaneous exploration of objects or on the use of a touchscreen system. Compared with age-matched WT littermates, a mild deficit in SPS function was observed in the object recognition task in 5xFAD mice, whereas both groups showed similar performance in the touchscreen-based task. These results were observed in the absence of changes in locomotor activity or anxiety-like behavior that could have interfered with the tasks assessing SPS function. Our results indicate an early vulnerability of the SPS function in 5xFAD mice in the paradigm based on spontaneous exploration of objects. Our work opens up the possibility of examining the early neurobiological processes involved in the decline of episodic memory and may help to propose new therapeutic strategies in the context of AD.

Pathways to selective vulnerability in neuromodulatory subcortical structures during the early pathogenic stages of Alzheimer’s disease

AbstractBackgroundThe two main catecholaminergic members of the isodendritic core nuclei are the substantia nigra (SN) and the locus coeruleus (LC). Despite cytoarchitectural and neurochemical similarities between the two nuclei, the LC is significantly more vulnerable to early degenerative changes in tauopathies like Alzheimer’s disease (AD) as compared to the SN. Here, we seek to use the gradient of vulnerability in these catecholaminergic nuclei to identify pathways associated with vulnerability in early AD pathological stages.MethodThis cohort includes individuals with no neuropathologic entities and Alzheimer’s disease proteinopathic stages. Individuals with TDP‐43, Lewy Body, or Chronic Traumatic Encephalopathy pathologic entities were excluded. The LC and SN was dissected from frozen human brainstem tissue using macroscopic anatomic features. To compare the LC and SN, only cases below Braak III with sufficient RNA from both nuclei were included. The Nanostring nCounter platform was used to probe specific pathways related to neurodegenerative processes. DBH and SLC6A3 served as confirmatory readouts of accurate anatomic sampling of the LC and SN. Differential gene expression analysis was used to evaluate patterns of gene expression that differentiate the two nuclei. Annotated gene sets were evaluated using global significance scores (GSS), a representation of cumulative t‐statistics for relevant genes.ResultThe LC and SN were collected from 26 cases (Figure 1) eligible for this analysis. Accurate dissections were confirmed by differential expression of DBH (p = 1.38e‐9) and SLC6A3 (p = 4.5e‐16). Among the differentially expressed genes (Figure 2), genes associated with microglia activation (GSS = 2.35), oxidative stress (GSS = 2.17), and lipid metabolism (GSS = 2.00) significantly differentiated the LC and SN.ConclusionThe LC and SN serve as examples of differentially vulnerable nuclei at the earliest neuropathologic stages of AD. Cell intrinsic factors, physiological demands, vascular contributions, and exposure to extrinsic factors like toxins are thought to contribute to the LC’s early vulnerability. Here, we show that neuroinflammation and oxidative stress pathways are likely central to differential vulnerability at the earliest stages of Alzheimer’s disease and may represent targets for intervention in prodromal stages.

Financial toxicity in patients with newly diagnosed pancreatic cancer: A prospective cohort study.

29 Background: Financial toxicity (FT) refers to the financial strain and distress experienced by patients due to the costs associated with cancer care. Patients with pancreatic ductal adenocarcinoma (PDA) experience unique challenges including limited treatment options, aggressive disease progression, complex multidisciplinary care needs and an overall limited prognosis. The aim of this preliminary analysis was to measure FT in patients newly diagnosed with PDA and determine factors associated FT. Methods: In this prospective cohort study, patients with newly diagnosed PDA prior to treatment initiation were enrolled through a pancreatic multi-disciplinary clinic at a single institution. The Comprehensive Score for Financial Toxicity (COST), a validated instrument for measuring FT, was used to measure participant’s baseline FT upon initial clinic visit and at two-month intervals via online survey. Mean baseline COST scores were compared using a two-sided t test for binary variables and an ANOVA test for categorical variables with >2 categories. Demographic information including age, race, educational experience, income and insurance status was also collected by questionnaire. Results: Between July 2021 and March 2023, 63 patients were enrolled of which 45 participants completed the baseline surveys (71% response rate). Patients with higher stage disease experienced higher baseline financial toxicity, with mean COST score 38.0 for resectable disease, 26.9 for borderline resectable disease, 22.1 for unresectable disease and 17.5 for metastatic disease (p = 0.03). Participants enrolled in Medicaid experienced the highest FT (mean COST 16.0), while those enrolled in Medicare reported the lowest FT (mean COST 31.8). Participants having private insurance fell in-between with a mean COST score 22.1. Baseline FT also varied inversely with household income with participants with annual household incomes <$50,000 experiencing the most FT (mean COST = 12.7) and participants with annual household incomes >$200,000 experiencing the least FT (mean COST = 34.6). Conclusions: Patients with more advanced pancreatic cancer not only face a worse prognosis but also experience heightened financial strain even before initiation of therapy, emphasizing the early vulnerability of these individuals both medically and financially. Future analyses will measure FT longitudinally after treatment initiation and measure the association between FT, response to therapy and mortality. [Table: see text]

What's the impact of voice-hearing experiences on the social relating of young people: A comparison between help-seeking young people who did and did not hear voices.

Limited research has explored the specific impact of voice-hearing experiences upon the social relating of adolescents. This study examined the associations of voice-hearing in youth with social relating, and putative explanatory factors. An observational, cross-sectional design using a clinical comparison group was employed to examine historical and concurrent associations with voice-hearing. Thirty-four young people (age 14-18 years) with voice-hearing experiences and 34 young people who did not hear voices were recruited from NHS mental health services. Participants completed measures about social relating and potential explanatory factors. Analyses of covariance were used to examine between-group differences. Voice-hearers scored higher on negative schematic beliefs (self-beliefs, partial η2 = .163, p = .001; other-beliefs, partial η2 = .152, p =. 002) and depressive and anxiety symptoms (partial η2 = .23 and partial η2 = .24, p-s <. 001 respectively). The two groups did not differ significantly on childhood trauma levels (partial η2 = .02, p = .273), however, the voice-hearing group scored lower on premorbid adjustment (partial η2 = .19, p < .001). Hearing voices in help-seeking youth could be an indicator for social relating issues and holding negative schematic beliefs, and may be an indicator for of increased psychopathological complexity. Although poorer premorbid adjustment might indicate an early vulnerability to social relating difficulties, voice-hearing might be an aggravating factor and one that requires treatment.

Late effects of prematurity: Psychiatric outcomes of 17-year-olds born very preterm.

Very preterm (VPT) birth is a known early vulnerability factor, impacting both physical and mental health over the life-span. The additional burden of psychiatric illness in VPT adolescents is likely to adversely affect critical developmental tasks and personal, social and academic/vocational trajectories. Our aim was to examine the magnitude and extent of the risk of psychological burden by determining the prevalence of psychiatric disorders in our prospectively followed-up VPT and full-term (FT) control cohorts, in this period of developmental transition at age 17 years. Rates of psychiatric disorder in the VPT and FT control cohorts were ascertained at clinical interview of the adolescents and their care giver(s) by an adolescent psychiatrist. VPT birth was associated with a greater risk of generalised anxiety disorder (VPT vs. FT risk ratio (RR) 2.33; 95% confidence interval (CI): 1.16, 4.67, P = 0.02), as well as attentional problems (VPT vs. FT RR 3.46; 95% CI: 1.01, 11.88, P = 0.03). Although care givers of VPT adolescents reported many social and communication difficulties, and observation at clinical interview supported this, our data did not reach clinical threshold for group differences in autistic spectrum disorder. For all other psychiatric disorders, there was no difference between VPT and FT control adolescents. Our longitudinal cohort follow-up study examining the late effects of VPT birth has demonstrated increased rates of clinically significant psychiatric disorder in this period of important developmental transition. Families and health professionals need to be aware of the increased risk so they can monitor for symptoms and seek effective mental health treatments and support.

Dominant Affective Temperaments and its variance among people with depression, bipolar disorder, and a non-clinical sample: Validation of the Affective Temperament Questionnaire (ATQ)

Affective temperaments are frequently described as a biologically determined early emerging variation in emotional reactivity, with solid temporal stability. We aimed to analyse affective temperament variation and dominance while adapting and translating the Affective Temperament Questionnaire (ATQ) to European Portuguese in both clinical (Major Depressive Disorder – MDD and Bipolar Disorder – BD) and non-clinical samples. ATQ was administered to 42 subjects with MDD, 64 with BD and 411 non-clinical. A 3-factor model CFA was performed (comprising hyperthymic, cyclothymic and dysthymic temperaments), revealing good adjustment and acceptable internal consistency levels. ATQ subscales showed a general higher internal consistency in people with mood disorders. Support for convergent validity was found. BD and MDD presented higher prevalence in Cyclothymic and Dysthymic temperaments than non-clinical, although they did not differ significantly between them regarding the last one. Findings suggest ATQ is a valid and reliable self-report measure to assess affective temperaments in the Portuguese population and proved to be acceptable for either clinical or non-clinical samples. This measure can be applied to detect early vulnerability to affective disorders, which can be very helpful in clinical settings and primary care.

Longitudinal basal forebrain atrophy in association with amyloid‐β positivity and dementia severity

AbstractBackgroundDysfunction of the cholinergic basal forebrain (BF) system and deposition of amyloid‐β (Aβ) are early pathological features in Alzheimer’s disease (AD). Degeneration of the BF in association with Aβ burden and cognitive decline has not been well studied, particularly in AD prior to dementia. We assessed the longitudinal trajectory patterns of the global BF volume, and the relationship to Aβ levels and clinical disease severity in older adults. The hippocampal volume (HV) trajectories were also assessed for reference.MethodVolumetric measures of the BF and HV were quantified from the MRIs of 521 participants (age = 72.6±5.9, 52.8% female, CDR range 0‐1) from the Australian Imaging, Biomarker and Lifestyle (AIBL) study, who had Aβ‐PET imaging and longitudinal structural MRI (follow‐up over 4.3±2.6 years). Aβ load was quantified using CapAIBL and Aβ+ was defined for centiloid values &gt;20. Participants were classified at baseline based on their being cognitively unimpaired (CU, CDR = 0) or symptomatic (CDR = 0.5‐1) and Aβ status, which were CU Aβ‐, CU Aβ+ (preclinical AD), symptomatic Aβ‐ and symptomatic Aβ+ (prodromal AD and AD) (Table 1). BF and HV volumes were standardized using the mean and standard deviation of the relevant measures in the CU Aβ‐ group at baseline. Linear mixed effect models were used to compare the changes over time (slope) of BF and HV in different clinical groups. The magnitude of the difference in slopes between groups was assessed using Cohen’s d (summarised in Table 2). ResultIn CU Aβ‐, age‐related atrophy was greater in the BF compared to the HV (Cohen’s d = 0.811). Compared to the CU Aβ‐ group, the rate of atrophy was significantly faster for BF and HV in the preclinical AD group, and this decline was even greater in the prodromal AD and AD group (Figure 1 and Table 2). The symptomatic Aβ‐ group showed greater rate of BF atrophy than the CU Aβ‐ group, while there was no difference in the rate of HV atrophy.ConclusionThese findings provided prospective evidence confirming early vulnerability of the BF in aging as well as differentiated BF degeneration that was associated with baseline Aβ positivity and dementia severity.

Transforming the Well-Being of Persons with Autism

ABSTRACT The prospects for attaining well-being do not appear to be improving for most persons with Autism. We believe it is essential to understand the obstacles preventing persons from experiencing life satisfaction and optimism for the future. The current paper seeks to address this question and provide an alternate model that we believe can significantly increase the potential for autistic persons to achieve greater well-being. We first review recent findings concerning the well-being of autistic adults. Next, we present evidence supporting our belief that a significant factor suppressing autistic well-being is the failure to develop Dynamic Intelligence, the mental resources needed to function successfully in situations resembling Complex Dynamic Systems. This section includes a brief qualitative study of four young men with Autism who participated as children in Relationship Development Intervention (RDI). RDI is a family-based program where through careful assessment, support and training, RDI consultants provide parents with Autism a new opportunity to form and manage an Experience Guiding Relationship (EGR) with their autistic children. The Experience Guiding Relationship is the universal pathway for developing the mental resources needed to thrive in Complex, Dynamic environments. We provide strong evidence supporting our belief that due to a diverse range of early vulnerabilities, future Autistic infants and their parents cannot form this critical relationship. The final section offers recommendations for adapting intervention goals and methods for persons with Autism.

Excessive Crying, Behavior Problems, and Amygdala Volume: A Study From Infancy to Adolescence

Excessive crying in infancy has been associated with increased risk of later behavioral problems. To identify individuals at risk for behavioral problems and to understand the mechanisms underlying excessive crying and irritability in infancy, research into the neurobiology of excessive crying is needed. We examined whether excessive crying and irritability in infancy are associated with behavioral problems and amygdala volume among children and adolescents. This study included 4,751 singleton children from the prospective population-based Generation R Study cohort, born in the Netherlands in 2002 to 2006. Excessive crying (>3 hours on at least 1 day/wk) and irritability (Mother and Baby Scales questionnaire) were parent-rated at 3 months. Amygdala volume was measured at 10 years using magnetic resonance imaging, and internalizing and externalizing were parent-rated at 1.5, 3, 6, 10, and 14 years and self-rated at 14 years. Covariates included child age, sex, national origin, gestational age, and maternal age, psychopathology score, parity, education, relationship status, and family income. Children who cried excessively in infancy had higher parent-rated internalizing (effect estimate= 0.20 SD-units, 95% CI= 0.14, 0.27) and externalizing (0.17 SD-units, 95% CI= 0.10, 0.24) throughout childhood (linear mixed models), and smaller amygdala volume at 10 years (-0.19 SD-units, 95% CI=-0.32,-0.06) (linear regression model). The pattern of associations for both behavioral problems and amygdala volume was similar for irritability. Excessive crying and irritability in infancy may reflect an early vulnerability to behavioral problems and may be linked with neurobiological differences in the development of the amygdala.

A systematic review of locus coeruleus degeneration detected by neuromelanin sensitive MRI technique in patients with Alzheimer’s disease

AbstractBackgroundThe locus coeruleus(LC) is a bilateral nucleus located in the dorsal pontine tegmentum and is the major source of noradrenaline(NA), which plays a key role in cognition. While cognitive decline in Alzheimer disease(AD) has primarily been related to dysfunction within the cholinergic system in the nucleus basalis, there is considerable research evidence indicating extensive LC degeneration in AD, with some suggesting that it is among the earliest pathologies. Therefore, the early vulnerability of the LC to AD is of considerable clinical significance, as this raises the possibility that changes of the LC activity may provide early detection markers for diagnosis as well as early intervention targets to delay AD progression. However, the contribution of LC degeneration to cognitive decline in the development of AD has been underappreciated due to methodological difficulties, with most evidence coming from animal and post‐mortem studies. The absence of reliable non‐invasive direct measures of the LC remains the biggest challenge. Recent research indicates that LC visibility is driven by neuromelanin content of noradrenergic neurons and the intrinsic neuromelanin‐sensitive MRI technique enables direct visualisation of the LC.MethodsA systematic search of the literature was performed on electronic databases including PubMed, Web of Science, and Embase. Human imaging studies employing neuromelanin‐sensitive MRI technique to measure LC degeneration were included in this review. Screening, data extraction, and quality assessment were undertaken following PRISMA guidelines for preferred reporting of systematic reviews.ResultsLC‐contrast ratio or LC‐signal intensity detected by the neuromelanin‐sensitive MRI were found to be significantly reduced in patient groups with Alzheimer's disease compared with the healthy control group in all included studies, with recent evidence indicating its significant association with levels of CSF amyloid.ConclusionsThe current systematic review strongly supports the use of the neuromelanin‐sensitive MRI technique to detect the LC degeneration as a biomarker for AD neuropathology. Future research are warranted to characterize how LC signals evolve at different stages of AD, which could lead to novel intervention approaches to delay or prevent cognitive decline.

Serum unsaturated phosphatidylcholines predict longitudinal basal forebrain degeneration in Alzheimer's disease.

Basal forebrain cholinergic neurons are among the first cell types affected by Alzheimer's disease pathology, but the cause of their early vulnerability is unknown. The lipid phosphatidylcholine is an essential component of the cell membrane, and phosphatidylcholine levels have been shown to be abnormal in the blood and brain of Alzheimer's disease patients. We hypothesized that disease-related changes in phosphatidylcholine metabolism may disproportionately affect basal forebrain cholinergic neurons due to their extremely large size, plasticity in adulthood and unique reliance on phosphatidylcholine for acetylcholine synthesis. To test this hypothesis, we examined whether serum phosphatidylcholine levels predicted longitudinal basal forebrain degeneration in Alzheimer's disease. All data were collected by the Alzheimer's Disease Neuroimaging Initiative. Participants were divided into a normal CSF group (controls; n = 77) and an abnormal CSF group (preclinical and clinical Alzheimer's disease; n = 236) based on their CSF ratios of phosphorylated tau and amyloid beta at baseline. Groups were age-matched (t = 0.89, P > 0.1). Serum lipidomics data collected at baseline were clustered by chemical similarity, and enrichment analyses were used to determine whether serum levels of any lipid clusters differed between the normal and abnormal CSF groups. In a subset of patients with longitudinal structural MRI (normal CSF n = 62, abnormal CSF n = 161), two timepoints of MRI data were used to calculate grey matter annual percent change for each participant. Multivariate partial least squares analyses tested for relationships between neuroimaging and lipidomics data which are moderated by CSF pathology. Our clustering analyses produced 23 serum lipid clusters. Of these clusters, six were altered in the abnormal CSF group, including a cluster of unsaturated phosphatidylcholines. In the subset of participants with longitudinal structural MRI data, a priori nucleus basalis of Meynert partial least squares analyses detected a relationship between unsaturated phosphatidylcholines and degeneration in the nucleus basalis which is moderated by Alzheimer's disease CSF pathology (P = 0.0008). Whole-brain grey matter partial least squares analyses of all 23 lipid clusters revealed that only unsaturated phosphatidylcholines and unsaturated acylcarnitines exhibited an Alzheimer's disease-dependent relationship with longitudinal degeneration (P = 0.0022 and P = 0.0018, respectively). Only the unsaturated phosphatidylcholines predicted basal forebrain degeneration in the whole-brain analyses. Overall, this study provides in vivo evidence for a selective relationship between phosphatidylcholine and basal forebrain degeneration in human Alzheimer's disease, highlighting the importance of phosphatidylcholine to basal forebrain grey matter integrity.

A-266 Neuropsychological Profile of a 5-Year-Old Boy with Gould Syndrome

Abstract Objective: Gould syndrome (COL4A1/A2-related disorders) is an extremely rare, genetic disorder characterized by cerebral vasculature defects, ocular dysgenesis, myopathy, and cerebral cortical abnormalities. Many individuals with COL4A1 mutations exhibit seizures, stroke, visual field defects, and hydrocephalus. To date, research regarding neuropsychological sequelae of Gould syndrome has been sparse. Therefore, this presentation aims to present clinical considerations for pediatric patients with Gould syndrome. Method: Patient is a 5-year-old Hispanic boy born at 35-weeks following perinatal stroke, pre-term birth, and suspected cyanosis. After birth, genetic testing revealed a COL4A1p.G1234R gene mutation (i.e., Gould syndrome). Patient’s medical history is also notable for cerebral palsy, epilepsy, encephalopathy, hypertonia, global developmental delays with language regression, and attention-deficit/hyperactivity disorder. Previous brain MRIs have found decreased white matter density in both cerebral hemispheres. Abbreviated neuropsychological testing was completed during an inpatient pre-surgical epilepsy evaluation. Patient was non-verbal. Results: Non-verbal intellectual ability was Below Average (IQ=74). Receptive language was Average (SS=93). Further, bilateral fine-motor speed and dexterity and visual motor integration were Exceptionally Low. Standardized questionnaires revealed ongoing concerns related to attention, hyperactivity, and poor adaptive functioning. Diagnostic impressions included Global Developmental Delay. Conclusion: Gould syndrome can include a variety of neurological sequelae depending on neurological defects and incidents. These findings are consistent with the “early vulnerability” position of brain development, which proposes that earlier age at brain insult may result in greater impairments in cognitive functioning (Jacomb et al., 2018). Therefore, early intervention and targeted long-term interventions appears imperative to improve function outcomes for pediatric patients with Gould syndrome.

Resilience Factors Preventing Schizophrenia in Ultra-high Risk Patients: Lessons from Genetics

Over the past decades, researchers and psychiatrists in the field of psychosis have moved from a conception of a chronic presentation to a more dynamic paradigm. Accordingly, schizophrenia is now conceptualized as a progressive illness that typically emerges during late adolescence and follows different stages: early vulnerability, ultra-high risk state, first episode of psychosis, and chronic disease. Only one-quarter of the ultra-high risk patients will convert to a full-blown psychotic episode within 3 years while the others, called non-converters, will remain at-risk, develop other psychiatric disorders, or fully recover. The reasons for this differential outcome are not yet understood but this concept opens the way to scientific research to determine the protective factors involved in resilience for non-converters. Based on the Gene X Environment interaction model, schizophrenia results from genetic vulnerability and environmental aggressions which can have an impact on the epigenome and gene expression. Recent studies have shown that genetic variants play a role in the resilience of psychosis. Polygenic risk scores, computed as the addition of genetic polymorphisms, can modulate the effects of genetic at-risk deletions (i.e. del22q11) that predispose to psychosis and may also influence the cognitive symptoms of ultra-high risk patients. Resilience, defined as the ability to withstand adversity, is not only related to external skills or psychotherapeutic care but could also be explained by internal molecular factors. Identifying the genetic factors of resilience might help to stratify the risk and to develop precision medicine in psychiatry.DisclosureNo significant relationships.

Cancer and aging: A call to action.

Background:The intersection of cancer and aging is an emerging public health challenge in developed countries because of the aging and expansion of the population.Aims:We convened a panel of experts to share their insights on this topic at the inaugural University of Florida Health Cancer Center’s (UFHCC’s) Cancer and Aging Symposium, which was held virtually in February 2022.Methods:We featured presentations from four leading scientists, whose research spans multiple disciplines including basic science, translational research, geriatric oncology, and population science.Results:Each speaker offered their unique perspective and insight on the intersection between cancer and aging and discussed their current and ongoing research in this field. In addition to this panel of experts, scientists from the National Institutes of Health and the National Cancer Institute, as well as a UFHCC-affiliated citizen scientist, shared their perspectives on strategies to move the field forward. Some of the key open questions and opportunities for future research offered by these presenters in aging and cancer include but are not limited to infusing health disparities research into the field of cancer and aging, assessing the value of geriatric assessment in identifying early vulnerabilities that may affect response to emerging cancer therapies in older patients, and assessing biological age and other biomarkers (e.g., clonal hematopoiesis) in relation to clinical endpoints and the development of primary, secondary, and tertiary cancer prevention interventions.Conclusion:Research is needed to accelerate knowledge regarding the dynamic interplay of cancer and aging and optimize care in diverse older adults to achieve equity in cancer outcomes.

The interplay between social interaction quality and wellbeing in military personnel during their initial two-years of service

ABSTRACT This research examined the nature of social interaction profiles in the initial two-years of military service, profile association to early vulnerability to psychological distress, and the association between supervisor interaction qualities in the likelihood of profile membership. Data were collected as part of a larger longitudinal study. Participants who completed key variables at either 3–12 months post-enlistment (N = 5,233; 85.6% male) or 15–24 months post-enlistment (N = 2,162; 79.2% male) were included in the cross-sectional profile analysis of social interaction quality from military and nonmilitary sources. Cross-sectional latent profile analyses and transition analysis were used to investigate the social interaction profiles at each time-point, the effect of leader interactions on movement between profiles, and related psychological distress outcomes. Social interaction quality, and in particular colleague interactions, was predictably associated with psychological distress. Leadership interactions were associated with the nature of colleague social interactions. Greater positive social interactions with leadership was related to a reduced likelihood of experiencing less frequent negative interactions with colleagues. The findings implicate a possible role for supervisors in perpetuating positive or negative colleague interactions. Moreover, a trajectory of vulnerability to psychological distress may start in the initial two-years of military service and emerge from the psychosocial context.

Breastfeeding and cortisol in hair in children

BackgroundOne of the most important protective health factors for children is breast-feeding, but the mechanisms for this effect are not fully elucidated. Our objective was to assess if the duration of breastfeeding influences cortisol in hair, used as a biomarker for stress in children still at school-age.MethodsABIS (All Babies in Southeast Sweden) is a prospective population-based child cohort study of 17,055 children born Oct 1st1997- Oct 1st 1999, with the aim to study development of immune-mediated diseases. Questionnaires were answered at birth and then at regular follow-ups, and biological samples were collected. As a biomarker of stress, we measured the child’s cortisol in hair collected at 8 years of age, those randomly selected N = 126 children among those with enough hair samples for analyses of hair at 8 years of age. Duration of breastfeeding had been registered as well as psycho-social factors related to breastfeeding and/or stress.ResultsThere was a negative correlation (r = − 0.23, p = 0.01) between total duration of breastfeeding and hair cortisol levels at 8 years of age. In a multivariate analysis this association persisted (p = 0.01) even when adjusted for other potential intervening factors like age of mother at delivery and early psychosocial vulnerability in the family, an index based on 11 factors (Multivariate model: df = 5, adj R2 = 0.15, F = 5.38, p < 0.01).ConclusionOur results show that longer breastfeeding is associated with lower cortisol levels in the child many years later. These associations should be more elaborated in further studies, and these findings also give some implications for public health. Mothers should be encouraged to breastfeed their children also in the modern society, since breastfeeding promotes health in the child. This information could be given via the obstetric departments and later at the well-baby clinics.

Semantic Recollection in Parkinson's Disease: Functional Reconfiguration and MAPT Variants.

Decline in semantic cognition in early stages of Parkinson’s disease (PD) is a leading risk factor for future dementia, yet the underlying neural mechanisms are not understood. The present study addressed this gap by investigating the functional connectivity of regions involved in semantic recollection. We further examined whether microtubule-associated protein tau (MAPT) risk variants, which may accelerate cognitive decline, altered the strength of regional functional connections. Cognitively normal PD and healthy elder controls underwent fMRI while performing a fame-discrimination task, which activates the semantic network. Analyses focused on disturbances in fame-modulated functional connectivity in PD for regions that govern semantic recollection and interrelated processes. Group differences were found in multiple connectivity features, which were reduced into principal components that reflected the strength of fame-modulated regional couplings with other brain areas. Despite the absence of group differences in semantic cognition, two aberrant connectivity patterns were uncovered in PD. One pattern was related to a loss in frontal, parietal, and temporal connection topologies that governed semantic recollection in older controls. Another pattern was characterized by functional reconfiguration, wherein frontal, parietal, temporal and caudate couplings were strengthened with areas that were not recruited by controls. Correlations between principal component scores and cognitive measures suggested that reconfigured frontal coupling topologies in PD supported compensatory routes for accessing semantic content, whereas reconfigured parietal, temporal, and caudate connection topologies were detrimental or unrelated to cognition. Increased tau transcription diminished recruitment of compensatory frontal topologies but amplified recruitment of parietal topologies that were unfavorable for cognition. Collectively, the findings provide a new understanding of early vulnerabilities in the functional architecture of regional connectivity during semantic recollection in cognitively normal PD. The findings also have implications for tracking cognitive progression and selecting patients who stand to benefit from therapeutic interventions.