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1.
Geroscience ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874693

ABSTRACT

Long COVID, also known as PASC (post-acute sequelae of SARS-CoV-2), is a complex infection-associated chronic condition affecting tens of millions of people worldwide. Many aspects of this condition are incompletely understood. Among them is how this condition may manifest itself in older adults and how it might impact the older population. Here, we briefly review the current understanding of PASC in the adult population and examine what is known on its features with aging. Finally, we outline the major gaps and areas for research most germane to older adults.

3.
Mol Autism ; 15(1): 8, 2024 01 31.
Article in English | MEDLINE | ID: mdl-38291493

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD. METHODS: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models. RESULTS: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found. LIMITATIONS: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores. CONCLUSIONS: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child , Animals , Humans , Male , Female , Macaca mulatta , Social Behavior , Arginine Vasopressin/cerebrospinal fluid , Oxytocin
4.
Compr Psychoneuroendocrinol ; 16: 100202, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38108026

ABSTRACT

This narrative review charts my unconventional path to becoming a social neuroscientist and describes my research findings - some baffling, some serendipitous, some pivotal - in the field of neuropeptide biology. I trace my childhood as a Bell Labs "brat" to my adolescence as a soccer-playing party girl, to my early days as a graduate student, when I first encountered oxytocin and vasopressin. These two molecules instantly captivated - and held - my attention and imagination. For more than 25 years, a core goal of my research program has been to better understand how these neuropeptides regulate social functioning across a range of species (e.g., meadow voles, mice, squirrel monkeys, rhesus monkeys, and humans), and to translate fundamental insights from this work to guide development of novel pharmacotherapies to treat social impairments in clinical populations. I also discuss my experience of being a woman and a mother in STEM, and identify the important people and events which helped shape my career and the scientist I am today.

5.
Article in English | MEDLINE | ID: mdl-37701064

ABSTRACT

In this paper, we propose a method for removing linguistic information from speech for the purpose of isolating paralinguistic indicators of affect. The immediate utility of this method lies in clinical tests of sensitivity to vocal affect that are not confounded by language, which is impaired in a variety of clinical populations. The method is based on simultaneous recordings of speech audio and electroglotto-graphic (EGG) signals. The speech audio signal is used to estimate the average vocal tract filter response and amplitude envelop. The EGG signal supplies a direct correlate of voice source activity that is mostly independent of phonetic articulation. These signals are used to create a third signal designed to capture as much paralinguistic information from the vocal production system as possible-maximizing the retention of bioacoustic cues to affect-while eliminating phonetic cues to verbal meaning. To evaluate the success of this method, we studied the perception of corresponding speech audio and transformed EGG signals in an affect rating experiment with online listeners. The results show a high degree of similarity in the perceived affect of matched signals, indicating that our method is effective.

7.
LGBT Health ; 10(S1): S1-S5, 2023 09.
Article in English | MEDLINE | ID: mdl-37754920

ABSTRACT

Violence affects every community but is particularly prevalent among sexual and gender minority (SGM) people. Although research on violence within SGM populations is increasing, knowledge gaps remain that limit development of evidence-based policy, prevention, and intervention efforts to reduce the violence disparities the SGM community faces. In 2021, the National Institutes of Health (NIH) hosted a multiphase scientific workshop to identify and prioritize key research needs to further our understanding of violence affecting SGM communities and its health outcomes. In this perspective, we summarize the research needs identified. NIH supports this special issue as an outcome of the scientific workshop.


Subject(s)
Sexual and Gender Minorities , Humans , Sexual Behavior , Gender Identity , Violence , Outcome Assessment, Health Care
8.
Mol Autism ; 14(1): 25, 2023 07 21.
Article in English | MEDLINE | ID: mdl-37480043

ABSTRACT

BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N = 407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (σ2P) between sons that could uniquely be attributed to their shared genetics (σ2g), expressed as σ2g/σ2P (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h2). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability.


Subject(s)
Autistic Disorder , Nuclear Family , Animals , Humans , Female , Male , Macaca mulatta , Autistic Disorder/genetics , Social Interaction , Family
10.
Mol Psychiatry ; 28(1): 127-140, 2023 01.
Article in English | MEDLINE | ID: mdl-35999276

ABSTRACT

Oxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as a therapeutic agent in treating social impairments in patient populations. However, research has yet to uncover precisely how to manipulate this system for clinical benefit. Moreover, inconsistent use of standardized and validated oxytocin measurement methodologies-including the design and study of hormone secretion and biochemical assays-present unresolved challenges. Human studies measuring peripheral (i.e., in plasma, saliva, or urine) or central (i.e., in cerebrospinal fluid) oxytocin concentrations have involved very diverse methods, including the use of different assay techniques, further compounding this problem. In the present review, we describe the scientific value in measuring human endogenous oxytocin concentrations, common issues in biochemical analysis and study design that researchers face when doing so, and our recommendations for improving studies using valid and reliable methodologies.


Subject(s)
Neuropeptides , Oxytocin , Humans , Saliva/chemistry , Research Design , Plasma/chemistry
12.
Am J Primatol ; 84(12): e23442, 2022 12.
Article in English | MEDLINE | ID: mdl-36268602

ABSTRACT

Rhesus monkeys and humans are highly social primates, yet both species exhibit pronounced variation in social functioning, spanning a spectrum of sociality. Naturally occurring low sociality in rhesus monkeys may be a promising construct by which to model social impairments relevant to human autism spectrum disorder (ASD), particularly if low sociality is found to be stable across time and associated with diminished social motivation. Thus, to better characterize variation in sociality and social communication profiles, we performed quantitative social behavior assessments on N = 95 male rhesus macaques (Macaca mulatta) housed in large, outdoor groups. In Study 1, we determined the social classification of our subjects by rank-ordering their total frequency of nonsocial behavior. Monkeys with the greatest frequency of nonsocial behavior were classified as low-social (n = 20) and monkeys with the lowest frequency of nonsocial behavior were classified as high-social (n = 21). To assess group differences in social communication profiles, in Study 2, we quantified the rates of transient social communication signals, and whether these social signals were initiated by or directed towards the focal subject. Finally, in Study 3, we assessed the within-individual stability of sociality in a subset of monkeys (n = 11 low-social, n = 11 high-social) two years following our initial observations. Nonsocial behavior frequency significantly correlated across the two timepoints (Studies 1 and 3). Likewise, low-social versus high-social classification accurately predicted classification two years later. Low-social monkeys initiated less prosocial behavior than high-social monkeys, but groups did not differ in receipt of prosocial behavior, nor did they differ in threat behavior. These findings indicate that sociality is a stable, trait-like characteristic and that low sociality is linked to diminished initiation of prosocial behavior in rhesus macaques. This evidence also suggests that low sociality may be a useful construct for gaining mechanistic insight into the social motivational deficits often observed in people with ASD.


Subject(s)
Autism Spectrum Disorder , Male , Humans , Animals , Macaca mulatta , Altruism , Social Behavior , Cognition
13.
Neurosci Biobehav Rev ; 142: 104870, 2022 11.
Article in English | MEDLINE | ID: mdl-36113782

ABSTRACT

Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder. Global hypothalamic dysfunction is a core feature of PWS and has been implicated as a driver of many of PWS's phenotypic characteristics (e.g., hyperphagia-induced obesity, hypogonadism, short stature). Although the two neuropeptides (i.e., oxytocin [OXT] and arginine vasopressin [AVP]) most implicated in mammalian prosocial functioning are of hypothalamic origin, and social functioning is markedly impaired in PWS, there has been little consideration of how dysregulation of these neuropeptide signaling pathways may contribute to PWS's social behavior impairments. The present article addresses this gap in knowledge by providing a comprehensive review of the preclinical and clinical PWS literature-spanning endogenous neuropeptide measurement to exogenous neuropeptide administration studies-to better understand the roles of OXT and AVP signaling in this population. The preponderance of evidence indicates that OXT and AVP signaling are indeed dysregulated in PWS, and that these neuropeptide pathways may provide promising targets for therapeutic intervention in a patient population that currently lacks a pharmacological strategy for its debilitating social behavior symptoms.


Subject(s)
Prader-Willi Syndrome , Animals , Humans , Prader-Willi Syndrome/genetics , Oxytocin/metabolism , Arginine Vasopressin , Hyperphagia , Social Behavior , Mammals
14.
J Psychiatr Res ; 155: 320-330, 2022 11.
Article in English | MEDLINE | ID: mdl-36174367

ABSTRACT

Persons with posttraumatic stress disorder (PTSD) frequently experience relationship failures in family and occupational domains resulting in loss of social supports. Prior research has implicated impairments in social cognition. The Reading the Mind in the Eyes Test (RMET) measures a key component of social cognition, the ability to infer the internal states of other persons based on features of the eyes region of the face; however, studies administering this popular test to persons with PTSD have yielded mixed results. This study assessed RMET performance in 47 male U.S. military Veterans with chronic, severe PTSD. Employing a within-subjects design that avoided selection biases, it aimed specifically to determine whether components of RMET performance, including accuracy, response latency, and stimulus dwell time, were improved by the company of a service dog, an intervention that has improved social function in other populations. RMET accuracies and response latencies in this PTSD sample were in the normal range. The presence of a familiar service dog did not improve RMET accuracy, reduce response latencies, or increase dwell times. Dog presence increased the speed of visual scanning perhaps consistent with reduced social fear.


Subject(s)
Stress Disorders, Post-Traumatic , Veterans , Animals , Dogs , Humans , Male , Service Animals
15.
Neurosci Biobehav Rev ; 140: 104770, 2022 09.
Article in English | MEDLINE | ID: mdl-35803395

ABSTRACT

Disorders involving hypothalamic and pituitary (HPIT) structures-including craniopharyngioma, Langerhans cell histiocytosis, and intracranial germ cell tumors-can disrupt brain and endocrine function. An area of emerging clinical concern in patients with these disorders is the co-occurring socio-behavioral dysfunction that persists after standard hormone replacement therapy. Although the two neuropeptides most implicated in mammalian social functioning (oxytocin and arginine vasopressin) are of hypothalamic origin, little is known about how disease-induced damage to HPIT structures may disrupt neuropeptide signaling and, in turn, impact patients' socio-behavioral functioning. Here we provide a clinical primer on disorders of HPIT involvement and a review of neuropeptide signaling and socio-behavioral functioning in relevant animal models and patient populations. This collective evidence suggests that neuropeptide signaling disruptions contribute to socio-behavioral deficits experienced by patients with disorders of HPIT involvement. A better understanding of the biological underpinnings of patients' socio-behavioral symptoms is now needed to enable the development of the first targeted pharmacological strategies by which to manage patients' socio-behavioral dysfunction.


Subject(s)
Neuropeptides , Oxytocin , Animals , Brain , Hypothalamus , Mammals , Vasopressins
16.
Mol Psychiatry ; 27(6): 2650-2658, 2022 06.
Article in English | MEDLINE | ID: mdl-35365807

ABSTRACT

Autism spectrum disorder (ASD) is a prevalent and poorly understood neurodevelopmental disorder. There are currently no laboratory-based diagnostic tests to detect ASD, nor are there any disease-modifying medications that effectively treat ASD's core behavioral symptoms. Scientific progress has been impeded, in part, by overreliance on model organisms that fundamentally lack the sophisticated social and cognitive abilities essential for modeling ASD. We therefore saw significant value in studying naturally low-social rhesus monkeys to model human social impairment, taking advantage of a large outdoor-housed colony for behavioral screening and biomarker identification. Careful development and validation of our animal model, combined with a strong commitment to evaluating the translational utility of our preclinical findings directly in patients with ASD, yielded a robust neurochemical marker (cerebrospinal fluid vasopressin concentration) of trans-primate social impairment and a first-in-class medication (intranasal vasopressin) shown in a small phase 2a pilot trial to improve social abilities in children with ASD. This translational research approach stands to advance our understanding of ASD in a manner not readily achievable with existing animal models, and can be adapted to investigate a variety of other human brain disorders which currently lack valid preclinical options, thereby streamlining translation and amplifying clinical impact more broadly.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Animals , Autism Spectrum Disorder/drug therapy , Autism Spectrum Disorder/therapy , Autistic Disorder/diagnosis , Disease Models, Animal , Humans , Macaca mulatta , Translational Research, Biomedical
17.
Mol Psychiatry ; 27(6): 2640-2649, 2022 06.
Article in English | MEDLINE | ID: mdl-35338314

ABSTRACT

Significant clinical improvement is often observed in patients who receive placebo treatment in randomized double-blind placebo-controlled trials. While a proportion of this "improvement" reflects experimental design limitations (e.g., reliance on subjective outcomes, unbalanced groups, reporting biases), some of it reflects genuine improvement corroborated by physiological change. Converging evidence across diverse medical conditions suggests that clinically-relevant benefits from placebo treatment are associated with the activation of brain reward circuits. In parallel, evidence has accumulated showing that such benefits are facilitated by clinicians that demonstrate warmth and proficiency during interactions with patients. Here, we integrate research on these neural and social aspects of placebo effects with evidence linking oxytocin and social reward to advance a neurobiological account for the social facilitation of placebo effects. This account frames oxytocin as a key mediator of treatment success across a wide-spectrum of interventions that increase social connectedness, thereby providing a biological basis for assessing this fundamental non-specific element of medical care.


Subject(s)
Oxytocin , Placebo Effect , Administration, Intranasal , Double-Blind Method , Humans , Oxytocin/pharmacology , Randomized Controlled Trials as Topic , Reward , Social Facilitation
18.
Violence Against Women ; 28(15-16): 3635-3656, 2022 12.
Article in English | MEDLINE | ID: mdl-34962182

ABSTRACT

The study aims to expand our understanding of escalation from intimate partner violence to intimate partner homicide (IPH) by exploring the known circumstances leading up to a lethal event. The study draws on qualitative data from law enforcement reports and coroner/medical examiner reports within the National Violent Death Reporting System to identify themes preceding and surrounding IPH incidents. Findings support the utility of risk assessments in identifying escalation while illustrating the complex ways that violence between current or former intimate partners can escalate to lethality, particularly the role of separation and the use of firearms.


Subject(s)
Firearms , Intimate Partner Violence , Humans , Homicide , Sexual Partners , Violence
19.
Mol Autism ; 12(1): 50, 2021 07 08.
Article in English | MEDLINE | ID: mdl-34238350

ABSTRACT

BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.


Subject(s)
Autistic Disorder , Animals , Biomarkers , Humans , Macaca mulatta , Male , Phosphatidylinositol 3-Kinases , Reproducibility of Results , Social Behavior , Sociological Factors
20.
Autism Res ; 14(7): 1332-1346, 2021 07.
Article in English | MEDLINE | ID: mdl-33847078

ABSTRACT

People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low-social monkeys show an increased burden of medical morbidities compared to their high-social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low-social; n = 79 high-social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale-Revised (mSRS-R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low-social monkeys incurred higher rates of traumatic injury compared to high-social monkeys. Nonsocial scores and mSRS-R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low-social monkeys are consistent with well-documented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model. LAY SUMMARY: People with autism exhibit multiple medical problems at higher rates than the general population. We conducted a comprehensive medical record review of monkeys that naturally exhibit differences in sociality and found that low-social monkeys are more susceptible to traumatic injuries than high-social monkeys. These results are consistent with reports that people with autism also incur greater traumatic injury and peer bullying and add to growing evidence for the validity of this monkey model.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Animals , Autism Spectrum Disorder/epidemiology , Humans , Macaca mulatta , Morbidity , Social Behavior
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