Roy H. Perlis's research while affiliated with Harvard University and other places
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Publications (461)
Depression can affect individuals’ attitudes by enhancing cognitive biases and altering perceptions of control. We investigate the relationship between depressive symptoms and Americans’ attitudes regarding domestic extremist violence. We develop a theory that suggests the association between depression and support for political violence depends on...
Context. Prior birth cohorts have suggested an association between maternal infection in pregnancy and offspring risk for childhood obesity. Whether maternal SARS-CoV-2 infection is similarly associated with increased cardiometabolic risk for offspring is not known.
Objective. To determine whether in utero exposure to SARS-CoV-2 is associated with...
Introduction:
Maternal obesity is associated with increased risk of offspring obesity and cardiometabolic disease. Altered fetoplacental immune programming is a potential candidate mechanism. Differences in fetal placental macrophages, or Hofbauer cells (HBCs), have been observed in maternal obesity, and lipid metabolism is a key function of resid...
Background:
The CYFIP1 gene, located in the neurodevelopmental risk locus 15q11.2, is highly expressed in microglia, but its role in human microglial function as it relates to neurodevelopment is not well understood.
Methods:
We generated multiple CRISPR knockouts of CYFIP1 in patient-derived models of microglia to characterize function and phen...
While most of the efforts to uncover mechanisms contributing to bipolar disorder (BD) focused on phenotypes at the mature neuron stage, little research has considered events that may occur during earlier timepoints of neurodevelopment. Further, although aberrant calcium (Ca²⁺) signaling has been implicated in the etiology of this condition, the pos...
Background:
Longitudinal studies show that lower cognitive performance in adolescence and early adulthood is associated with higher risk of suicide death throughout adulthood. However, it is unclear whether this cognitive vulnerability originates earlier in childhood since studies conducted in children are scarce and have inconsistent results.
Me...
In polygenic score (PGS) analysis, the coefficient of determination (R2) is a key statistic to evaluate efficacy. R2 is the proportion of phenotypic variance explained by the PGS, calculated in a cohort that is independent of the genome-wide association study (GWAS) that provided estimates of allelic effect sizes. The SNP-based heritability (hSNP2,...
The mental health of children and adolescents has been the focus of two recent reports from the US Surgeon General’s office. The first noted the prevalence of distress among young Americans and the need to invest in more systematic and accessible care. The second, in early May, addressed the impact of loneliness on mental health, recognizing that t...
( Am J Obstet Gynecol . 2022;227:511.e1–511.e8)
Natural language processing (NLP) is a machine learning technique that has been shown to enhance clinical prediction tasks with improved outcomes. This newer strategy is under investigation for its contribution to address severe maternal morbidity (SMM) beyond already in place predelivery planning, co...
Public health requires collective action—the public best addresses health crises when individuals engage in prosocial behaviors. Failure to do so can have dire societal and economic consequences. This was made clear by the disjointed, politicized response to COVID-19 in the United States. Perhaps no aspect of the pandemic exemplified this challenge...
Introduction: Large language models perform well on a range of academic tasks including medical examinations. The performance of this class of models in psychopharmacology has not been explored.
Method: Chat GPT-plus, implementing the GPT-4 large language model, was presented with each of 10 previously-studied antidepressant prescribing vignettes i...
Background:
We aimed to characterize the prevalence of social disconnection and thoughts of suicide among older adults in the United States, and examine the association between them in a large naturalistic study.
Methods:
We analyzed data from 6 waves of a fifty-state non-probability survey among US adults conducted between February and December...
Importance:
Prior studies using large registries have suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific.
Objective:
To determine whether in utero exposure to SARS-CoV-2 is associated with sex-specific risk for neurodevelopmenta...
Importance:
Individuals with anorexia nervosa maintain extremely low body weights despite elevations in the circulating orexigenic hormone ghrelin. Whether circulating levels of endogenous ghrelin are associated with weight gain in anorexia nervosa is unknown.
Objective:
To examine the association between baseline ghrelin and future weight chang...
Researchers, media outlets, and political actors have expressed ongoing concerns about the spread of misinformation in the areas of health and politics. In past reports, we have discussed the prevalence and demographics of COVID-19 misinformation, its link to vaccination rates, its dependence on social media news consumption, and its shifts over ti...
In our latest survey, 24% of Americans report levels of depression that would typically trigger a referral for evaluation and treatment. Among 18-24-year-olds, that number jumps to 44%, including 24% of 18-24-year-olds meeting the criteria for moderate to severe or severe depression.• The rate of depression among 18-24-year-olds is slightly down ov...
Importance
Post-COVID-19 condition (PCC), or long COVID, has become prevalent. The course of this syndrome, and likelihood of remission, has not been characterized.
Objective
To quantify the rates of remission of PCC, and the sociodemographic features associated with remission.
Design
16 waves of a 50-state U.S. non-probability internet survey co...
Importance:
Little is known about the functional correlates of post-COVID-19 condition (PCC), also known as long COVID, particularly the relevance of neurocognitive symptoms.
Objective:
To characterize prevalence of unemployment among individuals who did, or did not, develop PCC after acute infection.
Design, setting, and participants:
This su...
Key Takeaways1. Comparing our October 2022 survey conducted immediately before Elon Musk purchased Twitter to our December 2022-January 2023 survey, the percentage of Americans who reported using Twitter dropped from 32.4% to 29.5%. This decline was driven by Democrats, 38% of whom reported using Twitter in our survey before Musk took over the comp...
Objective The aim of this study was to determine if a universally applied risk score threshold for severe maternal morbidity (SMM) resulted in different performance characteristics among subgroups of the population.
Study Design This is a retrospective cohort study of deliveries that occurred between July 1, 2016, and June 30, 2020, in a single hea...
Importance:
Although peer review is an important component of publication for new research, the viability of this process has been questioned, particularly with the added stressors of the COVID-19 pandemic.
Objective:
To characterize rates of peer reviewer acceptance of invitations to review manuscripts, reviewer turnaround times, and editor-ass...
KEY TAKEAWAYS1. About half of American adults report having been infected with COVID-19 at some point, with 35% saying they have tested positive for COVID-19 before.2. Individuals vaccinated against COVID-19 report being sick for fewer days than unvaccinated individuals.3. Due to the underreported use of at-home rapid tests, the data on reported te...
Research Objectives
To identify distinct post-acute COVID-19 phenotypes among adults hospitalized for severe SARS-CoV-2 infection and describe multidimensional outcomes and trajectories at 6 and 12 months post-hospitalization.
Design
Prospective, longitudinal data collection in functional, physical, cognitive, and psychological domains at 3, 6, an...
In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease. Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia. To design a disease-relevant assay, we first...
KEY TAKEAWAYS1. Despite being featured less in popular news media, Americans remain concerned about Russia’s invasion of Ukraine, with 78% reporting that they are either somewhat or very concerned.2. In response to a hypothetical Russian use of nuclear weapons, there was broad bipartisan agreement for an aggressive response, even if it meant more d...
Concerns over the integrity of the US voting system have been a prominent feature of recent election cycles. For the past two years, President Trump and his supporters have falsely claimed that widespread voter fraud cost Republicans the win in the 2020 presidential race. A number of prominent 2022 political candidates have questioned the legitimac...
Background: Symptoms of Coronavirus-19 (COVID-19) infection persist beyond 2 months in a subset of individuals, a phenomenon referred to as long COVID, but little is known about its functional correlates and in particular the relevance of neurocognitive symptoms.
Method: We analyzed a previously-reported cohort derived from 8 waves of a nonprobabil...
Importance: Prior studies using large registries suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific.
Objective: To determine whether in utero exposure to the novel coronavirus SARS-CoV-2 is associated with sex-specific risk for neu...
Key takeaways1. Inflation and the economy are Americans’ top ranked problems facing the country headed into the 2022 elections.2. Republicans and independents both rank inflation and the economy as their first and second most important issues, but Democrats rank climate change and racism as their top two issues, with inflation coming in a near thir...
Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A ( C4A ) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ...
This report contains some key takeaways, a brief write-up, some summary statistics, and a collection of open-ended responses surrounding public opinion of the August 8, 2022 FBI search of Donald Trump’s estate, Mar-A-Lago.Key takeaways• A large majority of Americans quickly became aware of the Mar-A-Lago search. Overall, 81 percent reported that th...
Politics and science have become increasingly intertwined. Salient scientific issues, such as climate change, evolution, and stem-cell research, become politicized, pitting partisans against one another. This creates a challenge of how to effectively communicate on such issues. Recent work emphasizes the need for tailored messages to specific group...
Background: The CYFIP1 gene, located in the neurodevelopmental risk locus 15q11.2, is highly expressed in microglia, but its role in human microglial function as it relates to neurodevelopment is not well understood.
Methods: We generated multiple CRISPR knockouts of CYFIP1 in patient-derived models of microglia to characterize function and phenoty...
Conspiratorial beliefs can endanger individuals and societies by increasing the likelihood of harmful behaviors such as the flouting of public health guidelines. While scholars have identified various correlates of conspiracy beliefs, one factor that has received scant attention is depressive symptoms. We use three large surveys to explore the conn...
Neuropsychiatric manifestations are common in both the acute and post-acute phase of SARS-CoV-2 infection, but the mechanisms of these effects are unknown. In a newly established brain organoid model with innately developing microglia, we demonstrate that SARS-CoV-2 infection initiate neuronal cell death and cause a loss of post-synaptic termini. D...
Importance
Risk-stratification tools are routinely used in obstetrics to assist care teams in assessing and communicating risk associated with delivery. Electronic health record data and machine learning methods may offer a novel opportunity to improve and automate risk assessment.
Objective
To compare the predictive performance of natural languag...
Importance:
Persistence of COVID-19 symptoms beyond 2 months, or long COVID, is increasingly recognized as a common sequela of acute infection.
Objectives:
To estimate the prevalence of and sociodemographic factors associated with long COVID and to identify whether the predominant variant at the time of infection and prior vaccination status are...
The COVID States Project has issued a series of reports since the beginning of the pandemic regarding approval of how state governors and the President have handled the pandemic. We also have a dashboard that allows examination of the approval levels of each governor and of the President over time (the latter, both nationally and state-by-state). I...
Background
Clinical guidelines recommend adding a second drug for patients with major depressive disorder who have a partial response, and switching antidepressants for those who show no response or intolerance. The authors compared this guidelines-based strategy to other strategies for the management of unresponsive depression.
Methods
1436 indiv...
This quality improvement study examines the standards of certification by the American Board of Dermatology for performance of micrographic dermatologic surgery.
Chromosome 16p11.2 reciprocal genomic disorder, resulting from recurrent copy-number variants (CNVs), involves intellectual disability, autism spectrum disorder (ASD), and schizophrenia, but the responsible mechanisms are not known. To systemically dissect molecular effects, we performed transcriptome profiling of 350 libraries from six tissues (co...
Importance:
Suicide rates have been increasing among youth in the US. While the heritability of suicide risk is well established, there is limited understanding of how genetic risk is associated with suicidal thoughts and behaviors in young children.
Objective:
To examine whether genetic susceptibility to suicide attempts (SAs) is associated wit...
Antiviral therapies, specifically Paxlovid1 and Molnupiravir2, are highly effective in reducing the risk of hospitalization or death from COVID-19. Clinical trials found that Paxlovid could reduce the risk of death by as much as 89%.3 In light of the massive number of COVID-19 deaths - 400,000 deaths last year, which places it third among leading c...
Treatment-resistant depression (TRD), often defined by absence of symptomatic remission following at least two adequate treatment trials, occurs in roughly a third of all individuals with major depressive disorder (MDD). Prior work has suggested a significant common variant genetic component of liability to TRD, with heritability estimates of 8% wh...
KEY TAKEAWAYS● Overall support for abortion across all nine scenarios increased following the Dobbs decision, with increases ranging from 1 to 5 percentage points. Among respondents for whom the abortion issue is “extremely important”, the corresponding increases were larger, ranging from 2 to 8 percentage points.● Support for abortion increases or...
Since the Supreme Court overturned the constitutional right to an abortion in Dobbs v. Jackson Women's Health Organization roughly two weeks ago, multiple states have enacted laws prohibiting or significantly restricting women from obtaining an abortion. The Court’s decision in Dobbs stated it was returning the “authority to regulate abortion…to th...
It is unclear how the 22q11.2 deletion predisposes to psychiatric disease. To study this, we generated induced pluripotent stem cells from deletion carriers and controls and utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Here, we show that upon differentiation into neural progenitor cells, the deletion acted i...
Neuropsychiatric symptoms may persist following acute COVID-19 illness, but the extent to which these symptoms are specific to COVID-19 has not been established. We utilized electronic health records across 6 hospitals in Massachusetts to characterize cohorts of individuals discharged following admission for COVID-19 between March 2020 and May 2021...
Importance:
Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring.
Objective:
To evaluate whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth.
Design, setting, and participants:
This...
Activity-induced neurogenesis has been extensively studied in rodents but the lack of ante mortem accessibility to human brain at the cellular and molecular levels limits studies of the process in humans. Using cerebral spheroids derived from human induced pluripotent stem cells (iPSCs), we investigated the effects of 4-aminopyridine (4AP) on neuro...
1 SUMMARY Recurrent deletion and duplication of ~743 kilobases of unique genomic sequence and segmental duplications at chromosome 16p11.2 underlie a reciprocal genomic disorder (RGD; OMIM 611913 and 614671) associated with neurodevelopmental and psychiatric phenotypes, including intellectual disability, autism spectrum disorder (ASD), and schizoph...
The path to FDA authorization for vaccines in young children has been complex. On February 1, 2022 Pfizer and BioNTech responded to requests from the Food and Drug Administration (FDA) to seek emergency authorization of their COVID-19 vaccine for children ages 6 months through 4 years on a rolling basis. This authorization would have allowed childr...
Fear of pain is a modifiable risk factor that predicts the development and persistence of chronic pain. It is due in part to patients’ beliefs that pain reflects injury or tissue damage—though this is often not the case. We recently developed a novel psychological treatment, Pain Reprocessing Therapy (PRT), aiming to help patients reattribute their...
The number of deaths associated with COVID-19 in the United States is approaching the grim milestone of 1 million people, or around 1 in 330 people. In many communities, this number is far higher.The magnitude of these losses—and their impact on the survivors—can be difficult to comprehend. A recent White House memorandum acknowledges this impact a...
For the past two years, the United States has endured what the World Health Organization has termed an infodemic of misinformation involving COVID-19 in general, and the COVID-19 vaccination in particular. We reviewed the current breadth and depth of the COVID misinformation problem in a recent report [#82]. In that report (based on our January 202...
Background:
While clinicians commonly learn heuristics to guide antidepressant treatment selection, surveys suggest real-world prescribing practices vary widely. We aimed to determine the extent to which antidepressant prescriptions were consistent with commonly-advocated heuristics for treatment selection.
Methods:
This retrospective longitudin...
In this report, we examine how many older Americans are unvaccinated against COVID-19, and who these unvaccinated individuals are. The risk of hospitalization and death from COVID-19 is far higher for older adults, making vaccination particularly critical in reducing the impact of the pandemic.KEY FINDINGS● 13% of older Americans are completely unv...
The Covid States Project has been tracking trends in executive approval of management of the COVID-19 outbreak throughout the pandemic. We find:● Generally, there has been a downward trend for approval of all governors since the beginning of the pandemic.● Republican respondents in particular have trended downwards in their approval of governors. R...
Background
Severe maternal morbidity (SMM) and mortality remain public health priorities in the United States, given their high rates relative to other high-income countries and the notable racial and ethnic disparities that exist. In general, accurate risk stratification methods are needed to help patients, providers, hospitals, and health systems...
Importance:
Both major depression and firearm ownership are associated with an increased risk for death by suicide in the United States, but the extent of overlap among these major risk factors is not well characterized.
Objective:
To assess the prevalence of current and planned firearm ownership among individuals with depression.
Design, setti...
Self-regulation is a key tenet of professionalism. We sought to assess the accuracy of self-attestation with respect to the administration of a newly defined field of board sub-specialization. One qualifying pathway to take the written examination for certification in Mohs and Dermatologic Surgery (MDS) is to self-attest to an active practice of Mo...
Misinformation remains an important public health concern, especially as it is widely seen as a factor affecting people’s behavior during the COVID-19 pandemic. In past reports, we have discussed the prevalence and demographics of COVID-19 misinformation, its link to vaccination rates, and its dependence on social media news consumption.Here, we ex...
Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients ( N = 3012) using fixed- and random-effects inverse variance-weighted meta-ana...
Activity-induced neurogenesis has been extensively studied in rodents but the lack of ante mortem accessibility to human brain at the cellular and molecular levels limits studies of the process in humans. Using cerebral spheroids derived from human induced pluripotent stem cells (iPSCs), we investigated the effects of increased neuronal activity on...
It has been approximately 9 months since the FDA authorized youth ages 12 to 17 to receive the Pfizer/BioNTech COVID-19 vaccine, and 3 months since authorization for kids ages 5 to 11. After each authorization, vaccination rates initially surged among those age groups. Now that more time has elapsed - along with the spike in cases due to the Omicro...
The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on the developing fetal brain is poorly understood. Other antenatal infections such as influenza have been associated with adverse neurodevelopmental outcomes in offspring. Although vertical transmission has been rarely observed in SARS-CoV-2 to da...
Background
: With the emergence of evidence-based treatments for treatment-resistant depression, strategies to identify individuals at greater risk for treatment resistance early in the course of illness could have clinical utility. We sought to develop and validate a model to predict treatment resistance in major depressive disorder using coded cl...
Recent years have seen armed protests, threats, and violence against government officials following mask mandates, COVID-19 related closures, and the 2020 election (including, most notably, the deadly January 6, 2021 attack on the US capitol). These events have sparked concern about the state of American democracy and the safety of government offic...
Background
Passive measures collected using smartphones have been suggested to represent efficient proxies for depression severity, but the performance of such measures across diagnoses has not been studied.
Methods
We enrolled a cohort of 45 individuals (11 with major depressive disorder, 11 with bipolar disorder, 11 with schizophrenia or schizoa...
The availability of home antigen testing alongside continued challenges in pursuing PCR and antigen tests outside of the home means it is likely that some positive cases are not represented in official counts of cases or positivity rates. Community survey methods could prove helpful in evaluating the extent to which such cases may be missing from o...
Importance:
Misinformation about COVID-19 vaccination may contribute substantially to vaccine hesitancy and resistance.
Objective:
To determine if depressive symptoms are associated with greater likelihood of believing vaccine-related misinformation.
Design, setting, and participants:
This survey study analyzed responses from 2 waves of a 50-s...
Multiple lines of evidence implicate dysregulated microglia-mediated synaptic pruning in the pathophysiology of schizophrenia. In vitro human cellular studies represent a promising means of pursuing this hypothesis, complementing efforts with animal models and postmortem human data while addressing their limitations. The challenges in culturing hom...
Although circular RNAs (circRNAs) are enriched in the brain, their relevance for brain function and psychiatric disorders is poorly understood. Here, we show that circHomer1 is inversely associated with relative HOMER1B mRNA isoform levels in both the orbitofrontal cortex (OFC) and stem-cell-derived neuronal cultures of subjects with psychiatric di...
Late Friday, the CDC updated its guidance regarding mask types for Americans, saying that people now “can choose” to wear higher quality respirators such as N95 or KN95 masks, if they wish. The updated guidance comes on the heels of President Biden’s announcement on Thursday that the nation has more than tripled its stockpile of N95s to help ensure...
How significant a problem is misinformation for the delivery of healthcare services? Misinformation, and any resulting misperceptions, certainly have the potential to negatively impact people’s attitudes and behaviors surrounding the COVID-19 pandemic. Whether or not someone internalizes misinformation depends on multiple factors, but one key consi...
Most suicide research focuses on acute precipitants and is conducted in high-risk populations. Yet, vulnerability to suicide is likely established years prior to its occurrence. In this study, we aimed to investigate the risk of suicide mortality conferred by prenatal sociodemographic and pregnancy-related factors. Offspring of participants ( N = 4...