Thomas Spencer's research while affiliated with Harvard Medical School and other places
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Publications (432)
In this issue of the Journal, the important story of height and weight issues related to stimulant medication in attention-deficit/hyperactivity disorder (ADHD) is yet again addressed, in the largest study to date.1 Controversy related to potential growth decrements in youth with ADHD receiving stimulants has been around for decades. In fact, in a...
Military service can add stress to military-connected family members, and this stress has been linked to their overall well-being. This study examined the acceptability and explored the effectiveness of a mind-body stress management program for military-connected families and whether it was more effective delivered in person or online. Participants...
Objective:
While the comparative efficacy of prolonged exposure (PE) and cognitive processing therapy (CPT) has been examined in outpatient settings, there is a dearth of literature on the relative effectiveness of these interventions when adapted for an intensive treatment format. In an expanded secondary analysis of a previous study, we sought t...
Perinatal nicotine exposure (PNE) produces frontal cortical hypo-dopaminergic state and attention and working memory deficits consistent with neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). Methylphenidate alleviates ADHD symptoms by increasing extracellular dopamine and noradrenaline. Kappa opioid receptor (KO...
The use of non-nutritive sweeteners such as saccharin is widely prevalent. Although saccharin is considered safe for human consumption, it produces behavioral changes in experimental animals. We report that saccharin’s behavioral effects are much more pervasive than currently recognized. In a mouse model, saccharin exposure produced motor impulsivi...
Background
and Purpose: Student veterans are an at-risk population given the challenges of military experience, reintegration to civilian life, and attending college. Therefore, there is a need for innovative programs to support student veterans. The present study sought to determine the acceptability and effectiveness of a 10-week mind-body stress...
Background
A growing body of research suggests that deficient emotional self-regulation (DESR) is common and morbid among attention-deficit/hyperactivity disorder (ADHD) patients. The main aim of the present study was to assess whether high and low levels of DESR in adult ADHD patients can be operationalized and whether they are clinically useful....
Objectives:
Given that veterans are significantly more likely to suffer from post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), depression, and anxiety than civilians, yet current gold-standard treatments for PTSD are not effective for all patients, the present study sought to examine the feasibility and acceptability of a collabo...
Objective:
Equine-assisted activities and therapies (EAATs) have been a growing adjunctive integrative health modality, as they allow participants to practice mindfulness, emotional regulation, and self-mastery or self-esteem building skills. Preliminary evidence suggests that these programs may be helpful in reducing posttraumatic stress disorder...
Background: U.S. Veterans are at risk for suicide, with an average of 30.1 veterans per every 100,000 dying by suicide each year. Family members who have survived a veteran’s death frequently struggle with Posttraumatic Stress Disorder (PTSD), Complicated Grief (CG), and depression. Survivors of intimate partner violence (IPV) are also at increased...
Objective: Telemedicine has been used successfully in several medical specialties with favorable patient outcomes, satisfaction, in a cost-effective manner. However, its use in the context of ADHD remains unclear. Our main aim was to investigate what is known about the use of telemedicine in ADHD. Method: We conducted a systematic search of the lit...
Introduction: Gender and sexual minority veterans may be at higher risk for psychopathology and posttraumatic stress disorder (PTSD) following deployment because they can lack unit cohesion and support due to historically hostile policies, e.g., “Don’t Ask, Don’t Tell.” Intensively-delivered trauma-focused cognitive behavioral therapy (CBT) can eff...
The net benefit of a treatment can be defined by the relationship between clinical improvement and risk of adverse events: the benefit‐risk ratio. The optimization of the benefit‐risk ratio can be achieved by identifying the most adequate dose (and/or dosage regimen) jointly with the best performing in‐vivo release properties of a drug. A general i...
Table S2. Estimated dissolution data parameters for the slow, medium, and fast formulations (RSE).
Figure S1. Mean MPH concentrations for the Ritalin IR formulation in linear and log‐linear scale.
Table S3. Estimated parameter values in the convolution analysis. SE is the standard error and RSE is the relative standard error of the parameters.
Table S4. Results of the regression analysis of the predicted vs. the observed concentrations.
Figure S3. Predicted MPH plasma concentrations (left panel) and the associated trajectories of the SKAMP scores (right panel) for the slow, medium, and fast formulations.
Table S1. Estimated MPH parameter values for the Ritalin IR formulation.
Figure S4. Comparison of the in vitro dissolution profiles of the optimized and the reference formulations.
Figure S2. Regression analysis of the predicted concentration by the convolution model vs. the observed concentrations (open circle) for the slow, medium, and fast formulations.
Model code. NONMEM control stream (IVIVC_NONMEM_code.txt) for the IVIVC analysis.
Objective:
Dasotraline is a potent inhibitor of presynaptic dopamine and norepinephrine reuptake with a pharmacokinetic profile characterized by slow absorption and a long elimination half-life. The aim of this study was to evaluate the efficacy and safety of dasotraline in children with attention-deficit/hyperactivity disorder (ADHD).
Methods:...
Introduction: Attention Deficit Hyperactivity Disorder (ADHD) also have significant symptoms and impairments from EFDs. However, research is needed to inform if EFD and ADHD symptoms are independent predictors of outcomes. Examining the individual influences of ADHD and EFD symptoms can further assist clinicians in understanding and better treating...
Tissue content of monoamines and their metabolites in the orbitofrontal cortex, medial prefrontal cortex, and striatum in the F1 generation (F1 water male n = 5–6; F1 nicotine male n = 6; F1 water female n = 6; F1 female nicotine n = 5–6).
(XLSX)
Use of tobacco products is injurious to health in men and women. However, tobacco use by pregnant women receives greater scrutiny because it can also compromise the health of future generations. More men smoke cigarettes than women. Yet the impact of nicotine use by men upon their descendants has not been as widely scrutinized. We exposed male C57B...
Data underlying S2 Fig.
(XLSX)
Data underlying Fig 1.
(XLSX)
(A) Spontaneous locomotor activity, (B) object-based attention, and (C) spatial working memory (Y-maze) in the F2 generation. (F2 water male n = 11–13; F2 female-derived nicotine male n = 11–13; F2 male-derived nicotine male n = 8–12; F2 water female n = 9–17, F2 female-derived nicotine female n = 8–13; F2 male-derived nicotine female n = 9–12; S3...
Dopamine receptor mRNA expression in the frontal cortex of the F1 generation (F1 water male n = 3–4; F1 nicotine male n = 4–5; F1 water female n = 3–4; F1 female nicotine n = 3–4).
(XLSX)
Data underlying S1 Fig.
(XLSX)
Data underlying Fig 3.
(XLSX)
(A) Spontaneous locomotor activity, (B) object-based attention, and (C) spatial working memory (Y-maze) in the F0 generation (water n = 8; nicotine n = 8–12; S5 Data).
(TIF)
Data underling Fig 2.
(XLSX)
Objectives:
To identify the relationship between the core Diagnostic and Statistical Manual of Mental Disorders (5th ed.) ADHD symptoms and executive function deficits (EFDs), to evaluate ADHD characteristics of those with executive dysfunction (ED), and to examine the predictive utility of the Adult ADHD Investigator Symptom Rating Scale (AISRS)...
Background:
Attention deficit hyperactivity disorder (ADHD) is associated with impulsive behavior and inattention, making it a potential risk factor for sport-related concussion (SRC). The objectives of this study were to determine whether ADHD is an antecedent risk factor for SRC and whether ADHD complicates recovery from SRC in youth athletes....
To conduct a comprehensive review on the agreement between clinician-rated and self-reported attention-deficit/hyperactivity disorder (ADHD) symptoms in adults, the following terms were searched in PubMed: "ADHD self-concordance," "Self-report AND ADHD AND Valid," "(self-report) AND ADHD AND clinician," and "(self-report) AND ADHD AND versus AND in...
Objective:
To investigate the informativeness of self-reports of ADHD symptoms in adults with ADHD in the clinical setting.
Method:
Subjects were clinically referred adults aged 19 years to 67 years of age of both sexes ( N = 54). All subjects were on stable doses of stimulant and were considered responders to treatment. ADHD symptoms were asses...
Background
Cigarette smoking by pregnant women is associated with a significant increase in the risk for cognitive disorders in their children. Preclinical models confirm this risk by showing that exposure of the developing brain to nicotine produces adverse behavioral outcomes. Here we describe behavioral phenotypes resulting from perinatal nicoti...
Two-way analysis of variance data for behavioral phenotypes.
(DOCX)
Bonferroni post hoc multiple comparison data for behavioral phenotypes.
(DOCX)
Objective:
Supratherapeutic doses of methylphenidate activate μ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed μ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD).
Methods:...
Objective:
The aim of this study is to validate the Adult ADHD Self-Report Scale (ASRS) and Adult ADHD Investigator Symptom Rating Scale (AISRS) expanded versions, including executive function deficits (EFDs) and emotional dyscontrol (EC) items, and to present ASRS and AISRS pilot normative data.
Method:
Two patient samples (referred and primary...
Objectives
Once-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, achieves stable plasma concentrations over 24 hours with once-daily dosing. This study evaluated dasotraline in children aged 6–12 years (NCT02428088).
Methods
Patients were randomized 1:1:1 to 6 weeks of once-daily, fixed-dose dasotraline 2 or 4...
BACKGROUND: Although executive function deficits (EFDs) are not a core part of the DSM-5 diagnostic criteria, many adults with Attention Deficit Hyperactivity Disorder (ADHD) also have significant symptoms and impairments from EFDs. Understanding the relationship between core ADHD symptoms of inattention (IA) and hyperactive-impulsivity (HI) and EF...
Objectives:
Assess agreement between self-ratings via the adult attention-deficit/hyperactivity disorder (ADHD) Self-Report Scale (ASRS)-v1.1 Symptom Checklist and clinician ratings via the adult ADHD Investigator Symptom Rating Scale (AISRS) expanded version using DSM-5 adult ADHD patients (referred sample) and ADHD controls (recruited from a pri...
Objective:
Methylphenidate activates μ-opioid receptors, which are linked to euphoria. μ-Opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. This study assessed whether the combination of naltrexone with methylphenidate is well-tolerated while preserving the clinical b...
Importance:
Recognition that adult attention-deficit/hyperactivity disorder (ADHD) is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD screening scales for use in community, workplace, and primary care settings. However, these scales are all calibrated to DSM-IV criteria, which are narrower than the rec...
Methylphenidate (MPH) is currently used to treat children with attention deficit hyperactivity disorder (ADHD). Several extended-release (ER) formulations characterized by a dual release process were developed to improve efficacy over an extended duration. In this study, a model-based approach using literature data was developed to: a) evaluate the...
Although DSM-5 stipulates that symptoms of attention-deficit hyperactivity disorder (ADHD) are the same for adults as children, clinical observations suggest that adults have more diverse deficits than children in higher-level executive functioning and emotional control. Previous psychometric analyses to evaluate these observations have been limite...
Objective:
Based on emerging preclinical findings suggesting that paternal smoking at conception may be a risk for ADHD in the offspring, we investigated whether a similar effect can be observed in humans.
Method:
We analyzed data from an opportunistic dataset of girl probands with ( N = 140) and without ( N = 122) ADHD with available informatio...
Prenatal exposure to nicotine via cigarette smoke or other forms of tobacco use is a significant environmental risk factor for attention deficit hyperactivity disorder (ADHD). The neurobiological mechanisms underlying the link between prenatal nicotine exposure (PNE) and ADHD are not well understood. Animal models, especially rodent models, are beg...
We examined whether non-traumatized subjects with Attention Deficit Hyperactivity Disorder (ADHD) have dysfunctional activation in brain structures mediating fear extinction, possibly explaining the statistical association between ADHD and other disorders characterized by aberrant fear processing such as PTSD. Medication naïve, non-traumatized youn...
Objective
To investigate whether specific symptoms of attention deficit hyperactivity disorder (ADHD) can help identify ADHD patients with mind wandering.
Methods
Subjects were adults ages 18–55 of both sexes ( n =41) who completed the Mind-Wandering Questionnaire (MWQ) and the ADHD module of the Schedule for Affective Disorders and Schizophrenia...
Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorall...
Supplementary figures and tables.
A recent meta-analysis documented a significant statistical association between mild traumatic brain injury (mTBI) and attention deficit hyperactivity disorder (ADHD) (Adeyemo et al., 2014), but the direction of this effect was unclear. In this study, we hypothesized that ADHD would be an antecedent risk factor for mTBI. Participants were student a...
Objective:
We aimed to provide an overview of the Massachusetts General Hospital (MGH) Longitudinal Studies of ADHD.
Methods:
We evaluated and followed samples of boys and girls with and without ADHD ascertained from psychiatric and pediatric sources and their families.
Results:
These studies documented that ADHD in both sexes is associated wi...
Children with deficits in emotional regulation operationalized by scores on the Child Behavior Checklist (CBCL) Attention Problems, Aggressive Behavior, and Anxious-Depressed subscales are more likely than others to manifest adverse outcomes. However, the transmission of this profile has not been well studied. The main aim of this study was to inve...
Objective: To conduct a systematic review and meta-analysis examining the relationship between attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD).
Data Sources: We reviewed literature through PubMed and PsycINFO without a specified date range, utilizing the search (posttraumatic stress disorder OR PTSD) AND (A...
This study examined whether exposure to maternal smoking during pregnancy in children with and without ADHD is associated with smoking in offspring and whether this association is selective to ADHD children.
Ninety-six exposed and 400 unexposed participants were derived from two longitudinal studies of boys and girls with and without ADHD. Maternal...
Whereas the adverse impact of attention-deficit/hyperactivity disorder (ADHD) on emotional and psychosocial well-being has been well investigated, its impact on physical health has not. The main aim of this study was to assess the impact of ADHD on lifestyle behaviors and measures of adverse health risk indicators. Subjects were 100 untreated adult...
Background
Previous work shows that children with high scores (2SD, combined score≥210) on the Attention Problems, Aggressive Behavior, and Anxious-Depressed (A-A-A) subscales of the Child Behavior Checklist (CBCL) are more likely than other children to meet criteria for bipolar (BP)-I disorder. However, the utility of this profile as a screening t...
Objective:
This study investigated the association between mild traumatic brain injury (mTBI) and ADHD, which increases risk of injuries and accidents.
Method:
We conducted a systematic review and meta-analysis of studies that examined the relationship between mTBI and ADHD.
Results:
Five studies, comprising 3,023 mTBI patients and 9,716 contr...
Objective:
To evaluate the efficacy and safety of memantine hydrochloride as an adjunct to stimulant pharmacotherapy for treating executive function deficits (EFDs) in adults with ADHD.
Method:
This was a 12-week, double-blind, placebo-controlled, randomized clinical trial of memantine added to open-label treatment with stimulant medication. Bec...
Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic r...
Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment
Objective:
ADHD and post-traumatic stress disorder (PTSD) are often comorbid yet despite the increased comorbidity between the two disorders, to our knowledge, no data have been published regarding the neuropsychological profile of adults with comorbid ADHD and PTSD. Likewise, previous empirical studies of the neuropsychology of PTSD did not contr...
Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder affecting children and adults. Genetic and environmental factors are associated with the etiology of ADHD. Among the environmental factors, exposure of the developing brain to nicotine is considered a major risk factor. Recent evidence suggests that environmental influenc...
Objective:
We assessed the neural correlates of adult ADHD in treatment-naïve participants, an approach necessary for identifying neural substrates unconfounded by medication effects.
Method:
The sample consisted of 24 medication-naïve adults with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnosed ADHD and 24 healt...
Much psychiatric genetic research has focused on a 40-base pair variable number of tandem repeats (VNTR) polymorphism located in the 3'-untranslated region (3'UTR) of the dopamine active transporter (DAT) gene (SLC6A3). This variant produces two common alleles with 9- and 10-repeats (9R and 10R). Studies associating this variant with in vivo DAT ac...
To evaluate the impact of therapeutic oral doses of stimulants on the brains of ADHD subjects as measured by magnetic resonance imaging (MRI)-based neuroimaging studies (morphometric, functional, spectroscopy).
We searched PubMed and ScienceDirect through the end of calendar year 2011 using the keywords (1) psychostimulants or methylphenidate or am...
Despite ongoing concerns that traumatized children with severe symptoms of emotional dysregulation may be inappropriately receiving a diagnosis of pediatric bipolar-I (BP-I) disorder, this issue has not been adequately examined in the literature. Because both pediatric BP-I disorder and posttraumatic stress disorder (PTSD) are familial disorders, i...
Objectives:
Preclinical studies link prenatal nicotine exposure with the development of both ADHD-like phenotype in rodents and blockade of extinction learning in a fear conditioning paradigm, a preclinical model of posttraumatic stress disorder (PTSD). While these findings suggest that either ADHD, prenatal nicotine exposure, or both could be a r...
Objective: To investigate whether neuropsychological deficits account for the association between deficient emotional self-regulation (DESR) and ADHD. Method: DESR was identified in adults with and without ADHD who reported extreme frequency of items from the Barkley Current Behavior Scale (>95th percentile of control participants). A neuropsycholo...
Attention-deficit/hyperactivity disorder (ADHD) is characterized by clinically significant functional impairment due to symptoms of inattention and/or hyperactivity and impulsivity. Previous research suggests a link, in child samples, between ADHD and posttraumatic stress disorder (PTSD), which is characterized by (1) chronically reexperiencing a t...
While symptoms of deficient emotional self-regulation (DESR) such as low frustration tolerance, temper outbursts, emotional impulsivity, and mood lability are commonly associated with attention deficit hyperactivity disorder (ADHD), little is known about their nature. The main aim of this post hoc study was to examine the correlates of DESR in a la...
Background:
The main aim of this study was to examine the relationship between dopamine transporter (DAT) binding in the striatum in individuals with and without attention-deficit/hyperactivity disorder (ADHD), attending to the 3'-untranslated region of the gene (3'-UTR) and intron8 variable number of tandem repeats (VNTR) polymorphisms of the DAT...
BACKGROUND: Although the DSM-IV provides explicit criteria for the diagnosis of BP-I disorder, this is a complex diagnosis that requires high levels of clinical expertise. Previous work shows children with a unique profile of the CBCL of high scores (2SD) on the attention problems (AP), aggressive behavior (AGG), and anxious-depressed (AD) (A-A-A)...
Objective:
This study sought to address the link between attention deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) in youth by providing a comprehensive comparison of clinical correlates of ADHD subjects with and without PTSD across multiple non-overlapping domains of functioning and familial patterns of transmissio...
Objective:
Although attention-deficit hyperactivity disorder (ADHD) is a well-known risk factor for cigarette smoking, prospective studies aimed at reducing smoking risk in this population are critically needed.
Study design:
This was a 2-year, prospective, open-label clinical trial of extended-release methylphenidate for smoking prevention in a...
Cigarette smoking, nicotine replacement therapy, and smokeless tobacco use during pregnancy are associated with cognitive disabilities later in life in children exposed prenatally to nicotine. The disabilities include attention deficit hyperactivity disorder (ADHD) and conduct disorder. However, the structural and neurochemical bases of these cogni...
