Gerald Nestadt

Gerald Nestadt
Johns Hopkins Medicine | JHUSOM · Department of Psychiatry and Behavioral Sciences

Professor

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257
Publications
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28,395
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Publications

Publications (257)
Article
Objectives: Olfactory dysfunction is reproducibly reported in psychotic disorders, particularly in association with negative symptoms. The superior frontal gyrus (SFG) has been frequently studied in patients with psychotic disorders, in particular with their associations with negative symptoms. The relationship between olfactory functions and brai...
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Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch–JAG pathway molecules in association with schizophrenia (SZ). The microarray profiling study underscored JAG1 as the m...
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Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and bi...
Preprint
Recent reports have indicated that the occurrence of symptom exacerbation in early-stage psychosis could result in brain changes, which are likely to underlie the poorer disease outcome. Thus, it is important to identify neuroimaging signature associated with symptom exacerbation in early-stage psychosis. We studied 85 patients with psychosis withi...
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Background Psychiatric comorbidity is defined as the joint occurrence of two or more mental or substance use disorders. Widespread psychiatric comorbidity has been reported in treatment and population-based studies. The aim of this study was to measure the extent and impact of psychiatric comorbidity in a cohort of the Baltimore Epidemiologic Catch...
Article
The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the presen...
Article
Background Although general anxiety has increased markedly since the onset of the COVID-19 pandemic, little has been reported about the demographic distribution of COVID-19 related worry, its relationship with psychological features, and its association with depression symptoms in the United States (US). Methods 2117 participants, selected to repr...
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Bipolar disorder (BD) is a common, highly heritable disorder that affects 1–2% of the world’s population. To date, most genetic studies of BD have focused on common gene variation, and while robustly associated loci have been identified, a substantial proportion of the heritability remains missing and could be partially attributable to rare variati...
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Obsessive–compulsive disorder (OCD) affects 1–2% of the population, and, as with other complex neuropsychiatric disorders, it is thought that rare variation contributes to its genetic risk. In this study, we performed exome sequencing in the largest OCD cohort to date (1,313 total cases, consisting of 587 trios, 41 quartets and 644 singletons of af...
Article
The experience of doubt, the lack of confidence in one's perceptions, internal states, memory and attention, can be due to the variability in occurrence of a phenomenon or can be driven by the internal experience of uncertainty based on subjective evaluation of the environment. Although the experience of some doubt is adaptive in normal cognitive f...
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Background Obsessive-compulsive personality disorder (OCPD) is characterized by pervasive and persistent traits including preoccupation with orderliness, perfectionism, and control. Relatively little is known about the potential relationship between OCPD traits and physical health. Methods We investigated the association between OCPD traits and se...
Preprint
Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and bi...
Article
Full-text available
Background: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. Objective: The goals of this study were to compare the prevalen...
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Background Contamination-prevention behaviors such as mask wearing and physical distancing are crucial to reduce coronavirus transmission during the COVID-19 pandemic. We hypothesized that engagement in these behaviors could provoke obsessions and phobias in vulnerable individuals in the community. Methods A total of 2,117 participants, systematic...
Preprint
Full-text available
The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the presen...
Article
Obsessive-compulsive disorder (OCD) affects approximately one person in 40 and causes substantial suffering. Evidence-based treatments can benefit many; however, optimal treatment can be difficult to access. Diagnosis is frequently delayed, and pharmacological and psychotherapeutic interventions often fail to follow evidence-based guidelines. To am...
Article
Prior research has shown that onset or exacerbation of OCD is associated with menstruation, pregnancy, and the post-partum period. However, the underlying cause is unclear. The goal of this study was to assess whether pregnancy and birth complications were associated with OCD symptoms exacerbation, among women with established OCD. Two-hundred and...
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Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian...
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Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p...
Preprint
Objective 7 Tesla (T) longitudinal magnetic resonance spectroscopy (MRS) offers a precise measurment of metabolic levels in human brain via a non-invasive approach. Studying longitudinal changes in neurometabolites could help identify trait and state markers for diseases and understand inconsistent findings from different researchers due to differe...
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Background The human serotonin transporter (SERT) gene polymorphism (5HTTLPR) has been associated with multiple psychiatric disorders, including major depression, anxiety disorders, and substance use disorders. This study investigated the association between 5HTTLPR and psychiatric morbidity and comorbidity in a psychiatrist-examined population sam...
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Background The Research Domain Criteria seeks to bridge knowledge from neuroscience with clinical practice by promoting research into valid neurocognitive phenotypes and dimensions, irrespective of symptoms and diagnoses as currently conceptualized. While the Research Domain Criteria offers a vision of future research and practice, its 39 functiona...
Chapter
There is strong evidence that obsessive–compulsive disorder (OCD) has a genetic basis. This chapter focuses on recent findings on the genetics of OCD from genetic epidemiological (family and twin) studies, as well as from molecular genetic studies (linkage studies, candidate gene association studies, and genome-wide association studies), of common...
Article
The glutamate transporter gene SLC1A1 has been shown to have an association with obsessive-compulsive disorder (OCD), and serotonin reuptake inhibitor (SRI) treatment response. One polymorphism (rs3056) in SLC1A1 has been associated with altered brain volumes in OCD. We investigated the association of this polymorphism with OCD and its relationship...
Article
General personality dimensions are associated with clinical severity and treatment response in individuals with depression and many anxiety disorders, but little is known about these relationships in individuals with obsessive–compulsive disorder (OCD). Individuals in the current study included 705 adults with OCD who had participated in family and...
Article
Background: This study addresses the strength of associations between trichotillomania (TTM) and other DSM-IV Axis I conditions in a large sample (n = 2606) enriched for familial obsessive-compulsive disorder (OCD), to inform TTM classification. Methods: We identified participants with TTM in the Johns Hopkins OCD Family Study (153 families) and...
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Doubt is subjective uncertainty about one’s perceptions and recall. It can impair decision-making and is a prominent feature of obsessive-compulsive disorder (OCD). We propose that evaluation of doubt during decision-making provides a useful endophenotype with which to study the underlying pathophysiology of OCD and potentially other psychopatholog...
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Objective: To evaluate the lifetime prevalence of infectious, inflammatory, and autoimmune disorders in a multisite study of probands with childhood-onset obsessive compulsive disorder (OCD) and their first-degree relatives. Methods: Medical questionnaires were completed by 1401 probands and 1045 first-degree relatives in the OCD Collaborative Gen...
Chapter
This chapter describes seventeen important mental disorders and reviews studies of the prevalence of the disorders from around the world, presenting median and interquartile ranges for more than four hundred research studies. The range of prevalences is below 0.5% for eating disorders and schizophrenia, and above 5% for attention deficit hyperactiv...
Article
Importance The use of high-field magnetic resonance spectroscopy (MRS) in multiple brain regions of a large population of human participants facilitates in vivo study of localized or diffusely altered brain metabolites in patients with first-episode psychosis (FEP) compared to healthy participants. Objective To compare metabolite levels in 5 brain...
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Obsessive-compulsive disorder (OCD) has been seen to run in families and genetics help to understand its heritability. In this review, we summarize older studies which focused on establishing the familial nature of OCD, including its various dimensions of symptoms, and we focus on recent findings from studies using both the candidate gene approach...
Article
Background Obsessive Compulsive Disorder (OCD) is a complex neuropsychiatric disorder that affects approximately 1% of the population. It is likely that the genetic architecture underlying the disorder is complex, and that furthermore some subset of it involves rare and de novo variants of relatively large effect size. Methods We have generated wh...
Article
Objective: First-episode schizophrenia and schizoaffective patients (SZ+) show olfactory impairments, but how these relate to cognitive dysfunction remains unclear. We examined the relationship between cognitive and olfactory dysfunction in SZ+ and the clinical utility of these measures in the assessment of SZ+ patients. Method: First-episode SZ...
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Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from...
Article
Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 con...
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This study investigated cultural differences in beliefs about the etiology and management of OCD. Participants were 428 individuals from 13 countries in North America, Western Europe and South Asia who completed a questionnaire about a hypothetical individual who experienced OCD. Principal components analysis of the questionnaire items identified f...
Preprint
Full-text available
Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a crossdisorder GWAS meta-analysis of 3,495 AN cases, 2,688 OCD cases and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (r g = 0.49 ± 0.13, p...
Article
Background: Hoarding behavior may distinguish a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Little is known about the relationship between executive dysfunction and hoarding in individuals with OCD. Methods: The study sample included 431 adults diagnosed with DSM-IV OCD. Participants were assess...
Article
Two obsessive–compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one stu...
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Objective: The aim of this study was to identify any potential genetic overlap between attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). We hypothesized that since these disorders share a sub-phenotype, they may share common risk alleles. In this manuscript, we report the overlap found between these two disord...
Article
Background: Clinicians have long considered doubt to be a fundamental characteristic of obsessive-compulsive disorder (OCD). However, the clinical relevance of doubt in OCD has not been addressed. Methods: Participants included 1182 adults with OCD who had participated in family and genetic studies of OCD. We used a clinical measure of the sever...
Article
Obsessive-compulsive disorder (OCD) is a polygenic neuropsychiatric disorder characterized by repetitive thoughts and behaviors that cause distress. The pathogenic repeat expansion [GGGGCC]n found at the C9orf72 locus is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and has also been documented in p...
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BACKGROUND: Previous research has suggested a link between antidepressants use and the development of cerebrovascular events, but there has never been any study investigating the risk of stroke in obsessive-compulsive disorder (OCD) patients treated with a selective serotonin reuptake inhibitor (SSRI). METHODS: A retrospective observational cohort...
Article
The diagnosis of obsessive-compulsive disorder (OCD) is based on the presence of specific symptoms and their consequence in the lives of those that exhibit them. It is likely that these symptoms emerge from a neurocognitive vulnerability in the mental life of the individual which has a basis in neurophysiology. The prominence of doubt/uncertainty/l...
Article
Background: To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage. Methods: Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD...
Article
Schizophrenia is a common, clinically heterogeneous disorder associated with lifelong morbidity and early mortality. Several genetic variants associated with schizophrenia have been identified, but the majority of the heritability remains unknown. In this study, we report on a case-control sample of Ashkenazi Jews (AJ), a founder population that ma...
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Inflammation and maternal or fetal infections have been suggested as risk factors for schizophrenia (SZ) and bipolar disorder (BP). It is likely that such environmental effects are contingent on genetic background. Here, in a genome-wide approach, we test the hypothesis that such exposures increase the risk for SZ and BP and that the increase is de...
Article
Effects of season of birth (SOB) have been documented in numerous neuropsychiatric disorders. To date, few studies have evaluated this issue in obsessive-compulsive disorder (OCD). The aim of this study was to investigate the birth seasonality in OCD. This study was based on Taiwan National Health Insurance Research Database. Data for the birth-yea...
Article
Women with obsessive-compulsive disorder (OCD) often report that symptoms first appear or exacerbate during reproductive cycle events; however, little is known about these relationships. The goals of this study were to examine, in a US and a European female OCD sample, onset and exacerbation of OCD in reproductive cycle events, and to investigate t...
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Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association stud...
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Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent ass...
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OBJECTIVE Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. METHOD The p...
Article
Some individuals with obsessive–compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical exam...
Article
Introduction: Depression and anxiety disorders have been found to be highly comorbid in epidemiologic studies. Furthermore, the presence of the short allele of the serotonin transporter gene (5HTT) has been found to be associated with an increased prevalence of major depressive disorder (MDD), bipolar disorder, anxiety disorders, as well as persona...
Article
Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. Afte...
Article
Background Several copy number variants (CNVs) have been implicated as susceptibility factors for schizophrenia (SZ). Some of these same CNVs also increase risk for autism spectrum disorders, suggesting an etiologic overlap between these conditions. Recently, de novo duplications of a region on chromosome 7q11.23 were associated with autism spectru...
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Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,0...
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Subjects from the Epidemiologic Catchment Area Program, interviewed during 1979-1983, were linked to data in the National Death Index through 2007 to estimate the association of mental and behavioral disorders with death. There were more than 25 years of follow-up for 15,440 individuals, with 6,924 deaths amounting to 307,881 person-years of observ...
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The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neuro...
Article
Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,0...
Article
Objective: To determine the association between personality domains and 11-year cognitive decline in a sample from a population-based study. Method: Data from Waves 3 (1993-1996) and 4 (2003-2004) of the Baltimore cohort of the Epidemiologic Catchment Area (ECA) st