Mark Allen Geyer

Mark Allen Geyer
University of California, San Diego | UCSD · Department of Psychiatry

PhD

About

731
Publications
74,306
Reads
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55,768
Citations
Citations since 2016
65 Research Items
13118 Citations
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Additional affiliations
June 2002 - present
VA San Diego Healthcare System
Position
  • Director, Neuropsychopharmacology Unit of MIRECC
February 1972 - present
University of California, San Diego
Position
  • Distinguished Professor of Psychiatry and Neurosciences

Publications

Publications (731)
Article
Little is understood about cognitive mechanisms that confer risk and resiliency for posttraumatic stress disorder (PTSD). Prepulse Inhibition (PPI) is a measure of pre-attentional response inhibition that is a stable cognitive trait disrupted in many neuropsychiatric disorders characterized by poor behavioral or cognitive inhibition, including PTSD...
Article
Human immunodeficiency virus (HIV) continues to infect millions worldwide, negatively impacting neurobehavioral function. Further understanding of the combined effects of HIV and methamphetamine use is crucial, as methamphetamine use is prevalent in people with HIV. The HIV-associated protein Tat may contribute to cognitive dysfunction, modeled pre...
Article
Full-text available
Autism spectrum disorder (ASD) is often signaled by atypical cries during infancy. Copy number variants (CNVs) provide genetically identifiable cases of ASD, but how early atypical cries predict a later onset of ASD among CNV carriers is not understood in humans. Genetic mouse models of CNVs have provided a reliable tool to experimentally isolate t...
Article
Full-text available
Background HIV-associated Neurocognitive Disorder (HAND) is commonly observed in persons living with HIV (PWH), and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the ge...
Article
Background Bipolar disorder is a life-threatening disorder linked to dopamine transporter (DAT) polymorphisms, with reduced DAT levels seen in positron emission tomography and postmortem brains. Aims The purpose of this study was to examine the effects of approved antipsychotics on DAT dysfunction-mediated mania behavior in mice. Methods DAT knoc...
Article
Bipolar disorder (BD) and cannabis use are highly comorbid and are each associated with cognitive impairment. Given the prevalence of cannabis use in people with BD, it is important to understand whether the two interact to impact cognitive function. We performed a systematic scoping review to determine what is currently known in this field. We sys...
Article
Background Older adults (≥50 years) represent the fastest-growing population of people who use cannabis, potentially due to the increasing promotion of cannabis as medicine by dispensaries and cannabis websites. Given healthy aging and cannabis use are both associated with cognitive decline, it is important to establish the effects of cannabis on c...
Article
Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy. One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH). Such dependence may further increase cognitive impairment among PWH...
Preprint
Full-text available
Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy (ART). One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH+). Such dependence may further increase cognitive impairment am...
Article
Full-text available
To reveal post-traumatic stress disorder (PTSD) genetic risk influences on tissue-specific gene expression, we use brain and non-brain transcriptomic imputation. We impute genetically regulated gene expression (GReX) in 29,539 PTSD cases and 166,145 controls from 70 ancestry-specific cohorts and identify 18 significant GReX-PTSD associations corres...
Preprint
Middle-to-older-aged adults (>50 years) represent the fastest-growing cannabis-using population. Given aging and cannabis use are associated with cognitive decline, it is important to establish the effects of cannabis on cognitive function in this population. This systematic scoping review used PRISMA guidelines to critically examine the extent of...
Preprint
Bipolar disorder (BD) and cannabis use are highly comorbid and are each associated with cognitive impairment. It is therefore important to understand the relationship between cannabis use and cognition in people with BD, as cannabis use in BD may be associated with greater cognitive impairment. We performed a scoping review to determine how much an...
Article
Objectives Bipolar disorder (BD) is a debilitating psychiatric illness affecting 2‐5% of the population. Although mania is the cardinal feature of BD, inattention and related cognitive dysfunction are observed across all stages. Since cognitive dysfunction confers poor functional outcome in patients, understanding the relevant neural mechanisms rem...
Preprint
Full-text available
PTSD has significant genetic heritability; however, it is unclear how genetic risk influences tissue-specific gene expression. We used brain and non-brain transcriptomic imputation models to impute genetically regulated gene expression (GReX) in 9,087 PTSD-cases and 23,811 controls and identified thirteen significant GReX-PTSD associations. The res...
Article
Full-text available
Background There is evidence that mGlu2/3 receptors regulate 5-HT2A signaling, interactions that have been theorized to play a role in the antipsychotic-like effects of mGlu2/3 agonists as well as the hallucinogenic effects of 5-HT2A agonists. One approach to unraveling this interaction is through the chronic administration of agonists at the two r...
Article
Cognitive impairments, e.g., reward learning, are present in various psychiatric disorders and warrant treatment. Improving reward-related learning could synergistically enhance psychosocial treatments and cognition generally. A critical first step is to understand the mechanisms underlying reward learning. The dopamine system has been implicated i...
Article
Non-medical use of prescription stimulants amongst college students is common, with claims of cognitive and academic benefits. The mechanism, magnitude, and pervasiveness of the cognitive enhancing effects of stimulants in healthy adults remain poorly understood however. The present study determined the effects of dextroamphetamine (D-amp) on the 5...
Article
Athina Markou and others argue forcefully for the adoption of a “translational-back translational strategy” involving studies of the effects of drugs with established safety profiles in proof of principle studies in humans, which in turn encourage parallel studies using experimental animals to provide vital data on the neural systems and neuropharm...
Article
Full-text available
Athina Markou and others argue forcefully for the adoption of a "translational-back translational strategy" for central nervous system drug discovery involving novel application of drugs with established safety profiles in proof-of-principle studies in humans, which in turn encourage parallel studies using experimental animals to provide vital data...
Article
Full-text available
PTSD has been associated consistently with abnormalities in fear acquisition and extinction learning and retention. Fear acquisition refers to learning to discriminate between threat and safety cues. Extinction learning reflects the formation of a new inhibitory-memory that competes with a previously learned threat-related memory. Adjudicating the...
Article
Efforts to replicate results from both basic and clinical models have highlighted problems with reproducibility in science. In psychiatry, reproducibility issues are compounded because the complex behavioral syndromes make many disorders challenging to model. We develop translatable tasks that quantitatively measure psychiatry-relevant behaviors ac...
Article
Background: The catechol-O-methyltransferase (COMT) Val158Met gene influences cognition and behavior in psychiatric illnesses; its low-activity allele, methionine (Met), may be associated with behavior reflecting catecholamine overactivity. Heightened motor activity and increased positive valence are central features of bipolar disorder (BD) and h...
Article
Full-text available
Objectives: Amphetamine improves vigilance as assessed by continuous performance tests (CPT) in children and adults with attention deficit hyperactivity disorder (ADHD). Less is known, however, regarding amphetamine effects on vigilance in healthy adults. Thus, it remains unclear whether amphetamine produces general enhancement of vigilance or if...
Article
The wake-promoting drug modafinil is frequently used off-label to improve cognition in psychiatric and academic populations alike. The domain-specific attentional benefits of modafinil have yet to be quantified objectively in healthy human volunteers using tasks validated for comparison across species. Further, given that modafinil is a low-affinit...
Article
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Correction to article number 15805 published in June 2017 in Nature Communications, vol 8.
Article
Full-text available
Background: Risk for posttraumatic stress disorder (PTSD) is thought to be mediated by gene × environment (G×E) interactions that affect core cognitive processes such as fear learning. The catechol-O-methyltransferase (COMT) val158met polymorphism has been associated with risk for PTSD and impaired fear inhibition. We used a large, relatively homog...
Article
Full-text available
Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag n...
Article
Background: It is unknown how traumatic brain injury (TBI) increases risk for posttraumatic stress disorder (PTSD). One potential mechanism is via alteration of fear-learning processes that could affect responses to trauma memories and cues. We utilized a prospective, longitudinal design to determine if TBI is associated with altered fear learning...
Article
Full-text available
RationaleSmoking is the leading cause of preventable death in the USA, but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. Objectives We examined nicotine withdr...
Article
Full-text available
RationaleBipolar disorder (BD) is a unique mood disorder defined by periods of depression and mania. The defining diagnosis of BD is the presence of mania/hypomania, with symptoms including hyperactivity and risk-taking. Since current treatments do not ameliorate cognitive deficits such as risky decision-making, and impulsivity that can negatively...
Conference Paper
Background: The wake-promoting drug modafinil, is frequently used off-label to improve attention and cognitive control in student populations and has been suggested to similarly improve cognition in psychiatric populations like schizophrenia. The attentional benefits of modafinil have yet to be objectively quantified in healthy human volunteers (Mi...
Conference Paper
Background: Prepulse inhibition (PPI) is a measure of sensorimotor gating shown to be disrupted in schizophrenia. Since dysfunctions of the catecholamine signaling in the cortical circuitry has been associated with reduced PPI, associations between PPI and gene mutations involved in these signaling pathways need to be investigated. The catechol-O-m...
Article
Full-text available
Background: Patients with schizophrenia (SZ) exhibit numerous cognitive deficits that negatively impact their global functioning. Reward-associative learning deficits of SZ patients may be particularly important given that most efficacious behavioral therapies utilize reward learning-based programs to improve global functioning. Because the dopamin...
Article
Dopamine (DA) is required for reinforcement learning. Hence, disruptions in DA signaling may contribute to the learning deficits associated with psychiatric disorders. The DA D1 receptor (D1R) has been linked to learning and is a target for cognitive/motivational enhancement in patients with schizophrenia. Separating the striatal D1R contribution t...
Article
Obsessive-compulsive disorder (OCD) is a disabling and chronic psychiatric disorder, but despite its severity and prevalence, relatively little is known about its neurobiology. Substantial evidence suggests that abnormalities in structure and function of cortico-striato-thalamo-cortical (CSTC) circuits underlie OCD pathophysiology (Ahmari and Dough...
Article
Background: Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, w...
Article
Full-text available
RationaleThe five-choice serial reaction time task (5-CSRTT) is regularly used to study attention and impulsivity. In the 5-CSRTT, rodents initiate a trial, then after an inter-trial interval (ITI), a light appears in one of five holes. Responding in the lit vs. unlit hole reflects attention (accuracy), while responding prematurely before a light a...
Article
Our 1992 paper, ‘The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications’, reviewed a series of (then) new and preliminary findings from cross-species studies of prepulse inhibition of the startle reflex, and commented on their implications. At the time that the report was composed, Pub...
Article
The quantification of unconditioned motoric activity is one of the oldest and most commonly utilized tools in behavioral studies. Although typically measured in reference to psychiatric disorders, e.g., amphetamine-induced hyperactivity used as a model of schizophrenia, bipolar disorder (BD), and Tourette's syndrome, the motoric behavior of psychia...
Article
Full-text available
A recent article identified five key technical determinants that make substantial contributions to the outcome of drug R&D projects (Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nat. Rev. Drug Discov. 13, 419–431 (2014)) 1. Careful consideration of such determinants might be particularly valuable in th...
Article
Timing deficits are observed in patients with schizophrenia. Serotonergic hallucinogens can also alter the subjective experience of time. Characterizing the mechanism through which the serotonergic system regulates timing will increase our understanding of the linkage between serotonin (5-HT) and schizophrenia, and will provide insight into the mec...
Article
Background: Deficits in sensorimotor gating have been hypothesized to underlie the inability to inhibit repetitive thoughts and behaviors. To test this hypothesis, this study assessed prepulse inhibition (PPI), a measure of sensorimotor gating, across three psychiatric disorders (obsessive-compulsive disorder [OCD], social anxiety disorder [SAD],...
Article
Background: Heightened startle response is a symptom of PTSD, but evidence for exaggerated startle in PTSD is inconsistent. This prospective study aimed to clarify whether altered startle reactivity represents a trait risk-factor for developing PTSD or a marker of current PTSD symptoms. Methods: Marines and Navy Corpsmen were assessed before (n...
Article
Although the cognitive and biological characteristics of Alzheimer's disease (AD) are well known and mouse models of AD are available, current treatments for AD-related cognitive deficits have quite limited efficacy. The development of tasks with cross-species validity may enable better prediction of the efficacy of potential new treatments. In thi...
Article
Full-text available
Rationale Cross-species quantification of physiological behavior enables a better understanding of the biological systems underlying neuropsychiatric diseases such as bipolar disorder (BD). Cardinal symptoms of manic BD include increased motor activity and goal-directed behavior, thought to be related to increased catecholamine activity, potentiall...
Chapter
Because of the ethical and regulatory hurdles associated with human studies, much of what is known about the psychopharmacology of hallucinogens has been derived from animal models. However, developing reliable animal models has proven to be a challenging task due to the complexity and variability of hallucinogen effects in humans. This chapter foc...
Article
Full-text available
Although early-life stress is a significant risk factor for developing anxiety disorders, including posttraumatic stress disorder (PTSD), the underlying mechanisms are unclear. Corticotropin releasing hormone (CRH) is disrupted in individuals with PTSD and early-life stress and hence may mediate the effects of early-life stress on PTSD risk. We hyp...
Article
Full-text available
Importance: Disrupted autonomic nervous system functioning as measured by heart rate variability (HRV) has been associated with posttraumatic stress disorder (PTSD). It is not clear, however, whether reduced HRV before trauma exposure contributes to the risk for development of PTSD. Objective: To examine whether HRV before combat deployment is a...
Article
Psychiatric patients with bipolar disorder suffer from states of depression and mania, during which a variety of symptoms are present. Current treatments are limited and neurocognitive deficits in particular often remain untreated. Targeted therapies based on the biological mechanisms of bipolar disorder could fill this gap and benefit patients and...