Lars Fredrik Jarskog

Lars Fredrik Jarskog
University of North Carolina at Chapel Hill | UNC · Department of Psychiatry

MD

About

142
Publications
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7,131
Citations
Additional affiliations
August 2010 - present
University of North Carolina at Chapel Hill
Position
  • Professor

Publications

Publications (142)
Article
Poor health and low cardiorespiratory fitness (CRF) contribute substantially to the shortened lifespan of individuals with schizophrenia spectrum disorders (SSDs). Increasing physical activity has demonstrated value; however, there are limited interventions that are accessible and adequately address motivational challenges. This paper reports on an...
Article
Background Premature mortality in individuals with schizophrenia spectrum disorders (SSDs) is largely due to high rates of chronic health conditions. Although exercise has been shown to improve health in this population, scalable and accessible interventions are limited. Aim To examine the impact of Physical Activity Can Enhance Life (PACE-Life),...
Article
Background: Challenges in employment are highly prevalent among people with schizophrenia regardless of their employment history. Although supportive employment can be effective, few participants sustain meaningful competitive employment. Our goal was to identify the correlates of developing sustained unemployment. Methods: We examined employment o...
Article
Black Americans are disproportionately diagnosed with schizophrenia and experience worse objective functional outcomes (e.g., hospitalizations) than their White counterparts. However, we have a limited understanding of the psychological pathways through which Black Americans with schizophrenia reach worse outcomes. This study assessed race and doma...
Article
Individuals with schizophrenia spectrum disorders (SSD) consistently show deficits in social cognition (SC) which is associated with real world outcomes. Psychosocial treatments have demonstrated reliable improvements in SC abilities, highlighting the need for accurate identification of SC deficits for efficient and individualized treatment plannin...
Article
Full-text available
Individuals with schizophrenia (SZ) display cognitive deficits that have been identified as major determinants of poor functioning and disability, representing a serious public health concern and an important target for interventions. At present, available treatments offer only minimal to moderate benefits to ameliorate cognitive deficits. Thus, th...
Article
Face perception is a highly developed function of the human visual system. Previous studies of event-related potentials (ERPs) have identified a face-selective ERP component (negative peak at about 170 ms after stimulus onset, N170) in healthy participants. In contrast, patients with schizophrenia exhibit reduced amplitude of the N170, which may re...
Article
Full-text available
Background: Impairments in social functioning are central to Schizophrenia (SCZ). Patients with SCZ have challenges in the ability to evaluate their functioning. A correlate of self-assessments in SCZ is depression, wherein negligible depression predicts overestimation. Healthy individuals misestimate their functioning, but mild dysthymia predicts...
Article
Full-text available
In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is...
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Objective To evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD). Method Patients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term mainte...
Preprint
Face perception is a highly developed function of the human visual system. Previous studies of event-related potentials (ERPs) have identified a face-selective ERP component (negative peak at about 170 milliseconds after stimulation onset, N170) in healthy participants. In contrast, patients with schizophrenia exhibit reduced amplitude of the N170,...
Article
Full-text available
Objective: Cognitive impairment in schizophrenia is a core feature of the disorder. Computerized cognitive training has shown promise in pilot studies. A 26-week randomized blinded placebo-controlled trial was conducted to investigate the effect of a novel computerized cognitive training program on cognitive and functional capacity outcomes. Meth...
Article
Autistic traits are a feature of schizophrenia and has been found to impair social functioning and social cognition. Other influences on social outcomes in schizophrenia include depression and social avoidance. However, challenges in self-assessment of abilities and functioning (i.e., introspective accuracy)and self-assessment bias also contribute...
Presentation
Background Impairments in self-assessment in schizophrenia have been shown to have functional and clinical implications. Prior studies have suggested that overconfidence can be associated with poorer cognitive performance in people with schizophrenia, and that metacognitive awareness of performance may underlie other symptoms such as delusions and...
Article
Full-text available
Negative symptoms and depression persist in one third of patients with schizophrenia. Previous studies suggested that depression has more impact on self-perceived compared to observer-rated social functions. Reduced emotional experience, a subdomain of negative symptoms, predicts social functioning deficits, although its role in self-assessment is...
Article
Full-text available
Impairments in self-assessment in schizophrenia have been shown to have functional and clinical implications. Prior studies have suggested that overconfidence can be associated with poorer cognitive performance in people with schizophrenia, and that reduced awareness of performance may be associated with disability. However, overconfidence is commo...
Article
Study Objective To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis. Background In the 12-week ARM-TD and AIM-TD studies, the odds of res...
Article
Background Tardive dyskinesia (TD) is an often-irreversible movement disorder that may intensify the stigma of patients with psychiatric disorders and worsen quality of life. In two randomized, double-blind, placebo (PBO)-controlled, 12-week trials, ARM-TD and AIM-TD (‘parent studies’), deutetrabenazine (DTB) demonstrated statistically significant...
Article
Study Objective To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years. Background In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of o...
Article
Background Tardive dyskinesia (TD) results from exposure to dopamine-receptor antagonists (DRAs), such as typical and atypical antipsychotics. Clinicians commonly manage TD by reducing the dose of or stopping the causative agent; however, this may cause psychiatric relapse and worsen quality of life. In the 12-week ARM-TD and AIM-TD trials, deutetr...
Article
Transcranial alternating current stimulation (tACS) modulates endogenous neural oscillations in healthy human participants by the application of a low-amplitude electrical current with a periodic stimulation waveform. Yet, it is unclear if tACS can modulate and restore neural oscillations that are reduced in patients with psychiatric illnesses such...
Article
The effects of intranasal oxytocin, a neuropeptide involved in prosocial behavior and modulation of neural networks underlying social cognition and emotion regulation, have been studied in schizophrenia. We tested the hypothesis that twice-daily intranasal oxytocin administered for 12-weeks would improve tertiary and exploratory outcomes of self-re...
Article
Background: Individuals with schizophrenia are impaired in their ability to recognize emotions based on vocal cues and these impairments are associated with poor global outcome. Basic perceptual processes, such as auditory pitch processing, are impaired in schizophrenia and contribute to difficulty identifying emotions. However, previous work has...
Article
Current social skill assessments for individuals with schizophrenia require extensive administration times, training, and coding procedures, thus limiting their clinical utility. The purpose of this study was to investigate the psychometric properties of the Brief Impression Questionnaire (BIQ), a novel measure designed to utilize immediate impress...
Article
Previous research on attributions in schizophrenia has focused on whether individuals make hostile, intentional attributions for ambiguous negative events. It is unclear, however, whether individuals with schizophrenia differ from controls in their general judgments of intentionality judgments in nonconflict and emotionally neutral situations. Rese...
Article
Background: Approximately 30% of patients with schizophrenia experience auditory hallucinations that are refractory to antipsychotic medications. Here, we evaluated the feasibility and efficacy of transcranial alternating current stimulation (tACS) that we hypothesized would improve auditory hallucination symptoms by enhancing synchronization betw...
Article
Full-text available
Objective: The rates of obesity and cigarette smoking are much higher in patients with schizophrenia compared to the general population. This study was to examine whether naltrexone and bupropion combination treatment can help weight loss and smoking cessation in patients with schizophrenia. Methods: Obese male schizophrenia patients with current c...
Article
Full-text available
Introduction In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated. Objective To evaluate the long-term safety/tolerability and efficacy of deutetrabenazine in patients with TD. Wee...
Article
Introduction Tardive dyskinesia (TD) is an involuntary movement disorder that is often irreversible, can affect any body region, and can be debilitating. In the ARM-TDand AIM-TD studies, deutetrabenazine treatment demonstrated statistically and clinically significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compare...
Article
Introduction Tardive dyskinesia (TD) is an involuntary movement disorder resulting from exposure to dopamine-receptor antagonists. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo, and was generally well tolerated....
Article
Objective: This study examined the effect of adjunctive telmisartan on psychopathology and cognition in olanzapine- or clozapine-treated patients with schizophrenia. Method: In a 12-week randomized, double-blind, placebo-controlled study, patients diagnosed with schizophrenia or schizoaffective disorder received either telmisartan (80 mg once pe...
Article
Background: Tardive dyskinesia results from exposure to dopamine receptor antagonists, such as typical and atypical antipsychotics. If clinically appropriate, clinicians often manage this disorder by lowering the dose of, or discontinuing, the causative drug. There is a significant unmet need for a treatment option that does not disrupt treatment...
Article
Full-text available
Objective: To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD). Methods: One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) sc...
Article
The present study evaluated the psychometric properties of a role-play measure of empathy, the Performance of Empathic Expression Rating Scale (PEERS), in a sample of 60 individuals with schizophrenia and 51 healthy controls. The role-play ratings assess a person's ability to interact empathically with a confederate in an emotionally charged situat...
Article
Social cognition is impaired in people with schizophrenia and these deficits are strongly correlated with social functioning. Oxytocin is a hypothalamic peptide that contributes to maternal infant bonding and has diverse pro-social effects in adults. This study tested the hypothesis that 12 weeks of intranasal oxytocin will improve social cognitive...
Article
Introduction: AQW051, an α7-nicotinic acetylcholine receptor partial agonist, enhanced cognitive function in rodent models of learning and memory. This study evaluated brain activation during performance of a working memory task (WMT) and an episodic memory task (EMT), and the effect of AQW051 on task-related brain activation and performance in su...
Article
Background: Auditory hallucinations are resistant to pharmacotherapy in about 25% of adults with schizophrenia. Treatment with noninvasive brain stimulation would provide a welcomed additional tool for the clinical management of auditory hallucinations. A recent study found a significant reduction in auditory hallucinations in people with schizoph...
Article
This article reviews the recent evidence for therapeutic strategies for patients with treatment-resistant schizophrenia (TRS) not responding to or only partially responding to clozapine. A number of pharmacological and nonpharmacological biological approaches for clozapine-resistant TRS have been evaluated in clinical trials. Among these, the evide...
Article
This Phase II exploratory study assessed GSK239512, a brain penetrant histamine H3 receptor antagonist, versus placebo on cognitive impairment in 50 stable outpatients with schizophrenia. Subjects were randomized to placebo or GSK239512 for 7weeks (4weeks titration). GSK239512 was associated with a small positive effect size (ES) on the CogState Sc...
Article
Full-text available
Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perf...
Article
Objective: Clozapine, an evidence-based treatment of refractory schizophrenia, is associated with increased weight gain and metabolic dysregulation compared with most antipsychotics in short-term clinical trials. However, there are limited data describing comparative long-term metabolic risks. In this report, we examined whether short-term differe...
Article
Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how trea...
Article
Full-text available
Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perf...
Article
Full-text available
Objective: The purpose of this study was to determine whether metformin promotes weight loss in overweight outpatients with chronic schizophrenia or schizoaffective disorder. Method: In a double-blind study, 148 clinically stable, overweight (body mass index [BMI] ≥27) outpatients with chronic schizophrenia or schizoaffective disorder were rando...
Article
Full-text available
Schizophrenia is associated with extensive neurocognitive and behavioral impairments. Studies indicate that N-acetylaspartate (NAA), a marker of neuronal integrity, and choline, a marker of cell membrane turnover and white matter integrity, may be altered in schizophrenia. Davunetide is a neurotrophic peptide that can enhance cognitive function in...
Article
Purpose of review: The current article provides a brief review of the clinical efficacy and safety outcomes from selected phase I and II clinical trials of compounds in development acting on targets beyond the dopamine D2 receptor in patients with schizophrenia. Recent findings: A number of experimental pharmacological targets have been studied...
Article
Background: The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. Methods: In a randomized, double...
Article
The introduction of second-generation antipsychotics (SGAs), heralded by clozapine in 1990, represented an important advance in the pharmacologic treatment of schizophrenia. However, several recent comparative effectiveness trials found that non-clozapine SGAs provided little or no advantage in efficacy over first-generation antipsychotics, and all...
Article
Existing 67-channel event-related potentials, obtained during recognition and working memory paradigms with words or faces, were used to examine early visual processing in schizophrenia patients prone to auditory hallucinations (AH, n = 26) or not (NH, n = 49) and healthy controls (HC, n = 46). Current source density (CSD) transforms revealed disti...
Article
Full-text available
Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychose...
Article
Oxytocin has numerous prosocial and antipsychotic-like effects in animals. Prosocial effects of acute intranasal oxytocin administration have also been reported in human subjects. We conducted a randomized, placebo-controlled trial testing the effects of twice daily intranasal oxytocin treatment for 14 days on psychotic symptoms and social cognitio...
Article
In a previous pilot study, MK-0777--a γ-aminobutyric acid (GABA)(A) α2/α3 partial agonist--was reported to improve delayed memory and cognitive measures of prefrontal cortical function in people with schizophrenia. The current study was designed to further examine the efficacy and safety of MK-0777 for the treatment of cognitive impairments in schi...
Article
Full-text available
The heterogeneity of schizophrenia remains an obstacle for understanding its pathophysiology. Studies using a tone discrimination screening test to classify patients have found evidence for 2 subgroups having either a specific deficit in verbal working memory (WM) or deficits in both verbal and nonverbal memory. This study aimed to (a) replicate in...
Article
Although the etiology of schizophrenia remains unknown, diverse neuropathological evidence suggests a disorder of synaptic connectivity. Apoptosis is a form of cell death that helps determine synaptic circuitry during neurodevelopment and altered regulation of apoptosis has been implicated in schizophrenia. Prostate apoptosis response-4 (Par-4) is...
Article
Full-text available
Until recently, the social cognitive impairment in schizophrenia has been underappreciated and remains essentially untreated. Deficits in emotional processing, social perception and knowledge, theory of mind, and attributional bias may contribute to functional social cognitive impairments in schizophrenia. The amygdala has been implicated as a key...
Article
We previously reported a preserved 'old-new effect' (enhanced parietal positivity 300-800 ms following correctly-recognized repeated words) in schizophrenia over mid-parietal sites using 31-channel nose-referenced event-related potentials (ERP) and reference-free current source densities (CSD). However, patients showed poorer word recognition memor...
Article
The prefrontal cortex (PFC) is associated with higher cognitive functions including attention and working memory and has been implicated in the regulation of impulsivity as well as the pathology of complex mental illnesses. N-methyl D-aspartate (NMDA) antagonist treatment with dizocilpine induces cell death which is greatest in the frontal cortex o...
Article
Neural cell adhesion molecule (NCAM) is a membrane-bound cell recognition molecule that exerts important functions in normal neurodevelopment including cell migration, neurite outgrowth, axon fasciculation, and synaptic plasticity. Alternative splicing of NCAM mRNA generates three main protein isoforms: NCAM-180, -140, and -120. Ectodomain shedding...