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Brain function during stages of working memory in schizophrenia and psychotic bipolar disorder.
Huang AS, Rogers BP, Anticevic A, Blackford JU, Heckers S, Woodward ND
(2019) Neuropsychopharmacology 44: 2136-2142
MeSH Terms: Adult, Bipolar Disorder, Brain, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Schizophrenia, Schizophrenic Psychology, Spatial Memory, Young Adult
Show Abstract · Added January 31, 2020
Working memory (WM) is impaired in psychotic disorders and linked to functional outcome. Most neurobiological models emphasize prefrontal cortex (PFC) dysfunction in the etiology of WM impairment. However, WM is composed of multiple processes, including encoding and maintenance, and the delineation of the neurobiology of these sub-processes has not been well characterized in schizophrenia and psychotic bipolar disorder. Functional MRI was obtained during an event-related spatial delayed match-to-sample task from 58 healthy individuals, 72 individuals with schizophrenia and 41 people with bipolar I disorder with psychotic features in order to: 1) characterize neural responses during encoding, maintenance and retrieval stages of WM using complementary region-of-interest and whole brain approaches; 2) determine whether schizophrenia and psychotic bipolar disorder exhibit similar abnormalities in WM-related brain function; and 3) elucidate the associations between WM-related brain function, task performance, and neuropsychological functioning. Both schizophrenia and psychotic bipolar disorder groups showed encoding- and maintenance-related impairments in the posterior parietal cortex (PPC) and frontal eye fields (FEF). BOLD response in the PPC and FEF, during encoding and maintenance respectively, was associated with task performance independent of group. Additionally, encoding-related activation in the PPC correlated with general neuropsychological functioning independent of group. Only encoding-related activation in the right ventral striatum differed between schizophrenia and psychotic bipolar disorder; individuals with schizophrenia showed significantly lower activation than both psychotic bipolar disorder and healthy groups. Our results are consistent with emerging evidence implicating PPC dysfunction in WM impairment and suggest interventions targeting neural activation in PPC may improve WM and neuropsychological functioning across psychotic disorders.
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13 MeSH Terms
Neuropsychological functioning in early and chronic stages of schizophrenia and psychotic bipolar disorder.
Menkes MW, Armstrong K, Blackford JU, Heckers S, Woodward ND
(2019) Schizophr Res 206: 413-419
MeSH Terms: Adolescent, Adult, Bipolar Disorder, Chronic Disease, Cognition, Cognitive Dysfunction, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology, Young Adult
Show Abstract · Added January 31, 2020
BACKGROUND - Neuropsychological impairment is common in schizophrenia and psychotic bipolar disorder. It has been hypothesized that the pathways leading to impairment differ between disorders. Cognitive impairment in schizophrenia is believed to result largely from atypical neurodevelopment, whereas bipolar disorder is increasingly conceptualized as a neuroprogressive disorder. The current investigation tested several key predictions of this hypothesis.
METHODS - Current neuropsychological functioning and estimated premorbid intellectual ability were assessed in healthy individuals (n = 260) and a large, cross-sectional sample of individuals in the early and chronic stages of psychosis (n = 410). We tested the following hypotheses: 1) cognitive impairment is more severe in schizophrenia in the early stage of psychosis; and 2) cognitive decline between early and chronic stages is relatively greater in psychotic bipolar disorder. Additionally, individuals with psychosis were classified as neuropsychologically normal, deteriorated, and compromised (i.e. below average intellectual functioning) to determine if the frequencies of neuropsychologically compromised and deteriorated patients were higher in schizophrenia and psychotic bipolar disorder, respectively.
RESULTS - Neuropsychological impairment in the early stage of psychosis was more severe in schizophrenia. Psychotic bipolar disorder was not associated with relatively greater cognitive decline between illness stages. The frequency of neuropsychologically compromised patients was higher in schizophrenia; however, substantial portions of both schizophrenia and psychotic bipolar disorder patients were classified as neuropsychologically compromised and deteriorated.
CONCLUSIONS - While schizophrenia is associated with relatively greater neurodevelopmental involvement, psychotic bipolar disorder and schizophrenia cannot be strictly dichotomized into purely neuroprogressive and neurodevelopmental illness trajectories; there is evidence of both processes in each disorder.
Copyright © 2018 Elsevier B.V. All rights reserved.
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17 MeSH Terms
Childhood temperament is associated with distress, anxiety and reduced quality of life in schizophrenia spectrum disorders.
Feola B, Armstrong K, Woodward ND, Heckers S, Blackford JU
(2019) Psychiatry Res 275: 196-203
MeSH Terms: Adult, Anxiety, Child, Cognition, Comorbidity, Female, Humans, Male, Personality, Personality Disorders, Quality of Life, Schizophrenia, Schizophrenic Psychology, Social Behavior, Stress, Psychological, Substance-Related Disorders, Temperament
Show Abstract · Added January 31, 2020
Schizophrenia is conceptualized as a neurodevelopmental disorder and pre-morbid differences in social function and cognition have been well-established. Less is known about pre-morbid temperament and personality. Inhibited temperament-the predisposition to respond to novelty with wariness, fear, or caution-is a premorbid risk factor for anxiety, depression, and substance use but is understudied in schizophrenia. Participants were patients with schizophrenia spectrum disorders (n = 166) and healthy controls (n = 180). Patients completed measures of childhood inhibited temperament, clinical symptoms (anxiety, depression, PANSS factors), and quality of life. Patients had significantly higher levels of inhibited temperament relative to healthy controls. In patients with schizophrenia, higher inhibited temperament was significantly associated with co-morbid anxiety disorders, greater anxiety and depression symptoms, higher PANSS Distress scores, lower PANSS Excitement scores, and lower quality of life. The current findings replicate and extend previous research with a larger sample and are consistent with vulnerability in an affective path to psychosis. In schizophrenia, higher inhibited temperament was associated with a cluster of mood and anxiety symptoms. Inhibited temperament was not associated with psychosis symptoms. Patients with high inhibited temperament may especially benefit from treatments that specifically target anxiety and depression.
Copyright © 2019. Published by Elsevier B.V.
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MeSH Terms
Impact of substance use disorder on gray matter volume in schizophrenia.
Quinn M, McHugo M, Armstrong K, Woodward N, Blackford J, Heckers S
(2018) Psychiatry Res Neuroimaging 280: 9-14
MeSH Terms: Adolescent, Adult, Amygdala, Cerebral Cortex, Diagnosis, Dual (Psychiatry), Female, Frontal Lobe, Gray Matter, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Occipital Lobe, Organ Size, Schizophrenia, Schizophrenic Psychology, Substance-Related Disorders, Young Adult
Show Abstract · Added March 26, 2019
Substance use may confound the study of brain structure in schizophrenia. We used voxel-based morphometry (VBM) to examine whether differences in regional gray matter volumes exist between schizophrenia patients with (n = 92) and without (n = 66) clinically significant cannabis and/or alcohol use histories compared to 88 healthy control subjects. Relative to controls, patients with schizophrenia had reduced gray matter volume in the bilateral precentral gyrus, right medial frontal cortex, right visual cortex, right occipital pole, right thalamus, bilateral amygdala, and bilateral cerebellum regardless of substance use history. Within these regions, we found no volume differences between patients with schizophrenia and a history of cannabis and/or alcohol compared to patients with schizophrenia without a clinically significant substance use history. Our data support the idea that a clinically meaningful history of alcohol or cannabis use does not significantly compound the gray matter deficits associated with schizophrenia.
Copyright © 2018. Published by Elsevier B.V.
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18 MeSH Terms
Personality traits predicting quality of life and overall functioning in schizophrenia.
Ridgewell C, Blackford JU, McHugo M, Heckers S
(2017) Schizophr Res 182: 19-23
MeSH Terms: Adolescent, Adult, Aged, Analysis of Variance, Extraversion, Psychological, Female, Humans, Male, Middle Aged, Neuroticism, Personality Disorders, Personality Inventory, Quality of Life, Schizophrenia, Schizophrenic Psychology, Surveys and Questionnaires, Young Adult
Show Abstract · Added March 30, 2020
INTRODUCTION - Clinical symptoms and sociodemographic variables predict level of functioning and quality of life in patients with schizophrenia. However, few studies have examined the effect of personality traits on quality of life and overall functioning in schizophrenia. Personality traits are premorbid to illness and may predict the way patients experience schizophrenia. The aim of this study was to examine the individual and additive effects of two core personality traits-neuroticism and extraversion-on quality of life and functioning.
METHODS - Patients with schizophrenia-spectrum disorders (n=153) and healthy controls (n=125) completed personality and quality of life questionnaires. Global functioning was assessed during a clinician-administered structured interview. Neuroticism and extraversion scores were analyzed both as continuous variables and as categorical extremes (High versus Normal Neuroticism, Low versus Normal Extraversion).
RESULTS - Quality of life was significantly associated with neuroticism, extraversion, and the neuroticism×diagnosis and extraversion×diagnosis interactions. For patients, a lower neuroticism score (in the normal range) was associated with quality of life scores comparable to controls; whereas high neuroticism scores in patients were associated with the lowest quality of life. For overall functioning, only diagnosis had a significant effect.
CONCLUSION - Neuroticism modulates quality of life and may provide an important key to improving the life of patients with schizophrenia.
Copyright © 2016 Elsevier B.V. All rights reserved.
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MeSH Terms
Altered threat and safety neural processing linked to persecutory delusions in schizophrenia: a two-task fMRI study.
Perez DL, Pan H, Weisholtz DS, Root JC, Tuescher O, Fischer DB, Butler T, Vago DR, Isenberg N, Epstein J, Landa Y, Smith TE, Savitz AJ, Silbersweig DA, Stern E
(2015) Psychiatry Res 233: 352-66
MeSH Terms: Adult, Cohort Studies, Delusions, Emotions, Fear, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Photic Stimulation, Psychomotor Performance, Schizophrenia, Schizophrenic Psychology, Young Adult
Show Abstract · Added January 4, 2020
Persecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social "real world" and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal-parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model.
Ghoshal A, Rook JM, Dickerson JW, Roop GN, Morrison RD, Jalan-Sakrikar N, Lamsal A, Noetzel MJ, Poslusney MS, Wood MR, Melancon BJ, Stauffer SR, Xiang Z, Daniels JS, Niswender CM, Jones CK, Lindsley CW, Conn PJ
(2016) Neuropsychopharmacology 41: 598-610
MeSH Terms: Animals, Antipsychotic Agents, Cognition, Disease Models, Animal, Long-Term Synaptic Depression, Male, Mice, Inbred C57BL, Mice, Knockout, Patch-Clamp Techniques, Phencyclidine, Pyridines, Pyrroles, Receptor, Muscarinic M1, Schizophrenia, Schizophrenic Psychology, Social Behavior
Show Abstract · Added February 18, 2016
Schizophrenia patients exhibit deficits in signaling of the M1 subtype of muscarinic acetylcholine receptor (mAChR) in the prefrontal cortex (PFC) and also display impaired cortical long-term depression (LTD). We report that selective activation of the M1 mAChR subtype induces LTD in PFC and that this response is completely lost after repeated administration of phencyclidine (PCP), a mouse model of schizophrenia. Furthermore, discovery of a novel, systemically active M1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of selective potentiation of M1 on induction of LTD and behavioral deficits in PCP-treated mice. Interestingly, VU0453595 fully restored impaired LTD as well as deficits in cognitive function and social interaction in these mice. These results provide critical new insights into synaptic changes that may contribute to behavioral deficits in this mouse model and support a role for selective M1 PAMs as a novel approach for the treatment of schizophrenia.
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4 Members
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16 MeSH Terms
Response inhibition and response monitoring in a saccadic double-step task in schizophrenia.
Thakkar KN, Schall JD, Logan GD, Park S
(2015) Brain Cogn 95: 90-8
MeSH Terms: Adult, Executive Function, Female, Humans, Inhibition, Psychological, Male, Models, Psychological, Psychomotor Performance, Reaction Time, Saccades, Schizophrenia, Schizophrenic Psychology
Show Abstract · Added July 28, 2015
BACKGROUND - Cognitive control impairments are linked to functional outcome in schizophrenia. The goal of the current study was to investigate precise abnormalities in two aspects of cognitive control: reactively changing a prepared response, and monitoring performance and adjusting behavior accordingly. We adapted an oculomotor task from neurophysiological studies of the cellular basis of cognitive control in nonhuman primates.
METHODS - 16 medicated outpatients with schizophrenia (SZ) and 18 demographically-matched healthy controls performed the modified double-step task. In this task, participants were required to make a saccade to a visual target. Infrequently, the target jumped to a new location and participants were instructed to rapidly inhibit and change their response. A race model provided an estimate of the time needed to cancel a planned movement. Response monitoring was assessed by measuring reaction time (RT) adjustments based on trial history.
RESULTS - SZ patients had normal visually-guided saccadic RTs but required more time to switch the response to the new target location. Additionally, the estimated latency of inhibition was longer in patients and related to employment. Finally, although both groups slowed down on trials that required inhibiting and changing a response, patients showed exaggerated performance-based adjustments in RTs, which was correlated with positive symptom severity.
CONCLUSIONS - SZ patients have impairments in rapidly inhibiting eye movements and show idiosyncratic response monitoring. These results are consistent with functional abnormalities in a network involving cortical oculomotor regions, the superior colliculus, and basal ganglia, as described in neurophysiological studies of non-human primates using an identical paradigm, and provide a translational bridge for understanding cognitive symptoms of SZ.
Copyright © 2015 Elsevier Inc. All rights reserved.
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2 Members
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12 MeSH Terms
Impaired effort allocation in patients with schizophrenia.
Treadway MT, Peterman JS, Zald DH, Park S
(2015) Schizophr Res 161: 382-5
MeSH Terms: Adult, Anticipation, Psychological, Decision Making, Female, Humans, Male, Motivation, Probability, Psychological Tests, Reward, Schizophrenia, Schizophrenic Psychology
Show Abstract · Added July 28, 2015
A hallmark of negative symptoms in schizophrenia is reduced motivation and goal directed behavior. While preclinical models suggest that blunted striatal dopamine levels can produce such reductions, this mechanism is inconsistent with evidence for enhanced striatal dopamine levels in schizophrenia. In seeking to reconcile this discrepancy, one possibility is that negative symptoms reflect a failure of striatal motivational systems to mobilize appropriately in response to reward-related information. In the present study, we used a laboratory effort-based decision-making task in a sample of patients with schizophrenia and healthy controls to examine allocation of effort in exchange for varying levels of monetary reward. We found that patients and controls did not differ in the overall amount of effort expenditure, but patients made significantly less optimal choices in terms of maximizing rewards. These results provide further evidence for a selective deficit in the ability of schizophrenia patients to utilize environmental cues to guide reward-seeking behavior.
Copyright © 2014 Elsevier B.V. All rights reserved.
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12 MeSH Terms
The course of neuropsychological impairment and brain structure abnormalities in psychotic disorders.
Woodward ND
(2016) Neurosci Res 102: 39-46
MeSH Terms: Bipolar Disorder, Brain, Cognition Disorders, Humans, Neuropsychological Tests, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology
Show Abstract · Added February 15, 2016
Neuropsychological impairment and abnormalities in brain structure are commonly observed in psychotic disorders, including schizophrenia and bipolar disorder. Shared deficits in neuropsychological functioning and abnormalities in brain structure suggest overlapping neuropathology between schizophrenia and bipolar disorder which has important implications for psychiatric nosology, treatment, and our understanding of the etiology of psychotic illnesses. However, the emergence and trajectory of brain dysfunction in psychotic disorders is less well understood. Differences in the course and progression of neuropsychological impairment and brain abnormalities among psychotic disorders may point to unique neuropathological processes. This article reviews the course of neuropsychological impairment and brain structure abnormalities in schizophrenia and bipolar disorder.
Copyright © 2014. Published by Elsevier Ireland Ltd.
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8 MeSH Terms