Biomedical subjects

Randall Newmark

Publications and source records attributed to Randall Newmark.

9 recordsLinked to original sources

PubMed2007

Amygdala-prefrontal disconnection in borderline personality disorder.

Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.

Adult↗

PubMed2006

Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia.

We acquired diffusion tensor and structural MRI images on 103 patients with schizophrenia and 41 age-matched normal controls. The vector data was used to trace tracts from a region of interest in the anterior limb of the internal capsule to the prefrontal cortex. Patients with schizophrenia had tract paths that were significantly shorter in length from the center of internal capsule to prefrontal white matter. These tracts, the anterior thalamic radiations, are important in frontal-striatal-thalamic pathways. These results are consistent with findings of smaller size of the anterior limb of the internal capsule in patients with schizophrenia, diffusion tensor anisotropy decreases in frontal white matter in schizophrenia and hypothesized disruption of the frontal-striatal-thalamic pathway system.

Journal Article↗

PubMed2006

Diffusion tensor imaging in schizophrenia.

BACKGROUND: Alignment of white matter axons as inferred from diffusion tensor imaging has indicated changes in schizophrenia in frontal and frontotemporal white matter. METHODS: Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired in 64 patients with schizophrenia and 55 normal volunteers. Anatomical images were acquired with a magnetization prepared rapid gradient echo sequence, and diffusion tensor images used a pulsed gradient spin-echo acquisition. Images were aligned and warped to a standard brain, and anisotropy in normal volunteers and patients was compared using significance probability mapping. RESULTS: Patients showed widespread areas of reduced anisotropy, including the frontal white matter, the corpus callosum, and the frontal longitudinal fasciculus. CONCLUSIONS: These findings, which are consistent with earlier reports of frontal decreases in anisotropy, demonstrate that the effects are most prominent in frontal and callosal areas and are particularly widespread in frontal white matter regions.

Adolescent↗

PubMed2006

Positron emission tomography imaging of risperidone augmentation in serotonin reuptake inhibitor-refractory patients.

We studied 15 nondepressed patients with obsessive-compulsive disorder (OCD) who were nonresponders to serotonin reuptake inhibitors with an additive trial of risperidone. Positron emission tomography with (18)F-deoxyglucose and magnetic resonance imaging was obtained at baseline and following 8 weeks of either risperidone or placebo in a double-blind parallel group design. Risperidone treatment was associated with significant increases in relative metabolic rate in the striatum, cingulate gyrus, the prefrontal cortex, especially in the orbital region, and the thalamus. Four of 9 patients who received risperidone showed clinical improvement (CGI score of 1 or 2 at 8 weeks) while none of the 6 patients who received placebo showed improvement. Patients with low relative metabolic rates in the striatum and high relative metabolic rates in the anterior cingulate gyrus were more likely to show a clinical response. These metabolic predictors of clinical response are consistent with earlier PET studies showing similar prediction when either neuroleptics or serotonin reuptake inhibitor treatments are administered individually. Our results are consistent with a frontostriatal circuit change related to both dopaminergic and serotonergic systems and with the presence of psychopharmacological subtypes within OCD.

Adult↗

PubMed2006

Hippocampal volume in aging combat veterans with and without post-traumatic stress disorder: relation to risk and resilience factors.

OBJECTIVE: To examine whether there are post-traumatic stress disorder (PTSD) related differences in hippocampal volume in middle-aged and elderly veterans and to examine the relationship of neuroendocrine activity, memory performance, and measures of risk and resilience for PTSD to hippocampal volume in this cohort. METHODS: Seventeen veterans with chronic PTSD and 16 veterans without chronic PTSD received an MRI scan followed by neuroendocrine assessment (24-h urinary cortisol excretion and the lysozyme IC(50-DEX), a measure of glucocorticoid receptor (GR) responsiveness), and cognitive testing. RESULTS: Veterans with PTSD did not differ from those without PTSD in hippocampal volume, but they did show significantly lower urinary cortisol levels, and poorer memory performance on the Wechsler Logical Memory test and Digit Span test. Smaller left hippocampal volumes were observed in veterans who developed PTSD in response to their first reported traumatic exposure, compared to veterans who had first experienced a traumatic event to which they did not develop PTSD, prior to experiencing a subsequent event that led to PTSD. In contrast, the two neuroendocrine measures were associated with risk factors related to early trauma exposure. CONCLUSION: Although hippocampal volume was not found to differ between subjects with and without PTSD, smaller hippocampal volumes in PTSD may be associated with specific risk and resilience factors. These may be distinct from vulnerability markers associated with increased responsiveness to glucocorticoids and/or other neuroendocrine measures that have been observed in combat-related PTSD.

Aged↗

PubMed2006

The relationship between hippocampal volume and declarative memory in a population of combat veterans with and without PTSD.

Both reduced hippocampal volume and cognitive alterations have been found in posttraumatic stress disorder (PTSD). The purpose of this article was to examine the relationship between hippocampal volume, combat exposure, symptom severity, and memory performance in a sample of combat veterans with and without a history of PTSD. Subjects were 33 male veteran volunteers (16 PTSD+, 17 PTSD-) who underwent an MRI and neuropsychological testing with the California Verbal Learning Test (CVLT), a measure of declarative memory. Relationships between hippocampal volume (i.e., right + left hippocampal volume/whole brain volume) and performance on the CVLT were determined using partial correlational analysis controlled for age and Wechsler Adult Intelligence Scale, Third Edition (WAIS-III) vocabulary scores. Percent hippocampal volume for the entire sample was positively associated with several aspects of memory performance as reflected by the CVLT. In the PTSD+ group, CVLT performance was negatively correlated with lifetime, but not current CAPS symptoms. CVLT performance appears to be strongly correlated with hippocampal volume in a group of trauma survivors with and without PTSD. Insofar as CVLT performance in the PTSD group was negatively associated with worst episode, but not to current PTSD symptoms, memory performance in combat veterans may reflect some aspect of risk related to the magnitude of the psychological response to trauma, rather than current symptoms that may be interfering with cognitive performance. It will be of interest to study cognitive abilities that may relate to the likelihood of specific PTSD symptoms and to track changes in CVLT performance and hippocampal volume over time in persons with and without a history of trauma exposure.

Aged↗

PubMed2005

Reduced anterior and posterior cingulate gray matter in borderline personality disorder.

BACKGROUND: Structural abnormalities in prefrontal and cingulate gyrus regions-important in affective processing, impulse control and cognition may contribute to the psychopathology of borderline personality disorder (BPD). Previous MRI studies examining volume have reported that compared with healthy controls, BPD patients have decreases in right anterior cingulate, no differences in dorsolateral prefrontal cortex, and mixed findings for prefrontal cortex. We extended this investigation by examining gray and white matter volume of frontal and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy controls. METHODS: MRI scans were acquired in 50 BPD patients (n = 13 with comorbid diagnosis of BPD and Schizotypal Personality Disorder (SPD) and n = 37 without SPD) and 50 healthy controls, and gray/white matter volume in cingulate gyrus and frontal lobe BAs were assessed. Normal BPD and BPD subgroup comparisons were conducted. RESULTS: Compared with controls, BPD patients showed reduced gray matter volume in BA 24 and 31 of the cingulate. BPD patients without comorbid SPD had isolated gray matter volume loss in BA 24, but were spared for BA 31 in contrast to BPD patients with SPD. There were no group differences in whole cingulate or frontal lobe volume. CONCLUSIONS: The finding of more pervasive cingulate shrinkage in the patients with BPD and SPD comorbidity resembles recent observations with the same methods in patients with schizophrenia. The pattern of reduced anterior and posterior cingulate gray matter volume in BPD patients, particularly those comorbid for SPD is consistent with the affective and attentional deficits observed in these personality disorders.

Adult↗

PubMed2004

Correlations between MRI-assessed volumes of the thalamus and cortical Brodmann's areas in schizophrenia.

BACKGROUND: We compared the thalamic-cortical volumetric correlational patterns in patients with schizophrenia and normal comparison subjects, and evaluated their relations to outcome. METHODS: High-resolution MR images were acquired in patients with schizophrenia (n=106) and normal comparison subjects (n=42). Patients were divided into good-outcome (n=52) and poor-outcome (Kraepelinian, n=54) subtypes based on their ability for self-care. Correlations between the relative gray and white matter volumes of the individual cortical Brodmann's areas and five dorsoventral levels of the thalamus were assessed. RESULTS: Compared to normal subjects, schizophrenia patients lacked significant thalamic gray matter volume correlations with the prefrontal and medial temporal cortical regions in the right hemisphere, and with frontal, cingulate, posterior parietal and occipital regions in the left hemisphere, while normal white matter volume cortical-thalamic correlations along the cingulate gyrus and in the temporal lobe were not found in schizophrenia patients in both hemispheres. In contrast to both normal comparison subjects and good-outcome group, schizophrenia patients with poor outcomes showed significant bilateral gray matter volume correlations between the dorsal thalamus and ventral prefrontal cortex, while the group differences in the white matter volume correlations were mostly restricted to the cingulate arch. CONCLUSIONS: Whereas patients with schizophrenia exhibit deficiencies in cortical-thalamic correlational patterns, poor outcome is associated with abnormal interregional correlations not observed in either normal subjects or patients with good outcomes. This latter finding may be explained by a core neurodevelopmental disturbance that results in aberrant cortical-thalamic connectivity in poor-outcome schizophrenia.

Adult↗

PubMed2004

Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression.

RATIONALE: Impulsive aggressive personality disordered patients have been shown to have decreased relative glucose metabolism in orbito-frontal cortex and anterior cingulate gyrus compared with normal subjects. In addition, patients with impulsive aggression have an attenuation of symptoms with selective serotonin reuptake inhibitor (SSRI) treatment. OBJECTIVES: The goals of the present study were to attempt to replicate the finding of improvement in impulsive aggression in borderline personality disorder with SSRIs and to investigate the specific cortical areas modified by medication, which might underlie the observed clinical improvement using (18)FDG-PET. METHODS: Ten impulsive aggressive patients with borderline personality disorder were imaged with (18)F-deoxyglucose positron emission tomography at baseline and after receiving fluoxetine at 20 mg/day for 12 weeks. Anatomical MRIs were coregistered to PET and relative metabolic rates were obtained in 39 Brodmann areas. RESULTS: Brodmann areas 11 and 12 in the orbito-frontal cortex showed significant increases in relative metabolic rate. Significant clinical improvement was also observed as assessed by the Overt Aggression Scale-Modified. CONCLUSIONS: These changes are consistent with a normalizing effect of fluoxetine on prefrontal cortex metabolism in impulsive aggressive disorder.

Adult↗