Biomedical subjects

Perry F Renshaw

Publications and source records attributed to Perry F Renshaw.

At least 37 records · Page 2Linked to original sources

PubMed2006

Brain white-matter hyperintensities and treatment outcome in major depressive disorder.

BACKGROUND: An increased incidence of brain white-matter hyperintensities has been described in major depressive disorder, butthe impact of such hyperintensities on treatment outcome is still controversial. AIMS: To investigate the relationship of brain white-matter hyperintensities with cardiovascular risk factors and with treatment outcome in younger people with major depressive disorder. METHOD: We assessed brain white-matter hyperintensities and cardiovascular risk factors in 84 people with major depressive disorder prior to initiating antidepressant treatment. We also assessed hyperintensities in 35 matched controls. RESULTS: We found no significant difference in the prevalence of white-matter hyperintensities between the depression and the control groups. Left-hemisphere subcortical hyperintensities correlated with lower rates of treatment response. We found no correlation between global hyperintensity measures and clinical outcome. Brain white-matter hyperintensities correlated with hypertension and age and withtotal cardiovascular risk score. CONCLUSIONS: Subcortical white-matter hyperintensities in the left hemisphere (but notin other brain areas) maybe associated with poor response to antidepressant treatment in major depression.

Adolescent↗

PubMed2006

Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry.

The effects of type 1 diabetes and key metabolic variables on brain structure are not well understood. Sensitive methods of assessing brain structure, such as voxel-based morphometry (VBM), have not previously been used to investigate central nervous system changes in a diabetic population. Using VBM, we compared type 1 diabetic patients aged 25-40 years with disease duration of 15-25 years and minimal diabetes complications with an age-matched, nondiabetic control group. We investigated whether lower than expected gray matter densities were present, and if so, whether they were associated with glycemic control and history of severe hypoglycemic events. In comparison with control subjects, diabetic patients showed lower density of gray matter in several brain regions. Moreover, in the patient group, higher HbA(1c) levels and severe hypoglycemic events were associated with lower density of gray matter in brain regions responsible for language processing and memory. Our study represents the first comprehensive study of gray matter density changes in type 1 diabetes and suggests that persistent hyperglycemia and acute severe hypoglycemia have an impact on brain structure.

Adolescent↗

PubMed2005

Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part I).

The objective of the present work was to study the interrelationship between white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle including serum folate, vitamin B12, and homocysteine levels in a relatively young sample of outpatients with major depressive disorder (MDD), and to compare the severity of white matter hyperintensities in MDD patients and healthy volunteers. Fifty MDD outpatients (34% women, age 40.6+/-10.3 years), free of psychotropic medications for at least 2 weeks before enrollment, underwent magnetic resonance imaging (MRI) scans of the brain to detect T2 WMHs and also had (1) serum folate, vitamin B12, homocysteine and cholesterol levels measured, and (2) cardiovascular risk factors assessed during the same study visit. Thirty-five healthy comparison subjects (40% women, age 39.2+/-9.8 years) also underwent brain MRI scans. Hypofolatemia, hypertension and age independently predicted a greater severity of total brain WMHs. Separately, the same factors also predicted a greater severity of subcortical WMHs. Hypofolatemic and hypertensive patients had more severe WMHs than normal controls. In light of the adverse impact of WMHs on a number of health-related outcomes later in life, hypofolatemia and hypertension may represent modifiable risk factors to prevent the occurrence of such adverse outcomes.

Adolescent↗

PubMed2005

Prefrontal and temporal gray matter density decreases in opiate dependence.

RATIONALE: There have been only a few structural brain-imaging studies, with varied findings, of opiate-dependent subjects. Voxel-based morphometry (VBM) is suitable for studying whole brain-wise structural brain changes in opiate-dependent subjects. OBJECTIVES: The objective of the current study is to explore gray matter density in opiate-dependent subjects. METHODS: Gray matter density in 63 opiate-dependent subjects and 46 age- and sex-matched healthy comparison subjects was compared using VBM. RESULTS: Relative to healthy comparison subjects, opiate-dependent subjects exhibited decreased gray matter density in bilateral prefrontal cortex [Brodmann areas (BA) 8, 9, 10, 11, and 47], bilateral insula (BA 13), bilateral superior temporal cortex (BA 21 and 38), left fusiform cortex (BA 37), and right uncus (BA 28). CONCLUSIONS: This study reports that opiate-dependent subjects have gray matter density decreases in prefrontal and temporal cortex, which may be associated with behavioral and neuropsychological dysfunction in opiate-dependent subjects.

Adult↗

PubMed2005

Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II).

The objective of this study was to investigate the relative impact of brain white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle metabolism (including serum folate, vitamin B12 and homocysteine levels) on the outcome of antidepressant treatment in non-elderly subjects with major depressive disorder (MDD). Fifty MDD subjects were administered brain magnetic resonance imaging (MRI) scans at 1.5 T to detect T2 WMHs. The severity of brain WMHs was classified with the Fazekas scale (range=0-3). We assessed cardiovascular risk factors in all MDD subjects (age, gender, smoking, diabetes, family history, hypertension, cholesterol). MDD patients also had serum folate, vitamin B12 and homocysteine levels measured. All MDD subjects received treatment with fluoxetine 20 mg/day for 8 weeks. In a logistic regression, the severity of subcortical WMHs and the presence of hypofolatemia were independent predictors of lack of clinical response to antidepressant treatment. Separately, hypofolatemia also predicted lack of remission to antidepressant treatment. These associations were independent of the presence of smoking, diabetes, family history, hypercholesterolemia, hyperhomocysteinemia and low B12 levels. Although preliminary, the results of the present work suggest that subcortical brain WMHs and hypofolatemia may have an independent negative impact on the likelihood of responding to antidepressant treatment in non-geriatric subjects with MDD.

Adolescent↗

PubMed2005

Decreased cerebral blood flow of the right anterior cingulate cortex in long-term and short-term abstinent methamphetamine users.

BACKGROUND: The aim of the current study was to explore changes of relative regional cerebral blood flow (rCBF) in short-term and long-term abstinent methamphetamine (MA) users. METHODS: Relative rCBF in 40 abstinent MA users and 23 healthy comparison subjects was compared by the technetium-99m-hexamethyl-propylene amine oxime ((99m)Tc-HMPAO) single photon emission computed tomography (SPECT). Relative rCBF in areas that were found to differ significantly was also compared in groups of MA users with short-term (<6 months) and long-term (>or=6 months) abstinence. RESULTS: MA users showed decreased relative rCBF in the right anterior cingulate cortex (Brodmann area 32) relative to healthy comparison subjects. Long-term abstinent MA users had significantly greater rCBF than short-term abstinent MA users. CONCLUSIONS: We report that abstinent MA users have decreased rCBF in the anterior cingulate cortex with smaller relative decreases in subjects with prolonged abstinence.

Adult↗

PubMed2005

Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment.

RATIONALE: There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA agonists decreases cocaine self-administration. OBJECTIVES: The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole, venlafaxine, or placebo. METHODS: CD subjects enrolled in a treatment trial for cocaine dependence were recruited for this proton (1H) magnetic resonance spectroscopy (MRS) study. GABA levels in the prefrontal lobe were measured before and after treatment. RESULTS: Mean percentage changes in GABA levels were as follows: pramipexole +17.0+/-28.0%, venlafaxine +13.0+/-11.0%, and placebo -2.1+/-19.5%. Pramipexole-treated subjects had significantly increased brain GABA levels compared to placebo (p=0.031). Venlafaxine treatment was nonsignificantly associated with increased GABA levels compared to placebo (p=0.16). The overall statistical model for the effect of drug treatment vs placebo on brain GABA levels, including adjustment for baseline levels, was highly significant (p=0.002). Despite significant changes in GABA levels, there were no significant differences in the number of urine samples positive for cocaine metabolites. CONCLUSIONS: This study demonstrates that 1H MRS can measure changes in GABA levels following pharmacologic treatment. The increase in GABA levels, although significant, is modest compared to other MRS studies of depression or epilepsy associated with clinical improvements. The failure to see larger increases in GABA levels and an associated reduction in cocaine consumption may reflect the relatively low doses of medication used.

Adult↗

PubMed2005

Disrupted white matter tract integrity of anterior cingulate in trauma survivors.

The objective of this study was to examine the integrity of whole-brain white matter in posttraumatic stress disorder patients. Twenty posttraumatic stress disorder patients who survived the Taegu subway fire incident and 20 healthy volunteers participated in this study. Statistical parametric mapping was used to evaluate the global differences in fractional anisotropy values between the two groups. The results show that posttraumatic stress disorder patients had significantly lower fractional anisotropy values in the left anterior cingulate regions. Posttraumatic stress disorder symptom severity negatively correlated to the level of decrease in anterior cingulate fractional anisotropy values. The outcome of the current study suggests that the disruption of the left anterior cingulate white matter tract integrity may play an important role in the pathophysiology of posttraumatic stress disorder.

Adult↗

PubMed2005

Increased white matter hyperintensities in male methamphetamine abusers.

BACKGROUND: The current study was conducted to compare the prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance (MR) imaging in methamphetamine (MA) abusers. METHODS: Thirty-three MA abusers and 32 age- and gender-matched healthy comparison subjects were studied. Axial T-2 weighted images and fluid attenuated inversion recovery axial images were obtained using 3.0 T MR scanner. The severity of WMH was assessed separately for deep and periventricular WMH. Ordinal logistic regression models were used to assess the odds ratio for WMH. RESULTS: MA abusers had greater severity of WMH than the healthy comparison subjects (odds ratio: 7.06, 8.46, and 4.56 for all, deep, and periventricular WMH, respectively). Severity of deep WMH correlated with total cumulative dose of MA (p = 0.027). Male MA abusers had greater severity of WMH than female MA abusers (odds ratio = 10.00). While male MA abusers had greater severity of WMH than male comparison subjects (odds ratio = 18.86), there was no significant difference in WMH severity between female MA abusers and female comparison subjects. CONCLUSIONS: The current study reports increased WMH in MA abusers, which may be related to MA-induced cerebral perfusion deficits. In addition, female MA abusers had less severe WMH than male MA abusers, possibly due to estrogen's protective effect against ischemic or neurotoxic effects of MA.

Adult↗

PubMed2005

Prefrontal grey-matter changes in short-term and long-term abstinent methamphetamine abusers.

Authors explored grey-matter density in 29 methamphetamine abusers and 20 healthy comparison subjects using voxel-based morphometry. Grey-matter density changes and performances on the Wisconsin Card Sorting test (WCST) were also compared between 11 short-term (<6 months) and 18 long-term (>or=6 months) abstinent methamphetamine abusers. Methamphetamine abusers had lower grey-matter density in the right middle frontal cortex (corrected p<0.05) and more total errors in the WCST (p<0.01) relative to healthy comparison subjects. Grey-matter density decrease in the right middle frontal cortex correlated with total errors in the WCST in methamphetamine abusers (r=-0.45). Long-term abstinent abusers had significantly less right middle frontal grey-matter density decrease (p<0.01) and total errors in the WCST (p<0.01) than short-term abstinent abusers, but more than the healthy comparison subjects. We report that methamphetamine abusers have prefrontal grey-matter deficit, which may, in part, recover with long-term abstinence.

Adult↗

PubMed2005

Antidepressant-like effects of cranial stimulation within a low-energy magnetic field in rats.

BACKGROUND: Evidence suggests that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) has mood-elevating actions in humans during the depressive phases of bipolar disorder. We examined whether a low-energy component of EP-MRSI (low-field magnetic stimulation [LFMS]) has antidepressant-like, locomotor-stimulating, or amnestic effects in rats. METHODS: We examined the effects of LFMS on immobility in the forced swim test (FST) and activity within an open field in separate groups of rats. After exposure to forced swimming, rats received LFMS (three 20-min sessions at 1.5 G/cm and .75 V/m) before behavioral testing. We also examined the effects of LFMS on fear conditioning (FC), a learning paradigm that also involves exposure to stressful conditions. RESULTS: Low-field magnetic stimulation reduced immobility in the FST, an antidepressant-like effect qualitatively similar to that of standard antidepressants. Low-field magnetic stimulation did not alter locomotor activity or FC. CONCLUSIONS: Low-field magnetic stimulation has antidepressant-like effects in rats that seem unrelated to locomotor-activating or amnestic effects. These findings raise the possibility that electromagnetic fields can affect the brain biology and might have physiologic consequences that offer novel approaches to therapy for psychiatric disorders. These same consequences might render MRI-based scans more invasive than previously appreciated.

Animals↗

PubMed2005

Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats.

BACKGROUND: Brain phospholipid metabolism and membrane fluidity may be involved in the pathophysiology of mood disorders. We showed previously that cytidine, which increases phospholipid synthesis, has antidepressant-like effects in the forced swim test (FST) in rats, a model used in depression research. Because cytidine and uridine both stimulate synthesis of cytidine 5'-diphosphocholine (CDP-choline, a critical substrate for phospholipid synthesis), we examined whether uridine would also produce antidepressant-like effects in rats. We also examined the effects of omega-3 fatty acids (OMG), which increase membrane fluidity and reportedly have antidepressant effects in humans, alone and in combination with uridine. METHODS: We first examined the effects of uridine injections alone and dietary supplementation with OMG alone in the FST. We then combined sub-effective treatment regimens of uridine and OMG to determine whether these agents would be more effective if administered together. RESULTS: Uridine dose-dependently reduced immobility in the FST, an antidepressant-like effect. Dietary supplementation with OMG reduced immobility when given for 30 days, but not for 3 or 10 days. A sub-effective dose of uridine reduced immobility in rats given sub-effective dietary supplementation with OMG. CONCLUSIONS: Uridine and OMG each have antidepressant-like effects in rats. Less of each agent is required for effectiveness when the treatments are administered together.

Animals↗

PubMed2005

Lithium-induced alterations in nucleoside triphosphate levels in human brain: a proton-decoupled 31P magnetic resonance spectroscopy study.

We examined how lithium's demonstrated effects on various cellular processes in human brain would be reflected in the (31)P magnetic resonance spectra of living human beings with respect to brain high-energy phosphate metabolites. Eight healthy volunteers received a baseline (31)P magnetic resonance spectroscopy (MRS) scan, after which they received lithium carbonate, 900 mg/day, for 14 days. Follow-up MRS scans were obtained on day 7 and on day 14. We detected a lithium-induced decrease in alpha-, beta-, gamma- and total nucleoside triphosphate NTP levels with chronic administration of lithium. On day 7, significant decreases were noted in gamma-NTP (14%) and total NTP (11%) levels. There was a trend for a decrease in beta-NTP (11%) levels. On day 14, significant decreases were noted in alpha-NTP (7%) and total NTP (8%) levels. There was a trend for a decrease in beta-NTP (16%) levels. Lithium caused a 25% reduction in inorganic phosphate (P(i)) levels on day 14. The theoretical relevance of the lithium-induced alterations on brain high-energy phosphates to the lithium-induced modifications of neuroplasticity is discussed.

Adolescent↗

PubMed2005

Functional magnetic resonance imaging studies of schizophrenic patients during word production: effects of D-cycloserine.

The objective of the present study was to examine patterns of cortical activation underlying D-cycloserine's therapeutic efficacy in schizophrenic patients using functional magnetic resonance imaging (fMRI). We measured frontal and temporal lobe activation following a word fluency task in 12 subjects meeting DSM-IV criteria for schizophrenia at baseline and after 8 weeks of supervised treatment, using a double-blind, placebo-controlled design. Half of the patients received D-cycloserine (n = 6) as a supplement to their conventional neuroleptic treatment while the other half (n = 6) was augmented with placebo. Patients receiving D-cycloserine, but not placebo, demonstrated a significant increase in temporal lobe activation. This increased activation was significantly associated with a reduction in negative symptoms. These results suggest that the addition of D-cycloserine to conventional neuroleptics may improve negative symptoms through enhanced temporal lobe function.

Antipsychotic Agents↗

PubMed2005

Amygdala and hippocampus volumes in pediatric major depression.

BACKGROUND: The purpose of this study was to measure amygdala and hippocampus volumes in pediatric major depressive disorder (MDD) and to address the question of neuroanatomical continuity with adult-onset depression. METHODS: We studied 20 children and adolescents with MDD (17 female subjects) and 24 healthy comparison subjects (16 female subjects) using 1.5 Tesla magnetic resonance imaging. Group differences in left and right amygdala and hippocampus volumes were examined using repeated measures analyses of covariance, adjusting for age, gender, and whole brain volume. RESULTS: Depressed children had significant reductions of left and right amygdala volumes compared with healthy subjects. Hippocampus volumes did not differ between the groups. No significant correlations were found between amygdala volumes and depressive symptom severity, age at onset, or illness duration. CONCLUSIONS: Smaller amygdalas are present early in the course of pediatric depression and may predispose to the development of this disorder or perhaps more generally of childhood mood disorders. Future research should examine the longitudinal course and functional correlates of amygdala volume abnormalities in childhood-onset depression, including their possible moderation by gender.

Adolescent↗

PubMed2005

Two-dimensional, J-resolved spectroscopic imaging of GABA at 4 Tesla in the human brain.

A method for measuring brain gamma-amino butyric acid (GABA) levels is presented that combines 2D J-resolved magnetic resonance spectroscopy (J-MRS) techniques with chemical-shift imaging (2D-JMRSI) at 4 Tesla (T). The results of phantom and in vivo experiments agree well in demonstrating that the (2)CH(2) GABA resonance situated at 2.97 ppm can be resolved from the neighboring creatine (Cr) resonance at 3.03 ppm and quantified. Single-voxel, J-resolved standard and metabolite-nulled in vivo experiments on six healthy subjects reveal a broad component from the underlying macromolecules (MM) that resonates at and around 3.00 ppm, which is estimated to contribute approximately 15% to the J-resolved GABA resonance in this large voxel at a repetition time (TR) of 4.5 s. With our 2D-JMSRI at 1.25 s TR, the macromolecule resonance contribution to our GABA measurements is approximated to be 12%. Six healthy human subjects underwent scanning at 4T with this sequence, yielding a global brain GABA concentration of 0.76 +/- 0.20 mM after correction for 12% macromolecule contribution.

Algorithms↗

PubMed2005

Grey and white matter GABA level differences in the human brain using two-dimensional, J-resolved spectroscopic imaging.

A novel, two-dimensional, J-resolved chemical-shift imaging sequence was used to collect gamma-aminobutyric acid (GABA) spectroscopic imaging data on six healthy subjects at 4 T. Using image segmentation and a linear-regression analysis relating brain GABA level to tissue-type, a consistent and significant (n = 6, p < 0.01) elevation of mean GABA levels was measured in the cortical grey matter (0.96 +/- 0.24 mm) compared with white matter (0.44 +/- 0.16 mm) across all six subjects. The results suggest an approximately two-fold elevation of GABA levels in cortical grey matter compared with white matter in vivo. Our findings are consistent with ex vivo studies in the literature of both animal and human brain and demonstrate the significant potential of this technique for detecting and quantifying tissue-specific neurochemical pathology in vivo.

Animals↗

PubMed2005

White matter hyperintensities and their association with suicidality in depressed young adults.

INTRODUCTION: Researchers and clinicians have increasingly recognized that biological markers may help identify patients who are at risk for suicide. The objective of this retrospective, cross-sectional study was to compare the prevalence and location of white matter hyperintensities (WMH) in young inpatients with major depressive disorder (MDD) with and without histories of suicide attempts. METHODS: T2-weighted magnetic resonance images (MRI) of 102 young psychiatric inpatients with MDD were rated for the presence of WMH. Medical charts were reviewed to ascertain history of suicide attempt, demographic and clinical variables. Fisher's Exact Tests and logistic regression modeling were used to test the association between WMH and suicidality. RESULTS: Bivariate analysis showed that the prevalence of periventricular WMH was significantly higher in subjects with past suicide attempts (Fisher's Exact Test, p=0.02). Logistic regression analyses controlling for age, sex, and several clinical risk factors supported this finding (odds ratio=5.7; 95% confidence interval: 1.6, 21.2). LIMITATIONS: Due to the retrospective, cross-sectional design of our study, we are unable to determine if the WMH preceded or followed past suicide attempts. The generalizability of our findings is limited since this group of inpatients is more severely ill than the general psychiatric population. CONCLUSIONS: The increased prevalence of periventricular WMH in young adults with MDD and a history of suicide attempt, compared to similarly depressed adults without such a history, is consistent with our findings in children and youth, and suggests there might be neurobiological in addition to psychosocial risk factors for suicide.

Adolescent↗