Biomedical subjects

Yvette I Sheline

Publications and source records attributed to Yvette I Sheline.

13 recordsLinked to original sources

PubMed2006

Antidepressant efficacy of olanzapine as monotherapy in major depressive disorder, without psychosis: a pilot study.

In this pilot study we assessed the efficacy of olanzapine as monotherapy in the treatment of major depressive disorder, without psychosis. We also demonstrated the in vivo 5-HT2A receptor occupancy of olanzapine using positron emission tomography. An open-label prospective 6-week study design with 14 patients who met the inclusion and exclusion criteria for the study were enrolled from the general community of the St. Louis metropolitan area. All patients met DSM-IV criteria for major depressive disorder without psychosis, had a Hamilton Depression Rating Scale (HAMD17) score >18 and were between the ages of 18 and 65. The primary measure of efficacy was the change in HAMD 17 total score from baseline to endpoint. The data were collected between 1998 and 2004. There was a significant reduction in the HAMD17 scores from baseline to endpoint. Half the patients (n=6) showed > or =50% reduction in their HAMD17 scores. This study points to the potential of olanzapine as a therapeutic agent for the treatment of major depressive disorder without psychosis.

Antidepressive Agents↗

PubMed2006

Cerebral blood flow changes during vagus nerve stimulation for depression.

Positron emission tomography (PET oxygen-15 labeled water or PET [15O]H2O) was used to identify changes in regional cerebral blood flow (rCBF) in response to acute vagus nerve stimulation (VNS) in four subjects with treatment-resistant major depression (TRMD). Four 90-s PET [15O]H2O scans were performed on each subject in an off-on sequence (2 VNS de-activated; 2 VNS activated). PET images were aligned, normalized for global uptake, and resampled to standard atlas space. Statistical t-images were used to evaluate change. VNS-induced increases in rCBF were found in the bilateral orbitofrontal cortex, bilateral anterior cingulate cortex, and right superior and medial frontal cortex. Decreases were found in the bilateral temporal cortex and right parietal area. Regions of change were consistent with brain structures associated with depression and the afferent pathways of the vagus nerve.

Adult↗

PubMed2006

Cognitive function in late life depression: relationships to depression severity, cerebrovascular risk factors and processing speed.

BACKGROUND: A number of studies have examined clinical factors linked to worse neuropsychological performance in late life depression (LLD). To understand the influence of LLD on cognition, it is important to determine if deficits in a number of cognitive domains are relatively independent, or mediated by depression- related deficits in a basic domain such as processing speed. METHODS: Patients who met DSM-IV criteria for major depression (n = 155) were administered a comprehensive neuropsychological battery of tasks grouped into episodic memory, language, working memory, executive function, and processing speed domains. Multiple regression analyses were conducted to determine contributions of predictor variables to cognitive domains. RESULTS: Age, depression severity, education, race and vascular risk factors all made significant and independent contributions to one or more domains of cognitive function, with all five making independent contributions to processing speed. Age of onset made no independent contribution, after accounting for age and vascular risk factors. Of the five cognitive domains investigated, changes in processing speed were found to most fully mediate the influence of predictor variables on all other cognitive domains. CONCLUSIONS: While slowed processing speed appears to be the most core cognitive deficit in LLD, it was closely followed by executive function as a core cognitive deficit. Future research is needed to help clarify mechanisms leading to LLD- related changes in processing speed, including the potential role of white matter abnormalities.

Activities of Daily Living↗

PubMed2006

Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults.

BACKGROUND: Vitamin D deficiency is common in older adults and has been implicated in psychiatric and neurologic disorders. This study examined the relationship among vitamin D status, cognitive performance, mood, and physical performance in older adults. METHODS: A cross-sectional group of 80 participants, 40 with mild Alzheimer disease (AD) and 40 nondemented persons, were selected from a longitudinal study of memory and aging. Cognitive function was assessed using the Short Blessed Test (SBT), Mini-Mental State Exam (MMSE), Clinical Dementia Rating (CDR; a higher Sum of Boxes score indicates greater dementia severity), and a factor score from a neuropsychometric battery; mood was assessed using clinician's diagnosis and the depression symptoms inventory. The Physical Performance Test (PPT) was used to measure functional status. Serum 25-hydroxyvitamin D levels were measured for all participants. RESULTS: The mean vitamin D level in the total sample was 18.58 ng/mL (standard deviation: 7.59); 58% of the participants had abnormally low vitamin D levels defined as less than 20 ng/mL. After adjusting for age, race, gender, and season of vitamin D determination, vitamin D deficiency was associated with presence of an active mood disorder (odds ratio: 11.69, 95% confidence interval: 2.04-66.86; Wald chi(2) = 7.66, df = 2, p = 0.022). Using the same covariates in a linear regression model, vitamin D deficiency was associated with worse performance on the SBT (F = 5.22, df = [2, 77], p = 0.044) and higher CDR Sum of Box scores (F = 3.20, df = [2, 77], p = 0.047) in the vitamin D-deficient group. There was no difference in performance on the MMSE, PPT, or factor scores between the vitamin D groups. CONCLUSIONS: In a cross-section of older adults, vitamin D deficiency was associated with low mood and with impairment on two of four measures of cognitive performance.

Aged↗

PubMed2005

Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory.

Alzheimer's disease (AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. In total, data from 764 participants were compared across five in vivo imaging methods. Convergence of effects was seen in posterior cortical regions, including posterior cingulate, retrosplenial, and lateral parietal cortex. These regions were active in default states in young adults and also showed amyloid deposition in older adults with AD. At early stages of AD progression, prominent atrophy and metabolic abnormalities emerged in these posterior cortical regions; atrophy in medial temporal regions was also observed. Event-related functional magnetic resonance imaging studies further revealed that these cortical regions are active during successful memory retrieval in young adults. One possibility is that lifetime cerebral metabolism associated with regionally specific default activity predisposes cortical regions to AD-related changes, including amyloid deposition, metabolic disruption, and atrophy. These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment.

Adolescent↗

PubMed2004

Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography.

BACKGROUND: Serotonin 5-HT(2A) receptors play an important role in the regulation of many functions that are disturbed in patients with major depressive disorder. Postmortem and positron emission tomography studies have reported both increased and decreased 5-HT(2A) receptor binding in different limbic and paralimbic regions. METHODS: We conducted a quantitative 5-HT(2A) receptor binding study using positron emission tomography and [(18)F]altanserin of four regions hypothesized to have altered levels of 5-HT(2A) receptors in major depressive disorder. Using a four-compartment model, the 5-HT(2A) receptor distribution was estimated by calculating the regional [(18)F]altanserin k(3)/k(4) ratio in which k(3) is the rate of binding to the receptor and k(4) is the rate of dissociation from the receptor. Forty-six antidepressant-free patients with major depressive disorder and 29 healthy control subjects were enrolled. RESULTS: 5-HT(2A) receptor binding in the hippocampus was reduced by 29% in depressed subjects (p =.004). In other regions, 5-HT(2A) receptor binding was decreased (averaging 15%) but not significantly. Both groups had similar age-dependent decreases in 5-HT(2A) receptors throughout all brain regions. CONCLUSIONS: Altered serotoninergic function in the hippocampus is likely involved in the disturbances of mood regulation in major depressive disorder, although the specific role of the 5-HT(2A) receptor changes is still unclear.

Adult↗

PubMed2004

Decreased hippocampal 5-HT(2A) receptor binding in older depressed patients using [18F]altanserin positron emission tomography.

Serotonin receptor changes have been associated with the pathophysiology and treatment of major depression. Only one other study has investigated serotonin receptor changes in older depressed patients. We used positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT(2A) receptor, to examine the relationship between 5-HT(2A) receptor density and depression. Depressed subjects (n = 16), age > 50 years, were recruited as part of a larger study. Older depressed subjects consisted of early-onset recurrent depression (EORD, n = 11) and late-onset depression (LOD, n = 5). An age-matched control group (n = 9) was also recruited. All subjects were right-handed, nonsmokers and antidepressant-free. Regions of interest were determined on a summed MPRAGE scan transformed into Talairach space and coregistered with the PET images. Depressed subjects had less hippocampal 5-HT(2A) receptor binding than controls (p = 0.05). No significant differences in receptor binding were found between EORD and LOD subjects. Depressed subjects not previously treated for depression (n = 6) had less hippocampal 5-HT(2A) receptor binding (p = 0.04) than previously treated subjects (n = 10). It may be that prior medication treatment provides a compensatory upregulation of the 5-HT(2A) receptor.

Aged↗

PubMed2004

Cerebral perfusion response to successful treatment of depression with different serotoninergic agents.

In 19 patients with major depressive disorder, effective treatment with selective serotonin reuptake inhibitors (SSRIs) or amesergide (AMSG) was associated with increased cerebral perfusion in anterior cingulate cortex (SSRI and AMSG) and in medial prefrontal cortex (AMSG). Both selective serotonin reuptake inhibitors and AMSG exert antidepressant action through the serotonin (5-HT) system as reuptake inhibitors. Amesergide differs from SSRIs in that it is also a highly selective 5-HT antagonist, which may in part account for differences in cerebral blood flow response to treatment.

Adult↗

PubMed2003

Neuroimaging studies of mood disorder effects on the brain.

Studies of early-onset recurrent depression, late life depression associated with neurologic disorders, and bipolar illness have revealed structural brain changes within a neuroanatomical circuit. This circuit, originally described by, has been termed the limbic-cortical-striatal-pallidal-thalamic tract and is comprised of structures which are extensively interconnected. In three-dimensional magnetic resonance imaging studies of affective illness, many of the structures that comprise this tract have been found to have volume loss or structural abnormalities. Mechanisms proposed to explain volume loss in depression include glucocorticoid neurotoxicity, decreased brain-derived growth factor, decreased neurogenesis, and loss of plasticity.

Bipolar Disorder↗

PubMed2003

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.

Adult↗

PubMed2003

Mechanisms of depression in epilepsy from a clinical perspective.

The epilepsies are a complex group of disorders commonly associated with brain dysfunction, social isolation, and vocational difficulty. Each of these factors may contribute to increased prevalence of depressive disorders in epilepsy, but the specific mechanisms are not completely understood. The brain regions commonly involved in various types of epilepsies, such as the hippocampus and amygdala in temporal lobe epilepsy and subcortical nuclei in idiopathic generalized epilepsies, are important components of current models of depression. Increased understanding of mechanisms of depression in epilepsy is not only crucial for improving care of many persons with seizures, but may also yield useful information about principal mechanisms underlying both depression and epileptogenesis.

Brain↗

PubMed2003

Untreated depression and hippocampal volume loss.

OBJECTIVE: The purpose of this study was to investigate the effect of antidepressant treatment on hippocampal volumes in patients with major depression. METHOD: For 38 female outpatients, the total time each had been in a depressive episode was divided into days during which the patient was receiving antidepressant medication and days during which no antidepressant treatment was received. Hippocampal gray matter volumes were determined by high resolution magnetic resonance imaging and unbiased stereological measurement. RESULTS: Longer durations during which depressive episodes went untreated with antidepressant medication were associated with reductions in hippocampal volume. There was no significant relationship between hippocampal volume loss and time depressed while taking antidepressant medication or with lifetime exposure to antidepressants. CONCLUSIONS: Antidepressants may have a neuroprotective effect during depression.

Adult↗

PubMed2002

Greater loss of 5-HT(2A) receptors in midlife than in late life.

OBJECTIVE: Earlier work has shown markedly lower density of serotonin 2A (5-HT(2A)) receptors in elderly subjects than in young healthy subjects. In this study the authors used positron emission tomography (PET) and [(18)F]altanserin, a ligand with high affinity for the 5-HT(2A) receptor, to examine the relationship between 5-HT(2A) receptor density and age in more detail. METHOD: The 22 subjects ranged in age from 21 to 69 years (mean=43.4, SD=13.3) and were healthy comparison subjects in a study of depression. Regions of interest were determined on magnetic resonance images and were transferred to coregistered PET data. The data were derived from dynamic PET scanning and arterial sampling with resulting plasma activity data corrected for labeled metabolites. Compartmental modeling was used to estimate the radioligand distribution volume. By comparing the distribution volume (DV) of different regions to the cerebellum distribution volume, DV(ratio)-1, which is proportional to the binding potential, was calculated. RESULTS: The decrease in 5-HT(2A) binding was not linear but on average was approximately 17% per decade from age 20. The correlations between age and 5-HT(2A) DV(ratio)-1 were significant for the global measure and for the medial gyrus rectus, anterior cingulate, posterior medial prefrontal cortex, hippocampus, and occipital cortex. Most of the fall off in receptor binding occurred up through midlife, and there was less decrease in late life. There were no decreases in regional brain volumes of corresponding magnitudes. CONCLUSIONS: 5-HT(2A) receptor binding decreases dramatically in a variety of brain regions up through midlife.

Adult↗