Altered bed nucleus of the stria terminalis and amygdala responses to threat in combat veterans with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) significantly impacts many veterans. Although PTSD has been linked to alterations in the fear brain network, the disorder likely involves alterations in both the fear and anxiety networks. Fear involves responses to imminent, predictable threat and is driven by the amygdala, whereas anxiety involves responses to potential, unpredictable threat and engages the bed nucleus of the stria terminalis (BNST).

Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study.

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer's dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer's dementia cases and controls. APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls.

The relationship between domain-specific subjective cognitive decline and Alzheimer's pathology in normal elderly adults.

We evaluated the associations of subjective (self-reported everyday cognition [ECog]) and objective cognitive measures with regional amyloid-β (Aβ) and tau accumulation in 86 clinically normal elderly subjects from the Alzheimer's Disease Neuroimaging Initiative. Regression analyses were conducted to identify whether individual ECog domains (Memory, Language, Organization, Planning, Visuospatial, and Divided Attention) were equally or differentially associated with regional [F]florbetapir and [F]flortaucipir uptake and how these associations compared to those obtained with objective cognitive measures. A texture analysis, the weighted 2-point correlation, was used as an additional approach for estimating the whole-brain tau burden without positron emission tomography intensity normalization.

Longitudinal Positron Emission Tomography in Preventive Alzheimer's Disease Drug Trials, Critical Barriers from Imaging Science Perspective.

Recent Alzheimer's trials have recruited cognitively normal people at risk for Alzheimer's dementia. Due to the lack of clinical symptoms in normal population, conventional clinical outcome measures are not suitable for these early trials. While several groups are developing new composite cognitive tests that could serve as potential outcome measures by detecting subtle cognitive changes in normal people, there is a need for longitudinal brain imaging techniques that can correlate with temporal changes in these new tests and provide additional objective measures of neuropathological changes in brain.

Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment.

Background: Semiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-β (Aβ) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test-retest (18)F-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions.

Methods: We calculated the correlation between (18)F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aβ1-42 levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years.

Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI).

Psychiatric illness and resident assaults among veterans in long-term care facilities.

This article describes a quality improvement program to reduce the prevalence of physical assaults in a university-affiliated, 234-bed Veterans Affairs (VA) long-term care (LTC) facility, which experienced a rise in the number of physical assaults to >4 per 1,000 bed days of care in four LTC units. Analysis of 55 events (29 patients) at this VA LTC site during 2007 revealed 19 resident assailants (8% total population), 10 victims, and 30% repeat events. Of the residents who exhibited assaultive behavior, 44% had dementia and 32% had schizophrenia as a major diagnosis.

Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities.

Genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) have consistently observed strong evidence of association with polymorphisms in APOE. However, until recently, variants at few other loci with statistically significant associations have replicated across studies. The present study combines data on 483,399 single nucleotide polymorphisms (SNPs) from a previously reported GWAS of 492 LOAD cases and 496 controls and from an independent set of 439 LOAD cases and 608 controls to strengthen power to identify novel genetic association signals.

Genomic convergence to identify candidate genes for Alzheimer disease on chromosome 10.

A broad region of chromosome 10 (chr10) has engendered continued interest in the etiology of late-onset Alzheimer Disease (LOAD) from both linkage and candidate gene studies. However, there is a very extensive heterogeneity on chr10. We converged linkage analysis and gene expression data using the concept of genomic convergence that suggests that genes showing positive results across multiple different data types are more likely to be involved in AD.

No association between SNP rs498055 on chromosome 10 and late-onset Alzheimer disease in multiple datasets.

SNP rs498055 in the predicted gene LOC439999 on chromosome 10 was recently identified as being strongly associated with late-onset Alzheimer disease (LOAD). This SNP falls within a chromosomal region that has engendered continued interest generated from both preliminary genetic linkage and candidate gene studies. To independently evaluate this interesting candidate SNP we examined four independent datasets, three family-based and one case-control.

Effect of heterogeneity on the chromosome 10 risk in late-onset Alzheimer disease.

With the exception of ApoE (APOE), no universally accepted genetic association has been identified with late-onset Alzheimer disease (AD). A broad region of chromosome 10 has engendered continued interest generated from both preliminary genetic linkage and candidate gene studies. To better examine this region, we combined unbiased genetic linkage with candidate gene association studies.

Association analysis of genetic polymorphisms in the CDC2 gene with late-onset Alzheimer disease.

Background: Alzheimer disease (AD) is a complex neurodegenerative disorder resulting from multiple genetic and non-genetic factors. Linkage studies indicated that chromosome 10 has at least one locus for this disease. The cell division cycle 2 (CDC2) gene, which is close to one of the linkage regions, has previously been associated with the risk of AD with an odds ratio of 1.

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult.

Treatment enhances ultradian rhythms of CSF monoamine metabolites in patients with major depressive episodes.

Unipolar and bipolar depressions show abnormal behavioral manifestations of ultradian (less than 24 h) rhythms, but abnormal rhythms of the central neurotransmitters thought to be important for depression pathophysiology (eg dopamine (DA) and serotonin (5-HT)) have not been shown in this time frame. Since antidepressant treatments normalize disrupted rhythms in depression (eg rapid-eye-movement sleep and hormonal rhythms), we hypothesized that depression-related changes in ultradian oscillations of DA and 5-HT might be revealed during antidepressant treatment. Cerebrospinal fluid (CSF) samples collected q10 min for 24 h in 13 patients experiencing major depressive episodes (MDE) before and after treatment for 5 weeks with sertraline or bupropion were assayed for levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and their ratio was calculated.

Association of a critical CSF tryptophan threshold level with depressive relapse.

This work studies association between relapse during acute tryptophan depletion (ATD) and CSF level of tryptophan (TRP) in remitted depressives treated with sertraline or bupropion. Eight medication-responding depressives ingested an ATD amino acid mixture during 48-h continuous CSF sampling before and after treatment. Mood rating scores were compared with nadir levels of TRP in CSF.

Serial cerebrospinal fluid tryptophan and 5-hydroxy indoleacetic acid concentrations in healthy human subjects.

The role of the serotonergic system in the pathogenesis of behavioral disorders such as depression, alcoholism, obsessive-compulsive disorder, and violence is not completely understood. Measurement of the concentration of neurotransmitters and their metabolites in cerebrospinal fluid (CSF) is considered among the most valid, albeit indirect, methods of assessing central nervous system function in man. However, most studies in humans have measured lumbar CSF concentrations only at single time points, thus not taking into account rhythmic or episodic variations in levels of neurotransmitters, precursors, or metabolites.

Steroid receptor-mediated modulation of CD4+CD62L+ cell homing. Implications for drug abusers.

Naive human T cells home to peripheral lymph nodes via the leukocyte endothelial cell adhesion molecule-1 (LECAM-1, l-selectin, CD62L, Leu8 antigen) they express. We enriched populations of CD4+CD62L+ cells (attachment of Leu8+ T cells to flasks coated with anti-mouse IgG (AIS); Leu8+ T cells, 82.3% pure (+/- 2.

Disruption of circadian MHPG rhythmicity in major depression.

Plasma concentrations of total (free plus conjugated) 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined every 3 hr for a 24-hr period in 32 unipolar depressed patients, 11 bipolar depressed patients, and 12 healthy subjects. Each subject's circadian MHPG rhythmicity was modeled by a sinusoidal function. Temporal parameters were estimated by linear least squares regression with a fixed 24-hr period.

Binge eating disorder affects outcome of comprehensive very-low-calorie diet treatment.

To determine the effects of binge eating disorder (BED) on weight loss and maintenance in women undergoing treatment for obesity, we studied the weight changes of 38 women (body mass index > 30 kg/m2), 21 of whom met proposed criteria for BED and 17 of whom reported few problems with binge eating, during and after a 26-week comprehensive very-low-calorie diet (VLCD) treatment program. All 17 subjects without and 16/21 subjects with BED returned for four follow-up visits over 12 months (p = 0.05).

The antidepressant response to tricyclics in major depressives is accelerated with adjunctive use of methylphenidate.

Standard tricyclic antidepressant (TCA) treatment usually entails response latencies of 2 to 4 weeks. To accelerate the antidepressant response, methylphenidate (MPH) was administered together with standard antidepressants in an open label trial. Twenty inpatients (9 females, 11 males) met DSM-III-R criteria for major depressive episode (15 unipolar and 2 bipolar), depression NOS (n = 2), or Research Diagnostic Criteria for schizoaffective illness, depressed type (n = 1).

Thyroid function in bulimia nervosa.

Bulimia nervosa is characterized by episodes of binge eating. Bulimic patients have diminished caloric requirements and reduced metabolic rate. Because thyroid function is an important modulator of metabolic rate, we sought to clarify conflicting reports concerning this parameter in bulimic patients.

Case report of anorexia nervosa associated with Wilson's disease.

Wilson's disease is a recessively inherited disorder of copper metabolism with prominent hepatic, hematopoietic, central nervous system (CNS), and ocular involvement. Psychiatric manifestations are notoriously variable. The following case history of a patient with both anorexia nervosa and Wilson's disease is presented and discussed in the context of organic CNS lesions associated with anorexia nervosa-like syndromes.

Normal dexamethasone suppression in obese binge and nonbinge eaters with rapid weight loss.

Natural or experimental starvation is frequently associated with hypercortisolism, reflected as incomplete suppression of serum cortisol after dexamethasone. To determine whether rapid weight loss per se or some other aspect of starvation induces disruption of the hypothalamic-pituitary-adrenal (HPA) axis, we evaluated 2 categories of obese women (body mass index > 30 kg/m2) undergoing rapid weight loss: binge eaters (n = 12) and nonbinge eaters (n = 8). We performed psychometric evaluation and 1 mg overnight dexamethasone suppression tests in the obese subjects, as well as in 12 race- and age-matched normal-weight women.