Elizabeth Liebson

Depression and Plasma Amyloid β Peptides in the Elderly With and Without the Apolipoprotein E4 Allele

Depression associated with low plasma amyloid-β peptide 42 (Aβ42) leading to a high ratio of Aβ40/Aβ42, a biomarker of Alzheimer disease (AD), may represent a unique depression subtype. The relationship between low plasma Aβ42 in depression and the major risk factor of AD, apolipoprotein E4 (ApoE4), is unknown. With the goal of clarifying this relationship, we analyzed 1060 homebound elders with ApoE characterization and depression status in a cross-sectional study. Plasma Aβ40 and Aβ42 were measured, and cognition were evaluated. In the absence of the ApoE4 allele, depressed subjects had lower plasma Aβ42 [median (Q1, Q3): 17.1 (11.6, 27.8) vs. 20.2 (12.9, 32.9) pg/mL, P=0.006], a higher Aβ40/Aβ42 ratio [median (Q1, Q3): 7.1 (4.6, 11.3) vs. 6.9 (3.4, 9.7), P=0.03], and lower cognitive function (mean±SD of Mini-Mental State Examination: 24.5±3.1 vs. 25.5±3.3, P<0.0001) than those without depression. In contrast, these relationships were not observed in the presence of ApoE4. Instead, regardless the depression status ApoE4 carriers had lower plasma Aβ42 and a higher Aβ40/Aβ42 ratio than non-ApoE4 carriers. Using multivariate logistic regression, it was found that depression was not associated with ApoE4 allele, but with the interaction between plasma Aβ42 and ApoE4 (odds ratio=3.94, 95% confidence interval=1.50, 10.33, P=0.005), denoting low plasma Aβ42 in the absence of ApoE4. Both ApoE4 carriers and non-ApoE4 carriers with depression had lower Aβ42 and a higher Aβ40/Aβ42 ratio in plasma compared with non-ApoE4 carriers without depression in the homebound elderly. As a combination of low plasma Aβ42 and high plasma Aβ40 has been shown to increase the risk of AD in 2 large cohort studies, amyloid-associated depression shown in this study may suggest a risk factor of AD in the absence of ApoE4.

Depression and Glycemic Intake in the Homebound Elderly

BACKGROUND Depression is associated with an increase in the incidence of type 2 diabetes, but the mechanism is unclear. We aimed to study the relationship between depression and glycemic intake in the elderly, and examine whether antidepressant use modified this relationship. DESIGN, SETTING AND PARTICIPANTS We evaluated 976 homebound elders in a cross-sectional study. Depression was defined by having a Center for Epidemiological Studies Depression (CES-D) score ≥16. Antidepressant use was documented. Glycemic index (GI), Glycemic load (GL), and fasting blood insulin levels were measured. RESULTS Depressed elders had slightly higher GI (Mean±SD: 55.8±3.8 vs. 55.1±3.7, P=0.003) and higher insulin levels (Median: 84.0 vs. 74.4pmol/ml, P=0.05) than non-depressed elders. Depressed elders receiving antidepressants, primarily selective serotonin reuptake inhibitors (SSRI), had lower GI (Mean±SD: 55.1±4.7 vs. 56.2±3.4, P=0.002) and GL (Median: 170.3 vs. 6826.3, P=0.03) than those not taking antidepressants. After adjusting for potential confounding variables, GI remained positively associated with depression (β=+0.65, SE=0.28, P=0.02); the logarithm of GL was positively associated with depression (β=+0.33, SE=0.17, P=0.05) and negatively associated with antidepressant use (β=-0.54, SE=0.18, P=0.003). CONCLUSIONS Prospective studies are needed to examine whether high glycemic intake is a mediating factor between late life depression and the risk of type 2 diabetes.

The relationship between plasma amyloid-β peptides and the medial temporal lobe in the homebound elderly

The ratio of high amyloid‐β peptide40 (Aβ40) and low Aβ42 in plasma predicts the risk of Alzheimers disease (AD) and is associated with episodic recall in depression. We thus examined the relationship between plasma Aβ levels and brain volumes.

Positive Association between Plasma Amylin and Cognition in a Homebound Elderly Population

Our recent study reported that amylin, a pancreatic peptide that readily crosses the blood-brain barrier, improves learning and memory in Alzheimers disease mouse models. However, the relationship between peripheral amylin and cognition in humans is unknown. In this follow-up study, using a cross-sectional, homebound elderly population, improvement in cognitive function with increasing quartiles of plasma amylin was suggested by positive association with verbal memory (p = 0.0002) and visuoconstruction tasks (p = 0.004), and inverse association with timed measures of attention (p < 0.0001) and executive function (p = 0.04). After adjusting for demographic information, apolipoprotein E4 allele, diabetes, stroke, kidney function, and lipid profile, log10 of plasma amylin remained associated with these cognitive domains. In contrast, plasma amyloid-β peptide was not associated with these specific cognitive domains. Our study suggests that peripheral amylin may be protective for cognitive decline, especially in the domains affected by Alzheimers disease.

Early-onset dementia: diagnostic considerations and implications for families.

Ms. A is a 43-year-old widowed woman brought to the psychiatric emergency room by her older son after she was evicted from the hotel room where she was living. He stated that she could no longer ta...

Association between Amylin and Amyloid-β Peptides in Plasma in the Context of Apolipoprotein E4 Allele

Amylin, a pancreatic peptide that readily crosses the blood brain barrier (BBB), and amyloid-beta peptide (Aβ), the main component of amyloid plaques and a major component of Alzheimers disease (AD) pathology in the brain, share several features. These include having similar β-sheet secondary structures, binding to the same receptor, and being degraded by the same protease. Thus, amylin may be associated with Aβ, but the nature of their relationship remains unclear. In this study, we used human samples to study the relationship between plasma amylin and Aβ in the context of the apolipoprotein E alleles (ApoE). We found that concentrations of Aβ1-42 (P<0.0001) and Aβ1-40 (P<0.0001) increased with each quartile increase of amylin. Using multivariate regression analysis, the study sample showed that plasma amylin was associated with Aβ1-42 (β = +0.149, SE = 0.025, P<0.0001) and Aβ1-40 (β = +0.034, SE = 0.016, P = 0.04) as an outcome after adjusting for age, gender, ethnicity, ApoE4, BMI, diabetes, stroke, kidney function and lipid profile. This positive association between amylin and Aβ1-42 in plasma was found regardless of the ApoE genotype. In contrast, the relationship between amylin and Aβ1-40 in plasma seen in ApoE4 non-carriers disappeared in the presence of ApoE4. Using AD mouse models, our recent study demonstrates that intraperitoneal (i.p.) injection of synthetic amylin enhances the removal of Aβ from the brain into blood, thus resulting in increased blood levels of both amylin and Aβ. The positive association between amylin and Aβ, especially Aβ1-42, in human blood samples is probably relevant to the findings in the AD mouse models. The presence of ApoE4 may attenuate amylins capacity to remove Aβ, especially Aβ1-40, from the AD brain.

Prescription stimulant use is associated with earlier onset of psychosis

A childhood history of attention deficit hyperactivity disorder (ADHD) is common in psychotic disorders, yet prescription stimulants may interact adversely with the physiology of these disorders. Specifically, exposure to stimulants leads to long-term increases in dopamine release. We therefore hypothesized that individuals with psychotic disorders previously exposed to prescription stimulants will have an earlier onset of psychosis. Age of onset of psychosis (AOP) was compared in individuals with and without prior exposure to prescription stimulants while controlling for potential confounding factors. In a sample of 205 patients recruited from an inpatient psychiatric unit, 40% (n = 82) reported use of stimulants prior to the onset of psychosis. Most participants were prescribed stimulants during childhood or adolescence for a diagnosis of ADHD. AOP was significantly earlier in those exposed to stimulants (20.5 vs. 24.6 years stimulants vs. no stimulants, p < 0.001). After controlling for gender, IQ, educational attainment, lifetime history of a cannabis use disorder or other drugs of abuse, and family history of a first-degree relative with psychosis, the association between stimulant exposure and earlier AOP remained significant. There was a significant gender × stimulant interaction with a greater reduction in AOP for females, whereas the smaller effect of stimulant use on AOP in males did not reach statistical significance. In conclusion, individuals with psychotic disorders exposed to prescription stimulants had an earlier onset of psychosis, and this relationship did not appear to be mediated by IQ or cannabis.

What can we learn about brain donors? Use of clinical information in human postmortem brain research

Postmortem studies on the human brain reside at the core of investigations on neurologic and psychiatric disorders. Ground-breaking advances continue to be made on the pathologic basis of many of these disorders, at molecular, cellular, and neural connectivity levels. In parallel, there is increasing emphasis on improving methods to extract relevant demographic and clinical information about brain donors and, importantly, translate it into measures that can reliably and effectively be incorporated in the design and data analysis of postmortem human investigations. Here, we review the main source of information typically available to brain banks and provide examples on how this information can be processed. In particular, we discuss approaches to establish primary and secondary diagnoses, estimate exposure to therapeutic treatment and substance abuse, assess agonal status, and use time of death as a proxy in investigations on circadian rhythms. Although far from exhaustive, these considerations are intended as a contribution to ongoing efforts from tissue banks and investigators aimed at establishing robust, well-validated methods for collecting and standardizing information about brain donors, further strengthening the scientific rigor of human postmortem studies.

Toward Objective, Multifaceted Characterization of Psychotic Disorders: Lexical, Structural, and Disfluency Markers of Spoken Language

Psychotic disorders are forms of severe mental illness characterized by abnormal social function and a general sense of disconnect with reality. The evaluation of such disorders is often complex, as their multifaceted nature is often difficult to quantify. Multimodal behavior analysis technologies have the potential to help address this need and supply timelier and more objective decision support tools in clinical settings. While written language and nonverbal behaviors have been previously studied, the present analysis takes the novel approach of examining the rarely-studied modality of spoken language of individuals with psychosis as naturally used in social, face-to-face interactions. Our analyses expose a series of language markers associated with psychotic symptom severity, as well as interesting interactions between them. In particular, we examine three facets of spoken language: (1) lexical markers, through a study of the function of words; (2) structural markers, through a study of grammatical fluency; and (3) disfluency markers, through a study of dialogue self-repair. Additionally, we develop predictive models of psychotic symptom severity, which achieve significant predictive power on both positive and negative psychotic symptom scales. These results constitute a significant step toward the design of future multimodal clinical decision support tools for computational phenotyping of mental illness.

Intensely Suicidal Behavior with a First Manic Episode

CASE HISTORYPresenting ProblemMs. A is a 20-year-old single woman with a history of major depressive episodes who was brought to an emergency department by her parents after she attempted to jump off the roof of their vacation home in the setting of several days of poor sleep, decreased appetite, ra