Neurobiology Informed, Mobile Technology Augmented Interventions for Late-Life Depression and Suicidality

Depression is a major risk factor of suicide in late life. Evidence based psychotherapies for late-life depression are underutilized, mainly because of their complexity. In response, we created “Engage”, an innovative streamlined psychotherapy that relies on neurobiology findings to identify core behavioral pathology of late-life depression and targets it with simple cognitive-behavioral strategies of known efficacy, co-designed with community therapists so that its interventions can be mastered my community based clinicians. We demonstrated that “Engage” is non-inferior to the evidence based Problem Solving Therapy and documented that behavioral activation precedes improvement of depression. We have also shown that activities with important others have the strongest behavioral activation value. “Engage” served as a model for three novel, mobile technology augmented psychotherapies that address the clinical and psychosocial context of distinct populations of depressed older adults. Our interventions and mobile apps provide interventions for emotion regulation as a way of reducing suicidality.

Überprüfung der Faktorenstruktur einer deutschen Fragebogenversion der Behavioral Pathology in Alzheimerʼs Disease Scale

ZusammenfassungZiel der Arbeit war die Untersuchung der Faktorenstruktur einer deutschen Fragebogenversion der Behavioral Pathology in Alzheimerʼs Disease Scale (BEHAVE-AD), welche Verhaltensauffälligkeiten unabhängig von kognitiven Symptomen bei Menschen mit Demenz (MmD) erfasst. Die theoretisch beschriebene 7-Faktoren-Lösung der BEHAVE-AD wurde noch nicht zufriedenstellend für eine deutsche Fragebogenversion überprüft. Daher wurde dies in der vorliegenden Studie über eine konfirmatorische Faktorenanalyse vorgenommen. Es wurden die Einschätzungen von 322 pflegenden Angehörigen von MmD bezüglich der Verhaltensauffälligkeiten ihres an Demenz erkrankten Angehörigen analysiert. Die 7 Faktoren der Originalversion im Interviewformat (paranoide und wahnhafte Vorstellungen, Halluzinationen, Aktivitätsstörungen, Aggressivität, Störungen im Tagesrhythmus, affektive Störungen sowie Ängste und Phobien) konnten in der deutschsprachigen Fragebogenversion der BEHAVE-AD nicht bestätigt werden. Eine anschließend durchgeführte explorative Faktorenanalyse (N=118) weist auf eine 4-Faktoren-Lösung hin, welche sich in die Kategorien Paranoide Ideen und Aggressivität, Halluzinationen und Agitiertheit, Ängste und Phobien und Affektive Störungen aufteilen lässt.

General anesthesia, germ cells and the missing heritability of autism: an urgent need for research

Agents of general anesthesia (GA) are commonly employed in surgical, dental and diagnostic procedures to effectuate global suppression of the nervous system, but in addition to somatic targets, the subject’s germ cells—from the embryonic primordial stage to the mature gametes—may likewise be exposed. Although GA is generally considered safe for most patients, evidence has accumulated that various compounds, in particular the synthetic volatile anesthetic gases (SVAGs) such as sevoflurane, can exert neurotoxic, genotoxic and epigenotoxic effects, with adverse consequences for cellular and genomic function in both somatic and germline cells. The purpose of this paper is to review the evidence demonstrating that GA, and in particular, SVAGs, may in some circumstances adversely impact the molecular program of germ cells, resulting in brain and behavioral pathology in the progeny born of the exposed cells. Further, we exhort the medical and scientific communities to undertake comprehensive experimental and epidemiological research programs to address this critical gap in risk assessment.

Alcohol Drinking Exacerbates Neural and Behavioral Pathology in the 3xTg-AD Mouse Model of Alzheimer’s Disease

ABSTRACTAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents the most common cause of dementia in the United States. Although the link between alcohol use and AD has been studied, preclinical research has potential to elucidate neurobiological mechanisms that underlie this interaction. This study was designed to test the hypothesis that non-dependent alcohol drinking exacerbates the onset and magnitude of AD-like neural and behavioral pathology. We first evaluated the impact of voluntary 24-h, 2-bottle choice home-cage alcohol drinking on the prefrontal cortex and amygdala neuroproteome in C57BL/6J mice and found a striking association between alcohol drinking and AD-like pathology. Bioinformatics identified the AD-associated proteins MAPT (Tau), amyloid beta precursor protein (APP), and presenilin-1 (PSEN-1) as the main modulators of alcohol-sensitive protein networks that included AD-related proteins that regulate energy metabolism (ATP5D, HK1, AK1, PGAM1, CKB), cytoskeletal development (BASP1, CAP1, DPYSL2 [CRMP2], ALDOA, TUBA1A, CFL2, ACTG1), cellular/oxidative stress (HSPA5, HSPA8, ENO1, ENO2), and DNA regulation (PURA, YWHAZ). To address the impact of alcohol drinking on AD, studies were conducted using 3xTg-AD mice that express human MAPT, APP, and PSEN-1 transgenes and develop AD-like brain and behavioral pathology. 3xTg-AD and wildtype mice consumed alcohol or saccharin for 4 months. Behavioral tests were administered during a 1-month alcohol free period. Alcohol intake induced AD-like behavioral pathologies in 3xTg-AD mice including impaired spatial memory in the Morris Water Maze, diminished sensorimotor gating as measured by prepulse inhibition, and exacerbated conditioned fear. Multiplex immunoassay conducted on brain lysates showed that alcohol drinking upregulated primary markers of AD pathology in 3xTg-AD mice: Aβ 42/40 ratio in the lateral entorhinal and prefrontal cortex and total Tau expression in the lateral entorhinal cortex and amygdala at 1-month post alcohol exposure. Immunocytochemistry showed that alcohol use upregulated expression of pTau (Ser199/Ser202) in the hippocampus, which is consistent with late stage AD. According to the NIA-AA Research Framework, these results suggest that alcohol use is associated with Alzheimer’s pathology. Results also showed that alcohol use was associated with a general reduction in Akt/mTOR signaling via several phosphoproteins (IR, IRS1, IGF1R, PTEN, ERK, mTOR, p70S6K, RPS6) in multiple brain regions including hippocampus and entorhinal cortex. Dysregulation of Akt/mTOR phosphoproteins suggests alcohol may target this pathway in AD progression. These results suggest that nondependent alcohol drinking increases the onset and magnitude of AD-like neural and behavioral pathology in 3xTg-AD mice.

Prefrontal Cortex in Control: Broadening the Scope to Identify Mechanisms

Sometime in the past two decades, neuroimaging and behavioral research converged on pFC as an important locus of cognitive control and decision-making, and that seems to be the last thing anyone has agreed on since. Every year sees an increase in the number of roles and functions attributed to distinct subregions within pFC, roles that may explain behavior and neural activity in one context but might fail to generalize across the many behaviors in which each region is implicated. Emblematic of this ongoing proliferation of functions is dorsal ACC (dACC). Novel tasks that activate dACC are followed by novel interpretations of dACC function, and each new interpretation adds to the number of functionally specific processes contained within the region. This state of affairs, a recurrent and persistent behavior followed by an illusory and transient relief, can be likened to behavioral pathology. In Journal of Cognitive Neuroscience, 29:10 we collect contributed articles that seek to move the conversation beyond specific functions of subregions of pFC, focusing instead on general roles that support pFC involvement in a wide variety of behaviors and across a variety of experimental paradigms.