VIP, From Gene to Behavior and Back: Summarizing my 25 Years of Research

Vasoactive intestinal peptide (VIP) is an interesting example of a 28-amino acid neuropeptide that is abundantly expressed in discrete brain regions/neurons and hence may contribute to brain function. This short review summarizes my own point of view and encompasses 25 years of work and over 100 publications targeting the understanding of VIP production and biological activity. The review starts with our original cloning of the VIP gene, it then continues to discoveries of regulation of VIP synthesis and the establishment of the first VIP transgenic mice. The review ends with the identification of novel VIP analogs that helped decipher VIP's important role during development, in regulation of the biological clock(s) and diurnal rhythms, sexual activity, learning and memory as well as social behavior, and cancer. This review cites only articles that I have coauthored and gives my own perspective of this exciting ever-growing field.     

150 Years of Freud-Kraepelin Dualism

The year 2006 marked the 150th Birthday of Emil Kraepelin and Sigmund Freud. Kraepelin and Freud were two very different yet very similar men. The comparison between their biographies shows many parallels in their lives and personalities. They were, in their time, the two most influential individuals in psychiatry. They wrote and thought about similar topics in the field yet came to quite different conclusions. Both did not show public respect for each other but wrote about the importance of integrating their respective approaches into the study of the mind/brain problem. Psychiatry today continues to struggle with the integration of the biological and psychodynamic approach.     

Genetics of Alzheimer’s disease: From pathogenesis to clinical usage

Alzheimer’s disease (AD) is the most common type of dementia and has caused a major global health concern. Understanding the etiology of AD can be beneficial for the diagnosis and intervention of this disease. Genetics plays a vital role in the pathogenesis of AD. Research methods in genetics such as the linkage analysis, study of candidate genes, genome-wide association study (GWAS), and next-generation sequencing (NGS) technology help us map the genetic information in AD, which can not only provide a new insight into the pathogenesis of AD but also be beneficial for early targeted intervention of AD. This review summarizes the pathogenesis as well as the diagnostic and therapeutic value of genetics in AD.     

The Genetics of Alzheimer’s Disease in Brazil: 10 Years of Analysis in a Unique Population

Alzheimer’s Disease (AD) is the most common type of dementia among the elderly, with devastating consequences for the patient, their relatives, and caregivers. More than 300 genetic polymorphisms have been involved with AD, demonstrating that this condition is polygenic and with a complex pattern of inheritance. This paper aims to report and compare the results of AD genetics studies in case-control and familial analysis performed in Brazil since our first publication, 10 years ago. They include the following genes/markers: Apolipoprotein E (APOE), 5-hidroxytryptamine transporter length polymorphic region (5-HTTLPR), brain-derived neurotrophin factor (BDNF), monoamine oxidase A (MAO-A), and two simple-sequence tandem repeat polymorphisms (DXS1047 and D10S1423). Previously unpublished data of the interleukin-1α (IL-1α) and interleukin-1 β (IL-1β) genes are reported here briefly. Results from others Brazilian studies with AD patients are also reported at this short review. Four local families studied with various markers at the chromosome 21, 19, 14, and 1 are briefly reported for the first time. The importance of studying DNA samples from Brazil is highlighted because of the uniqueness of its population, which presents both intense ethnical miscegenation, mainly at the east coast, but also clusters with high inbreeding rates in rural areas at the countryside. We discuss the current stage of extending these studies using high-throughput methods of large-scale genotyping, such as single nucleotide polymorphism microarrays, associated with bioinformatics tools that allow the analysis of such extensive number of genetics variables, with different levels of penetrance. There is still a long way between the huge amount of data gathered so far and the actual application toward the full understanding of AD, but the final goal is to develop precise tools for diagnosis and prognosis, creating new strategies for better treatments based on genetic profile.     

Understanding Early Age of Onset: a Review of the Last 5 Years

The age at onset of bipolar disorder ranging from childhood to adolescent to adult has significant implications for frequency, severity and duration of mood episodes, comorbid psychopathology, heritability, response to treatment, and opportunity for early intervention. There is increasing evidence that recognition of prodromal symptoms in at-risk populations and mood type at onset are important variables in understanding the course of this illness in youth. Very early childhood onset of symptoms including anxiety/depression, mood lability, and subthreshold manic symptoms, along with family history of a parent with early onset bipolar disorder, appears to predict the highest risk of early onset disorder with the most severe course.     

Do gender and age moderate the symptom structure of PTSD? Findings from a national clinical sample of children and adolescents

A substantial body of evidence documents that the frequency and intensity of posttraumatic stress disorder (PTSD) symptoms are linked to such demographic variables as female sex (e.g., Kaplow et al., 2005) and age (e.g., Meiser-Stedman et al., 2008). Considerably less is known about relations between biological sex and age with PTSD's latent factor structure. This study systematically examined the roles that sex and age may play as candidate moderators of the full range of factor structure parameters of an empirically supported five-factor PTSD model (Elhai et al., 2011). The sample included 6591 trauma-exposed children and adolescents selected from the National Child Traumatic Stress Network's Core Data Set. Confirmatory factor analysis using invariance testing (Gregorich, 2006) and comparative fit index difference values (Cheung and Rensvold, 2002) reflected a mixed pattern of test item intercepts across age groups. The adolescent subsample produced lower residual error variances, reflecting less measurement error than the child subsample. Sex did not show a robust moderating effect. We conclude by discussing implications for clinical assessment, theory building, and future research.     

The Role of Schools in Early Adolescents’ Mental Health: Findings From the MYRIAD Study

ObjectiveRecent studies suggest mental health in youths is deteriorating. The current policy in the United Kingdom emphasizes the role of schools for mental health promotion and prevention, but little data exist on what aspects of schools influence mental health in pupils. This study explored school-level influences on the mental health of young people in a large school-based sample from the United Kingdom.MethodBaseline data from a large cluster randomized controlled trial collected between 2016 and 2018 from mainstream secondary schools selected to be representative in relation to their quality rating, size, deprivation, mixed or single-sex pupil population, and country were analyzed. Participants were pupils in their first or second year of secondary school. The study assessed whether school-level factors were associated with pupil mental health.ResultsThe study included 26,885 pupils (response rate = 90%; age range, 11‒14 years; 55% female) attending 85 schools in the United Kingdom. Schools accounted for 2.4% (95% CI: 2.0%‒2.8%; p < .0001) of the variation in psychopathology, 1.6% (95% CI: 1.2%‒2.1%; p < .0001) of depression, and 1.4% (95% CI: 1.0%‒1.7%; p < .0001) of well-being. Schools in urban locations, with a higher percentage of free school meals and of White British, were associated with poorer pupil mental health. A more positive school climate was associated with better mental health.ConclusionSchool-level variables, primarily related to contextual factors, characteristics of pupil population, and school climate, explain a small but significant amount of variability in mental health of young people. This information might be used to identify schools that are in need of more resources to support mental health of young people.Clinical trial registration informationMYRIAD: My Resilience in Adolescence, a Study Examining the Effectiveness and Cost-Effectiveness of a Mindfulness Training Programme in Schools Compared With Normal School Provision; https://www.isrctn.com/; 86619085.     

Effects of Oestrogen on Cognition: What Have We Learned From Basic Research?

The results of clinical and basic research conducted over the past two decades have implicated a role for oestrogen in modulating cognitive function. This review focuses on what the results of research using female rodent models have revealed about the effects of oestrogen on mammalian cognition. Increased levels of oestrogen are associated with increased dendritic spine and synapse density in the hippocampus, a brain area important for learning and memory. However, the role of oestrogen in the modulation of performance on tasks of learning and memory is complex because it exerts enhancing effects on some tasks and impairing effects on others. Hypotheses have been offered to explain these varied actions, including differentiating the effects of oestrogen on cognitive processes required to complete tasks and analysing the influence of fluctuating levels of oestrogen on the strategies selected by animals to solve tasks. It is proposed that, when these hypotheses are viewed together and within the context of oestrogen action in the hippocampus and potentially other brain areas, a framework for understanding the varied effects of oestrogen on cognition emerges. The hippocampal-dependent memory system supports the flexible expression of memories and the hippocampal-independent memory system supports development of individual representations. Because of the effects exerted by oestrogen on the structure and function of the hippocampus, it would be expected to enhance performance across a variety of tasks that require hippocampal-dependent flexible expression of memories and would not enhance performance on tasks that involve hippocampal-independent individual representations. This review offers a theoretical model by which the divergent results of studies assessing the role of oestrogen on cognition can be reconciled and suggests that effects of oestrogen on cognition are best understood within the framework of oestrogen action in the brain and the role of those brain areas affected by oestrogen in the mediation of learning and memory.     

Cancer Care Coordination: a Systematic Review and Meta-Analysis of Over 30 Years of Empirical Studies

Background

According to a landmark study by the Institute of Medicine, patients with cancer often receive poorly coordinated care in multiple settings from many providers. Lack of coordination is associated with poor symptom control, medical errors, and higher costs.

Purpose

The aims of this systematic review and meta-analysis were to (1) synthesize the findings of studies addressing cancer care coordination, (2) describe study outcomes across the cancer continuum, and (3) obtain a quantitative estimate of the effect of interventions in cancer care coordination on service system processes and patient health outcomes.

Methods

Of 1241 abstracts identified through MEDLINE, EMBASE, CINAHL, and the Cochrane Library, 52 studies met the inclusion criteria. Each study had US or Canadian participants, comparison or control groups, measures, times, samples, and/or interventions. Two researchers independently applied a standardized search strategy, coding scheme, and online coding program to each study. Eleven studies met the additional criteria for the meta-analysis; a random effects estimation model was used for data analysis.

Results

Cancer care coordination approaches led to improvements in 81 % of outcomes, including screening, measures of patient experience with care, and quality of end-of-life care. Across the continuum of cancer care, patient navigation was the most frequent care coordination intervention, followed by home telehealth; nurse case management was third in frequency. The meta-analysis of a subset of the reviewed studies showed that the odds of appropriate health care utilization in cancer care coordination interventions were almost twice (OR = 1.9, 95 % CI = 1.5–3.5) that of comparison interventions.

Conclusions

This review offers promising findings on the impact of cancer care coordination on increasing value and reducing healthcare costs in the USA.

     

Housing First for People With Severe Mental Illness Who Are Homeless: A Review of the Research and Findings From the At Home–Chez soi Demonstration Project

Objective:

To provide a review of the extant research literature on Housing First (HF) for people with severe mental illness (SMI) who are homeless and to describe the findings of the recently completed At Home (AH)–Chez soi (CS) demonstration project. HF represents a paradigm shift in the delivery of community mental health services, whereby people with SMI who are homeless are supported through assertive community treatment or intensive case management to move into regular housing.

Method:

The AH–CS demonstration project entailed a randomized controlled trial conducted in 5 Canadian cities between 2009 and 2013. Mixed methods were used to examine the implementation of HF programs and participant outcomes, comparing 1158 people receiving HF to 990 people receiving standard care.

Results:

Initial research conducted in the United States shows HF to be a promising approach, yielding superior outcomes in helping people to rapidly exit homelessness and establish stable housing. Findings from the AH–CS demonstration project reveal that HF can be successfully adapted to different contexts and for different populations without losing its fidelity. People receiving HF achieved superior housing outcomes and showed more rapid improvements in community functioning and quality of life than those receiving treatment as usual.

Conclusions:

Knowledge translation efforts have been undertaken to disseminate the positive findings and lessons learned from the AH–CS project and to scale up the HF approach across Canada.     

Findings From the Pittsburgh Youth Study: Cognitive Impulsivity and Intelligence as Predictors of the Age–Crime Curve

ObjectiveThis article first summarizes key research findings from the Pittsburgh Youth Study from 1987 to the present, and focuses on delinquency in 1,517 young men who have been followed up from late childhood into their 20s. Second, the article addresses how indicators of self-control prospectively predict later offending, and whether the prediction shows individual difference in the age–crime curve, particularly the up-slope, peak, and down-slope of that curve.MethodLongitudinal analyses were conducted on a sample of boys in the middle sample of the Pittsburgh Youth Study (n = 422), whose cognitive impulsivity and intelligence were assessed at about age 12 years. Criminal records on the sample were until age 28.ResultsThe results show that cognitive impulsivity and intelligence, measured between ages 12 and 13 by means of psychometric tests, predicted the age–crime curve. The age–arrest curve was substantially higher in boys with high cognitive impulsivity and in boys with low IQ. However, there was a significant interaction between cognitive impulsivity and intelligence. For boys with high IQ, cognitive impulsivity was associated with a greater escalation in the prevalence of offending during early adolescence, followed by a more rapid decline in offending as boys entered early adulthood with a slight subsequent increase in criminal offending then occurring late 20. In contrast, there was no evidence that cognitive impulsivity independently influenced criminal offending at any developmental period for boys with low IQ.ConclusionsThe results are discussed in terms of interventions to reduce individuals' delinquency from childhood through early adulthood and lower the age–crime curve for populations. However, the association was complex because it was moderated by both age and intelligence.     

Is There a Continuum of Behavioural Dependence in Problem Gambling? Evidence from 15 Years of Australian Prevalence Research

A common assumption in many public frameworks is that the harms and behavioural risk factors associated with gambling disorder lie on a continuum. At one end is lower risk or recreational gambling, and at the other, problem or disordered gambling. Movements along this continuum are associated with gradual increases or decreases in the level of behaviour and associated harm. This perspective is often advanced in opposition to more clinical or categorical frameworks that view problem gambling as a distinct clinical category from the other groups. In this paper, we investigate these competing perspectives with reference to 15 years of Australian prevalence studies. We examine the relationship between PGSI severity classifications and the endorsement of the principal criteria of the DSM-5 (e.g. tolerance, chasing, impaired control). The results showed that while elements of behavioural dependence increase across the PGSI categories (low to moderate to problem), problem gamblers have disproportionately greater endorsement. The PGSI severity and behavioural dependence relationship corresponds more strongly to a J-curve than a linear or r-curve and therefore lends greater support of a more categorical conceptualisation of the disorder.

     

From Normal Gait to Loss of Ambulation in 6 Months: a Novel Presentation of SCA17

Spinocerebellar ataxias are a group of rare and heterogeneous autosomal dominant disorders characterized by progressive ataxia and other features. Spinocerebellar ataxia 17 (SCA17) is one of the 32 subtypes described to date and is secondary to CAG/CAA repeat expansion in the gene coding for the TATA-box binding protein (TBP). SCA17 is clinically heterogeneous and typically presents with slowly evolving ataxia, dysarthria, dementia, depression, and other movement disorders such as chorea. More than 41 CAG/CAA repeats are considered diagnostic of SCA17, with more than 49 being associated with full penetrance. We report one patient presenting with isolated rapidly evolving ataxia who was found to have 44 CAG/CAA repeats in the TBP gene. This suggests that, while SCA17 typically slowly progresses over years, its repertoire of presentations should be expanded to include rapidly progressive isolated ataxia resembling paraneoplastic disorders or prion disease.