Predictors of Functional Impairment in Bipolar Disorder: Results From 13 Cohorts From Seven Countries by the Global Bipolar Cohort Collaborative.

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD.

Methods: Thirteen cohorts from 7 countries included = 5882 individuals with BD across multiple sites.

Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative.

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD.

Methods: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites.

"Supporting Wellness": A depression and bipolar support alliance mixed-methods investigation of lived experience perspectives and priorities for mood disorder treatment.

Background: The lived experience of people with mood disorders may be leveraged to inform priorities for research, define key treatment outcomes, and support decision-making in clinical care. The aim of this mixed-methods project was to provide insight into how people with depression and bipolar disorder experience the impact of symptoms, their treatment preferences, and their definitions of wellness.

Methods: The project was implemented in two phases.

Building brain capital.

Brains are indispensable drivers of human progress. Why not invest more heavily in them? We seek to place Brain Capital at the center of a new narrative to fuel economic and societal recovery and resilience.

A Brain Capital Grand Strategy: toward economic reimagination.

‘I have not found among my possessions anything which I hold more dear than, or value so much as, my knowledge of the actions of great people, acquired by long experience in contemporary affairs, and a continual study of antiquity.’ The Prince, Machiavelli

What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group.

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD.

Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action.

Bipolar disorder (BD) is a major healthcare and socio-economic challenge. Despite its substantial burden on society, the research activity in BD is much smaller than its economic impact appears to demand. There is a consensus that the accurate identification of the underlying pathophysiology for BD is fundamental to realize major health benefits through better treatment and preventive regimens.

The Next 50 Years of Neuroscience.

On the 50th anniversary of the Society for Neuroscience, we reflect on the remarkable progress that the field has made in understanding the nervous system, and look forward to the contributions of the next 50 years. We predict a substantial acceleration of our understanding of the nervous system that will drive the development of new therapeutic strategies to treat diseases over the course of the next five decades. We also see neuroscience at the nexus of many societal topics beyond medicine, including education, consumerism, and the justice system.

Distinct ipRGC subpopulations mediate light's acute and circadian effects on body temperature and sleep.

The light environment greatly impacts human alertness, mood, and cognition by both acute regulation of physiology and indirect alignment of circadian rhythms. These processes require the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), but the relevant downstream brain areas involved remain elusive. ipRGCs project widely in the brain, including to the central circadian pacemaker, the suprachiasmatic nucleus (SCN).

Analysis of tauopathy research funding between 2006 and 2016 reveals critical gaps in research priorities.

Neurodegenerative diseases encompass a range of diagnoses, such as Alzheimer's disease and Parkinson's disease. Despite decades of advancements in understanding the neurobiology of individual diseases, this class has few disease-modifying therapeutics and a paucity of biomarkers for diagnosis or progression. However, tau protein aggregation has emerged as a potential unifying factor across several neurodegenerative diseases, which has prompted a rapid growth in tau-related funding.

Neuroscience Has the Power to Change the Criminal Justice System.

As a neuroscientist working in the Department of Justice for the past year, I observed that many of the challenges of crime and justice have solutions rooted in our understanding of neuroscience. However, the neuroscience community seems absent from conversations regarding these solutions.

Abnormal wake/sleep pattern in a novel gain-of-function model of DISC1.

Sleep disturbances are common in psychiatric disorders, but the causal relationship between the two and the underlying genetic factors is unclear. The DISC1 gene is strongly linked to mood disorders and schizophrenia in a Scottish pedigree. In an earlier study we found a sleep homeostasis disturbance in a Drosophila model overexpressing wild-type human DISC1.

Disordered ripples are a common feature of genetically distinct mouse models relevant to schizophrenia.

We present results from a novel comparative approach to the study of mechanisms of psychiatric disease. Previous work examined neural activity patterns in the hippocampus of a freely behaving mouse model associated with schizophrenia, the calcineurin knockout mouse. Here we examined a genetically distinct mouse that exhibits a similar set of behavioral phenotypes associated with schizophrenia, a transgenic model expressing a putative dominant-negative DISC1 (DN-DISC1).

Photoreceptor regulation of spatial visual behavior.

Purpose: To better understand how photoreceptors and their circuits support luminance-dependent spatial visual behavior.

Methods: Grating thresholds for optokinetic tracking were measured under defined luminance conditions in mice with genetic alterations of photoreceptor activity.

Results: The luminance conditions that enable cone- and rod-mediated behavior, and the luminance range over which rod and cone functions overlap, were characterized.

Aberrant light directly impairs mood and learning through melanopsin-expressing neurons.

The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep-wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules.

Measuring circadian and acute light responses in mice using wheel running activity.

Circadian rhythms are physiological functions that cycle over a period of approximately 24 hours (circadian- circa: approximate and diem: day). They are responsible for timing our sleep/wake cycles and hormone secretion. Since this timing is not precisely 24-hours, it is synchronized to the solar day by light input.

Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities.

In mammals, synchronization of the circadian pacemaker in the hypothalamus is achieved through direct input from the eyes conveyed by intrinsically photosensitive retinal ganglion cells (ipRGCs). Circadian photoentrainment can be maintained by rod and cone photoreceptors, but their functional contributions and their retinal circuits that impinge on ipRGCs are not well understood. Using mice that lack functional rods or in which rods are the only functional photoreceptors, we found that rods were solely responsible for photoentrainment at scotopic light intensities.

Distinct contributions of rod, cone, and melanopsin photoreceptors to encoding irradiance.

Photoreceptive, melanopsin-expressing retinal ganglion cells (mRGCs) encode ambient light (irradiance) for the circadian clock, the pupillomotor system, and other influential behavioral/physiological responses. mRGCs are activated both by their intrinsic phototransduction cascade and by the rods and cones. However, the individual contribution of each photoreceptor class to irradiance responses remains unclear.

Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation.

Light detected in the retina modulates several physiological processes including circadian photo-entrainment and pupillary light reflex. Intrinsically photosensitive retinal ganglion cells (ipRGCs) convey rod-cone and melanopsin-driven light input to the brain. Using EEGs and electromyograms, we show that acute light induces sleep in mice during their nocturnal active phase whereas acute dark awakens mice during their diurnal sleep phase.

Multiple photoreceptors contribute to nonimage-forming visual functions predominantly through melanopsin-containing retinal ganglion cells.

In the absence of functional rod and cone photoreceptors, mammals retain the ability to detect light for a variety of physiological functions such as circadian photoentrainment and pupillary light reflex. This is attributed to a third class of photoreceptors, the intrinsically photosensitive retinal ganglion cells that express the photopigment melanopsin. Even though in the absence of rods and cones, mammals retain the ability to detect light for various nonimage-forming visual functions, rods and cones can compensate for the absence of the melanopsin protein in nonvisual light-dependent physiological behaviors.