Recent advances in neuropsychiatry

Brain-derived neurotrophic factor (BDNF) is widely accepted for its involvement in resilience and antidepressant drug action, is a common genetic locus of risk for mental illnesses, and remains one of the most prominently studied molecules within psychiatry. Stress, which arguably remains the "lowest common denominator" risk factor for several mental illnesses, targets BDNF in disease-implicated brain regions and circuits. Altered stress-related responses have also been observed in animal models of BDNF deficiency in vivo, and BDNF is a common downstream intermediary for environmental factors that potentiate anxiety- and depressive-like behavior...

De novo and inherited rare genetic disorders (RGDs) are a major cause of human morbidity, frequently involving neuropsychiatric symptoms. Recent advances in genomic technologies and data sharing have revolutionized the identification and diagnosis of RGDs, presenting an opportunity to elucidate the mechanisms underlying neuropsychiatric disorders by investigating the pathophysiology of high-penetrance genetic risk factors. Here we seek out the best path forward for achieving these goals. We think future research will require consistent approaches across multiple RGDs and developmental stages, involving both the characterization of shared neuropsychiatric dimensions in humans and the identification of neurobiological commonalities in model systems...

Most large pharmaceutical companies have downscaled or closed their clinical neuroscience research programs in response to the low clinical success rate for drugs that showed tremendous promise in animal experiments intended to model psychiatric pathophysiology. These failures have raised serious concerns about the role of preclinical research in the identification and evaluation of new pharmacotherapies for psychiatry. In the absence of a comprehensive understanding of the neurobiology of psychiatric disorders, the task of developing "animal models" seems elusive...

Alzheimer's disease (AD) is one of the main causes of dementia in the western world. It is clinically characterized by memory impairment, deterioration of intellectual faculties and loss of professional skills. AD brains exhibit significant atrophy, predominantly in the temporal and parietal lobes, while light microscopy reveals deposition of senile plaques and neurofibrillary degeneration initially in the entorhinal cortex, the hippocampus, and in the acoustic and visual cortices, in the frontal lobe and the cerebellum in the advanced stages...

Neuropsychiatric disorders, including depression, anxiety, schizophrenia, and Alzheimer's disease (AD), are diseases that are directly or indirectly associated with cerebral dysfunction and contribute significantly to disability in adult populations worldwide. Important limitations surround the currently available pharmacologic agents for neuropsychiatric disorders and, moreover, many patients fail to respond to these therapies. Acupuncture might be a complementary therapy for neuropsychiatry disorders. In this review, we investigate the current evidence for the treatment efficacy of acupuncture in depression, anxiety, schizophrenia, and AD...

The prevalence of Autism Spectrum Disorder (ASD) is growing rapidly, affecting 1 in 59 children in the United States in 2018. Individuals with ASD currently receive fragmented care that threatens their health and well-being. Challenges of autism care include disconnections between the medical system and school supports, poor care coordination between primary care and specialists, and saturation of neuropsychiatry-based centers' capacity to care for the ASD population. ASD treatment also lacks of a coordinated system of care for patients' multi-system comorbidities...

Gilles de la Tourette syndrome (GTS) is a chronic tic disorder characterised by the presence of multiple motor and vocal tics with onset during development. Tics are the most common hyperkinetic symptoms in childhood and co-morbid behavioural conditions (especially obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, affective symptoms, and impulsivity) are present in the majority of patients. Although GTS is no longer considered a rare medical curiosity, its exact pathophysiology remains elusive...

Proton magnetic resonance spectroscopy (1 H MRS) is a well-established technique for quantifying the brain regional biochemistry in vivo . In most studies, however, the 1 H MRS is acquired during rest with little to no constraint on behavior. Measured metabolite levels, therefore, reflect steady-state concentrations whose associations with behavior and cognition are unclear. With the recent advances in MR technology-higher-field MR systems, robust acquisition techniques and sophisticated quantification methods-1 H MRS is now experiencing a resurgence...

The discovery in 2001 of a G protein-coupled receptor family, subsequently termed trace amine-associated receptors (TAAR), triggered a resurgence of interest in so-called trace amines. Initial optimism quickly faded, however, as the TAAR family presented a series of challenges preventing the use of standard medicinal chemistry and pharmacology technologies. Consequently the development of basic tools for probing TAAR and translating findings from model systems to humans has been problematic. Despite these challenges the last 5years have seen considerable advances, in particular with respect to TAAR1, which appears to function as an endogenous rheostat, maintaining central neurotransmission within defined physiological limits, in part through receptor heterodimerization yielding biased signaling outputs...

Since the recognition of asthma as a syndrome with complex pathophysiological signs and symptoms, recent research has sought to classify asthma phenotypes based on its clinical and molecular pathological features. Psychological stress was first recognized as a potential immune system modulator of asthma at the end of the 19th century. The activation of the central nervous system (CNS) upon exposure to psychological stress is integral for the initiation of signal transduction processes. The stress hormones, including glucocorticoids, epinephrine, and norepinephrine, which are secreted following CNS activation, are involved in the immunological alterations involved in psychological stress-induced asthma exacerbation...

In the context of modeling epilepsy and neuropsychiatric comorbidities, we review the Wistar Audiogenic Rat (WAR), first introduced to the neuroscience international community more than 25years ago. The WAR strain is a genetically selected reflex model susceptible to audiogenic seizures (AS), acutely mimicking brainstem-dependent tonic-clonic seizures and chronically (by audiogenic kindling), temporal lobe epilepsy (TLE). Seminal neuroethological, electrophysiological, cellular, and molecular protocols support the WAR strain as a suitable and reliable animal model to study the complexity and emergent functions typical of epileptogenic networks...

Despite decades of research, visions of transforming neuropsychiatry through the development of brain imaging-based "growth charts" or "lab tests" have remained out of reach. In recent years, there is renewed enthusiasm about the prospect of achieving clinically useful tools capable of aiding the diagnosis and management of neuropsychiatric disorders. The present work explores the basis for this enthusiasm. We assert that there is no single advance that currently has the potential to drive the field of clinical brain imaging forward...

Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions...

PURPOSE OF REVIEW: The present article addresses intriguing questions related to the clinical intervention in distinct neuropsychiatric syndromes of patients with dementia. RECENT FINDINGS: We reviewed 154 articles published between 2015 and 2016 targeting psychopharmacological and nonpharmacological interventions, and safety-tolerability concerns. We selected 115 articles addressing the purpose of this study. Of these, 33 were chosen because they were dedicated to subtopics: agitation (42), depression (33), apathy (18), sleep disorders/anxiety (8), and psychosis (4)...

Deficits in reward and motivation are common symptoms characterizing several psychiatric and neurological disorders. Such deficits may include anhedonia, defined as loss of pleasure, as well as impairments in anticipatory pleasure, reward valuation, motivation/effort, and reward learning. This chapter describes recent advances in the development of behavioral tasks used to assess different aspects of reward processing in both humans and non-human animals. While earlier tasks were generally developed independently with limited cross-species correspondence, a newer generation of translational tasks has emerged that are theoretically and procedurally analogous across species and allow parallel testing, data analyses, and interpretation between human and rodent behaviors...

PURPOSE OF REVIEW: This article presents a multidimensional, integrative approach to clinical assessment and management of neurobehavioral disorders. RECENT FINDINGS: Behavioral neurology and neuropsychiatry has grown as a subspecialty along with increased recognition of two common brain disorders: dementia and traumatic brain injury. Alzheimer disease is a highly prevalent dementia and a prototypical memory disorder, which has led to a primary focus on cognitive screening and assessment...

Major depressive disorder continues to challenge medical and psychological resources worldwide. A marked surge has occurred recently in China in neuroimaging studies of major depressive disorder. Those studies represent an emerging trend in neuropsychiatry in that such research has previously been extremely rare in China. The present article provides a systematic review of reports published in English by research institutes in China on resting-state functional connectivity studied by MRI in depressed subjects and healthy control subjects...

In recent years there has been an increasing awareness of the role of P2X7, a receptor for extracellular ATP, in modulating physiopathological mechanisms in the central nervous system. In particular, P2X7 has been shown to be implicated in neuropsychiatry, chronic pain, neurodegeneration and neuroinflammation. Remarkably, P2X7 has also been shown to be a 'gene modifier' in amyotrophic lateral sclerosis (ALS): the receptor is upregulated in spinal cord microglia in human and rat at advanced stages of the disease; in vitro, activation of P2X7 exacerbates pro-inflammatory responses in microglia that have an ALS phenotype, as well as toxicity towards neuronal cells...

Some of the most interesting questions in biology today, in my view, derive from the real advances in neuropsychiatry that have come largely from human genetics. Research in autism spectrum disorders (ASDs) has been leading the way, mainly because it has become especially well funded and has recently attracted many outstanding scientists. (I must make it clear that I am an outsider in this field, as I have never worked on any neuropsychiatric disorder).

Advances in neuroscience have revolutionized our understanding of the central nervous system. Neuroimaging technologies, in particular, have begun to reveal the complex anatomical, physiological, biochemical, genetic, and molecular organizational structure of the organ at the center of that system: the human brain. More recently, neuroimaging technologies have enabled the investigation of normal brain function and are being used to gain important new insights into the mechanisms behind many neuropsychiatric disorders...