Time course of the effects of lisdexamfetamine dimesylate in two phase 3, randomized, double-blind, placebo-controlled trials in adults with binge-eating disorder.

Objective: This study examined the time course of efficacy-related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol-defined moderate to severe binge-eating disorder (BED).

Methods: In two 12-week, double-blind, placebo-controlled studies, adults meeting DSM-IV-TR BED criteria were randomized 1:1 to receive placebo or dose-optimized LDX (50 or 70 mg). Analyses across visits used mixed-effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE] scores, percentage body weight change) and chi-square tests (Clinical Global Impressions-Improvement [CGI-I; from the perspective of BED symptoms] scale dichotomized as improved or not improved).

Treatment of Bipolar Disorder in a Lifetime Perspective: Is Lithium Still the Best Choice?

Lithium preparations have been successfully used to treat bipolar disorder (BD), and remain the best established long-term treatment for the disorder. In fact, lithium is a cornerstone of treatment to minimize the risk of recurrences and improve inter-episodic symptomatology. We reviewed the available evidence for the use of lithium in the treatment of BD, including its efficacy, limitations, and potential benefits also in consideration of the different formulations available.

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M, M, and M receptor knockout mice.

Muscarinic M/M receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (S) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications.

Derivation of mouse embryonic stem cell lines from tyrosine hydroxylase reporter mice crossed with a human SNCA transgenic mouse model of Parkinson's disease.

Mouse embryonic stem cell (mESC) lines were derived by crossing heterozygous transgenic (tg) mice expressing green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase (TH) promoter, with homozygous alpha-synuclein (aSYN) mice expressing human mutant SNCA under the control of the mouse Prion promoter (MoPrP), or wildtype (WT) mice. The expression of GFP and human aSYN was validated by immunocytochemistry in midbrain neuron cultures upon differentiation of mESC lines using stromal cell-derived inducing activity. These mESC lines can help to study the impact of human aSYN expression in neurons and oligodendrocytes, and also trace GFP-expressing midbrain neurons.

Improving perceptions of cognitive-behavioral therapy with brief website exposure: Does neuroscientific allure impact attitudes?

Background And Objectives: The current study aimed to determine whether brief exposure to a webpage about cognitive-behavioral therapy (CBT) for the anxiety disorders improved knowledge and perceptions of this treatment. Further, this study tested whether participants were uniquely compelled by CBT if the mechanism of change cited neurological processes.

Method: Participants (N = 389) recruited online viewed a webpage screenshot that described CBT for anxiety.

Aggression Protects Against the Onset of Major Depressive Episodes in Individuals With Bipolar Spectrum Disorder.

A growing body of research suggests that bipolar spectrum disorders (BSDs) are associated with high aggression. However, little research has prospectively examined how aggression may affect time to onset of hypomanic/manic versus major depressive episodes. In a longitudinal study, we tested the hypothesis that aggression would prospectively predict a shorter time to the onset of hypomanic/manic episodes and a longer time to the onset of major depressive episodes, based on the behavioral approach system theory of BSDs.

Early onset of cardiometabolic risk factor profiles in drug naïve adolescents and young adults with first-episode schizophrenia.

Objective And Method: We performed a case-control study, which included antipsychotic-naïve first-episode schizophrenia (FES) of adolescents and young adults and general population controls, to investigate the early-onset cardiometabolic risk factors in FES.

Results: FES had more frequent lower HDL-C when compared to controls. However, the distribution of BMI and the frequency of hypercholesterolemia, elevated LDL-C, hypertriglyceridemia in FES were not significantly different to controls.

Isolating the Unique Effects of the Unified Protocol Treatment Modules Using Single Case Experimental Design.

The Unified Protocol (UP) for the Transdiagnostic Treatment of Emotional Disorders is a cognitive-behavioral intervention designed to treat the range of anxiety, depressive, and related disorders. Thus far, the UP treatment modules have only been studied when they are delivered in their entirety and presented in a standard sequence. To personalize the presentation of the UP modules for a given patient's presentation (e.

Preclinical Analysis of Fetal Human Mesencephalic Neural Progenitor Cell Lines: Characterization and Safety In Vitro and In Vivo.

We have developed a good manufacturing practice for long-term cultivation of fetal human midbrain-derived neural progenitor cells. The generation of human dopaminergic neurons may serve as a tool of either restorative cell therapies or cellular models, particularly as a reference for phenotyping region-specific human neural stem cell lines such as human embryonic stem cells and human inducible pluripotent stem cells. We cultivated 3 different midbrain neural progenitor lines at 10, 12, and 14 weeks of gestation for more than a year and characterized them in great detail, as well as in comparison with Lund mesencephalic cells.

Cumulative exposure to work-related traumatic events and current post-traumatic stress disorder in New York City's first responders.

Background And Objectives: Cumulative exposure to work-related traumatic events (CE) is a foreseeable risk for psychiatric disorders in first responders (FRs). Our objective was to examine the impact of work-related CE that could serve as predictor of posttraumatic stress disorder (PTSD) and/or depression in FRs.

Design: Cross-sectional examination of previous CE and past-month PTSD outcomes and depression in 209 FRs.

Long-Term Predictions from Early Adolescent Attachment State of Mind to Romantic Relationship Behaviors.

Attachment state of mind was investigated as a long-term predictor of romantic relationship competence. A secure early adolescent attachment state of mind was hypothesized to predict more constructive dyadic behaviors during conflict discussions and support seeking interactions in late adolescence and early adulthood. Utilizing multi-method data from a community sample of 184 individuals, followed from ages 14 to 21, adolescents with a secure attachment state of mind at age 14 were found to be in relationships that displayed more constructive dyadic conflict discussion behaviors and dyadic supportive behaviors at both ages 18 and 21.

Seq-ing Markers of Midbrain Dopamine Neurons.

Transplantation of human pluripotent stem cell-derived dopaminergic neurons is a promising approach to treating Parkinson's disease. In this issue of Cell Stem Cell, Kee et al. (2017) and Kirkeby et al.

Parabrachial Pituitary Adenylate Cyclase-Activating Polypeptide Activation of Amygdala Endosomal Extracellular Signal-Regulated Kinase Signaling Regulates the Emotional Component of Pain.

Background: Chronic pain and stress-related psychopathologies, such as depression and anxiety-associated abnormalities, are mutually reinforcing; however, the neuronal circuits and mechanisms that underlie this reinforcement are still not well understood. Pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate PAC1 receptor (Adcyap1r1) are expressed in peripheral nociceptive pathways, participate in anxiety-related responses and have been have been linked to posttraumatic stress disorder and other mental health afflictions.

Methods: Using immunocytochemistry, pharmacological treatments and behavioral testing techniques, we have used a rodent partial sciatic nerve chronic constriction injury model (n = 5-8 per group per experiment) to evaluate PACAP plasticity and signaling in nociceptive and stress-related behaviors.

Sensitive periods of substance abuse: Early risk for the transition to dependence.

Early adolescent substance use dramatically increases the risk of lifelong substance use disorder (SUD). An adolescent sensitive period evolved to allow the development of risk-taking traits that aid in survival; today these may manifest as a vulnerability to drugs of abuse. Early substance use interferes with ongoing neurodevelopment to induce neurobiological changes that further augment SUD risk.

Comparison of a non-stationary voxelation-corrected cluster-size test with TFCE for group-Level MRI inference.

Two powerful methods for statistical inference on MRI brain images have been proposed recently, a non-stationary voxelation-corrected cluster-size test (CST) based on random field theory and threshold-free cluster enhancement (TFCE) based on calculating the level of local support for a cluster, then using permutation testing for inference. Unlike other statistical approaches, these two methods do not rest on the assumptions of a uniform and high degree of spatial smoothness of the statistic image. Thus, they are strongly recommended for group-level fMRI analysis compared to other statistical methods.

QTc interval lengthening in first-episode schizophrenia (FES) patients in the earliest stages of antipsychotic treatment.

Antipsychotic use is reported to be associated with a higher risk of sudden cardiac death and new users are especially susceptible to that risk. In this study, we focused on the ability of antipsychotics to prolong the QTc interval at the earliest stages of antipsychotic use. We employed a retrospective cohort study design in a naturalistic setting where having three ECG measurements over time (at baseline and after drug exposure) in antipsychotic-naïve, first-episode schizophrenia (FES) inpatients.

Acute and chronic effects of clozapine on cholinergic transmission in cultured mouse superior cervical ganglion neurons.

Cholinergic dysfunction contributes to cognitive deficits in schizophrenia. The atypical antipsychotic clozapine improves cognition in patients with schizophrenia, possibly through modulation of the cholinergic system. However, little is known about specific underlying mechanisms.

Network analysis of depression and anxiety symptom relationships in a psychiatric sample.

Background: Researchers have studied psychological disorders extensively from a common cause perspective, in which symptoms are treated as independent indicators of an underlying disease. In contrast, the causal systems perspective seeks to understand the importance of individual symptoms and symptom-to-symptom relationships. In the current study, we used network analysis to examine the relationships between and among depression and anxiety symptoms from the causal systems perspective.

Cardiometabolic risk in first-episode schizophrenia (FES) patients with the earliest stages of both illness and antipsychotic treatment.

Objective: It is well established that schizophrenia patients have high cardiovascular morbidity and mortality. However, the underlying risk factors in the earliest stages of both schizophrenia illness and antipsychotics treatment are less clear. This study aimed to characterize the metabolic features of those patients.

Adaptation of a paradigm for examining the development of fear beliefs through the verbal information pathway in preschool-age children.

Verbal threat information has been shown to induce fear beliefs in school-age children (i.e. 6-12 years; for a review see Muris & Field, 2010).

Effects of the GLP-1 Agonist Exendin-4 on Intravenous Ethanol Self-Administration in Mice.

Background: Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to decrease ethanol (EtOH) drinking in rodent assays. The GLP-1 system also powerfully modulates food and fluid intake, gastrointestinal functions, and metabolism. To begin to understand the neurobiological mechanisms by which GLP-1 receptor ligands may be able to control EtOH intake, it is important to ascertain whether they can modulate the direct reinforcing effects of EtOH, without the confound of effects on ingestive behaviors generally.