A systematic review and risk of bias analysis of in vitro studies on trophoblast response to immunological triggers.

An increasing amount of evidence suggests that immune responses may affect trophoblast functioning, which in turn may play a role in gestational disorders and fetal development. This systematic review offers the first summary of in vitro studies on the trophoblast response to immunological triggers, in conjunction with a risk of bias analysis. A search in Pubmed and Embase yielded 110 relevant studies.

A systematic approach to identify gaps in neuroimmunology: TNF-α and fear learning deficits, a worked example.

Background: The pathophysiology of several neurodegenerative and neuropsychiatric disorders is linked to an altered immune system. However, it is often unclear how the immune system specifically affects these disorders since neuroimmune interactions are very complex. In this paper, we introduce an adjusted version of the adverse outcome pathway (AOP) approach from toxicology to the field of neuroimmunology.

The fetal programming effect of maternal immune activation (MIA) on the offspring's immune system.

The first 1000 days of life is a critical period of development in which adverse circumstances can have long-term consequences for the child's health. Maternal immune activation is associated with increased risk of neurodevelopmental disorders in the child. Aberrant immune responses have been reported in individuals with neurodevelopmental disorders.

The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies.

Rationale: Selective serotonin reuptake inhibitors (SSRIs) are the first choice of treatment for anxiety-like disorders. However, which aspects of anxiety are affected by SSRIs is not yet fully understood.

Objective: We aimed to systematically review the effect of six clinically effective SSRIs on four aspects of unconditioned anxiety: approach-avoidance behaviour (elevated plus maze), repetitive behaviour (marble burying), distress behaviour (ultrasonic vocalization), and activation of the autonomous nervous system (stress-induced hyperthermia).

Anxiolytic effects of endocannabinoid enhancing compounds: A systematic review and meta-analysis.

The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed the evidence for anxiety-reduction by compounds that facilitate endocannabinoid signaling in humans and animals. To identify areas of specific potential, effects of moderators were assessed.

The effect of SSRIs on fear learning: a systematic review and meta-analysis.

Rationale: Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. Fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well known.

Pharmacological modulation of conditioned fear in the fear-potentiated startle test: a systematic review and meta-analysis of animal studies.

Rationale And Objectives: Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear.

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool.

Background: Preclinical research suggests that cannabidiol (CBD) may have therapeutic potential in pathological anxiety. Dosing guidelines to inform future human studies are however lacking.

Aim: We aimed to predict the therapeutic window for anxiety-reducing effects of CBD in humans based on preclinical models.

Blood-brain barrier permeability following conventional photon radiotherapy - A systematic review and meta-analysis of clinical and preclinical studies.

Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood-brain barrier (BBB), resulting in an increased permeability into the surrounding brain parenchyma. Although this effect is generally acknowledged, it remains unclear how and to what extent different radiation schemes affect BBB integrity.

Cannabidiol enhancement of exposure therapy in treatment refractory patients with social anxiety disorder and panic disorder with agoraphobia: A randomised controlled trial.

Preclinical research suggests that enhancing CB1 receptor agonism may improve fear extinction. In order to translate this knowledge into a clinical application we examined whether cannabidiol (CBD), a hydrolysis inhibitor of the endogenous CB1 receptor agonist anandamide (AEA), would enhance the effects of exposure therapy in treatment refractory patients with anxiety disorders. Patients with panic disorder with agoraphobia or social anxiety disorder were recruited for a double-blind parallel randomised controlled trial at three mental health care centres in the Netherlands.

The poly(I:C)-induced maternal immune activation model; a systematic review and meta-analysis of cytokine levels in the offspring.

The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development in the offspring. Here, we present the first systematic review and meta-analysis on the effects of maternal poly(I:C) injection on immune mediators in the offspring and provide an openly accessible systematic map of the data including methodological characteristics. Pubmed and EMBASE were searched for relevant publications, yielding 45 unique papers that met inclusion criteria.

Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants.

Trace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-phenyl-iodotyramine (o-PIT), together with TAAR1-knockout (KO) mice.

Humans are animals, but are animals human enough? A systematic review and meta-analysis on interspecies differences in renal drug clearance.

Various animal models are used to study pharmacokinetics (PK) of drugs in development. Human renal clearance (CLr) should be predictable through interpolation from animal data by allometric scaling. Based on this premise, we quantified interspecies differences in CLr, and related them to drug properties.

Cannabidiol enhancement of exposure therapy in treatment refractory patients with phobias: study protocol of a randomized controlled trial.

Background: Phobic anxiety disorders are among the most prevalent psychiatric disorders and are burdensome in terms of loss of quality of life and work productivity. Evidence-based treatments are relatively successful in the majority of patients, especially exposure therapy. However, a substantial subset of patients fails to achieve or stay in remission.

Activation of somatodendritic 5-HT autoreceptors reduces the acquisition and expression of cued fear in the rat fear-potentiated startle test.

Rationale: Fear conditioning is an important factor in the etiology of anxiety disorders. Previous studies have demonstrated a role for serotonin (5-HT) receptors in fear conditioning. However, the relative contribution of somatodendritic 5-HT autoreceptors and post-synaptic 5-HT heteroreceptors in fear conditioning is still unclear.

Nicotine improves probabilistic reward learning in wildtype but not alpha7 nAChR null mutants, yet alpha7 nAChR agonists do not improve probabilistic learning.

Cognitive impairments, e.g., reward learning, are present in various psychiatric disorders and warrant treatment.

Cell reprogramming approaches in gene- and cell-based therapies for Parkinson's disease.

Degeneration of dopamine (DA) neurons in the substantia nigra pars compacta is the pathological hallmark of Parkinson's disease (PD). In PD multiple pathogenic mechanisms initiate and drive this neurodegenerative process, making the development of effective treatments challenging. To date, PD patients are primarily treated with dopaminergic drugs able to temporarily enhance DA levels, therefore relieving motor symptoms.

The contribution of contextual fear in the anxiolytic effect of chlordiazepoxide in the fear-potentiated startle test.

This study evaluated the extent to which a reduction in contextual fear contributes to the anxiolytic effect of benzodiazepines in the fear-potentiated startle response. To this end, chlordiazepoxide, an anxiolytic often used as positive control in preclinical drug studies, and zolpidem, known to have sedative properties and to be devoid of anxiolytic effects, were tested in two contexts: the same context as training had taken place and an alternative context. In addition, the level of muscle relaxation was assessed in a grip strength test.

No effect of sex and estrous cycle on the fear potentiated startle response in rats.

The prevalence of anxiety disorders is higher in women than in men. Yet preclinical studies on anxiety are mostly performed in male subjects. This may have limited our understanding of mechanisms contributing to anxiety disorders.

Blockade of dopamine D-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels.

Background: Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.

CRF but not glucocorticoid receptor antagonists reduce separation-induced distress vocalizations in guinea pig pups and CRF overexpressing mouse pups. A combination study with paroxetine.

Rationale: Given the large number of patients that does not respond sufficiently to currently available treatment for anxiety disorders, there is a need for improved treatment.

Objectives: We evaluated the anxiolytic effects of corticotropin releasing factor (CRF) receptor antagonists and glucocorticoid receptor (GR) antagonists in the separation-induced vocalization test in guinea pigs and transgenic mice with central CRF overexpression. Furthermore, we explored effects of these drugs when given in combination with a suboptimal dose of a selective serotonin re-uptake inhibitor (SSRI).

Lifelong disturbance of serotonin transporter functioning results in fear learning deficits: Reversal by blockade of CRF1 receptors.

The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety.

Back to the future of psychopharmacology: A perspective on animal models in drug discovery.

Psychopharmacology has had some bad publicity lately. Frankly, there have been some major problems along the way in developing new effective drugs for psychiatric disorders. After a prolonged period of high investments but low success rates, big pharmaceutical companies seem to retract their activities in the psychopharmacology field.