Multi-omics data integration methods and their applications in psychiatric disorders.

To study mental illness and health, in the past researchers have often broken down their complexity into individual subsystems (e.g., genomics, transcriptomics, proteomics, clinical data) and explored the components independently.

The Relationship Between Frontostriatal Connectivity and Striatal Dopamine Function in Schizophrenia: An 18F-DOPA PET and Diffusion Tensor Imaging Study in Treatment Responsive and Resistant Patients.

Objective: Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC).

Moderate excess alcohol consumption and adverse cardiac remodelling in dilated cardiomyopathy.

Objective: The effect of moderate excess alcohol consumption is widely debated and has not been well defined in dilated cardiomyopathy (DCM). There is need for a greater evidence base to help advise patients. We sought to evaluate the effect of moderate excess alcohol consumption on cardiovascular structure, function and outcomes in DCM.

Dopamine dysregulation in psychotic relapse after antipsychotic discontinuation: an [F]DOPA and [C]raclopride PET study in first-episode psychosis.

Although antipsychotic drugs are effective for relieving the psychotic symptoms of first-episode psychosis (FEP), psychotic relapse is common during the course of the illness. While some FEPs remain remitted even without medication, antipsychotic discontinuation is regarded as the most common risk factor for the relapse. Considering the actions of antipsychotic drugs on presynaptic and postsynaptic dopamine dysregulation, this study evaluated possible mechanisms underlying relapse after antipsychotic discontinuation.

Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence.

Background: Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2).

Frontostriatal functional connectivity and striatal dopamine synthesis capacity in schizophrenia in terms of antipsychotic responsiveness: an [F]DOPA PET and fMRI study.

Background: Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine.

The relationship between dopamine receptor blockade and cognitive performance in schizophrenia: a [C]-raclopride PET study with aripiprazole.

Aripiprazole's effects on cognitive function in patients with schizophrenia are unclear because of the difficulty in disentangling specific effects on cognitive function from secondary effects due to the improvement in other schizophrenic symptoms. One approach to address this is to use an intermediate biomarker to investigate the relationship between the drug's effect on the brain and change in cognitive function. This study aims to investigate aripiprazole's effect on working memory by determining the correlation between dopamine D2/3 (D2/3) receptor occupancy and working memory of patients with schizophrenia.

Peroxiredoxin as a functional endogenous antioxidant enzyme in pronuclei of mouse zygotes.

Antioxidant mechanisms to adequately moderate levels of endogenous reactive oxygen species (ROS) are important for oocytes and embryos to obtain and maintain developmental competence, respectively. Immediately after fertilization, ROS levels in zygotes are elevated but the antioxidant mechanisms during the maternal-to-zygotic transition (MZT) are not well understood. First, we identified peroxiredoxin 1 (PRDX1) and PRDX2 by proteomics analysis as two of the most abundant endogenous antioxidant enzymes eliminating hydrogen peroxide (HO).

The effects of serotonin modulation on medial prefrontal connectivity strength and stability: A pharmacological fMRI study with citalopram.

Background: Static and dynamic functional connectivity are being increasingly used to measure the effects of disease and a range of different interventions on brain networks. While preliminary evidence suggests that static connectivity can be modulated by chronic antidepressants administration in healthy individuals and in major depression, much less is known about the acute effects of antidepressants especially on dynamic functional connectivity changes. Here we examine acute effects of antidepressants on dynamic functional connectivity within the default mode network.

LEFTY2 inhibits endometrial receptivity by downregulating Orai1 expression and store-operated Ca entry.

Unlabelled: Early embryo development and endometrial differentiation are initially independent processes, and synchronization, imposed by a limited window of implantation, is critical for reproductive success. A putative negative regulator of endometrial receptivity is LEFTY2, a member of the transforming growth factor (TGF)-β family. LEFTY2 is highly expressed in decidualizing human endometrial stromal cells (HESCs) during the late luteal phase of the menstrual cycle, coinciding with the closure of the window of implantation.

Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.

Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man.

The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for Cigarettes in Dependent and Occasional Cigarette Smokers.

Background: Dopaminergic functioning is thought to play critical roles in both motivation and addiction. There is preliminary evidence that dopamine agonists reduce the motivation for cigarettes in smokers. However, the effects of pramipexole, a dopamine D3 receptor preferring agonist, have not been investigated.

Cannabis Dampens the Effects of Music in Brain Regions Sensitive to Reward and Emotion.

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms.

Imaging vulnerable plaques by targeting inflammation in atherosclerosis using fluorescent-labeled dual-ligand microparticles of iron oxide and magnetic resonance imaging.

Objective: Identification of patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and a prelude to clinical sequelae. There are currently no clinical imaging tools to assess the inflammatory activity within plaques.

Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy.

Aims: Dilated cardiomyopathy (DCM) is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS) to assess the contribution of missense variants to sporadic DCM.

Methods And Results: 116,855 single nucleotide variants (SNVs) were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry.

Test-retest reproducibility of quantitative binding measures of [C]Ro15-4513, a PET ligand for GABA receptors containing alpha5 subunits.

Introduction: Alteration of γ-aminobutyric acid "A" (GABA) receptor-mediated neurotransmission has been associated with various neurological and psychiatric disorders. [C]Ro15-4513 is a PET ligand with high affinity for α5-subunit-containing GABA receptors, which are highly expressed in limbic regions of the human brain (Sur et al., 1998).

N-terminal acetylation promotes synaptonemal complex assembly in C. elegans.

N-terminal acetylation of the first two amino acids on proteins is a prevalent cotranslational modification. Despite its abundance, the biological processes associated with this modification are not well understood. Here, we mapped the pattern of protein N-terminal acetylation in Caenorhabditis elegans, uncovering a conserved set of rules for this protein modification and identifying substrates for the N-terminal acetyltransferase B (NatB) complex.

Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [F]DOPA PET Study.

Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia.

HMGB2 holds the key to the senescence-associated secretory phenotype.

The senescence-associated secretory phenotype (SASP) is a hallmark of senescence with an important physiological impact, but how it is established is unclear. In this issue, Aird et al. (2016.

PPARγ-coactivator-1α gene transfer reduces neuronal loss and amyloid-β generation by reducing β-secretase in an Alzheimer's disease model.

Current therapies for Alzheimer's disease (AD) are symptomatic and do not target the underlying Aβ pathology and other important hallmarks including neuronal loss. PPARγ-coactivator-1α (PGC-1α) is a cofactor for transcription factors including the peroxisome proliferator-activated receptor-γ (PPARγ), and it is involved in the regulation of metabolic genes, oxidative phosphorylation, and mitochondrial biogenesis. We previously reported that PGC-1α also regulates the transcription of β-APP cleaving enzyme (BACE1), the main enzyme involved in Aβ generation, and its expression is decreased in AD patients.

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses.

Rationale: Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence.

Objectives: The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning.

Regional Differences in Serotonin Transporter Occupancy by Escitalopram: An [C]DASB PK-PD Study.

Background And Objective: Escitalopram is one of the most commonly prescribed selective serotonin reuptake inhibitors (SSRIs). It is thought to act by blocking the serotonin transporter (SERT). However, its dose-SERT occupancy relationship is not well known, so it is not clear what level of SERT blockade is achieved by currently approved doses.