High-dose vitamin D3 supplementation in pregnancy and risk of neurodevelopmental disorders in the children at age 10: A randomized clinical trial.

Background: Vitamin D deficiency in pregnancy may increase the risk of autism and attention deficit hyperactivity disorder (ADHD).

Objective: The objective of this study was to estimate the effect of vitamin D3 supplementation in pregnancy on risk of autism and ADHD.

Design: This randomized clinical trial was part of the COpenhagen Prospective Study on Neuro-PSYCHiatric Development (COPYCH) project nested within the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising a population-based sample of 700 healthy mother-child pairs enrolled at week 24 of pregnancy.

Early auditory processing dysfunction in schizophrenia: Mechanisms and implications.

Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive deficits are a key feature of the disorder and a primary cause of long-term disability. Over the past decades, significant literature has accumulated demonstrating impairments in early auditory perceptual processes in schizophrenia.

Dopamine Synthesis Capacity and GABA and Glutamate Levels Separate Antipsychotic-Naïve Patients With First-Episode Psychosis From Healthy Control Subjects in a Multimodal Prediction Model.

Background: Disturbances in presynaptic dopamine activity and levels of GABA (gamma-aminobutyric acid) and glutamate plus glutamine collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsychotic-naïve patients with first-episode psychosis from healthy control subjects.

Methods: We included 23 patients (mean age 22.

Scalability of the Positive and Negative Syndrome Scale in first-episode schizophrenia assessed by Rasch models.

Objective: Historically, assessment of the psychometric properties of the Positive and Negative Syndrome Scale (PANSS) has had several foci: (1) calculation of reliability indexes, (2) extraction of subdimensions from the scale, and (3) assessment of the validity of the total score. In this study, we aimed to examine the scalability and to assess the clinical performance of the 30-item PANSS total score as well as the scalability of a shorter version (PANSS-6) of the scale.

Methods: A composite data set of 1073 patients with first-episode schizophrenia or schizophrenia spectrum disorder was subjected to Rasch analysis of PANSS data from baseline and 4-6 weeks follow-up.

Dopaminergic Activity in Antipsychotic-Naïve Patients Assessed With Positron Emission Tomography Before and After Partial Dopamine D Receptor Agonist Treatment: Association With Psychotic Symptoms and Treatment Response.

Background: Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of F-DOPA to F-dopamine (k) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with first-episode psychosis. We further explored the effect of treatment with a partial dopamine D receptor agonist (aripiprazole) on k and dopamine synthesis capacity (DSC) determined by the four-parameter model and by the conventional tissue reference method.

The role of depression in the prediction of a "late" remission in first-episode psychosis: An analysis of the OPTiMiSE study.

Objective: The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES).

Methods: We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" remitters (i.e.

Association of neurocognitive functioning with sleep stage dissociation and REM sleep instability in medicated patients with schizophrenia.

Many patients with schizophrenia present with impaired cognitive functioning and sleep disturbances. Dissociated stages of sleep represent instability within distinct sleep regulatory cerebral networks. Previous studies found increased rates of rapid eye movement (REM) sleep abnormalities in patients with schizophrenia and a positive association with psychopathology.

Rasch analysis of the PANSS negative subscale and exploration of negative symptom trajectories in first-episode schizophrenia - data from the OPTiMiSE trial.

The observed heterogeneity in negative symptom treatment response may be partly attributable to inadequate measurement tools or limitations in methods of analysis. Previous Item Response Theory models of the Positive and Negative Syndrome Scale (PANSS) have only examined samples of chronic patients and with mixed results. We examined the scalability of the negative subscale embedded in the PANSS and subsequently explored negative symptom trajectories across four weeks of amisulpride treatment.

Persistent negative symptoms in recent-onset psychosis: Relationship to treatment response and psychosocial functioning.

Negative symptoms are associated with poor clinical and psychosocial outcome in schizophrenia. Their prevalence and identification in first-episode patients remains controversial. In a large cohort of patients in the early stage of schizophrenia, schizophreniform or schizoaffective disorder, we investigated, over the different phases of the OPTiMiSE trial (baseline, 4, 10 and 22 weeks of treatment), the prevalence of negative symptoms of moderate severity, unconfounded by depression and extrapyramidal symptoms at baseline.

Neurochemical evidence that cysteamine modulates amphetamine-induced dopaminergic neuronal activity in striatum by decreasing dopamine release: an in vivo microdialysis study in freely moving rats.

Elevated striatal dopamine release is thought to be one of the hallmarks of schizophrenia and correlates with its positive symptoms. Cysteamine (2-aminoethane-1-thiol), a compound naturally found in mammalian cells, inhibits amphetamine-induced dopamine-mediated increases in locomotor activity and behavior and blocks amphetamine-induced deficits in sensorimotor gating, suggesting cysteamine interaction with the dopaminergic system. Therefore, in the present study, we examined, in vivo, in the striatum of awake, freely moving rats the effect of cysteamine on the basal and amphetamine-induced release of dopamine, given also the fact that amphetamine-induced psychosis is a widely accepted animal model of schizophrenia.

Significant improvement in treatment resistant auditory verbal hallucinations after 5 days of double-blind, randomized, sham controlled, fronto-temporal, transcranial direct current stimulation (tDCS): A replication/extension study.

Background: Transcranial direct current stimulation (tDCS) is a potentially novel treatment for antipsychotic-resistant auditory verbal hallucinations (AVH) in schizophrenia. Nevertheless, results have been mixed across studies.

Methods: 89 schizophrenia/schizoaffective subjects (active: 47; Sham: 42) were randomized to five days of twice-daily 20-min active tDCS vs.

Sleep efficiency and neurophysiological patterns in middle-aged men are associated with cognitive change over their adult life course.

Disrupted sleep is a contributing factor to cognitive ageing, while also being associated with neurodegenerative disorders. Little is known, however, about the relation of sleep and the gradual cognitive changes over the adult life course. Sleep electroencephalogram (EEG) patterns are potential markers of the cognitive progress.

Auditory System Target Engagement During Plasticity-Based Interventions in Schizophrenia: A Focus on Modulation of N-Methyl-D-Aspartate-Type Glutamate Receptor Function.

Cognitive deficits are predictive of long-term social and occupational functional deficits in schizophrenia but are currently without gold-standard treatments. In particular, augmentation of auditory cortical neuroplasticity may represent a rate-limiting first step before addressing higher-order cognitive deficits. We review the rationale for N-methyl-d-aspartate-type glutamate receptor (NMDAR) modulators as treatments for auditory plasticity deficits in schizophrenia, along with potential serum and electroencephalographic target engagement biomarkers for NMDAR function.

Investigation of sleep spindle activity and morphology as predictors of neurocognitive functioning in medicated patients with schizophrenia.

Neurocognitive impairment is a trait marker of schizophrenia, but no effective treatment has yet been identified. Sleep spindle deficits have been associated with diminished sleep-dependent memory learning. We examined whether this link could be extended into various cognitive domains by investigating the association of a neurocognitive test battery (the Brief Assessment of Cognition in Schizophrenia) with sleep spindle activity and morphology.

Mortality and use of psychotropic medication in sleep apnoea patients: a population-wide register-based study.

Background: This study aimed to evaluate all-cause mortality in relation to the use of benzodiazepines, antidepressants and antipsychotics in obstructive sleep apnoea (OSA) patients and matched controls.

Methods: Patients with a diagnosis of OSA and no pre-index use of psychotropic medication (n = 38,735) were compared with control subjects (n = 75,941) matched by age, gender, marital status and community location. National register data were used to obtain information on diagnoses (the Danish National Patient Registry), mortality (the Central Person Register) and psychotropic medication use (the Danish Register on Medicinal Product Statistics).

N-methyl-d-aspartate-type glutamate receptor modulators and related medications for the enhancement of auditory system plasticity in schizophrenia.

Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to cognitive deficits in schizophrenia, particularly dysfunction in neuroplasticity, defined as reduced learning during training on exercises that place implicit, increasing demands on early sensory (auditory and visual) information processing. Auditory mismatch negativity (MMN) can be both a target engagement biomarker for the NMDAR and a proxy measure of neurophysiological plasticity. This review covers the evidence for using NMDAR modulator and related compounds for enhancement of cognition, with a particular focus on early auditory processing/plasticity.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Tocilizumab, An Interleukin-6 Receptor Antibody, For Residual Symptoms in Schizophrenia.

Evidence from preclinical, epidemiological, and human studies indicates that inflammation, and in particular elevated interleukin-6 (IL-6) activity, may be related to clinical manifestations and pathophysiology of schizophrenia. Furthermore, studies in preclinical models suggest that decreasing IL-6 activity may mitigate or reverse some of these deficits. The purpose of this trial was to test whether an IL-6 receptor antibody, tocilizumab, would improve residual positive and negative symptoms and cognitive deficits in schizophrenia.

Neurophysiological Effects of Bitopertin in Schizophrenia.

Purpose/background: Deficits in N-methyl-D-aspartate receptor (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia and are associated with impaired generation of event-related potential measures including auditory mismatch negativity. Parallel studies of the NMDAR agonist D-serine have suggested that sensitivity of these measures to glutamate-based interventions is related to symptomatic and cognitive response. Bitopertin is a selective inhibitor of glycine transport.

Mismatch negativity (MMN) to spatial deviants and behavioral spatial discrimination ability in the etiology of auditory verbal hallucinations and thought disorder in schizophrenia.

Unlabelled: Persistent auditory verbal hallucinations (AVH) in schizophrenia are increasingly tied to dysfunction at the level of auditory cortex. AVH may reflect in part misattribution of internally generated thoughts to external spatial locations. Here, we investigated the association between persistent AVH and spatial localization abilities assessed both behaviorally and by mismatch negativity (MMN) to location deviants.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia - a short version for primary care.

Objective: Schizophrenia is a severe mental disorder and many patients are treated in primary care settings. Apart from the pharmacological management of disease-associated symptoms, the detection and treatment of side effects is of the utmost importance in clinical practice. The purpose of this publication is to offer relevant evidence-based recommendations for the biological treatment of schizophrenia in primary care.

Managing Negative Symptoms of Schizophrenia: How Far Have We Come?

The specific efficacy of antipsychotics on negative symptoms is questionable, suggesting an urgent need for specific treatments for negative symptoms. This review includes studies published since 2014 with a primary or secondary focus on treating negative symptoms in schizophrenia. Special emphasis is given to recently published meta-analyses.

Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms.

Background: Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia. The efficacy of NMDAR agonists in the treatment of persistent symptoms of schizophrenia has been variable, potentially reflecting limitations in functional target engagement. We recently demonstrated significant improvement in auditory mismatch negativity (MMN) with once-weekly treatment with d-serine, a naturally occurring NMDAR glycine-site agonist.