Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce.

Objectives: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders.

Behavioural phenotyping of thunder mice with a hypomorphic mutation of heterogeneous nuclear ribonuclear protein L-like (hnRNPLL) and reduced T cell function.

Heterogeneous nuclear ribonuclear protein l-like (hnRNPLL) is an RNA binding protein that regulates alternative splicing of mRNA and is abundantly expressed in memory T lymphocytes of the immune system and in the brain. A hypomorphic allele of the gene encoding hnRNPLL (Hnrpll) selectively reduces T cell accumulation in lymphoid tissues, but little is known about its effects in the brain. Therefore, we exposed Hnrpll mice to a test battery with relevance for a range of psychiatric illnesses.

Pyrrolidine dithiocarbamate activates the Nrf2 pathway in astrocytes.

Background: Endogenous defense against oxidative stress is controlled by nuclear factor erythroid 2-related factor 2 (Nrf2). The normal compensatory mechanisms to combat oxidative stress appear to be insufficient to protect against the prolonged exposure to reactive oxygen species during disease. Counterbalancing the effects of oxidative stress by up-regulation of Nrf2 signaling has been shown to be effective in various disease models where oxidative stress is implicated, including Alzheimer's disease.

Investigating facial affect processing in psychosis: a study using the Comprehensive Affective Testing System.

Facial affect processing (FAP) deficits in schizophrenia (SZ) and bipolar disorder (BD) have been widely reported; although effect sizes vary across studies, and there are limited direct comparisons of the two groups. Further, there is debate as to the influence of both psychotic and mood symptoms on FAP. This study aimed to address these limitations by recruiting groups of psychosis patients with either a diagnosis of SZ or BD and comparing them to healthy controls (HC) on a well validated battery of four FAP subtests: affect discrimination, name affect, select affect and match affect.

Investigating affective prosody in psychosis: a study using the Comprehensive Affective Testing System.

Affective prosody is substantially impaired in schizophrenia, yet little is known about affective prosody in bipolar disorder (BD). The aim of this study was to examine affective prosody performance in schizophrenia, schizoaffective disorder and BD on a newly released standardised assessment to further our understanding of BD performance. Fifty-four schizophrenia, 11 schizoaffective and 43 BD patients were compared with 112 healthy controls (HC) on four affective prosody subtests of the Comprehensive Affective Testing System (CATS).

Quetiapine monotherapy in bipolar II depression: combined data from four large, randomized studies.

Background: Despite being present in up to 1% of the population, few controlled trials have examined the efficacy of treatments for bipolar II depression. Pooled data are presented from four placebo-controlled studies (BOLDER I [5077US/0049] and II [D1447C00135]; EMBOLDEN I [D1447C00001] and II [D1447C00134]) that evaluated the efficacy of quetiapine monotherapy for depressive episodes in patients with bipolar II disorder.

Methods: All studies included an 8-week, double-blind treatment phase in which patients were randomly assigned to treatment with quetiapine 300 mg/day, quetiapine 600 mg/day, or placebo.

AMPA receptor expression is increased post-mortem samples of the anterior cingulate from subjects with major depressive disorder.

Background: Glutamate is thought to be involved in the pathophysiology of major depressive disorder and bipolar disorder; however, the molecular changes underlying abnormal glutamatergic signalling remain poorly understood. Whilst previous studies have suggested that the NMDA receptor may be involved in the pathophysiology of mood disorders, it is unclear whether the non-NMDA receptors are also involved. Therefore, we sought to examine whether the expression of the non-NMDA, ionotropic glutamate receptors, AMPA receptor and kainate receptor, is altered in mood disorders.

The role of estrogen and testosterone in female rats in behavioral models of relevance to schizophrenia.

Rationale: The sex steroid hormone, estrogen, may play a protective role in schizophrenia. We previously found that estrogen treatment inhibited serotonin-1A (5-HT(1A)) and dopamine D(2) receptor-mediated disruptions of prepulse inhibition (PPI), a measure of sensorimotor gating which is deficient in schizophrenia.

Objectives: The present study aimed to further explore the role of sex steroid hormones in schizophrenia.

N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and d-amphetamine-treated rats: relevance to schizophrenia and bipolar disorder.

Oxidative stress and reduced brain levels of glutathione have been implicated in schizophrenia and bipolar disorder. N-acetyl cysteine (NAC) is a precursor of glutathione and has additional effects on glutamate neurotransmission, neurogenesis and inflammation. While NAC treatment has shown benefits in both schizophrenia and bipolar disorder, the mechanisms of action are largely unknown.

Hippocampal serotonin depletion facilitates the enhancement of prepulse inhibition by risperidone: possible role of 5-HT(2C) receptors in the dorsal hippocampus.

Abnormalities in both the hippocampal region and in serotonergic transmission are evident in patients with schizophrenia. We previously found that rats with serotonergic lesions targeting the dorsal hippocampus show altered psychotropic drug-induced hyperlocomotion and prepulse inhibition (PPI), behavioural paradigms relevant to aspects of schizophrenia. The present study explored the effect of serotonin depletion (>70%) along the dorsoventral axis of the hippocampus, or of partial serotonin depletion (∼50%) in the ventral hippocampus, on PPI modulation by acute antipsychotic drug treatment.

The neurobiology of APOE in schizophrenia and mood disorders.

APOE is a major component of several lipoproteins. In addition to its role as a lipid transport protein APOE also serves a dual role as a glial derived, synaptic signalling molecule and thought to play an important role in synaptic plasticity and cognition. Polymorphisms within the APOE gene have been associated with the incidence of Alzheimer's disease.

Differential effect of amphetamine on c-fos expression in female aromatase knockout (ArKO) mice compared to wildtype controls.

Estrogen may be involved in psychosis by an interaction with central dopaminergic activity. Aromatase knockout mice are unable to produce estrogen and have been shown to display altered behavioural responses and effects of the dopamine releaser, amphetamine. This study investigates the effect of gonadal status on amphetamine-induced c-fos expression in the brains of female aromatase knockout and wildtype mice.

Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder.

Aberrant regulation of synaptic function is thought to play a role in the aetiology of psychiatric disorders, including schizophrenia and bipolar disorder. Normal neurotransmitter release is dependent on a complex group of presynaptic proteins that regulate synaptic vesicle docking, membrane fusion and fission, including synaptophysin, syntaxin, synaptosomal-associated protein-25 (SNAP-25), vesicle-associated membrane protein (VAMP), alpha-synuclein and dynamin I. In addition, structural and signalling proteins such as neural cell adhesion molecule (NCAM) maintain the integrity of the synapse.

Use of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to investigate group and gender differences in schizophrenia and bipolar disorder.

Objective: Gender differences exist in schizophrenia and bipolar disorder (BD), therefore the aim of the present study was to clarify the role of gender in cognitive deficits in these disorders.

Methods: Cognitive performance was examined in schizophrenia (24M : 14F) and BD (16M : 24F) patients compared with age-, IQ- and gender-matched control participants (21M : 22F). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess five cognitive domains: immediate memory/learning, visuospatial ability, language, attention, and delayed memory, which are summed to provide a Total score.

Amyloid PET Ligands for Dementia.

The progressive nature of neurodegeneration suggests an age-dependent process that ultimately leads to synaptic failure and neuronal damage in cortical areas of the brain critical for memory and higher mental functions. The increasing age of the population in developed countries suggests that, if unchecked, these disorders will become increasingly prevalent. In the absence of specific biologic markers, direct pathologic examination of brain tissue still is the only definitive method for establishing a diagnosis of Alzheimer disease (AD) and other types of dementia.

Low Density Lipoprotein Receptor-Related Protein and Apolipoprotein E Expression is Altered in Schizophrenia.

Our recent microarray study reported altered mRNA expression of several low density lipoprotein receptor-related proteins (LRP) associated with the first 4 years following diagnosis with schizophrenia. Whilst this finding is novel, apolipoprotein E (APOE), which mediates its activity through LRPs, has been reported by several studies to be altered in brains of subjects with schizophrenia. We used qPCR to measure the expression of LRP2, LRP4, LRP6, LRP8, LRP10 and LRP12 mRNA in Brodmann's area (BA) 46 of the dorsolateral prefrontal cortex in 15 subjects with short duration of illness schizophrenia (SDS) and 15 pair matched controls.

Modeling the positive symptoms of schizophrenia in genetically modified mice: pharmacology and methodology aspects.

In recent years, there have been huge advances in the use of genetically modified mice to study pathophysiological mechanisms involved in schizophrenia. This has allowed rapid progress in our understanding of the role of several proposed gene mechanisms in schizophrenia, and yet this research has also revealed how much still remains unresolved. Behavioral studies in genetically modified mice are reviewed with special emphasis on modeling psychotic-like behavior.

A serial analysis of gene expression profile of the Alzheimer's disease Tg2576 mouse model.

Serial analysis of gene expression (SAGE), a technique that allows for the simultaneous detection of expression levels of the entire genome without a priori knowledge of gene sequences, was used to examine the transcriptional expression pattern of the Tg2576 mouse model of Alzheimer's disease (AD). Pairwise comparison between the Tg2576 and nontransgenic SAGE libraries identified a number of differentially expressed genes in the Tg2576 SAGE library, some of which were not previously revealed by the microarray studies. Real-time PCR was used to validate a panel of genes selected from the SAGE analysis in the Tg2576 mouse brain, as well as the hippocampus and temporal cortex of sporadic AD and normal age-matched controls.

Targeting the progression of Parkinson's disease.

By the time a patient first presents with symptoms of Parkinson's disease at the clinic, a significant proportion (50-70%) of the cells in the substantia nigra (SN) has already been destroyed. This degeneration progresses until, within a few years, most of the cells have died. Except for rare cases of familial PD, the initial trigger for cell loss is unknown.

A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice.

The tripeptide, glutathione (gamma-glutamylcysteinylglycine) is the primary endogenous free radical scavenger in the human body. When glutathione (GSH) levels are reduced there is an increased potential for cellular oxidative stress, characterised by an increase and accruement of reactive oxygen species (ROS). Oxidative stress has been implicated in the pathology of schizophrenia and bipolar disorder.

Serotonergic lesions of the dorsal hippocampus differentially modulate locomotor hyperactivity induced by drugs of abuse in rats: implications for schizophrenia.

Rationale: Psychotomimetic drug-induced locomotor hyperactivity is a widely used animal model of psychotic states, such as in schizophrenia. We previously found that serotonergic lesions of the dorsal, but not ventral, hippocampus in rats result in enhanced phencyclidine-induced locomotor hyperactivity.

Objectives: The objective of this study was to investigate the effect of serotonin depletion in the dorsal and ventral hippocampus on hyperlocomotion induced by ketamine, cocaine, 3,4-methylenedioxymethampethamine (MDMA), methamphetamine, and D: -amphetamine.

Paradoxical condensation of copper with elevated beta-amyloid in lipid rafts under cellular copper deficiency conditions: implications for Alzheimer disease.

Redox-active copper is implicated in the pathogenesis of Alzheimer disease (AD), beta-amyloid peptide (Abeta) aggregation, and amyloid formation. Abeta.copper complexes have been identified in AD and catalytically oxidize cholesterol and lipid to generate H2O2 and lipid peroxides.

Executive functioning in schizophrenia: a thorough examination of performance on the Hayling Sentence Completion Test compared to psychiatric and non-psychiatric controls.

Background: The current study examined executive functioning in schizophrenia by assessing response initiation and suppression in a group of schizophrenia patients, and drawing comparisons with psychiatric and non-psychiatric control groups.

Method: The Hayling Sentence Completion Test was used as a measure of executive functioning and was completed by 39 schizophrenia patients, 40 bipolar disorder patients and 44 healthy control participants. Outcome measures included response initiation and response suppression latency and error rate.

beta-Amyloid as a molecular therapeutic target in Alzheimer's disease.

Alzheimer's disease is the most common form of dementia, primarily affecting individuals during or after their sixth decade of life. Despite decades of research, there are still no effective disease-modifying drugs available to treat this neurodegenerative disorder. Current FDA-approved medications primarily offer symptomatic relief and are based upon known neurotransmitter deficits.