The Role of Neuroglia in the Development and Progression of Schizophrenia.

Schizophrenia is a complex heterogenous disorder thought to be caused by interactions between genetic and environmental factors. The theories developed to explain the etiology of schizophrenia have focused largely on the dysfunction of neurotransmitters such as dopamine, serotonin and glutamate with their receptors, although research in the past several decades has indicated strongly that other factors are also involved and that the role of neuroglial cells in psychotic disorders including schizophrenia should be given more attention. Although glia were originally thought to be present in the brain only to support neurons in a physical, metabolic and nutritional capacity, it has become apparent that these cells have a variety of important physiological roles and that abnormalities in their function may make significant contributions to the symptoms of schizophrenia.

The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction.

Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This paper reviews the literature relevant to the underlying neurobiology of psychosis. The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs.

Chronic pregabalin treatment protects against spreading depolarization and alters hippocampal synaptic characteristics in a model of familial hemiplegic migraine-type 1.

Familial hemiplegic migraine type-1 (FHM-1) is a form of migraine with aura caused by mutations in the P/Q-type (Cav2.1) voltage-gated calcium channel. Pregabalin, used clinically in the treatment of chronic pain and epilepsy, inhibits P/Q-type calcium channel activity and recent studies suggest that it may have potential for the treatment of migraine.

The Gut-Brain Axis and the Microbiome in Anxiety Disorders, Post-Traumatic Stress Disorder and Obsessive-Compulsive Disorder.

A large body of research supports the role of stress in several psychiatric disorders in which anxiety is a prominent symptom. Other research has indicated that the gut microbiome-immune system- brain axis is involved in a large number of disorders and that this axis is affected by various stressors. The focus of the current review is on the following stress-related disorders: generalized anxiety disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder and obsessivecompulsive disorder.

Molecular Pathways of the Therapeutic Effects of Ayahuasca, a Botanical Psychedelic and Potential Rapid-Acting Antidepressant.

Ayahuasca is a psychoactive brew traditionally used in indigenous and religious rituals and ceremonies in South America for its therapeutic, psychedelic, and entheogenic effects. It is usually prepared by lengthy boiling of the leaves of the bush and the mashed stalks of the vine in water. The former contains the classical psychedelic N,N-dimethyltryptamine (DMT), which is thought to be the main psychoactive alkaloid present in the brew.

The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies.

Hikikomori: A Society-Bound Syndrome of Severe Social Withdrawal.

Background: Hikikomori, a severe and often prolonged social withdrawal observed primarily in young people, was first described in Japan, but cases have now been reported in many other countries.

Methods: A review paper on hikikomori has been prepared following the literature searches in 3 databases. Search terms related to hikikomori included epidemiology, globalization, diagnosis, treatment, comorbidity, and COVID-19.

An Overview of the Involvement of D-Serine in Cognitive Impairment in Normal Aging and Dementia.

Dementia, of which Alzheimer's disease (AD) is the most common form, is characterized by progressive cognitive deterioration, including profound memory loss, which affects functioning in many aspects of life. Although cognitive deterioration is relatively common in aging and aging is a risk factor for AD, the condition is not necessarily a part of the aging process. The N-methyl-D-aspartate glutamate receptor (NMDAR) and its co-agonist D-serine are currently of great interest as potential important contributors to cognitive function in normal aging and dementia.

The Relationship Between the Gut Microbiome-Immune System-Brain Axis and Major Depressive Disorder.

Major depressive disorder (MDD) is a prominent cause of disability worldwide. Current antidepressant drugs produce full remission in only about one-third of MDD patients and there are no biomarkers to guide physicians in selecting the best treatment for individuals. There is an urgency to learn more about the etiology of MDD and to identify new targets that will lead to improved therapy and hopefully aid in predicting and preventing MDD.

Paraneoplastic and autoimmune encephalitis: Alterations of mood and emotion.

Autoimmune encephalitis often produces signs and symptoms that appear to be at the interface between neurology and psychiatry. Since psychiatric symptoms are often prominent, patients are often first seen in a psychiatric setting. Therefore it is important that psychiatrists, as well as neurologists, be able to recognize autoimmune encephalitis, a task that is often difficult.

Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine.

Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and neurochemical effects in addition to inhibition of MAO, and findings on these effects have contributed to a body of evidence indicating that PLZ also has neuroprotective/neurorescue properties. These attributes are reviewed in this paper and include catabolism to the active metabolite β-phenylethylidenehydrazine (PEH) and effects of PLZ and PEH on the GABA-glutamate balance in brain, sequestration of reactive aldehydes, and inhibition of primary amine oxidase.

A review of effects of calorie restriction and fasting with potential relevance to depression.

In recent years, there has been a great deal of interest in the effects of calorie reduction (calorie restriction) and fasting on depression. In the current paper, we have reviewed the literature in this area, with discussion of the possible neurobiological mechanisms involved in calorie restriction and intermittent fasting. Factors which may play a role in the effects of these dietary manipulations on health include changes involving free fatty acids, ketone bodies, neurotransmitters, cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), cytokines, orexin, ghrelin, leptin, reactive oxygen species and autophagy.

A dynamic role for dopamine receptors in the control of mammalian spinal networks.

Dopamine is well known to regulate movement through the differential control of direct and indirect pathways in the striatum that express D and D receptors respectively. The spinal cord also expresses all dopamine receptors; however, how the specific receptors regulate spinal network output in mammals is poorly understood. We explore the receptor-specific mechanisms that underlie dopaminergic control of spinal network output of neonatal mice during changes in spinal network excitability.

The Effects of a Ketogenic Diet on Sensorimotor Function in a Thoracolumbar Mouse Spinal Cord Injury Model.

Spinal cord injury and peripheral nerve injuries are traumatic events that greatly impact quality of life. One factor that is being explored throughout patient care is the idea of diet and the role it has on patient outcomes. But the effects of diet following neurotrauma need to be carefully explored in animal models to ensure that they have beneficial effects.

Neuroimmunological antibody-mediated encephalitis and implications for diagnosis and therapy in neuropsychiatry.

The past decade has seen a surge of reports and investigations into cases of autoimmune-mediated encephalitis. The increasing recognition of these disorders is especially of relevance to the fields of neurology and psychiatry. Autoimmune encephalitis involves antibodies against synaptic receptors, neuronal cell surface proteins and intracellular targets.

Regulation of Diabetes: a Therapeutic Strategy for Alzheimer's Disease?

Accumulated evidence suggests that sporadic cases of Alzheimer's disease (AD) make up more than 95% of total AD patients, and diabetes has been implicated as a strong risk factor for the development of AD. Diabetes shares pathological features of AD, such as impaired insulin signaling, increased oxidative stress, increased amyloid-beta (Aβ) production, tauopathy and cerebrovascular complication. Due to shared pathologies between the two diseases, anti-diabetic drugs may be a suitable therapeutic option for AD treatment.

Gabapentin increases expression of δ subunit-containing GABA receptors.

Background: Gabapentin is a structural analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Its anticonvulsant, analgesic and anxiolytic properties suggest that it increases GABAergic inhibition; however, the molecular basis for these effects is unknown as gabapentin does not directly modify GABA type A (GABA) receptor function, nor does it modify synaptic inhibition. Here, we postulated that gabapentin increases expression of δ subunit-containing GABA (δGABA) receptors that generate a tonic inhibitory conductance in multiple brain regions including the cerebellum and hippocampus.

Age- and sex-dependent profiles of APP fragments and key secretases align with changes in despair-like behavior and cognition in young APPSwe/Ind mice.

Biological sex exerts distinct influences on brain levels of the β-amyloid (Aβ) peptide in both clinical depression and Alzheimer disease (AD), yet studies in animal models focus primarily on males. We examined behavioral 'despair'/depression (using the tail-suspension test) and memory (using the novel object recognition task) in J20 (hAPP) mice. Three month-old male (but not female) J20 mice exhibited less despair-like behavior, but more evidence of cognitive deficits.

D-Serine: Potential Therapeutic Agent and/or Biomarker in Schizophrenia and Depression?

D-Serine is a potent co-agonist at the NMDA glutamate receptor and has been the object of many preclinical studies to ascertain the nature of its metabolism, its regional and cellular distribution in the brain, its physiological functions and its possible clinical relevance. The enzymes involved in its formation and catabolism are serine racemase (SR) and D-amino acid oxidase (DAAO), respectively, and manipulations of the activity of those enzymes have been useful in developing animal models of schizophrenia and in providing clues to the development of potential new antipsychotic strategies. Clinical studies have been conducted in schizophrenia patients to evaluate body fluid levels of D-serine and/or to use D-serine alone or in combination with antipsychotics to determine its effectiveness as a therapeutic agent.

Fluoxetine and its metabolite norfluoxetine induce microglial apoptosis.

Inflammatory insult to the central nervous system (CNS) can lead to development of depression, and subsequently depression is the most frequent psychiatric comorbidity following ischemic stroke, often limiting recovery and rehabilitation in patients. The initiators of inflammatory pathways in the CNS are microglia activated in response to acute ischemic stress, and anti-depressants have been shown to have anti-inflammatory effects in the CNS, promoting neuronal survival following ischemic insult. We have previously shown that the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and citalopram promote neuronal survival after oxygen-glucose deprivation, an in vitro model of ischemia, by attenuating the release of glutamate and D-serine from activated microglia.

Multidimensional Connectomics and Treatment-Resistant Schizophrenia: Linking Phenotypic Circuits to Targeted Therapeutics.

Schizophrenia is a very complex syndrome that involves widespread brain multi-dysconnectivity. Neural circuits within specific brain regions and their links to corresponding regions are abnormal in the illness. Theoretical models of dysconnectivity and the investigation of connectomics and brain network organization have been examined in schizophrenia since the early nineteenth century.

Effect of voluntary wheel running on neuroactive steroid levels in murine experimental autoimmune encephalomyelitis.

Increasing evidence from both clinical and animal research has implicated changes in neuroactive steroids (rapid acting steroids that act as allosteric modulators at NMDA and/or GABA-A receptors) in multiple sclerosis. These changes have been linked to clinical differences in disease severity, prevention of disease development, as well as the disease state (relapsing vs progressive) in patients with multiple sclerosis. Previous research has also linked changes in neuroactive steroid levels to the beneficial effects of exercise in certain disorders such as traumatic brain injury and post-traumatic stress disorder.

Glycosylation States of Pre- and Post-synaptic Markers of 5-HT Neurons Differ With Sex and 5-HTTLPR Genotype in Cortical Autopsy Samples.

The serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) is thought to alter 5-HT signaling and contribute to behavioral and cognitive phenotypes in depression as well as Alzheimer disease (AD). We explored how well the short () and long () alleles of the 5-HTTLPR align with serotoninergic indices in 60 autopsied cortical samples from early-onset AD/EOAD and late-onset AD/LOAD donors, and age- and sex-matched controls. Stratifying data by either diagnosis-by-genotype or by sex-by-genotype revealed that the donor's 5-HTTLPR genotype, i.