Introducing < b > < i > Complex Psychiatry < /i > < /b >
Complex Psychiatry (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - May 13, 2020 Category: Neuroscience Source Type: research
Genomic Chaos Begets Psychiatric Disorder
The processes that created the primordial genome are inextricably linked to current day vulnerability to developing a psychiatric disorder as summarized in this review article. Chaos and dynamic forces including duplication, transposition, and recombination generated the protogenome. To survive early stages of genome evolution, self-organization emerged to curb chaos. Eventually, the human genome evolved through a delicate balance of chaos/instability and organization/stability. However, recombination coldspots, silencing of transposable elements, and other measures to limit chaos also led to retention of variants that inc...
Source: Molecular Neuropsychiatry - April 20, 2020 Category: Neuroscience Source Type: research
FMRP and CYFIP1 at the Synapse and Their Role in Psychiatric Vulnerability
There is increasing awareness of the role genetic risk variants have in mediating vulnerability to psychiatric disorders such as schizophrenia and autism. Many of these risk variants encode synaptic proteins, influencing biological pathways of the postsynaptic density and, ultimately, synaptic plasticity. Fragile-X mental retardation 1 (FMR1) and cytoplasmic fragile-X mental retardation protein (FMRP)-interacting protein 1 (CYFIP1) contain 2 such examples of highly penetrant risk variants and encode synaptic proteins with shared functional significance. In this review, we discuss the biological actions of FMRP and CYFIP1, ...
Source: Molecular Neuropsychiatry - March 2, 2020 Category: Neuroscience Source Type: research
Using Chronobiological Phenotypes to Address Heterogeneity in Bipolar Disorder
Bipolar disorder (BD) is a neuropsychiatric mood disorder characterized by recurrent episodes of mania and depression in addition to disruptions in sleep, energy, appetite, and cognitive functions-rhythmic behaviors that typically change on daily cycles. BD symptoms can also be provoked by seasonal changes, sleep, and/or circadian disruption, indicating that chronobiological factors linked to the circadian clock may be a common feature in the disorder. Research indicates that BD exists on a clinical spectrum, with distinct subtypes often intersecting with other psychiatric disorders. This heterogeneity has been a major cha...
Source: Molecular Neuropsychiatry - February 19, 2020 Category: Neuroscience Source Type: research
The Role of PTEN in Neurodevelopment
PTEN is a lipid and protein phosphatase that regulates cell growth and survival. Mutations to PTEN are highly penetrant for autism spectrum disorder (ASD). Here, we briefly review the evidence linking PTEN mutations to ASD and the mouse models that have been used to study the role of PTEN in neurodevelopment. We then focus on the cellular phenotypes associated with PTEN loss in neurons, highlighting the role PTEN plays in neuronal proliferation, migration, survival, morphology, and plasticity.Mol Neuropsychiatry 2019;5(suppl 1):60 –71 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - January 21, 2020 Category: Neuroscience Source Type: research
Genome-Wide Association Study of Sleep Disturbances in Depressive Disorders
Sleep disturbance affects about 75% of depressed individuals and is associated with poorer patient outcomes. The genetics in this field is an emerging area of research. Thus far, only core circadian genes have been examined in this context. We expanded on this by performing a genome-wide association study (GWAS) followed by a preplanned hypothesis-driven analysis with 27 genes associated with the biology of sleep. All participants were diagnosed by their referring physician, completed the Beck Depression Inventory (BDI), and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale at baseline. Our phenotype consisted...
Source: Molecular Neuropsychiatry - January 7, 2020 Category: Neuroscience Source Type: research
Estimating the Potential Impact of < b > < i > CYP2C19 < /i > < /b > and < b > < i > CYP2D6 < /i > < /b > Genetic Testing on Protocol-Based Care for Depression in Canada and the United States
The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) algorithm is the most recognized protocol-based care approach for moderate to severe depression. However, its implementation results in one-third of individuals receiving modest to no symptom remission. One possible explanation is the inter-individual differences in antidepressant metabolism due to CYP2C19 andCYP2D6genetic variation. Here, we aimed to determine the potential benefit of pairingCYP2C19 andCYP2D6testing with the five-step STAR*D algorithm. To estimate the proportion of individuals that could benefit fromCYP2C19 andCYP2D6 testing, we simulated...
Source: Molecular Neuropsychiatry - November 26, 2019 Category: Neuroscience Source Type: research
Contents Vol. 5, 2019
Mol Neuropsychiatry 2019;5:I –VI (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - October 17, 2019 Category: Neuroscience Source Type: research
DNA Variant in the < b > < i > RPGRIP1L < /i > < /b > Gene Influences Alternative Splicing
In this study we identify a common variant inRPGRIP1L, rs7203525, that influences alternative splicing, increasing the inclusion of exon 20 ofRPGRIP1L. We detected this alternative splicing association in human postmortem brain tissue samples and, using a minigene assay combined with in vitro mutagenesis, confirmed that the alternative splicing is attributable to the alleles of this variant. The predominateRPGRIP1L isoform expressed in adult brains does not contain exon 20; thus, a shift to include this exon may impact brain function.Mol Neuropsychiatry 2019;5(suppl 1):97 –105 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - September 25, 2019 Category: Neuroscience Source Type: research
Editorial
Mol Neuropsychiatry 2019;5:177 (Source: Molecular Neuropsychiatry)
Source: Molecular Neuropsychiatry - September 25, 2019 Category: Neuroscience Source Type: research
Research Domain Criteria: Strengths, Weaknesses, and Potential Alternatives for Future Psychiatric Research
The Research Domain Criteria (RDoC) paradigm was launched 10 years ago as a superior approach for investigation of mental illness. RDoC conceptualizes normal human behavior, emotion, and cognition as dimensional, with mental illnesses as dimensional extremes. We suggest that RDoC may have value for understanding normal human psychology and some conditions plausibly construed as extremes of normal variation. By contrast, for the most serious of mental illnesses, including dementia, autism, schizophrenia, and bipolar disorder, we argue that RDoC is conceptually flawed. RDoC conflates variation along dimensional axes of norma...
Source: Molecular Neuropsychiatry - August 13, 2019 Category: Neuroscience Source Type: research
Association of Myoinositol Transporters with Schizophrenia and Bipolar Disorder: Evidence from Human and Animal Studies
Evidence from animal and human studies has linkedmyo-inositol (MI) with the pathophysiology and/or treatment of psychiatric disorders such as schizophrenia and bipolar disorder. However, there is still controversy surrounding the definitive role of MI in these disorders. Given that brain MI is differentially regulated by three transporters – SMIT1, SMIT2 and/or HMIT (encoded by the genes:SLC5A3, SLC5A11,andSLC2A13, respectively) – we used available datasets to describe the distribution in mouse and human brain of the different MI transporters and to examine changes in mRNA expression of these transporters in patients w...
Source: Molecular Neuropsychiatry - August 8, 2019 Category: Neuroscience Source Type: research
The Genetic Relevance of Human Induced Pluripotent Stem Cell-Derived Microglia to Alzheimer ’s Disease and Major Neuropsychiatric Disorders
Microglia are the primary innate immune cell type in the brain that have been implicated in the pathogenesis of several neurodegenerative and neuropsychiatric disorders, most notably Alzheimer ’s disease (AD) and schizophrenia. Microglia generated from human induced pluripotent stem cells (hiPSCs) represent a promising in vitro cellular model for studying the neuroimmune interactions involved in these disorders. Among several methods of generating hiPSC-derived microglia (iMG) – var ying in duration and resultant purity – a recent protocol by Brownjohn et al. [Stem Cell Reports. 2018 Apr;10(4):1294–307] is partic...
Source: Molecular Neuropsychiatry - July 23, 2019 Category: Neuroscience Source Type: research
Regulation and Function of Activity-Dependent Homer in Synaptic Plasticity
Alterations in synaptic signaling and plasticity occur during the refinement of neural circuits over the course of development and the adult processes of learning and memory. Synaptic plasticity requires the rearrangement of protein complexes in the postsynaptic density (PSD), trafficking of receptors and ion channels and the synthesis of new proteins. Activity-induced short Homer proteins, Homer1a and Ania-3, are recruited to active excitatory synapses, where they act as dominant negative regulators of constitutively expressed, longer Homer isoforms. The expression of Homer1a and Ania-3 initiates critical processes of PSD...
Source: Molecular Neuropsychiatry - May 23, 2019 Category: Neuroscience Source Type: research
Strategies for Treatment-Resistant Depression: Lessons Learned from Animal Models
Around 300 million individuals are affected by major depressive disorder (MDD) in the world. Despite this high number of affected individuals, more than 50% of patients do not respond to antidepressants approved to treat MDD. Patients with MDD that do not respond to 2 or more first-line antidepressant treatments are considered to have treatment-resistant depression (TRD). Animal models of depression are important tools to better understand the pathophysiology of MDD as well as to help in the development of novel and fast antidepressants for TRD patients. This review will emphasize some discovery strategies for TRD from stu...
Source: Molecular Neuropsychiatry - May 21, 2019 Category: Neuroscience Source Type: research
