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Introducing Complex Psychiatry Mol. Neuropsychiatry Pub Date : 2020-05-14 Joel Gelernter, Renato Polimanti
Complex Psychiatry
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Genomic Chaos Begets Psychiatric Disorder Mol. Neuropsychiatry Pub Date : 2020-04-21 Donard S. Dwyer
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
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FMRP and CYFIP1 at the Synapse and Their Role in Psychiatric Vulnerability Mol. Neuropsychiatry Pub Date : 2020-03-03 Nicholas E. Clifton, Kerrie L. Thomas, Lawrence S. Wilkinson, Jeremy Hall, Simon Trent
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
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Using Chronobiological Phenotypes to Address Heterogeneity in Bipolar Disorder. Mol. Neuropsychiatry Pub Date : 2020-02-20 Robert Gonzalez,Suzanne D Gonzalez,Michael J McCarthy
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
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The Role of PTEN in Neurodevelopment. Mol. Neuropsychiatry Pub Date : 2020-01-21 Patrick D Skelton,Radu V Stan,Bryan W Luikart
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
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Genome-Wide Association Study of Sleep Disturbances in Depressive Disorders. Mol. Neuropsychiatry Pub Date : 2020-01-08 Lindsay M Melhuish Beaupre,Vanessa F Gonçalves,Clement C Zai,Arun K Tiwari,Ricardo S Harripaul,Deanna Herbert,Natalie Freeman,Daniel J Müller,James L Kennedy
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
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Estimating the Potential Impact of CYP2C19 and CYP2D6 Genetic Testing on Protocol-Based Care for Depression in Canada and the United States. Mol. Neuropsychiatry Pub Date : 2019-11-26 Mikayla Fan,Chad A Bousman
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 and CYP2D6genetic variation
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Strategies for Treatment-Resistant Depression: Lessons Learned from Animal Models. Mol. Neuropsychiatry Pub Date : 2019-11-27 Gislaine Zilli Réus,Airam Barbosa de Moura,Laura Araújo Borba,Helena Mendes Abelaira,João Quevedo
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
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Electroconvulsive Therapy and Schizophrenia: A Systematic Review. Mol. Neuropsychiatry Pub Date : 2019-06-14 Sana A Ali,Nandita Mathur,Anil K Malhotra,Raphael J Braga
Electroconvulsive therapy (ECT) is a remarkably effective treatment for major depressive disorder, but is less commonly utilized for treatment of psychotic disorders. Recent literature indicates that ECT can be a useful strategy for a wide range of psychotic disorders, including treatment-resistant schizophrenia. The purpose of this review is to examine the extant literature on ECT in schizophrenia
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Regulation and Function of Activity-Dependent Homer in Synaptic Plasticity. Mol. Neuropsychiatry Pub Date : 2019-05-23 Nicholas E Clifton,Simon Trent,Kerrie L Thomas,Jeremy Hall
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
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κ-Opioid Receptor Modulation of GABAergic Inputs onto Ventrolateral Periaqueductal Gray Dopamine Neurons. Mol. Neuropsychiatry Pub Date : 2019-05-17 Chia Li,Thomas L Kash
The κ-opioid receptor (KOR) system has been implicated in the regulation of many behaviors including pain. While there are numerous studies suggesting KOR regulation of pain being mediated spinally, there have been reports of pain-like behaviors regulated by central KOR signaling. In particular, oxytocin-induced analgesia appears to be mediated by KOR receptors within the ventrolateral periaqueductal
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Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review. Mol. Neuropsychiatry Pub Date : 2019-05-09 Eric A Woodcock,Ansel T Hillmer,Graeme F Mason,Kelly P Cosgrove
There is tremendous interest in the role of the neuroimmune system and inflammatory processes in substance use disorders (SUDs). Imaging biomarkers of the neuroimmune system in vivo provide a vital translational bridge between preclinical and clinical research. Herein, we examine two imaging techniques that measure putative indices of the neuroimmune system and review their application among SUDs.
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Sex-Specific Effects of Stress on Mood-Related Gene Expression. Mol. Neuropsychiatry Pub Date : 2019-04-30 Kelly Barko,William Paden,Kelly M Cahill,Marianne L Seney,Ryan W Logan
Women are twice as likely as men to be diagnosed with major depressive disorder (MDD). Recent studies report distinct molecular changes in depressed men and women across mesocorticolimbic brain regions. However, it is unclear which sex-related factors drive distinct MDD-associated pathology. The goal of this study was to use mouse experimental systems to investigate sex-specific mechanisms underlying
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Entrainment of Circadian Rhythms to Temperature Reveals Amplitude Deficits in Fibroblasts from Patients with Bipolar Disorder and Possible Links to Calcium Channels. Mol. Neuropsychiatry Pub Date : 2019-04-04 Victoria Nudell,Heather Wei,Caroline Nievergelt,Adam X Maihofer,Paul Shilling,Martin Alda,Wade H Berrettini,Kristen J Brennand,Joseph R Calabrese,William H Coryell,Jonathan M Covault,Mark A Frye,Fred Gage,Elliot Gershon,Melvin G McInnis,John I Nurnberger,Ketil J Oedegaard,Tatyana Shekhtman,Peter P Zandi,John R Kelsoe,Michael J McCarthy
Bipolar disorder (BD) is characterized by recurrent mood episodes, and circadian rhythm disturbances. Past studies have identified calcium channel genes as risk loci for BD. CACNA1C encodes an L-type calcium channel (LTCC) involved in the entrainment of circadian rhythms to light. Another calcium channel, i.e., the ryanodine receptor (RYR), is involved in -circadian phase delays. It is unknown whether
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Transcriptional Changes following Cellular Knockdown of the Schizophrenia Risk Gene SETD1A Are Enriched for Common Variant Association with the Disorder. Mol. Neuropsychiatry Pub Date : 2019-03-25 Darren Cameron,Derek J Blake,Nicholas J Bray,Matthew J Hill
Loss of function mutations in SETD1A are the first experiment-wide significant findings to emerge from exome sequencing studies of schizophrenia. Although SETD1A is known to encode a histone methyltransferase, the consequences of reduced S ETD1A activity on gene expression in neural cells have, to date, been unknown. To explore transcriptional changes through which genetic perturbation of SETD1A could
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Complex Neurological Phenotype in Female Carriers of NHE6 Mutations. Mol. Neuropsychiatry Pub Date : 2019-03-06 Matthew F Pescosolido,Brian C Kavanaugh,Nathalie Pochet,Michael Schmidt,Beth A Jerskey,Jeffrey M Rogg,Philip L De Jager,Tracy L Young-Pearse,Judy S Liu,Eric M Morrow
Mutations in NHE6 (also termed SLC9A6) cause the X-linked neurological disorder Christianson syndrome (CS) in males. The purpose of this study was to examine the phenotypic spectrum of female carriers of NHE6 mutations. Twenty female carriers from 9 pedigrees were enrolled, ranging from approximately age 2 to 65. A subset of female carriers was assessed using standardized neuropsychological measures
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Epigenetic Factors in Schizophrenia: Mechanisms and Experimental Approaches. Mol. Neuropsychiatry Pub Date : 2019-02-15 Melanie Föcking,Benjamin Doyle,Nayla Munawar,Eugene T Dillon,David Cotter,Gerard Cagney
Schizophrenia is a chronic mental disorder that is still poorly understood despite decades of study. Many factors have been found to contribute to the pathogenesis, including neurodevelopmental disturbance, genetic risk, and environmental insult, but no single root cause has emerged. While evidence from twin studies suggests a strong heritable component, few individual loci have been identified in
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Novel Complex Interactions between Mitochondrial and Nuclear DNA in Schizophrenia and Bipolar Disorder. Mol. Neuropsychiatry Pub Date : 2019-02-05 Anton Schulmann,Euijung Ryu,Vanessa Goncalves,Brandi Rollins,Michael Christiansen,Mark A Frye,Joanna Biernacka,Marquis P Vawter
Mitochondrial dysfunction has been associated with schizophrenia (SZ) and bipolar disorder (BD). This review examines recent publications and novel associations between mitochondrial genes and SZ and BD. Associations of nuclear-encoded mitochondrial variants with SZ were found using gene- and pathway-based approaches. Two control region mitochondrial DNA (mtDNA) SNPs, T16519C and T195C, both showed
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Social Isolation Rearing Induces Neuropsychiatric Diseases: Updated Overview. Mol. Neuropsychiatry Pub Date : 2019-01-24 Hamidreza Famitafreshi,Morteza Karimian
Neuropsychiatric and neurologic diseases cause a great burden for individuals, families, and societies. Social isolation rearing can trigger a variety of psychiatric diseases. New advances suggest that epigenetic factors along with other neurochemical changes can be an important topic in neuropsychiatric diseases. It is thought that the prevention of social isolation rearing that occurs around birth
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Cell Type-Specific Gene Expression of Alpha 5 Subunit-Containing Gamma-Aminobutyric Acid Subtype A Receptors in Human and Mouse Frontal Cortex. Mol. Neuropsychiatry Pub Date : 2019-01-23 Xiyue Hu,Brad R Rocco,Corey Fee,Etienne Sibille
Converging evidence suggests that deficits in somatostatin (SST)-expressing neuron signaling contributes to major depressive disorder. Preclinical studies show that enhancing this signaling, specifically at α5 subunit-containing γ-ami-nobutyric acid subtype A receptors (α5-GABAARs), provides a potential means to overcome low SST neuron function. The cortical microcircuit comprises multiple subtypes
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Research Domain Criteria: Cutting Edge Neuroscience or Galen's Humors Revisited? Mol. Neuropsychiatry Pub Date : 2019-01-16 Christopher A Ross,Russell L Margolis
The Research Domain Criteria (RDoC) scheme has guided the research agenda of the National Institute of Mental Health for the past decade. The essence of RDoC is its dimensional conception of mental illness, with the assumption that psychopathology is a manifestation of extremes along axes of neuropsychological variation. Research, it follows, should emphasize normal neuropsychological function and
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Regulation of the Expression of the Psychiatric Risk Gene Cacna1c during Associative Learning. Mol. Neuropsychiatry Pub Date : 2019-01-16 Lucy Sykes,Nicholas E Clifton,Jeremy Hall,Kerrie L Thomas
CACNA1C encodes the Cav1.2 L-type voltage-gated calcium channel. Generic variation in CACNA1C has been consistently identified as associated with risk for psychiatric disorders including schizophrenia, bipolar disorder, major depressive disorder and autism. Psychiatric risk loci are also enriched for genes involved in the regulation of synaptic plasticity. Here, we show that the expression of Cacna1c
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Exercise Reduces Salivary Morning Cortisol Levels in Patients with Depression. Mol. Neuropsychiatry Pub Date : 2018-12-19 Md Shafiqur Rahman,Xuan Zhao,Jia Jia Liu,Enid Quintana Torres,Babylonia Tibert,Parvin Kumar,Viktor Kaldo,Nils Lindefors,Yvonne Forsell,Catharina Lavebratt
PURPOSE OF THE STUDY Cortisol hypersecretion plays a role in depression pathophysiology. Internet-based cognitive behavioural therapy (ICBT) and physical exercise (PE) are new treatment alternatives for depression, and their long-lasting effect on cortisol is unknown. We investigated cortisol level changes after 12 weeks of ICBT, PE or treatment as usual (TAU). PROCEDURES The present pre-post repeated
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Sex-Specific Associations of Androgen Receptor CAG Trinucleotide Repeat Length and of Raloxifene Treatment with Testosterone Levels and Perceived Stress in Schizophrenia. Mol. Neuropsychiatry Pub Date : 2018-11-20 Samantha J Owens,Thomas W Weickert,Tertia D Purves-Tyson,Ellen Ji,Christopher White,Cherrie Galletly,Dennis Liu,Maryanne O'Donnell,Cynthia Shannon Weickert
Lower testosterone levels are associated with greater negative symptoms in men with schizophrenia. Testosterone signals via androgen receptor (AR). A functional variant in the AR gene (CAG trinucleotide repeat polymorphism) is associated with circulating testosterone and mood-related symptoms in healthy people. Raloxifene increases testosterone in healthy males and reduces symptom severity and improves
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OMICS Approaches to Unravel the Complexity of Psychiatric Disorders: Impact on Biomarker Discovery. Mol. Neuropsychiatry Pub Date : 2018-11-19 Daniel Martins-de-Souza
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Ketamine's Effects on the Glutamatergic and GABAergic Systems: A Proteomics and Metabolomics Study in Mice. Mol. Neuropsychiatry Pub Date : 2018-11-15 Katja Weckmann,Michael J Deery,Julie A Howard,Renata Feret,John M Asara,Frederik Dethloff,Michaela D Filiou,Christiana Labermaier,Giuseppina Maccarrone,Kathryn S Lilley,Marianne Mueller,Christoph W Turck
Ketamine, a noncompetitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect and is used for patients experiencing treatment-resistant depression. We carried out a time-dependent targeted mass spectrometry-based metabolomics profiling analysis combined with a quantitative based on in vivo 15N metabolic labeling proteome comparison
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Brain Gene Expression Pattern of Subjects with Completed Suicide and Comorbid Substance Use Disorder. Mol. Neuropsychiatry Pub Date : 2018-11-12 Brenda Cabrera,Nancy Monroy-Jaramillo,Gabriel Rodrigo Fries,Roberto Cuauhtemoc Mendoza-Morales,Fernando García-Dolores,Alejandra Mendoza-Larios,Carlos Diaz-Otañez,Consuelo Walss-Bass,David Colin Glahn,Patricia Ostrosky-Wegman,Cristobal Fresno,Humberto Nicolini
BACKGROUND/AIM Although individuals with substance use disorder (SUD) are at high risk of committing suicide, most studies of postmortem gene expression exclude subjects with SUD due to the potential confounding effect of drugs in the transcriptome. Thus, little is known about the gene expression profile in suicides with SUD. The identification of altered biological processes in suicides with SUD is
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Associations between the LEP -2548G/A Promoter and Baseline Weight and between LEPR Gln223Arg and Lys656Asn Variants and Change in BMI z Scores in Arab Children and Adolescents Treated with Risperidone. Mol. Neuropsychiatry Pub Date : 2018-11-07 Noor B Almandil,Rohit J Lodhi,Hongyan Ren,Frank M C Besag,David Rossolatos,Ruth Ohlsen,Caitlin Slomp,Diego L Lapetina,Giona Plazzotta,Macey L Murray,Abdulsalam A Al-Sulaiman,Paul Gringras,Ian C K Wong,Katherine J Aitchison
Data on baseline (antipsychotics-naïve) age, weight, and height, and change in these at 3 subsequent follow-up time points up to 313.6 days (95% CI 303.5-323.7) were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17-17.7) attending a pediatric neurology clinic in Saudi Arabia. Owing to differences in genotypic distributions in the subsamples
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The Sex Chromosome Hypothesis of Schizophrenia: Alive, Dead, or Forgotten? A Commentary and Review. Mol. Neuropsychiatry Pub Date : 2018-11-07 William K Bache,Lynn E DeLisi
The X chromosome has long been an intriguing site for harboring genes that have importance in brain development and function. It has received the most attention for having specific genes underlying the X-linked inherited intellectual disabilities, but has also been associated with schizophrenia in a number of early studies. An X chromosome hypothesis for a genetic predisposition for schizophrenia initially
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Perturbations of Neuron-Restrictive Silencing Factor Modulate Corticotropin-Releasing Hormone Gene Expression in the Human Cell Line BeWo. Mol. Neuropsychiatry Pub Date : 2018-11-07 Vasileios Kreouzis,Guo-Lin Chen,Gregory M Miller
Stress exacerbates disease, and understanding its molecular mechanisms is crucial to the development of novel therapeutic interventions to combat stress-related disorders. The driver of the stress response in the hypothalamic-pituitary-adrenal axis (HPA) is corticotropin-releasing hormone (CRH), a neuropeptide synthesized in the paraventricular nucleus of the hypothalamus. Evidence supports that CRH
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Attenuated Mismatch Negativity in Attenuated Psychosis Syndrome Predicts Psychosis: Can Galantamine-Memantine Combination Prevent Psychosis? Mol. Neuropsychiatry Pub Date : 2018-11-07 Maju Mathew Koola
Although first proposed in 1987, early diagnosis and intervention of psychotic disorders has only recently become a priority in the field. The interest in clinical high risk (CHR) for psychosis skyrocketed after attenuated psychosis syndrome (APS) was added to the DSM-5. There is evidence that in individuals with APS, attenuated mismatch negativity (MMN: functioning of the auditory sensory memory system)
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Epigenetic Age in Male Combat-Exposed War Veterans: Associations with Posttraumatic Stress Disorder Status. Mol. Neuropsychiatry Pub Date : 2018-11-07 Josine E Verhoeven,Ruoting Yang,Owen M Wolkowitz,Francesco S Bersani,Daniel Lindqvist,Synthia H Mellon,Rachel Yehuda,Janine D Flory,Jue Lin,Duna Abu-Amara,Iouri Makotkine,Charles Marmar,Marti Jett,Rasha Hammamieh
DNA methylation patterns change with age and can be used to derive an estimate of "epigenetic age," an indicator of biological age. Several studies have shown associations of posttraumatic stress disorder (PTSD) with worse somatic health and early mortality, raising the possibility of accelerated biological aging. This study examined associations between estimated epigenetic age and various variables
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X-Aptamer Technology Identifies C4A and ApoB in Blood as Potential Markers for Schizophrenia. Mol. Neuropsychiatry Pub Date : 2018-10-10 Consuelo Walss-Bass,Ganesh L R Lokesh,Elena Dyukova,David G Gorenstein,David L Roberts,Dawn Velligan,David E Volk
The field of proteomics is rapidly gaining territory as a promising alternative to genomic approaches in the efforts to unravel the complex molecular mechanisms underlying schizophrenia and other psychiatric disorders. X-aptamer tech-nology has emerged as a novel proteomic approach for high-sensitivity analyses, and we hypothesized that this technology would identify unique molecular signatures in
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Altered White Matter Diffusivity of the Cingulum Angular Bundle in Posttraumatic Stress Disorder. Mol. Neuropsychiatry Pub Date : 2018-07-19 Christopher L Averill,Lynnette A Averill,Kristen M Wrocklage,J Cobb Scott,Teddy J Akiki,Brian Schweinsburg,Steven M Southwick,John H Krystal,Chadi G Abdallah
PURPOSE OF THE STUDY Prior studies showed posttraumatic stress disorder (PTSD)-related alterations in white matter integrity, but most of these studies have used region-based approaches. We address this limitation by investigating the relationship between PTSD severity and fractional anisotropy (FA) using a tract-based approach. PROCEDURES Structural and diffusion magnetic resonance imaging were acquired
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Recent Advances in the Genetics of Schizophrenia. Mol. Neuropsychiatry Pub Date : 2018-07-13 Dimitrios Avramopoulos
The last decade brought tremendous progress in the field of schizophrenia genetics. As a result of extensive collaborations and multiple technological advances, we now recognize many types of genetic variants that increase the risk. These include large copy number variants, rare coding inherited and de novο variants, and over 100 loci harboring common risk variants. While the type and contribution
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The Complex Interaction of Mitochondrial Genetics and Mitochondrial Pathways in Psychiatric Disease. Mol. Neuropsychiatry Pub Date : 2018-07-13 Ari B Cuperfain,Zhi Lun Zhang,James L Kennedy,Vanessa F Gonçalves
While accounting for only 2% of the body's weight, the brain utilizes up to 20% of the body's total energy. Not surprisingly, metabolic dysfunction and energy supply-and-demand mismatch have been implicated in a variety of neurological and psychiatric disorders. Mitochondria are responsible for providing the brain with most of its energetic demands, and the brain uses glucose as its exclusive energy
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Further Evidence of an Association between NCAN rs1064395 and Bipolar Disorder. Mol. Neuropsychiatry Pub Date : 2018-07-13 Lu Wang,Weiqing Liu,Xingxing Li,Xiao Xiao,Lingyi Li,Fang Liu,Yuanfang He,Yan Bai,Hong Chang,Dong-Sheng Zhou,Ming Li
Genome-wide association studies suggest that rs1064395 in the neurocan gene (NCAN) is a potential risk factor for bipolar disorder (BPD), and further replication analyses in larger independent samples are needed. We herein analyzed rs1064395 in a Han Chinese sample of 1,146 BPD cases and 2,031 controls, followed by a meta-analysis of BPD samples from worldwide populations including a total of 15,318
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Dominant-Negative DISC1 Alters the Dopaminergic Modulation of Inhibitory Interneurons in the Mouse Prefrontal Cortex. Mol. Neuropsychiatry Pub Date : 2018-07-13 Ross A Cardarelli,Rolicia Martin,Hanna Jaaro-Peled,Akira Sawa,Elizabeth M Powell,Patricio O'Donnell
A truncated disrupted in schizophrenia 1 (Disc1) gene increases the risk of psychiatric disorders, probably affecting cortical interneurons. Here, we sought to determine whether this cell population is affected in mice carrying a truncated (Disc1) allele (DN-DISC1). We utilized whole cell recordings to assess electrophysiological properties and modulation by dopamine (DA) in two classes of interneurons:
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Association of Novel ALX4 Gene Polymorphisms with Antidepressant Treatment Response: Findings from the CO-MED Trial. Mol. Neuropsychiatry Pub Date : 2018-07-13 Bharathi S Gadad,Prithvi Raj,Manish K Jha,Thomas Carmody,Igor Dozmorov,Taryn L Mayes,Edward K Wakeland,Madhukar H Trivedi
Genome-wide association studies (GWAS) were conducted in participants of the CO-MED (Combining Medications to Enhance Depression Outcomes) trial, a randomized, 3-treatment arm clinical trial of major depressive disorder (MDD) designed to identify markers of differential treatment outcome (response and remission). The QIDS-SR (Quick Inventory of Depressive Symptomatology, Self-Reported version) was
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Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study. Mol. Neuropsychiatry Pub Date : 2018-06-12 Thomas W Sedlak,Leslie G Nucifora,Minori Koga,Lindsay S Shaffer,Cecilia Higgs,Teppei Tanaka,Anna M Wang,Jennifer M Coughlin,Peter B Barker,Jed W Fahey,Akira Sawa
Schizophrenia and other neuropsychiatric disorders await mechanism-associated interventions. Excess oxidative stress is increasingly appreciated to participate in the pathophysiology of brain disorders, and decreases in the major antioxidant, glutathione (GSH), have been reported in multiple studies. Technical cautions regarding the estimation of oxidative stress-related changes in the brain via imaging
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Exon Array Biomarkers for the Differential Diagnosis of Schizophrenia and Bipolar Disorder. Mol. Neuropsychiatry Pub Date : 2018-06-12 Marquis Philip Vawter,Robert Philibert,Brandi Rollins,Patricia L Ruppel,Terry W Osborn
This study developed potential blood-based biomarker tests for diagnosing and differentiating schizophrenia (SZ), bipolar disorder type I (BD), and normal control (NC) subjects using mRNA gene expression signatures. A total of 90 subjects (n = 30 each for the three groups of subjects) provided blood samples at two visits. The Affymetrix exon microarray was used to profile the expression of over 1.4
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Differential Impact of Obesity on CD69 Expression in Individuals with Bipolar Disorder and Healthy Controls. Mol. Neuropsychiatry Pub Date : 2018-06-12 Ana S Yamagata,Lucas B Rizzo,Raphael O Cerqueira,Janine Scott,Quirino Cordeiro,Roger S McIntyre,Rodrigo B Mansur,Elisa Brietzke
Preliminary evidence suggests that premature immunosenescence is involved in bipolar disorder (BD) pathophysiology. The cellular marker CD69 is expressed in T lymphocyte surface during their activation and its expression is negatively correlated with age. The objective of this study was to assess the moderating effects of obesity on the reduction of expression of CD69, a marker of immunosenescence
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Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients. Mol. Neuropsychiatry Pub Date : 2018-05-03 Clement C Zai,Arun K Tiwari,Gwyneth C Zai,Vincenzo de Luca,Sajid A Shaikh,Nicole King,John Strauss,James L Kennedy,John B Vincent
BACKGROUND A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide. METHODS We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our
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Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in Fez1-Deficient Mice. Mol. Neuropsychiatry Pub Date : 2018-04-26 Akiko Sumitomo,Ayumi Saka,Keisho Ueta,Kouta Horike,Kazuko Hirai,Nao J Gamo,Takatoshi Hikida,Keiichi I Nakayama,Akira Sawa,Takeshi Sakurai,Toshifumi Tomoda
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that, while prevalent, has a stagnant track record for advances in treatment. The limited availability of animal models with appropriate face and predictive validities has hampered progress in developing novel neurobiological hypotheses and testing new therapeutic options for this condition. Here, we report that mice deficient
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Improved Scalability of Neuron-Based Phenotypic Screening Assays for Therapeutic Discovery in Neuropsychiatric Disorders. Mol. Neuropsychiatry Pub Date : 2018-03-30 Timothy P Spicer,Christopher Hubbs,Thomas Vaissiere,Deanna Collia,Camilo Rojas,Murat Kilinc,Kyle Vick,Franck Madoux,Pierre Baillargeon,Justin Shumate,Kirill A Martemyanov,Damon T Page,Sathya Puthanveettil,Peter Hodder,Ronald Davis,Courtney A Miller,Louis Scampavia,Gavin Rumbaugh
There is a pressing need to improve approaches for drug discovery related to neuropsychiatric disorders (NSDs). Therapeutic discovery in neuropsychiatric disorders would benefit from screening assays that can measure changes in complex phenotypes linked to disease mechanisms. However, traditional assays that track complex neuronal phenotypes, such as neuronal connectivity, exhibit poor scalability
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Erratum. Mol. Neuropsychiatry Pub Date : 2018-03-30
[This corrects the article DOI: 10.1159/000480349.].
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Crossing the Worm-Brain Barrier by Using Caenorhabditis elegans to Explore Fundamentals of Human Psychiatric Illness. Mol. Neuropsychiatry Pub Date : 2018-03-30 Donard S Dwyer
Endophenotypes and Research Domain Criteria (RDoC) represent recent efforts to deconvolute psychiatric illnesses into fundamental symptom clusters or biological markers more closely linked to genetic influences. By taking this one step farther, these biomarkers can be reduced to protophenotypes - endophenotypes conserved during evolution - with counterparts in lower organisms including Caenorhabditis
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Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence. Mol. Neuropsychiatry Pub Date : 2018-03-30 Brandi L Rollins,Ling Morgan,Brooke E Hjelm,Adolfo Sequeira,Alan F Schatzberg,Jack D Barchas,Francis S Lee,Rick M Myers,Stanley J Watson,Huda Akil,Steven G Potkin,William E Bunney,Marquis P Vawter
Subjects with schizophrenia (SZ) and bipolar disorder (BD) show decreased protein and transcript levels for mitochondrial complex I. In vitro results suggest antipsychotic and antidepressant drugs may be responsible. We measured complex I activity in BD, SZ, and controls and presence of antipsychotic and antidepressant medications, mitochondrial DNA (mtDNA) copy number, and the mtDNA "common deletion"
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Interleukin-17 Alteration in First-Episode Psychosis: A Meta-Analysis. Mol. Neuropsychiatry Pub Date : 2018-03-30 Xinyu Fang,Yi Zhang,Weixing Fan,Wei Tang,Chen Zhang
Schizophrenia is accompanied with central nervous system and peripheral immune system imbalances. Interleukin-17 (IL-17) is implicated in various immune and inflammatory processes. Aberrant levels of IL-17 have been reported in patients with schizophrenia, whereas the results are not consistent. To clarify the relationship between IL-17 and schizophrenia, we performed a meta-analysis in this study
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A Genome-Wide Search for Bipolar Disorder Risk Loci Modified by Mitochondrial Genome Variation. Mol. Neuropsychiatry Pub Date : 2018-03-30 Euijung Ryu,Malik Nassan,Gregory D Jenkins,Sebastian M Armasu,Ana Andreazza,Susan L McElroy,Marquis P Vawter,Mark A Frye,Joanna M Biernacka
Mitochondrial DNA mutations have been reported to be associated with bipolar disorder (BD). In this study, we performed genome-wide analyses to assess mitochondrial single-nucleotide polymorphism (mtSNP) effects on BD risk and early-onset BD (EOBD) among BD patients, focusing on interaction effects between nuclear SNPs (nSNPs) and mtSNPs. Common nSNP and mtSNP data from European American BD cases (n
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Nuclear Receptors and Neuroinflammation in Schizophrenia. Mol. Neuropsychiatry Pub Date : 2018-01-16 Shan-Yuan Tsai,Vibeke S Catts,Janice M Fullerton,Susan M Corley,Stuart G Fillman,Cynthia Shannon Weickert
INTRODUCTION Several nuclear receptor family members have been associated with schizophrenia and inflammation. Vitamins A and D exert anti-inflammatory actions, but their receptors (mainly nuclear receptors) have not been extensively studied in either schizophrenia brains or in association with neuroinflammation. We examined the expression of vitamin A (RARs and RXRs) and vitamin D and protein disulphide-isomerase
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Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature. Mol. Neuropsychiatry Pub Date : 2017-12-13 Ashwini Saxena,Giselli Scaini,Daniela V Bavaresco,Camila Leite,Samira S Valvassori,André F Carvalho,João Quevedo
Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role
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Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants. Mol. Neuropsychiatry Pub Date : 2017-12-13 Julie Dagenhardt,Angeline Trinh,Halen Sumner,Jeffrey Scott,Eric Aamodt,Donard S Dwyer
Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2)
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Circuitry-Based Human Neuroanatomy for the Next Generation in Psychiatry and Neuroscience. Mol. Neuropsychiatry Pub Date : 2017-12-13 Takeshi Sakurai
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Altered Expression of Endoplasmic Reticulum Stress-Related Genes in the Middle Frontal Cortex of Subjects with Autism Spectrum Disorder. Mol. Neuropsychiatry Pub Date : 2017-12-13 Amanda Crider,Anthony O Ahmed,Anilkumar Pillai
The endoplasmic reticulum (ER) is an important organelle responsible for the folding and sorting of proteins. Disturbances in ER homeostasis can trigger a cellular response known as the unfolded protein response, leading to accumulation of unfolded or misfolded proteins in the ER lumen called ER stress. A number of recent studies suggest that mutations in autism spectrum disorder (ASD)-susceptible
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THC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons. Mol. Neuropsychiatry Pub Date : 2017-12-13 Ifeanyi V Obiorah,Hamza Muhammad,Khalifa Stafford,Erin K Flaherty,Kristen J Brennand
Given the cognitive and behavioral effects following in utero Δ9-tetrahydrocannabinol (THC) exposure that have been reported in humans and rodents, it is critical to understand the precise consequences of THC on developing human neurons. Here, we utilize excitatory neurons derived from human-induced pluripotent stem cells (hiPSCs), and report that in vitro THC exposure reduced expression of glutamate
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WNT/β-Catenin Pathway and Epigenetic Mechanisms Regulate the Pitt-Hopkins Syndrome and Schizophrenia Risk Gene TCF4. Mol. Neuropsychiatry Pub Date : 2017-09-08 Krista M Hennig,Daniel M Fass,Wen-Ning Zhao,Steven D Sheridan,Ting Fu,Serkan Erdin,Alexei Stortchevoi,Diane Lucente,Jannine D Cody,David Sweetser,James F Gusella,Michael E Talkowski,Stephen J Haggarty
Genetic variation within the transcription factor TCF4 locus can cause the intellectual disability and developmental disorder Pitt-Hopkins syndrome (PTHS), whereas single-nucleotide polymorphisms within noncoding regions are associated with schizophrenia. These genetic findings position TCF4 as a link between transcription and cognition; however, the neurobiology of TCF4 remains poorly understood.
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The Nuclear Proteome of White and Gray Matter from Schizophrenia Postmortem Brains. Mol. Neuropsychiatry Pub Date : 2017-09-08 Verônica M Saia-Cereda,Aline G Santana,Andrea Schmitt,Peter Falkai,Daniel Martins-de-Souza
Schizophrenia (SCZ) is a serious neuropsychiatric disorder that manifests through several symptoms from early adulthood. Numerous studies over the last decades have led to significant advances in increasing our understanding of the factors involved in SCZ. For example, mass spectrometry-based proteomic analysis has provided important insights by uncovering protein dysfunctions inherent to SCZ. Here
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Low-Density Neuronal Cultures from Human Induced Pluripotent Stem Cells. Mol. Neuropsychiatry Pub Date : 2017-09-08 Peter Dimitrion,Yun Zhi,Dennis Clayton,Gerard L Apodaca,Madeleine R Wilcox,Jon W Johnson,Vishwajit Nimgaonkar,Leonardo D'Aiuto
Induced pluripotent stem cell (iPSC)-based technologies offer an unprecedented possibility to investigate defects occurring during neuronal differentiation in neuropsychiatric and neurodevelopmental disorders, but the density and intricacy of intercellular connections in neuronal cultures challenge currently available analytic methods. Low-density neuronal cultures facilitate the morphometric and functional
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Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents. Mol. Neuropsychiatry Pub Date : 2017-09-08 Kiley Fagan,Amanda Crider,Anthony O Ahmed,Anilkumar Pillai
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with hallmark symptoms including social deficits, communication deficits and repetitive behaviors. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of ASD. The complement system represents one of the major effector mechanisms of the innate immune system, and regulates inflammation, and orchestrates