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Molecular Neuropsychiatry

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-GABAA Rs), provides a potential means to overcome low SST neuron function. The cortical microcircuit comprises multiple subtypes of inhibitory γ-aminobutyric acid (GABA) neurons and excitatory pyramidal cells (PYCs). In this study, multilabel fluorescence in situ hybridization was used to characterize α5-GABAA R gene expression in PYCs and three GABAergic neuron subgroups - vasoactive intestinal peptide (VIP)-, SST-, and parvalbumin (PV)-expressing cells - in the human and mouse frontal cortex...
February 2019: Molecular Neuropsychiatry
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 measure study analysed data derived from a randomised controlled trial evaluating the effects of 12 weeks' interventions of ICBT, PE and TAU in depressed primary care patients (Sweden 2011-2013) and aimed at prospectively evaluating the within-group effects of ICBT, PE and TAU on diurnal salivary cortisol levels in a small representative subsample ( n = 56, 38 and 27, respectively)...
February 2019: Molecular Neuropsychiatry
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 can reduce the occurrence of neuropsychiatric diseases. It has been suggested that the environment can induce epigenetic alternation...
February 2019: Molecular Neuropsychiatry
Heath D Schmidt, Laura E Rupprecht, Nii A Addy
Tobacco-related morbidity and mortality continue to be a significant public health concern. Unfortunately, current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, a better understanding of the neurobiological and neurophysiological mechanisms that promote smoking relapse is needed to develop novel smoking cessation medications. Here, we review preclinical studies focused on identifying the neurotransmitter and neuromodulator systems that mediate nicotine relapse, often modeled in laboratory animals using the reinstatement paradigm, as well as the plasticity-dependent neurophysiological mechanisms that facilitate nicotine reinstatement...
February 2019: Molecular Neuropsychiatry
Mohammed Al-Alawi, Hamed Al Sinawi, Roshe Rashid
Bipolar affective disorder (BPAD) is a chronic debilitating psychiatric illness seriously affecting the quality of patients' life. The available treatment is effective in about half of those suffering from the illness. The neurobiological basis of the disorder is not fully unraveled. With such lacunae, attempts have been made to decipher the underlying neuroimmunological process of the illness as is the case with other mental disorders. As a result, some inflammatory processes have been implicated in the etiology of BPAD, as described in this communication...
December 2018: Molecular Neuropsychiatry
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 its associated neurocircuitry. We argue that RDoC, dressed in terms of modern neurobiology, is in fact a return to the humoral theory of Galen, a dimensional approach in which physical and mental health requires a balance of the four basic bodily humors (blood, black bile, yellow bile, and phlegm)...
December 2018: Molecular Neuropsychiatry
Lucy Sykes, Nicholas E Clifton, Jeremy Hall, Kerrie L Thomas
CACNA1C encodes the Cav 1.2 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 is regulated in the rat hippocampus after context exposure, contextual fear conditioning and fear memory retrieval in a manner that correlates to specific memory processes...
December 2018: Molecular Neuropsychiatry
Maju Mathew Koola
Schizophrenia is, in part, a cognitive illness. There are no approved medications for cognitive impairments associated with schizophrenia (CIAS) and primary negative symptoms. Cholinergic and glutamatergic systems, alpha-7 nicotinic acetylcholine (α-7nACh) and N -methyl-D-aspartate (NMDA) receptors, kynurenic acid (KYNA), and mismatch negativity have been implicated in the pathophysiology of CIAS and negative symptoms. Galantamine is an acetylcholinesterase inhibitor that is also a positive allosteric modulator at the α4β2 and α7nACh receptors...
December 2018: Molecular Neuropsychiatry
Ming Li, Weihua Yue
Recent large-scale genetic approaches, such as genome-wide association studies, have identified multiple genetic variations that contribute to the risk of mental illnesses, among which single nucleotide polymorphisms (SNPs) within or near the vaccinia related kinase 2 ( VRK2 ) gene have gained consistent support for their correlations with multiple psychiatric and neurological disorders including schizophrenia (SCZ), major depressive disorder (MDD), and genetic generalized epilepsy. For instance, the genetic variant rs1518395 in VRK2 showed genome-wide significant associations with SCZ (35,476 cases and 46,839 controls, p = 3...
December 2018: Molecular Neuropsychiatry
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, results are reported for the white Arab population ( n = 144). Age- and gender-normed body mass index (BMI)-standardized z scores (BMI z ) were calculated (LMSgrowth program)...
October 2018: Molecular Neuropsychiatry
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 expression is epigenetically modified at the molecular level by environmental stimuli, causing changes in the stress response...
October 2018: Molecular Neuropsychiatry
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 in 160 male combat-exposed war veterans with ( n = 79) and without PTSD ( n = 81). DNA methylation was assessed in leukocyte genomic DNA using the Illumina 450K DNA methylation arrays...
October 2018: Molecular Neuropsychiatry
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 came from the X chromosome anomaly population data showing an excess of schizophrenia in Klinefelter's (XXY) males and triple X (XXX) females...
October 2018: Molecular Neuropsychiatry
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 from 67 combat-exposed US Veterans and processed using FSL/FreeSurfer TRActs Constrained by UnderLying Anatomy...
October 2018: Molecular Neuropsychiatry
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) is a robust biomarker that can predict transition to psychosis. The underlying pathophysiological mechanism of MMN is via the interaction of N -methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α-7nACh) receptors...
October 2018: Molecular Neuropsychiatry
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 source. Exploring the role of mitochondrial dysfunction in the etiology of psychiatric disease is a promising avenue to investigate further...
June 2018: Molecular Neuropsychiatry
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 to the risk vary among genetic variants, there is concordance in the functions of genes they implicate, such as those whose RNA binds the fragile X-related protein FMRP and members of the activity-regulated cytoskeletal complex involved in learning and memory...
June 2018: Molecular Neuropsychiatry
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 cases and 91,990 controls. The meta-analysis found that rs1064395 showed a genome-wide significant association with BPD ( p = 4...
June 2018: Molecular Neuropsychiatry
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: fast-spiking (FS) and low threshold-spiking (LTS) interneurons in wild-type and DN-DISC1 mice. In DN-DISC1 mice, FS interneurons, but not LTS interneurons, exhibited altered action potentials...
June 2018: Molecular Neuropsychiatry
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 used to measure response at week 6 (QIDS-SR ≤5) and remission at week 12 (QIDS-SR ≤6 and ≤8 at the last two study visits)...
June 2018: Molecular Neuropsychiatry
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