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Schizophrenia depression

Siri Ranlund, Maria Joao Rosa, Simone de Jong, James H Cole, Marinos Kyriakopoulos, Cynthia H Y Fu, Mitul A Mehta, Danai Dima
Psychiatric illnesses are complex and polygenic. They are associated with widespread alterations in the brain, which are partly influenced by genetic factors. There have been some attempts to relate polygenic risk scores (PRS) - a measure of the overall genetic risk an individual carries for a disorder - to brain structure using univariate methods. However, PRS are likely associated with distributed and covarying effects across the brain. We therefore used multivariate machine learning in this proof-of-principle study to investigate associations between brain structure and PRS for four psychiatric disorders; attention deficit-hyperactivity disorder (ADHD), autism, bipolar disorder and schizophrenia...
October 9, 2018: NeuroImage: Clinical
Eun Jin Kim, Yong-Chun Bahk, Hyeonju Oh, Won-Hye Lee, Jong-Sun Lee, Kee-Hong Choi
Cognition is an important factor that affects daily functioning and quality of life. Impairment in cognitive function is a common symptom present in various psychological disorders, which hinders patients from functioning normally. Given that cognitive impairment has devastating effects, enhancing this in patients should lead to improvements in compromised quality of life and functioning, including vocational functioning. Over the past 50 years, several attempts have been made to improve impaired cognition, and empirical evidence for cognitive remediation (CR) has accumulated that supports its efficacy for treating schizophrenia...
2018: Frontiers in Psychiatry
Sandra Sanchez-Roige, Abraham A Palmer, Pierre Fontanillas, Sarah L Elson, Mark J Adams, David M Howard, Howard J Edenberg, Gail Davies, Richard C Crist, Ian J Deary, Andrew M McIntosh, Toni-Kim Clarke
OBJECTIVE: Alcohol use disorders are common conditions that have enormous social and economic consequences. Genome-wide association analyses were performed to identify genetic variants associated with a proxy measure of alcohol consumption and alcohol misuse and to explore the shared genetic basis between these measures and other substance use, psychiatric, and behavioral traits. METHOD: This study used quantitative measures from the Alcohol Use Disorders Identification Test (AUDIT) from two population-based cohorts of European ancestry (UK Biobank [N=121,604] and 23andMe [N=20,328]) and performed a genome-wide association study (GWAS) meta-analysis...
October 19, 2018: American Journal of Psychiatry
Jieun Song, Marsha R Mailick, Jan S Greenberg
OBJECTIVE: Parents of individuals with developmental disorders or mental health problems often provide life-long care and support to their children, which negatively affects their health in part due to chronic stress. This study aimed to examine the experience of stigma as a source of chronic stress among parents of individuals with developmental disorders or mental health problems and the effect of stigma on parental health outcomes. METHOD: Using data from the Survey of Midlife in the United States (MIDUS 2 and 3), we constructed a sample for a longitudinal analysis including 128 parents of individuals with developmental disorders (e...
September 27, 2018: Social Science & Medicine
F Schürhoff, G Fond, F Berna, E Bulzacka, O Godin, L Boyer, D Misdrahi, M Andrianarisoa, L Brunel, N Coulon, B Aouizerate, D Capdevielle, I Chereau, T D'Amato, C Dubertret, J Dubreucq, C Faget, F Gabayet, J Mallet, R Rey, C Lancon, C Passerieux, A Schandrin, M Urbach, P Vidailhet, M Leboyer, P M Llorca
OBJECTIVES: The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort. METHODS: More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers...
October 13, 2018: L'Encéphale
Brian Dean, Clare Duncan, Andrew Gibbons
BACKGROUND: We previously reported that, compared to controls, there are lower levels of [3 H]LY341495 binding to metabotropic 2/3 receptors (GRM2/3) in Brodmann's area (BA) 24, but not 17 or 46, from subjects with major depressive disorders (MDD) but not bipolar disorders (BD) or schizophrenia. To be able to better interpret these data we have now measured levels of GRM2 in two of these cortical regions. METHODS: Using a rabbit anti-metabotropic GRM2 monoclonal antibody with Western blotting we measured levels of GRM2 in BA 24 and 46 from subjects with MDD, BD, schizophrenia and controls (n = 15 per group)...
October 6, 2018: Journal of Affective Disorders
Frances Rice, Lucy Riglin, Ajay K Thapar, Jon Heron, Richard Anney, Michael C O'Donovan, Anita Thapar
Importance: Depression often first manifests in adolescence. Thereafter, individual trajectories vary substantially, but it is not known what shapes depression trajectories in youth. Adult studies suggest that genetic risk for schizophrenia, a psychiatric disorder with a neurodevelopmental component, may contribute to an earlier onset of depression. Objective: To test the hypothesis that there are distinct trajectories of depressive symptoms and that genetic liability for neurodevelopmental psychiatric disorders (eg, schizophrenia, attention deficit/hyperactivity disorder [ADHD]), as well as for major depressive disorder (MDD), contribute to early-onset depression...
October 14, 2018: JAMA Psychiatry
Daniel S Tylee, Jiayin Sun, Jonathan L Hess, Muhammad A Tahir, Esha Sharma, Rainer Malik, Bradford B Worrall, Andrew J Levine, Jeremy J Martinson, Sergey Nejentsev, Doug Speed, Annegret Fischer, Eric Mick, Brian R Walker, Andrew Crawford, Struan F A Grant, Constantin Polychronakos, Jonathan P Bradfield, Patrick M A Sleiman, Hakon Hakonarson, Eva Ellinghaus, James T Elder, Lam C Tsoi, Richard C Trembath, Jonathan N Barker, Andre Franke, Abbas Dehghan, Stephen V Faraone, Stephen J Glatt
Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods...
October 16, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Ahmed Mhalla, Walid Bel Hadj Salah, Rim Mensi, Badii Amamou, Amal Messaoud, Leila Gassab, Wahiba Douki, Med Fadhel Najjar, Lotfi Gaha
INTRODUCTION: Cardiovascular diseases are common co morbidities of schizophrenia and constitute the main factors of high mortality in this pathology. Cardiovascular damages are favored by some risk factors, of which one of the most important is dyslipidemia. In this context, a study of lipid profile in schizophrenia is interesting.  The aims of this study were to compare the lipid profile of patients with schizophrenia to healthy controls and to investigate the associations between lipid parameters and demographics, clinical and treatment characteristics of the patients...
January 2018: La Tunisie Médicale
Leslie Citrome
Cariprazine is an oral antipsychotic approved in the US and EU for the treatment of schizophrenia. Cariprazine differs from other antipsychotics in that it is a dopamine D3 - and D2 -receptor partial agonist, with tenfold higher affinity for D3 receptors than for D2 receptors. Cariprazine is metabolized in two steps by CYP3A4 to didesmethyl-cariprazine (DDCAR). DDCAR has a long half-life of 1-3 weeks and is the predominant circulating active moiety. Efficacy and safety in persons with acute schizophrenia were assessed in four similarly designed, short-term, randomized, placebo-controlled clinical trials in nonelderly adults, with three studies considered positive and yielding a number needed to treat vs placebo for response (change from baseline ≥30% in Positive and Negative Syndrome Scale total score) of ten for the approved dose range of cariprazine 1...
2018: Neuropsychiatric Disease and Treatment
Anna Herman, Mostafa El Mansari, Nika Adham, Bela Kiss, Bence Farkas, Pierre Blier
Cariprazine (US: Vraylar®, Europe: Reagila®), an orally active and potent dopamine D3 preferring D3 /D2 receptor partial agonist, is approved to treat adults with schizophrenia (US and Europe) and manic or mixed episodes associated with bipolar I disorder (US). Cariprazine also displays partial agonism at serotonin (5-HT) 5 HT1A receptors and antagonism at 5 HT2A and 5 HT 2B receptors in vitro (Kiss et al., 2010). The objective of this study was to determine whether cariprazine can lead to functional alterations of monoamine systems in vivo determined by electrophysiological recordings from anaesthetised rats...
October 15, 2018: Molecular Pharmacology
Matthew Schafer, Joo-Won Kim, Joshmi Joseph, Junqian Xu, Sophia Frangou, Gaelle E Doucet
The habenula (Hb), a bilateral nucleus located next to the dorsomedial thalamus, is of particular relevance to psychiatric disorders based on preclinical evidence linking the Hb to depressive and amotivational states. However, studies in clinical samples are scant because segmentation of the Hb in neuroimaging data is challenging due to its small size and low contrast from the surrounding tissues. Negative affective states dominate the clinical course of schizophrenia and bipolar disorder and represent a major cause of disability...
2018: Frontiers in Psychiatry
Zsuzsanna Szepesi, Oscar Manouchehrian, Sara Bachiller, Tomas Deierborg
Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult to the CNS homeostasis. Although microglia have long been recognized as a crucial player in generating and maintaining inflammatory responses in the CNS, now it has become clear, that their function are much more diverse, particularly in the healthy brain. The innate immune response and phagocytosis represent only a little segment of microglia functional repertoire that also includes maintenance of biochemical homeostasis, neuronal circuit maturation during development and experience-dependent remodeling of neuronal circuits in the adult brain...
2018: Frontiers in Cellular Neuroscience
Serena B Gumusoglu, Hanna E Stevens
Early disruptions to neurodevelopment are highly relevant to understanding both psychiatric risk and underlying pathophysiology that can be targeted by new treatments. Much convergent evidence from the human literature associates inflammation during pregnancy with later neuropsychiatric disorders in offspring. Preclinical models of prenatal inflammation have been developed to examine the causal maternal physiological and offspring neural mechanisms underlying these findings. Here we review the strengths and limitations of preclinical models used for these purposes and describe selected studies that have shown maternal immune impacts on the brain and behavior of offspring...
August 27, 2018: Biological Psychiatry
Ying Fan, Min Chen, Jinqiang Zhang, Philippe Maincent, Xuefeng Xia, Wen Wu
Intranasal drug delivery is emerging as a reliable and promising pathway to deliver a wide range of therapeutic agents including small and large molecules, peptides and proteins, genes to the central nervous system for the treatment of brain diseases such as Alzheimer's disease, Parkinson's disease, depression, migraine, schizophrenia, and glioma. This presents noninvasive entry into the brain via direct nose-to-brain and/or indirect nose-to-blood-to-brain routes. Several nanocarrier-based strategies have been developed to transport therapeutic agents to the brain including nanoparticles, liposomes, and exosomes following intranasal delivery...
2018: Critical Reviews in Therapeutic Drug Carrier Systems
Leonardo Santana Novaes, Nilton Barreto Dos Santos, Guilherme Dragunas, Juliano Genaro Perfetto, Juan Carlos Leza, Cristoforo Scavone, Carolina Demarchi Munhoz
Chronic psychogenic stress can increase neuronal calcium influx and generate the intracellular accumulation of oxidative (ROS) and nitrosative (RNS) reactive species, disrupting synaptic transmission in the brain. These molecules impair the Na,K-ATPase (NKA) activity, whose malfunction has been related to neuropsychiatric disorders, including anxiety, depression, schizophrenia, and neurodegenerative diseases. In this study, we assessed how 14 days of restraint stress in rats affect NKA activity via oxidative/nitrosative damage in the frontal cortex (FCx), a crucial region for emotional and cognitive control...
October 11, 2018: Neuroscience
Shan Chen, Hai Sen Xia, Feng Zhu, Guang Zhong Yin, Zheng Kang Qian, Cai Xia Jiang, Xiao Chu Gu, Xu Yuan Yin, Wen Jie Tang, Tian Hong Zhang, Ji Jun Wang, Qiu Fang Jia, Li Hui
Albumin is a metal-binding protein with free-radical scavenging properties and is recognized as a vital antioxidant. Moreover, an excess of free radicals may contribute to depressive symptoms and the psychopathology of psychiatric disorders. This study examined serum albumin levels, depressive symptoms, and their association in patients with schizophrenia. Thirty-four patients with schizophrenia (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition) and 136 healthy controls were consecutively enrolled in this case-control study...
October 5, 2018: Psychiatry Research
G Singh, V Singh, J S Schneider
Sex differences in the risk for and expression of various brain disorders have been known for some time. Yet, the molecular underpinnings of these sex differences as well as how sex modifies normal brain development are still poorly understood. It has recently become known that epigenetic mechanisms play an essential role in establishing and maintaining sex differences in neurodevelopment and disease susceptibility. Epigenetic mechanisms such as post-translational modifications of histones (histone PTMs) integrate various hormonal and external environmental influences to affect genomic output, and this appears to occur in a sex-dependent manner...
October 10, 2018: Biochimica et biophysica acta. Molecular basis of disease
Philip Murphy, Richard P Bentall, Daniel Freeman, Suzanne O'Rourke, Paul Hutton
BACKGROUND: An influential psychological model of persecutory delusions proposed that they are caused by a bias towards holding others responsible for negative events (an externalising attributional bias), preventing the individual from becoming aware of underlying low self-esteem. An early version of the model predicted self-esteem would, therefore, be preserved in people with these delusions, but a later version suggested it would be unstable, and that there would be a discrepancy between explicit and implicit self-esteem, with the latter being lower...
October 9, 2018: Lancet Psychiatry
Lorena de la Fuente-Tomas, Mónica Sánchez-Autet, Leticia García-Álvarez, Leticia González-Blanco, Ángela Velasco, Pilar A Sáiz Martínez, María P Garcia-Portilla, Julio Bobes
Clinical staging is a diagnostic tool used in other medical specialties, which has resulted from the combination of a categorical and dimensional approach. In the last 2decades, the usefulness of its application in the field of psychiatry has been suggested, mainly as a tool for diagnostic help, and therapeutic and prognostic orientation. In this paper we review the clinical staging models that have been proposed to date for bipolar disorder, depression and schizophrenia. A literature search was performed in PubMed and Medline databases...
October 9, 2018: Revista de Psiquiatrí́a y Salud Mental
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