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Fluoxetine autism

Irving Zucker
Many drugs with unknown safety profiles are administered to pregnant women, placing their offspring at risk. I assessed whether behavioral outcomes for children exposed during gestation to antidepressants, anxiolytics, anti-seizure, analgesic, anti-nausea and sedative medications can be predicted by more extensive animal studies than are part of the FDA approval process. Human plus rodent data were available for only 8 of 33 CNS-active drugs examined. Similar behavioral and cognitive deficits, including autism and ADHD emerged in human offspring and in animal models of these disorders after exposure to fluoxetine, valproic acid, carbamazepine, phenytoin, phenobarbital and acetaminophen...
March 16, 2017: Neuroscience and Biobehavioral Reviews
Hoang Le, Bum Ju Ahn, Hye Shin Lee, Anna Shin, Sujin Chae, Sung Yi Lee, Min Wook Shin, Eun-Ji Lee, Jong-Ho Cha, Taekwon Son, Ji Hae Seo, Hee-Jun Wee, Hyo-Jong Lee, Yongwoo Jang, Eng H Lo, Sejin Jeon, Goo Taeg Oh, Daesoo Kim, Kyu-Won Kim
Over the last few decades, molecular neurobiology has uncovered many genes whose deficiency in mice results in behavioral traits associated with human neuropsychiatric disorders such as autism, obsessive-compulsive disorder (OCD), and schizophrenia. However, the etiology of these common diseases remains enigmatic with the potential involvement of a battery of genes. Here, we report abnormal behavioral phenotypes of mice deficient in a cell adhesion molecule Ninjurin 1 (Ninj1), which are relevant to repetitive and anxiety behaviors of neuropsychiatric disorders...
November 5, 2016: Molecular Neurobiology
Jos G M Hendriksen, Sylvia Klinkenberg, Phillipe Collin, Brenda Wong, Erik H Niks, Johan S Vles
We describe a case study of comorbid obsessive-compulsive disorder (OCD) in a nine-year-old boy with Duchenne muscular dystrophy (DMD). Patient history included persistent deficits in social communication and restrictive and repetitive patterns of behavior: a diagnosis of autism spectrum was formalized. Due to serious disruption on social functioning and negative development of the obsessive behavior we decided to start pharmacotherapy. Fluoxetine 5 mg/day was started and gradually increased to 20 mg/day...
October 2016: Neuromuscular Disorders: NMD
Gaurav Kaushik, Yu Xia, Luobin Yang, Michael A Thomas
BACKGROUND: A number of researchers have speculated that neurological disorders are mostly due to the interaction of common susceptibility genes with environmental, epigenetic and stochastic factors. Genetic factors such as mutations, insertions, deletions and copy number variations (CNVs) are responsible for only a small subset of cases, suggesting unknown environmental contaminants play a role in triggering neurological disorders like idiopathic autism. Psychoactive pharmaceuticals have been considered as potential environmental contaminants as they are detected in the drinking water at very low concentrations...
2016: BMC Genomics
Sura Alwan, Jan M Friedman, Christina Chambers
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications worldwide. However, over the past decade, their use during pregnancy, a period of extreme vulnerability to the onset of depression, has become highly concerning to patients and their healthcare providers in terms of safety to the developing fetus. Exposure to SSRIs in pregnancy has been associated with miscarriage, premature delivery, neonatal complications, birth defects-specifically cardiac defects-and, more recently, neurodevelopmental disorders in childhood, specifically autism spectrum disorders...
June 2016: CNS Drugs
Kara Gross Margolis, Zhishan Li, Korey Stevanovic, Virginia Saurman, Narek Israelyan, George M Anderson, Isaac Snyder, Jeremy Veenstra-VanderWeele, Randy D Blakely, Michael D Gershon
Autism spectrum disorder (ASD) is an increasingly common behavioral condition that frequently presents with gastrointestinal (GI) disturbances. It is not clear, however, how gut dysfunction relates to core ASD features. Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SERT, encoded by SLC6A4) have been identified in ASD. Expression of the most common SERT variant (Ala56) in mice increases 5-HT clearance and causes ASD-like behaviors. Here, we demonstrated that Ala56-expressing mice display GI defects that resemble those seen in mice lacking neuronal 5-HT...
June 1, 2016: Journal of Clinical Investigation
Gaurav Kaushik, David P Huber, Ken Aho, Bruce Finney, Shawn Bearden, Konstantinos S Zarbalis, Michael A Thomas
Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows...
May 27, 2016: Biochemical and Biophysical Research Communications
Hye-Young H Kim, Zeljka Korade, Keri A Tallman, Wei Liu, C David Weaver, Karoly Mirnics, Ned A Porter
A small library of pharmacologically active compounds (the NIH Clinical Collection) was assayed in Neuro2a cells to determine their effect on the last step in the biosynthesis of cholesterol, the transformation of 7-dehydrocholesterol (7-DHC) to cholesterol promoted by 7-dehydrocholesterol reductase, DHCR7. Of some 727 compounds in the NIH Clinical Collection, over 30 compounds significantly increased 7-DHC in Neuro2a cells when assayed at 1 μM. Active compounds that increased 7-DHC with a Z-score of +3 or greater generally gave rise to modest decreases in desmosterol and increases in lanosterol levels...
May 16, 2016: Chemical Research in Toxicology
Mari S Golub, Casey E Hogrefe, Alicia M Bulleri
Fluoxetine improves social interactions in children with autism, social anxiety and social phobia. It is not known whether this effect is mediated directly or indirectly by correcting the underlying pathology. Genetics may also influence the drug effect. Polymorphisms of the MAOA (monoamine oxidase A) gene interact with fluoxetine to influence metabolic profiles in juvenile monkeys. Juvenile nonhuman primates provide an appropriate model for studying fluoxetine effects and drug*gene interactions in children...
June 2016: Neuropharmacology
Gaurav Kaushik, Michael A Thomas, Ken A Aho
BACKGROUND: Most cases of idiopathic autism spectrum disorder (ASD) likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a fetus to minute concentrations of pharmaceuticals, such as carbamazepine (CBZ), venlafaxine (VNX) and fluoxetine (FLX). Unmetabolized pharmaceuticals reach drinking water through a variety of routes, including ineffectively treated sewage. Previous studies in our laboratory examined the extent to which gene sets were enriched in minnow brains treated with pharmaceuticals...
2015: BMC Bioinformatics
Kaylita Chantiluke, Nadia Barrett, Vincent Giampietro, Paramala Santosh, Michael Brammer, Andrew Simmons, Declan G Murphy, Katya Rubia
RATIONALE: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and have both performance and brain dysfunctions during motor response inhibition. Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders. AIMS: We therefore used functional magnetic resonance imaging (fMRI) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders, as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine...
June 2015: Psychopharmacology
A Simons, J Steyaert
Anxiety is common in children and adolescents with autism spectrum disorders and can cause severe dysfunction and suffering. An 11-year-old boy with an autism spectrum disorder and suffering from anxiety and mood problems responded positively to treatment with fluoxetine. After four weeks he developed clinically observable paroxysmal events accompanied by absence and confusion.
2014: Tijdschrift Voor Psychiatrie
Betty Zimmerberg, Sierra C Germeyan
Infants born to women with depressive symptoms are at higher risk for insecure attachment and behavioral problems. Thus current medical practice is to continue psychotropic medication of pregnant women with depression despite concerns about its behavioral teratology. There are few animal studies focused on long-term behavioral effects of prenatal antidepressant exposure; in addition, studies have not looked at individual differences in baseline affective state as a source of response variability. In this study, fluoxetine, a selective serotonin reuptake inhibitor (SSRI), was administered to male and female rat pups from postnatal days 2-7 to model exposure to antidepressants in the human third trimester...
March 2015: Developmental Psychobiology
K Chantiluke, N Barrett, V Giampietro, M Brammer, A Simmons, K Rubia
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often co-morbid and share performance and brain dysfunctions during working memory (WM). Serotonin agonists modulate WM and there is evidence of positive behavioural effects in both disorders. We therefore used functional magnetic resonance imaging (fMRI) to investigate shared and disorder-specific brain dysfunctions of WM in these disorders, and the effects of a single dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine...
April 2015: Psychological Medicine
Anissa Mouti, Dinah Reddihough, Catherine Marraffa, Philip Hazell, John Wray, Katherine Lee, Michael Kohn
BACKGROUND: Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off-label for children with autism. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be adequately examined to provide evidence to support current clinical practice. The aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the efficacy and safety of low dose fluoxetine compared with placebo, for reducing the frequency and severity of repetitive stereotypic behaviors in children and adolescents with an autism spectrum disorder (ASD)...
2014: Trials
Marko Uutela, Jesse Lindholm, Tomi Rantamäki, Juzoh Umemori, Kerri Hunter, Vootele Võikar, Maija L Castrén
Fluoxetine is used as a therapeutic agent for autism spectrum disorder (ASD), including Fragile X syndrome (FXS). The treatment often associates with disruptive behaviors such as agitation and disinhibited behaviors in FXS. To identify mechanisms that increase the risk to poor treatment outcome, we investigated the behavioral and cellular effects of fluoxetine on adult Fmr1 knockout (KO) mice, a mouse model for FXS. We found that fluoxetine reduced anxiety-like behavior of both wild-type and Fmr1 KO mice seen as shortened latency to enter the center area in the open field test...
2014: Frontiers in Cellular Neuroscience
Chun-Sheng Ruan, Shu-Fen Wang, Yan-Jun Shen, Yi Guo, Chun-Rui Yang, Fiona H Zhou, Li-Tao Tan, Li Zhou, Jian-Jun Liu, Wen-Yue Wang, Zhi-Cheng Xiao, Xin-Fu Zhou
Chronic stress causes a variety of psychiatric disorders such as anxiety and depression, but its mechanism is not well understood. Tripartite motif-containing protein 32 (TRIM32) was strongly associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety and obsessive compulsive disorder based on a study of copy number variation, and deletion of TRIM32 increased neural proliferation and reduced apoptosis. Here, we propose that TRIM32 is involved in chronic stress-induced affective behaviors...
August 2014: European Journal of Neuroscience
Swetha K Godavarthi, Ankit Sharma, Nihar Ranjan Jana
Angelman syndrome (AS) is a neuropsychiatric disorder characterized by autism, intellectual disability and motor disturbances. The disease is primarily caused by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient mice recapitulates many essential feature of AS. These AS mice have been shown to be under chronic stress and exhibits anxiety-like behaviour because of defective glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in these mice could lead to down-regulation of parvalbumin-positive interneurons in the hippocampus and basolateral amygdala from early post-natal days...
August 2014: Journal of Neurochemistry
Kaylita Chantiluke, Nadia Barrett, Vincent Giampietro, Michael Brammer, Andrew Simmons, Declan G Murphy, Katya Rubia
Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share brain function abnormalities during cognitive flexibility. Serotonin is involved in both disorders, and selective serotonin reuptake inhibitors (SSRIs) can modulate cognitive flexibility and improve behavior in both disorders. Thus, this study investigates shared and disorder-specific brain dysfunctions in these 2 disorders during reward reversal, and the acute effects of an SSRI on these. Age-matched boys with ADHD (15), ASD (18), and controls (21) were compared with functional magnetic resonance imaging (fMRI) during a reversal task...
July 2015: Cerebral Cortex
L Béhérec, G Quilici, A Rosier, P Gerardin, D Campion, O Guillin
BACKGROUND: Pervasive developmental disorders (PDD) are neurodevelepmental disorders that are characterized by severe deficits in socialisation and communication, and the existence of repetitive and stereotyped interests and behaviours. It is estimated more than 60/100,000 children are suffering from PDD. Comorbid disorders are common in people with PDD, including intellectual deficiency, symptoms of attention deficit-hyperactivity, aggression and disruption, and pervasive repetitive behaviours or thoughts...
April 2014: L'Encéphale
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