To investigate the impact of gestational exposure to selective serotonin reuptake inhibitors (SSRIs) on offspring neurodevelopment.
This is a cohort study using national register data in Finland ...between the years 1996 and 2010. Pregnant women and their offspring were categorized into 4 groups: SSRI exposed (n = 15,729); exposed to psychiatric disorder, no antidepressants (n = 9,651); exposed to SSRIs only before pregnancy (n = 7,980); and unexposed to antidepressants and psychiatric disorders (n = 31,394). We investigated the cumulative incidence of offspring diagnoses of depression, anxiety, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) for the 4 groups from birth to 14 years, adjusting for confounders.
The cumulative incidence of depression among offspring exposed prenatally to SSRIs was 8.2% (95% CI = 3.1-13.3%) by age 14.9 years, compared with 1.9% (95% CI = 0.9-2.9%) in the psychiatric disorder, no medication group (adjusted hazard ratio HR = 1.78; 95% CI = 1.12-2.82; p = .02) and to 2.8% (95% CI = 1.4-4.3%) in the SSRI discontinued group (HR = 1.84; 95% CI = 1.14-2.97; p = .01). Rates of anxiety, ASD, and ADHD diagnoses were comparable to rates in offspring of mothers with a psychiatric disorder but no medication during pregnancy. Comparing SSRI exposed to unexposed individuals, the HRs were significantly elevated for each outcome.
Prenatal SSRI exposure was associated with increased rates of depression diagnoses in early adolescence but not with ASD or ADHD. Until confirmed, these findings must be balanced against the substantial adverse consequences of untreated maternal depression.
As a key regulator of serotonergic activity and target of many antidepressant treatments, the serotonin transporter (SERT) represents a potential mediator of anxiety- and depression-related ...behaviors. Using mice lacking the SERT (SERT KO), we examined the role of SERT function in anxiety- and depression-related behaviors and serotonergic neuron function.
Serotonin transporter knockout mice were evaluated in paradigms designed to assess anxiety-, depression-, and stress-related behaviors. Dorsal raphe nucleus (DRN) function was assessed by quantitative serotonergic cell counting and extracellular electrical recording of neuronal firing properties.
Serotonin transporter knockout mice showed an increase in latency to feed in a novel situation, more immobility in a forced swim, increased escape latency in a shock escape paradigm, and decreased immobility in tail suspension. No differences in anxiety-related behaviors were seen in the open field and the elevated plus maze. Serotonin transporter knockout mice exhibit a 50% reduction in serotonergic cell number and a fourfold decrease in firing rate in the DRN.
Developmental loss of SERT produces altered behaviors in models of depression that are generally opposite to those produced by antidepressant treatment. The reduced serotonergic cell number and firing rate in the DRN of adult SERT KO mice suggest a mechanism for these altered behaviors.
Abstract We present a unique case of bladder perforation occurring intraoperatively during primary total hip arthroplasty. It is suspected that the patient's aberrant bladder anatomy, with idiopathic ...erosion of the quadrilateral space, predisposed the patient to bladder injury. Several preoperative risk factors for bladder injury were identified in the literature. These factors include cemented acetabular components, previous history of hip arthroplasty, history of pelvic trauma or intrapelvic surgery, and poor bone quality. Management of bladder injury, should it occur, includes bladder decompression with a Foley catheter, antibiotic administration, hemodynamic monitoring, and urology consult with close follow-up. This case reinforces the importance of urologic preoperative evaluation for anatomic variations of the bladder. In such cases, intraoperative Foley catheters to prevent distension may reduce the risk of perforation.
We present the analysis and results of recent high-energy gamma-ray observations of the BL Lac object 3C 66A conducted with the Solar Tower Atmospheric Cerenkov Effect Experiment (STACEE). During the ...2003-2004 observing season, STACEE extensively observed 3C 66A as part of a multiwavelength campaign on the source. A total of 33.7 hr of data was taken on the source, plus an equivalent-duration background observation. After cleaning the data set a total of 16.3 hr of live time remained, and a net on-source excess of 1134 events was seen against a background of 231,742 events. At a significance of 2.2 s this excess is insufficient to claim a detection of 3C 66A but is used to establish flux upper limits for the source.
Abstract Background Department of Radiology performed ultrasound for patients suspected of having intussusception in resource-limited settings might be either unavailable or significantly time ...delayed. Objective Our objective was to present a case of intussusception successfully diagnosed by point-of-care ultrasound and to review the sonographic appearance and diagnostic criteria for intussusception. Case Report An emergency physician utilized point-of-care ultrasound to diagnose intussusception in a young patient in Haiti. Conclusions In resource-limited settings, point-of-care ultrasound performed by a physician trained to diagnose intussusception can reduce the time to definitive management and thereby potentially reduce complications such as bowel ischemia and necrosis, dehydration, and sepsis.
Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The Nrg1 gene is a schizophrenia susceptibility gene. To understand the ...contribution of Nrg1 signaling to adult brain structure and behaviors, we studied the regulation of type III Nrg1 expression and evaluated the effect of decreased expression of the type III Nrg1 isoforms. Type III Nrg1 is transcribed by a promoter distinct from those for other Nrg1 isoforms and, in the adult brain, is expressed in the medial prefrontal cortex, ventral hippocampus, and ventral subiculum, regions involved in the regulation of sensorimotor gating and short-term memory. Adult heterozygous mutant mice with a targeted disruption for type III Nrg1 (Nrg1(tm1.1Lwr+/-)) have enlarged lateral ventricles and decreased dendritic spine density on subicular pyramidal neurons. Magnetic resonance imaging of type III Nrg1 heterozygous mice revealed hypofunction in the medial prefrontal cortex and the hippocampal CA1 and subiculum regions. Type III Nrg1 heterozygous mice also have impaired performance on delayed alternation memory tasks, and deficits in prepulse inhibition (PPI). Chronic nicotine treatment eliminated differences in PPI between type III Nrg1 heterozygous mice and their wild-type littermates. Our findings demonstrate a role of type III Nrg1 signaling in the maintenance of corticostriatal components and in the neural circuits involved in sensorimotor gating and short-term memory.
Gamma-ray bursts (GRBs) are the most powerful explosions known in the universe. Sensitive measurements of the high-energy spectra of GRBs can place important constraints on the burst environments and ...radiation processes. Until recently, there were no observations during the first few minutes of GRB afterglows in the energy range between 30 GeV and {approx}1 TeV. With the launch of the Swift GRB Explorer in late 2004, GRB alerts and localizations within seconds of the bursts became available. The Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE) was a ground-based, gamma-ray telescope with an energy threshold of {approx}150 GeV for sources at zenith. At the time of Swift's launch, STACEE was in a rare position to provide >150 GeV follow-up observations of GRBs as fast as three minutes after the burst alert. In addition, STACEE performed follow-up observations of several GRBs that were localized by the HETE-2 and INTEGRAL satellites. Between 2002 June and 2007 July, STACEE made follow-up observations of 23 GRBs. Upper limits are placed on the high-energy gamma-ray fluxes from 21 of these bursts.
The diverse physiological actions of dopamine are mediated by its interaction with two basic types of G protein-coupled receptor, D1 and D2, which stimulate and inhibit, respectively, the enzyme ...adenylyl cyclase. Alterations in the number or activity of these receptors may be a contributory factor in diseases such as Parkinson's disease and schizophrenia. Here we describe the isolation and characterization of the gene encoding a human D1 dopamine receptor. The coding region of this gene is intronless, unlike the gene encoding the D2 dopamine receptor. The D1 receptor gene encodes a protein of 446 amino acids having a predicted relative molecular mass of 49,300 and a transmembrane topology similar to that of other G protein-coupled receptors. Transient or stable expression of the cloned gene in host cells established specific ligand binding and functional activity characteristic of a D1 dopamine receptor coupled to stimulation of adenylyl cyclase. Northern blot analysis and in situ hybridization revealed that the messenger RNA for this receptor is most abundant in caudate, nucleus accumbens and olfactory tubercle, with little or no mRNA detectable in substantia nigra, liver, kidney, or heart. Several observations from this work in conjunction with results from other studies are consistent with the idea that other D1 dopamine receptor subtypes may exist.
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