Serotonin transporter gene polymorphism implicates reduced orbito-frontal cortex in obsessive–compulsive disorder

Atmaca, Murad; Önalan, Ebru Etem; Yıldırım, Hanefi; Yüce, Hüseyin; Koç, Mustafa; Korkmaz, Sevda; Mermi, Osman

doi:10.1016/j.janxdis.2011.03.002

Cited by 24 publications

(14 citation statements)

References 46 publications

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“…Consistent with these behavioral data, brain imaging studies demonstrate an association between the s allele and higher levels of amygdala activation in response to fearful stimuli (Furmark et al, 2004;Hariri et al, 2002;Kobiella et al, 2011;Murphy et al, 2013;Scharinger et al, 2010), reduced grey matter volumes in the dorsolateral PFC, amygdala and the HPC (Atmaca et al, 2011;Frodl et al, 2008;Kobiella et al, 2011;Pezawas et al, 2005), microstructural changes in the uncinate fasciclus, a white matter tract connecting limbic and frontal areas, including the amygdala and anterior cingulate cortex (Pacheco et al, 2009), and decreased coupling of the amygdala-anterior cingulate circuit (Heinz et al, 2005;Lemogne et al, 2011;Pezawas et al, 2005;Roiser et al, 2009;Shah et al, 2009;Volman et al, 2013). Importantly, functional coupling between the anterior cingulate cortex and the amygdala is correlated with trait anxiety (Hahn et al, 2011;Prater et al, 2013).…”

Section: Clinical Relevancementioning

confidence: 76%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

141

125

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Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context. While allowing for adaptation, such sensitive periods are also vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety-and depressionrelated behaviors, and (3) a dopamine-and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders.

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Section: Clinical Relevancementioning

confidence: 76%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

141

125

View full text Add to dashboard Cite

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“…As in OCD (Evans et al, 2004; Husted et al, 2006; Markarian et al, 2010) and as emphasized in the earlier two models (Sections 2 and 3), high stereotypic (H) deer mice also present with frontal cortical pathology, e.g., disordered redox balance (Guldenpfennig et al, 2011) and altered cyclic adenosine-monophosphate (cAMP)-phosphodiesterase (PDE) signaling (Korff et al, 2009). Finally, the 5-HT transporter (SERT) is the primary target for SSRI’s, while decreased SERT density in OCD (Atmaca et al, 2011; Matsumoto et al, 2010) is associated with increased symptom severity (Hesse et al, 2005; Reimold et al, 2007; Zitterl et al, 2008). H deer mice demonstrate decreased striatal but not frontal cortical SERT density (Wolmarans et al, 2013).…”

Section: Insights Into Ocd From the Deer Mouse: A Platform For Resmentioning

confidence: 99%

Obsessive-compulsive disorder: Insights from animal models

Szechtman

Ahmari

Beninger

et al. 2017

Neuroscience & Biobehavioral Reviews

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Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests.

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“…However, serotonergic binding results should be interpreted cautiously because binding effects appear to exert great impact through 5-HTTLPR genotypes (Willeit and Praschak-Rieder, 2010). At the structural level, magnetic resonance imaging was used to demonstrate that OCD patients carrying the S allele of 5-HTTLPR had smaller right OFC volumes than L allele carriers (Atmaca et al, 2011). At the genetic level, Lin et al (2007) used a meta-analysis to uncover a significant association between SS genotype and OCD (odds ratio = 1.21, 95% confidence interval = 1.01-1.45, p = 0.04).…”

Section: The Serotonergic Systemmentioning

confidence: 99%

“…Notably, genetic susceptibility effects are mediated by molecular and cellular mechanisms, which in turn modulate behavioral phenotypes by affecting the structural and functional properties of neural circuits (Atmaca et al, 2011;Hesse et al, 2011;MacMaster, 2010;Wu et al, 2012). Therefore, such translational studies that implement genetics and imaging techniques may reveal the etiology of OCD more precisely (MacMaster, 2010).…”

Section: Introductionmentioning

confidence: 99%

Imaging genetics in obsessive-compulsive disorder: Linking genetic variations to alterations in neuroimaging

Grünblatt

Hauser

Walitza

2014

Progress in Neurobiology

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Obsessive-compulsive disorder (OCD) occurs in ∼1-3% of the general population, and its often rather early onset causes major disabilities in the everyday lives of patients. Although the heritability of OCD is between 35 and 65%, many linkage, association, and genome-wide association studies have failed to identify single genes that exhibit high effect sizes. Several neuroimaging studies have revealed structural and functional alterations mainly in cortico-striato-thalamic loops. However, there is also marked heterogeneity across studies. These inconsistencies in genetic and neuroimaging studies may be due to the heterogeneous and complex phenotypes of OCD. Under the consideration that genetic variants may also influence neuroimaging in OCD, researchers have started to combine both domains in the field of imaging genetics. Here, we conducted a systematic search of PubMed and Google Scholar literature for articles that address genetic imaging in OCD and related disorders (published through March 2014). We selected 8 publications that describe the combination of imaging genetics with OCD, and extended it with 43 publications of comorbid psychiatric disorders. The most promising findings of this systematic review point to the involvement of variants in genes involved in the serotonergic (5-HTTLPR, HTR2A), dopaminergic (COMT, DAT), and glutamatergic (SLC1A1, SAPAP) systems. However, the field of imaging genetics must be further explored, best through investigations that combine multimodal imaging techniques with genetic profiling, particularly profiling techniques that employ polygenetic approaches, with much larger sample sizes than have been used up to now.

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Serotonin transporter gene polymorphism implicates reduced orbito-frontal cortex in obsessive–compulsive disorder

Cited by 24 publications

References 46 publications

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Obsessive-compulsive disorder: Insights from animal models

Imaging genetics in obsessive-compulsive disorder: Linking genetic variations to alterations in neuroimaging

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