General personality dimensions, impairment and treatment response in obsessive-compulsive disorder.

General personality dimensions are associated with clinical severity and treatment response in individuals with depression and many anxiety disorders, but little is known about these relationships in individuals with obsessive-compulsive disorder (OCD). Individuals in the current study included 705 adults with OCD who had participated in family and genetic studies of the disorder. Participants self-completed the Neuroticism, Extraversion, Openness Personality Inventory or Neuroticism, Extraversion, Openness Five-Factor Inventory-3.

Correction: Behavioral and synaptic alterations relevant to obsessivecompulsive disorder in mice with increased EAAT3 expression.

The original version of this Article contained an error in the spelling of the author Anna K Radke, which was incorrectly given as Anna R Radke. This has now been corrected in both the PDF and HTML versions of the Article.

Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression.

Obsessive-compulsive disorder (OCD) is a severe, chronic neuropsychiatric disorder with a strong genetic component. The SLC1A1 gene encoding the neuronal glutamate transporter EAAT3 has been proposed as a candidate gene for this disorder. Gene variants affecting SLC1A1 expression in human brain tissue have been associated with OCD.

Self-reported executive function and hoarding in adults with obsessive-compulsive disorder.

Background: Hoarding behavior may distinguish a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Little is known about the relationship between executive dysfunction and hoarding in individuals with OCD.

Methods: The study sample included 431 adults diagnosed with DSM-IV OCD.

Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice.

Background: Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric condition affecting 1-3% of the worldwide population. OCD has a strong genetic component, and the SLC1A1 gene that encodes neuronal glutamate transporter EAAT3 is a strong candidate for this disorder. To evaluate the impact of reduced EAAT3 expression in vivo, we studied male EAAT3 heterozygous and wild-type littermate mice using a battery of behavioral paradigms relevant to anxiety (open field test, elevated plus maze) and compulsivity (marble burying), as well as locomotor activity induced by amphetamine.

Genome Wide Association Study (GWAS) between Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD).

The aim of this study was to identify any potential genetic overlap between attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). We hypothesized that since these disorders share a sub-phenotype, they may share common risk alleles. In this manuscript, we report the overlap found between these two disorders.

An investigation of doubt in obsessive-compulsive disorder.

Background: Clinicians have long considered doubt to be a fundamental characteristic of obsessive-compulsive disorder (OCD). However, the clinical relevance of doubt in OCD has not been addressed.

Methods: Participants included 1182 adults with OCD who had participated in family and genetic studies of OCD.

Parental bonding and hoarding in obsessive-compulsive disorder.

Background: Hoarding behavior may indicate a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Empirical evidence supports a relationship between hoarding and emotional over-attachment to objects. However, little is known about the relationship between hoarding and parental attachment in OCD.

ADHD and executive functioning deficits in OCD youths who hoard.

Hoarding is common among youth with obsessive compulsive disorder (OCD), with up to 26% of OCD youth exhibiting hoarding symptoms. Recent evidence from adult hoarding and OCD cohorts suggests that hoarding symptoms are associated with executive functioning deficits similar to those observed in subjects with attention deficit hyperactivity disorder (ADHD). However, while hoarding behavior often onsets during childhood, there is little information about executive function deficits and ADHD in affected children and adolescents.

OBSESSIVE-COMPULSIVE PERSONALITY DISORDER: EVIDENCE FOR TWO DIMENSIONS.

Background: To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage.

Methods: Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors.

Methylone-induced hyperthermia and lethal toxicity: role of the dopamine and serotonin transporters.

Methylone (2-methylamino-1-[3,4-methylenedioxy-phenyl]propan-1-one), an amphetamine analog, has emerged as a popular drug of abuse worldwide. Methylone induces hyperthermia, which is thought to contribute toward the lethal consequences of methylone overdose. Methylone has been assumed to induce hyperthermic effects through inhibition of serotonin and/or dopamine transporters (SERT and DAT, respectively).

Attenuated methamphetamine-induced locomotor sensitization in serotonin transporter knockout mice is restored by serotonin 1B receptor antagonist treatment.

Repeated administration of methamphetamine (METH) enhances acute locomotor responses to METH administered in the same context, a phenomenon termed as 'locomotor sensitization'. Although many of the acute effects of METH are mediated by its influences on the compartmentalization of dopamine, serotonin systems have also been suggested to influence the behavioral effects of METH in ways that are not fully understood. The present experiments examined serotonergic roles in METH-induced locomotor sensitization by assessing: (a) the effect of serotonin transporter (SERT; Slc6A4) knockout (KO) on METH-induced locomotor sensitization; (b) extracellular monoamine levels in METH-treated animals as determined by in-vivo microdialysis; and (c) effects of serotonin (5-HT) receptor antagonists on METH-induced behavioral sensitization, with focus on effects of the 5-HT1B receptor antagonist SB 216641 and a comparison with the 5-HT2 receptor antagonist ketanserin.

Hoarding in Children and Adolescents with Obsessive-Compulsive Disorder.

Compared to studies in adults, there have been few studies of hoarding in children and adolescents with obsessive-compulsive disorder (OCD). In the current study, we evaluated OCD clinical features, Axis I disorders, and social reciprocity scores in 641 children and adolescents with OCD, of whom 163 (25%) had hoarding compulsions and 478 did not. We found that, as a group, youth with hoarding had an earlier age at onset and more severe lifetime OCD symptoms, poorer insight, more difficulty making decisions and completing tasks, and more overall impairment.

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.

Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.

Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date.

Method: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls.

Clinical correlates and genetic linkage of social and communication difficulties in families with obsessive-compulsive disorder: Results from the OCD Collaborative Genetics Study.

Some individuals with obsessive-compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical examinations on, and collected DNA samples from, 706 individuals with OCD in 221 multiply affected OCD families.

Developmental alterations in anxiety and cognitive behavior in serotonin transporter mutant mice.

Rationale: A promoter variant of the serotonin transporter (SERT) gene is known to affect emotional and cognitive regulation. In particular, the "short" allelic variant is implicated in the etiology of multiple neuropsychiatric disorders. Heterozygous (SERT(+/-)) and homozygous (SERT(-/-)) SERT mutant mice are valuable tools for understanding the mechanisms of altered SERT levels.

The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction.

The human SLC6 family is composed of approximately 20 structurally related symporters (co-transporters) that use the transmembrane electrochemical gradient to actively import their substrates into cells. Approximately half of the substrates of these transporters are amino acids, with others transporting biogenic amines and/or closely related compounds, such as nutrients and compatible osmolytes. In this short review, five leaders in the field discuss a number of currently important research themes that involve SLC6 transporters, highlighting the integrative role they play across a wide spectrum of different functions.

Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.

Characterization of SLITRK1 variation in obsessive-compulsive disorder.

Obsessive compulsive disorder (OCD) is a syndrome characterized by recurrent and intrusive thoughts and ritualistic behaviors or mental acts that a person feels compelled to perform. Twin studies, family studies, and segregation analyses provide compelling evidence that OCD has a strong genetic component. The SLITRK1 gene encodes a developmentally regulated stimulator of neurite outgrowth and previous studies have implicated rare variants in this gene in disorders in the OC spectrum, specifically Tourette syndrome (TS) and trichotillomania (TTM).

Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette's disorder.

To evaluate the hypothesis that functionally over-expressing alleles of the serotonin transporter (SERT) gene (solute carrier family 6, member 4, SLC6A4) are present in Tourette's disorder (TD), just as we previously observed in obsessive compulsive disorder (OCD), we evaluated TD probands (N = 151) and controls (N = 858). We genotyped the refined SERT-linked polymorphic region 5-HTTLPR/rs25531 and the associated rs25532 variant in the SLC6A4 promoter plus the rare coding variant SERT isoleucine-to-valine at position 425 (I425V). The higher expressing 5-HTTLPR/rs25531 LA allele was more prevalent in TD probands than in controls (χ(2)  = 5.

Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive-compulsive disorder as an example of overlapping clinical and genetic heterogeneity.

Individuals with obsessive-compulsive disorder (OCD) have also been shown to have comorbid lifetime diagnoses of major depressive disorder (MDD; rates greater than 70%), bipolar disorder (rates greater than 10%) and other anxiety disorders (e.g. panic disorder, post-traumatic stress disorder (PTSD)).

An evaluation of the serotonin system and perseverative, compulsive, stereotypical, and hyperactive behaviors in dopamine transporter (DAT) knockout mice.

Rationale: Mice lacking the dopamine transporter (DAT) display major behavioral alterations that include hyperactivity, perseverative locomotor patterns, and reduced prepulse inhibition of the acoustic startle reflex.

Objectives: The objectives of this study were to investigate perseverative, compulsive, stereotypical, and hyperactive behaviors, as well as serotonin and its involvement with these behaviors, in DAT gene-altered mice.

Results: In the open field, mean turn angle and meandering were decreased in DAT knockout (DAT-KO) mice.

5HTTLPR: White Knight or Dark Blight?

In over 100 neuroscience genetics reports on SLC6A4 published in the first part of 2012, >40% reported data from genotyping only the serotonin transporter-linked promoter region [5HTTLPR] indel, omitting genotyping of two nearby SNPs that substantially alter 5HTTLPR allele frequencies and functionality. And 25% of these papers did not report ethnicity of the subjects genotyped, another factor that alters allele frequencies. This field thus seems stultified.

Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome.

Dysfunction of the γ-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive-compulsive disorder. The purpose of this study was to identify a possible dysfunction of the γ-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls.