Functional MRI of the amygdala and bed nucleus of the stria terminalis during conditions of uncertainty in generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a common psychiatric disorder characterized by constant worry or anxiety over every day life activities and events. The neurobiology of the disorder is thought to involve a wide cortical and subcortical network that includes but is not limited to the amygdala and the bed nucleus of the stria terminalis (BNST). These two regions have been hypothesized to play different roles in stress and anxiety; the amygdala is thought to regulate responses to brief emotional stimuli while the BNST is thought to be involved in more chronic regulation of sustained anxiety.

Generalized anxiety modulates frontal and limbic activation in major depression.

Background: Anxiety is relatively common in depression and capable of modifying the severity and course of depression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited.

Methods: We used functional magnetic resonance imaging and two emotional information processing tasks to examine frontal and limbic activation in ten patients with major depression and comorbid with preceding generalized anxiety (MDD/GAD) and ten non-depressed controls.

A family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder in 378 families.

SLC1A encodes the neuronal and epithelial glutamate transporter and was previously tested as a candidate for obsessive-compulsive disorder (OCD) by several research groups. Recently, three independent research groups reported significant association findings between OCD and several genetic variants in SLC1A1. This study reports the results from a family-based association study, which examined the association between 13 single nucleotide polymorphisms (SNPs) within or in proximity to the SLC1A1 gene.

Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study.

SAP90/PSD95-associated protein (SAPAP) family proteins are post-synaptic density (PSD) components that interact with other proteins to form a key scaffolding complex at excitatory (glutamatergic) synapses. A recent study found that mice with a deletion of the Sapap3 gene groomed themselves excessively, exhibited increased anxiety-like behaviors, and had cortico-striatal synaptic defects, all of which were preventable with lentiviral-mediated expression of Sapap3 in the striatum; the behavioral abnormalities were also reversible with fluoxetine. In the current study, we sought to determine whether variation within the human Sapap3 gene was associated with grooming disorders (GDs: pathologic nail biting, pathologic skin picking, and/or trichotillomania) and/or obsessive-compulsive disorder (OCD) in 383 families thoroughly phenotyped for OCD genetic studies.

Sex-specific clinical correlates of hoarding in obsessive-compulsive disorder.

Little is known about whether the clinical correlates of hoarding behavior are different in men and women with obsessive-compulsive disorder (OCD). In the current study, we evaluated the association of hoarding with categories of obsessions and compulsions, psychiatric disorders, personality dimensions, and other clinical characteristics separately in 151 men and 358 women with OCD who were examined during the OCD Collaborative Genetics Study. We found that, among men but not women, hoarding was associated with aggressive, sexual, and religious obsessions and checking compulsions.

Further development of YBOCS dimensions in the OCD Collaborative Genetics study: symptoms vs. categories.

Despite progress in identifying homogeneous subphenotypes of obsessive-compulsive disorder (OCD) through factor analysis of the Yale Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC), prior solutions have been limited by a reliance on presupposed symptom categories rather than discrete symptoms. Furthermore, there have been few attempts to evaluate the familiality of OCD symptom dimensions. The purpose of this study was to extend prior work by this collaborative group in category-based dimensions by conducting the first-ever exploratory dichotomous factor analysis using individual OCD symptoms, comparing these results to a refined category-level solution, and testing the familiality of derived factors.

Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families.

Several clinical and genetic studies have reported gender differences in obsessive-compulsive disorder (OCD). Previously, we conducted a linkage genome scan using multipoint allele-sharing methods to test for linkage in 219 families participating in the OCD Collaborative Genetics Study. When these families were stratified by proband's gender, suggestive linkage to chromosome 11p15 at marker D11S2362 (KAC(all) = 2.

Social and communication difficulties and obsessive-compulsive disorder.

Background: The relationship between pervasive developmental disorder (PDD) and obsessive-compulsive disorder (OCD) has not been extensively studied despite having some phenomenological features in common. Abnormal social and communication behaviors (pragmatic behaviors) are key components of PDD and are also part of the broader autism phenotype (BAP). In this study we sought to establish if there is any association between the presence of abnormal pragmatic behaviors and OCD and whether this association delineates a familial subtype of OCD.

Evidence for potential relationship between SLC1A1 and a putative genetic linkage region on chromosome 14q to obsessive-compulsive disorder with compulsive hoarding.

Obsessive-compulsive disorder (OCD) is likely a disorder involving complex genetic transmission. This suggests that multiple genetic and environmental factors are involved in its etiology. This is complicated further by the probability of genetic heterogeneity for this phenotype.

Neural correlates of derived relational responding on tests of stimulus equivalence.

Background: An essential component of cognition and language involves the formation of new conditional relations between stimuli based upon prior experiences. Results of investigations on transitive inference (TI) highlight a prominent role for the medial temporal lobe in maintaining associative relations among sequentially arranged stimuli (A > B > C > D > E). In this investigation, medial temporal lobe activity was assessed while subjects completed "Stimulus Equivalence" (SE) tests that required deriving conditional relations among stimuli within a class (A identical with B identical with C).

Proton magnetic resonance spectroscopy in obsessive-compulsive disorder: a pilot investigation comparing treatment responders and non-responders.

Proton magnetic resonance spectroscopic imaging was performed to compare brain metabolism in patients with obsessive-compulsive OCD. Evaluation was done on responders and non-responders to pharmacotherapy and on healthy controls. The results showed significantly lower NAA/Cr ratios in the right basal ganglia in non-responders than in responders or in controls and higher Cho/Cr ratios in the right thalamus in non-responders than responders.

New knowledge derived from learned knowledge: functional-anatomic correlates of stimulus equivalence.

Forming new knowledge based on knowledge established through prior learning is a central feature of higher cognition that is captured in research on stimulus equivalence (SE). Numerous SE investigations show that reinforcing behavior under control of distinct sets of arbitrary conditional relations gives rise to stimulus control by new, derived relations. This investigation examined whether frontal-subcortical and frontal-parietal networks known to support reinforced conditional relations also support derived conditional relations.

Demographic and clinical characteristics associated with treatment status in family members with obsessive-compulsive disorder.

This study investigated the demographic and clinical factors that influence treatment status in family members with obsessive compulsive disorder (OCD). Six hundred and two subjects from the OCD Collaborative Genetics Study were interviewed using the Structured Clinical Interview for DSM-IV (SCID) to diagnose Axis I disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for assessment of OCD symptoms. The demographic and clinical data were compared between subjects who had received treatment and those who had not.

Arousal modulation in females with fragile X or Turner syndrome.

The present study was carried out to examine physiological arousal modulation (heart activity and skin conductance, across baseline and cognitive tasks, in females with fragile X or Turner syndrome and a comparison group of females with neither syndrome. Relative to the comparison group, for whom a greater increase in skin conductance was associated with poor arithmetic performance and less risk taking behavior, females with fragile X displayed a minimal increase in heart activity that was nevertheless associated with poor performance on mental arithmetic. In contrast, no arousal-cognitive performance relationship emerged for the group with Turner syndrome.

Significant linkage to compulsive hoarding on chromosome 14 in families with obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study.

Objective: Individuals with obsessive-compulsive disorder (OCD) who have compulsive hoarding behavior are clinically different from other OCD-affected individuals. The objective of this study was to determine whether there are chromosomal regions specifically linked to compulsive hoarding behavior in families with obsessive-compulsive disorder.

Methods: The authors used multipoint allele-sharing methods to assess for linkage in 219 multiplex OCD families collected as part of the OCD Collaborative Genetics Study.

Premenstrual symptomatology, alcohol consumption, and family history of alcoholism in women with premenstrual syndrome.

Objective: The purpose of this study was to examine the relationship among family history of alcoholism (FH), premenstrual syndrome (PMS) symptoms, and alcohol consumption in women with a PMS diagnosis.

Method: Participants (N = 46) were predominantly white (73%) women, of whom 17 (37%) reported multigenerational alcoholism on the paternal side (FH positive [FH+]) using the Family Alcohol and Drug Survey. Subjects recorded alcohol consumption and PMS symptoms using a daily record form for 3 consecutive months.

Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

Background: Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions.

Methods: Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales.

Carbon dioxide provocation of anxiety and respiratory response in bipolar disorder.

Background: Frequent bipolar/panic comorbidity implies bipolar individuals may experience CO2-provoked anxiety and changes in respiratory patterns similar to those experienced by individuals with panic disorder.

Methods: 16 euthymic bipolar individuals breathed air and air combined with 5% CO2 for 15 min each. Respiratory and subjective anxiety measures were collected.

Factor analysis of the Yale-Brown Obsessive Compulsive Scale in a family study of obsessive-compulsive disorder.

Our objective in this study was to determine whether symptoms of obsessive-compulsive disorder (OCD) cluster into groups that can usefully subclassify OCD. Psychiatrists or psychologists interviewed 221 subjects using the Lifetime Anxiety Version of the Schedule for Affective Disorders and Schizophrenia (SADS-LA) for the diagnosis of DSM-IV disorders, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for OCD symptoms. We analyzed 16 symptom categories from the Y-BOCS using exploratory factor analysis to identify latent symptom dimensions.

Hoarding in obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study.

Hoarding behavior occurs frequently in obsessive-compulsive disorder (OCD). Results from previous studies suggest that individuals with OCD who have hoarding symptoms are clinically different than non-hoarders and may represent a distinct clinical group. In the present study, we compared 235 hoarding to 389 non-hoarding participants, all of whom had OCD, collected in the course of the OCD Collaborative Genetics Study.

Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q.

Obsessive-compulsive disorder (OCD) is the tenth most disabling medical condition worldwide. Twin and family studies implicate a genetic etiology for this disorder, although specific genes have yet to be identified. Here, we present the first large-scale model-free linkage analysis of both extended and nuclear families using both 'broad' (definite and probable diagnoses) and 'narrow' (definite only) definitions of OCD.

Normal physiological emotions but differences in expression of conscious feelings in children with high-functioning autism.

To provide insight into what aspects of the emotional circuit might be affected in high-functioning autism, we measured indices of physiological emotions and of the expression of conscious feelings in 10 children with high-functioning autism or Asperger syndrome and 10 comparison participants. Pleasant, unpleasant, and neutral pictures were presented while skin conductance responses were measured. Self-report ratings of pleasantness and interestingness were taken between pictures.

The OCD collaborative genetics study: methods and sample description.

Results from twin and family studies suggest that obsessive-compulsive disorder (OCD) may be transmitted in families but, to date, genes for the disorder have not been identified. The OCD Collaborative Genetics Study (OCGS) is a six-site collaborative genetic linkage study of OCD. Specimens and blinded clinical data will be made available through the National Institute of Mental Health (NIMH) cell repository.