Phenomenological features and clinical impact of affective disorders in OCD: a focus on the bipolar disorder and OCD connection

Given the general population prevalence rates of obsessive compulsive disorder (OCD) and the affective disorders, one would expect the co-occurrence of these syndromes to be rare. Yet findings by our group and others have revealed extremely high rates of comorbidity in OCD with both depressive disorders (DD; 50%) and bipolar disorder (BPD; 10%). The current investigation sought to further clarify the role affective disorder comorbidity-particularly that with BPD-may play in the clinical expression of OCD. A total of 605 individuals with OCD were evaluated with the Structured Clinical Interview for DSM-IV. The sample included three groups: BPD (bipolar I or II; N = 79, 13.1%), DD (major depression or dysthymia; N = 388, 64.1%), and NAD (no affective disorder comorbidity; N = 138, 22.8%). Group-wise comparisons were conducted on comorbidity patterns, impairment measures, and clinical features of OCD. Analyses revealed a graded severity pattern, with the BPD group as the most severe, followed by the DD group, and finally the NAD group. Severity was reflected by the total number of Axis I disorders (P<.01), the number of psychiatric hospitalizations (P<.001), impairment measures (Ps<.05), and OCD symptoms (P<.01). It is worth noting that the impairment and OCD symptom severity findings were not attributable to the higher level of nonmood disorder comorbidities in the BPD and DD groups. Those individuals with comorbid affective disorders, particularly BPD, represent a clinically severe group compared to those without such comorbidity. Clarifying the phenomenological features of OCD-affective disorder comorbidity has important etiological and treatment implications

Exploring the Association Between Obsessive-Compulsive Symptoms and Loneliness: Consideration of Specificity and Gender

Loneliness, or perceived social isolation, is associated with a range of adverse physical and emotional outcomes. In particular, feeling lonely has been linked with anxiety, anger, stress, and depressive symptoms. Although loneliness has been extensively investigated with respect to depression and social anxiety, few studies have considered the relationship between loneliness and obsessive-compulsive symptoms (OCS). Loneliness may be particularly relevant to OCS given the social stigma associated with obsessions and compulsions along with high comorbidity between OCS and depression. The overarching aim of this investigation was to examine the relationship between OCS and loneliness in a young adult sample (N = 395) recruited from a large university. Participants completed self-report measures of OCS, loneliness, depression, and social anxiety. Higher levels of OCS were associated with greater perceived loneliness, and this relationship remained significant despite controlling for depression and social anxiety. OCS had a significant association with the isolation facet of loneliness, and loneliness in turn was uniquely associated with obsessions and checking symptoms. Gender differences were examined, which indicated that females with high OCS endorsed the greatest levels of loneliness. Implications for clinical research and treatment are discussed

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

ABSTRACT 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 (χ2 = 5.75; P = 0.017; odds ratio [OR], 1.35); and, in a secondary analysis, surprisingly, it was significantly more frequent in probands who had TD alone than in those who had TD plus OCD (Fisher's exact test; P = 0.0006; OR, 2.29). Likewise, the higher expressing LAC haplotype (5‐HTTLPR/rs25531/rs25532) was more frequent in TD probands than in controls (P = 0.024; OR, 1.33) and also in the TD alone group versus the TD plus OCD group (P = 0.0013; OR, 2.14). Furthermore, the rare gain‐of‐function SERT I425V variant was observed in 3 male siblings with TD and/or OCD and in their father. Thus, the cumulative count of SERT I425V becomes 1.57% in OCD/TD spectrum conditions versus 0.15% in controls, with a recalculated, family‐adjusted significance of χ2 = 15.03 (P < 0.0001; OR, 9.0; total worldwide genotyped, 2914). This report provides a unique combination of common and rare variants in one gene in TD, all of which are associated with SERT gain of function. Thus, altered SERT activity represents a potential contributor to serotonergic abnormalities in TD. The present results call for replication in a similarly intensively evaluated sample. © 2013 Movement Disorder Societ

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

The recent finding that the neuronal cadherin gene CDH2 confers a highly significant risk for canine compulsive disorder led us to investigate whether missense variants within the human ortholog CDH2 are associated with altered susceptibility to obsessive-compulsive disorder (OCD), Tourette disorder (TD) and related disorders. Exon resequencing of CDH2 in 320 individuals identified four non-synonymous single-nucleotide variants, which were subsequently genotyped in OCD probands, Tourette disorder probands and relatives, and healthy controls (total N=1161). None of the four variants was significantly associated with either OCD or TD. One variant, N706S, was found only in the OCD/TD groups, but not in controls. By examining clinical data, we found there were significant TD-related phenotype differences between those OCD probands with and without the N845S variant with regard to the co-occurrence of TD (Fisher\u27s exact test P=0.014, OR=6.03). Both N706S and N845S variants conferred reduced CDH2 protein expression in transfected cells. Although our data provide no overall support for association of CDH2 rare variants in these disorders considered as single entities, the clinical features and severity of probands carrying the uncommon non-synonymous variants suggest that CDH2, along with other cadherin and cell adhesion genes, is an interesting gene to pursue as a plausible contributor to OCD, TD and related disorders with repetitive behaviors, including autism spectrum disorders

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)). In addition, overlap exists in some common genetic variants (e.g. the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor (BDNF) gene), and rare variants in genes/chromosomal abnormalities (e.g. the 22q11 microdeletion syndrome) found across the affective/anxiety disorder spectrums. OCD has been proposed as a possible independent entity for DSM-5, but by others thought best retained as an anxiety disorder subtype (its current designation in DSM-IV), and yet by others considered best in the affective disorder spectrum. This review focuses on OCD, a well-studied but still puzzling heterogeneous disorder, regarding alterations in serotonergic, dopaminergic and glutamatergic neurotransmission in addition to other systems involved, and how related genes may be involved in the comorbidity of anxiety and affective disorders. OCD resembles disorders such as depression, in which gene × gene interactions, gene × environment interactions and stress elements coalesce to yield OC symptoms and, in some individuals, full-blown OCD with multiple comorbid disorders