Rudolf Hoehn-Saric

Hoarding in obsessive compulsive disorder: results from a case-control study

Hoarding occurs relatively frequently in obsessive-compulsive disorder (OCD), and there is evidence that patients with hoarding symptoms have more severe OCD and are less responsive to treatment. In the present study, we investigated hoarding symptoms in 126 subjects with OCD. Nearly 30% of the subjects had hoarding symptoms; hoarding was twice as prevalent in males than females. Compared to the 90 non-hoarding subjects, the 36 hoarding individuals had an earlier age at onset of, and more severe, obsessive-compulsive symptoms. Hoarders had greater prevalences of symmetry obsessions, counting compulsions, and ordering compulsions. Hoarders also had greater prevalences of social phobia, personality disorders, and pathological grooming behaviors (skin picking, nail biting, and trichotillomania). Hoarding and tics were more frequent in first-degree relatives of hoarding than non-hoarding probands. The findings suggest that the treatment of OCD patients with hoarding symptoms may be complicated by more severe OCD and the presence of co-occurring disorders. Hoarding appears to be transmitted in some OCD families and may differentiate a clinical subgroup of OCD.

SYSTEMATIC PREPARATION OF PATIENTS FOR PSYCHOTHERAPY. I. EFFECTS ON THERAPY BEHAVIOR AND OUTCOME.

OUR PREVIOUS studies have suggested that certain effects of psychotherapy and placebos on psychiatric outpatients may depend on the potentiation and activation of the patient’s favorable expectations.(Q) GOLDSTEIN(~) has pointed out the important role played by the patient’s expectations that he will improve, that he will receive a certain type of treatment, and that. he and the thergpist will behave in ctrtain ways. This paper reports a controlled study of the effects on psychiatric outpatients of a pre-treatment interview designed to clarify their expectations of psychotherapy and to increase the congruence of their behavior with therapists’ expectations as to how psychiatric patients should act. We tested the hypotheses that such an interview would favorably affect patient’s behavior during therapy and the outcome after four months of treatment. Because of the diversity and ambiguities of public conceptions of mental illness and psychotherapy, psychiatric patients reach the psychiatrist’s office with a wide variety of attitudes and expectations. Only the most sophisticated are perfectly clear about why they are there and what they expect (Ref. 4. p. 128). Less sophisticated patients may have unrealistic expectations for improvement: they may not understand their role in the therapeutic process@) and may be bewildered by a procedure that differs not only from usual medical treatment but from customary social interactions. As LENNARD and BERNSTEIN comment (Ref. 6, p. 26) : “Dissymetry of expectations not only interferes with the therapeutic task, but can actually lead to the premature death of a therapeutic system.” This might be an important reason why patients who are less educated and have a different cultural background than most therapists tend to terminate treatment prematurely.(‘W)

The relationship between obsessive-compulsive disorder and anxiety and affective disorders: Results from the Johns Hopkins OCD family study

OBJECTIVE This study investigates the relationship of specific anxiety and affective disorders to obsessive-compulsive disorder (OCD) in a blind, controlled family study. METHOD Eighty case and 73 control probands, as well as 343 case and 300 control first-degree relatives of these probands, participated in the study. Subjects were examined by psychologists or psychiatrists using the Schedule for Affective Disorder and Schizophrenia-Lifetime Anxiety version (SADS-LA). Two experienced psychiatrists independently reviewed all clinical materials, and final diagnoses were made according to DSM-IV criteria, by consensus procedure. RESULTS Except for bipolar disorder, all anxiety and affective disorders investigated were more frequent in case than control probands. Substance dependence disorders were not more frequent. Generalized anxiety disorder (GAD), panic disorder, agoraphobia, separation anxiety disorder (SAD) and recurrent major depression were more common in case than control relatives. These disorders occurred more frequently if the relative was diagnosed with OCD. Only GAD and agoraphobia were more frequent in case relatives independent of OCD. CONCLUSION GAD and agoraphobia share a common familial aetiology with OCD. The other anxiety and affective disorders, when comorbid with OCD, may emerge as a consequence of the OCD or as a more complex syndrome.

The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD family study

BACKGROUND Obsessive-compulsive disorder (OCD) and tic disorders have phenomenological and familial-genetic overlaps. An OCD family study sample that excludes Tourettes syndrome in probands is used to examine whether tic disorders are part of the familial phenotype of OCD. METHODS Eighty case and 73 control probands and their first-degree relatives were examined by experienced clinicians using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. DSM-IV psychiatric diagnoses were ascertained by a best-estimate consensus procedure. The prevalence and severity of tic disorders, age-at-onset of OCD symptoms, and transmission of OCD and tic disorders by characteristics and type of proband (OCD + tic disorder, OCD - tic disorder) were examined in relatives. RESULTS Case probands and case relatives had a greater lifetime prevalence of tic disorders compared to control subjects. Tic disorders spanning a wide severity range were seen in case relatives; only mild severity was seen in control relatives. Younger age-at-onset of OCD symptoms and possibly male gender in case probands were associated with increased tic disorders in relatives. Although relatives of OCD + tic disorder and OCD - tic disorder probands had similar prevalences of tic disorders, this result is not conclusive. CONCLUSIONS Tic disorders constitute an alternate expression of the familial OCD phenotype.

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. RESULTS After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01). CONCLUSIONS Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.

Replication Study Supports Evidence for Linkage to 9p24 in Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is characterized by intrusive and senseless thoughts and impulses (obsessions) and by repetitive behaviors (compulsions). Family, twin, and segregation studies support the presence of both genetic and environmental susceptibility factors, and the only published genome scan for OCD identified a candidate region on 9p24 at marker D9S288 that met criteria for suggestive significance (Hanna et al. 2002). In an attempt to replicate this finding, we genotyped 50 pedigrees with OCD, using microsatellite markers spanning the 9p24 candidate region, and analyzed the data, using parametric and nonparametric linkage analyses under both a narrow phenotype model (DSM-IV OCD definite; 41 affected sib pairs) and a broad phenotype model (DSM-IV OCD definite and probable; 50 affected sib pairs). Similar to what was described by Hanna et al. (2002), our strongest findings came with the dominant parameters and the narrow phenotype model: the parametric signal peaked at marker D9S1792 with an HLOD of 2.26 ( alpha =0.59), and the nonparametric linkage signal (NPL) peaked at marker D9S1813 with an NPL of 2.52 (P=.006). These findings are striking in that D9S1813 and D9S1792 lie within 0.5 cM (<350 kb) of the original 9p24 linkage signal at D9S288; furthermore, pedigree-based association analyses also implicated the 9p24 candidate region by identifying two markers (D9S288 and GATA62F03) with modest evidence (P=.046 and .02, respectively) for association.

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. We conducted a genome-scan analysis of 219 families collected as part of the OCD Collaborative Genetics Study. Suggestive linkage signals were revealed by multipoint analysis on chromosomes 3q27–28 (P=0.0003), 6q (P=0.003), 7p (P=0.001), 1q (P=0.003), and 15q (P=0.006). Using the ‘broad’ OCD definition, we observed the strongest evidence for linkage on chromosome 3q27-28. The maximum overall Kong and Cox LODall score (2.67) occurred at D3S1262 and D3S2398, and simulation based P-values for these two signals were 0.0003 and 0.0004, respectively, although for both signals, the simulation-based genome-wide significance levels were 0.055. Covariate-linkage analyses implicated a possible role of gene(s) on chromosome 1 in increasing the risk for an earlier onset form of OCD. We are currently pursuing fine mapping in the five regions giving suggestive signals, with a particular focus on 3q27–28. Given probable etiologic heterogeneity in OCD, mapping gene(s) involved in the disorder may be enhanced by replication studies, large-scale family-based linkage studies, and the application of novel statistical methods.

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. The authors treated compulsive hoarding as the phenotype of interest and also stratified families into those with and without two or more relatives affected with compulsive hoarding. RESULTS Using compulsive hoarding as the phenotype, there was suggestive linkage to chromosome 14 at marker D14S588 (Kong and Cox logarithm of the odds ratio [LOD] [KAC(all)=2.9]). In families with two or more hoarding relatives, there was significant linkage of OCD to chromosome 14 at marker C14S1937 (KAC(all)=3.7), whereas in families with fewer than two hoarding relatives, there was suggestive linkage to chromosome 3 at marker D3S2398 (KAC(all)=2.9). CONCLUSIONS The findings suggest that a region on chromosome 14 is linked with compulsive hoarding behavior in families with OCD.

Complex Segregation Analysis Provides Compelling Evidence for a Major Gene Underlying Obsessive-Compulsive Disorder and for Heterogeneity by Sex

Evidence from twin and family studies supports a genetic etiology for obsessive-compulsive disorder (OCD). The purpose of this study was to test whether a major gene is implicated in a proportion of families with OCD. Complex segregation analyses of 153 families (80 case and 73 control), ascertained in the Johns Hopkins OCD Family Study, provided strong evidence for a major gene. A Mendelian-dominant model, with significant sex effects and with residual familial effects, best explained the observed data. Stratification of the sample by the sex of probands provided further evidence of heterogeneity with respect to familial aggregation. Segregation analyses of 86 families with a female proband and of the 67 families with a male proband suggested that a Mendelian-dominant model with familial residual effects was the most parsimonious model explaining the inheritance of OCD in both subgroups.

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. We conducted family‐based association analyses using the FBAT and GenAssoc statistical packages. Thirty‐two percent of the 1,618 participants met criteria for a GD, and 65% met criteria for OCD. Four of six SNPs were nominally associated (P < 0.05) with at least one GD (genotypic relative risks: 1.6–3.3), and all three haplotypes were nominally associated with at least one GD (permuted P < 0.05). None of the SNPs or haplotypes were significantly associated with OCD itself. We conclude that Sapap3 is a promising functional candidate gene for human GDs, though further work is necessary to confirm this preliminary evidence of association.