Psychiatric disorders in first degree relatives of children and adolescents with obsessive compulsive disorder

One hundred and forty-five first-degree relatives (89 parents [96%] and 56 siblings [98%]) of 46 children and adolescents with severe primary obsessive compulsive disorder (OCD) were personally interviewed with clinical and structured psychiatric interviews. Parent interviews were scored by a rater blind to proband diagnosis. Thirty percent of probands had at least one first-degree relative with OCD: 25% of fathers and 9% of mothers received this diagnosis. Forty-five percent of fathers and 65% of mothers received one or more other psychiatric diagnoses. The increased familial rate of OCD over that expected from a general population, and over that found in parents of conduct disordered patients, is consistent with a genetic factor in OCD. Presenting obsessive compulsive symptoms of probands and their parents were usually dissimilar, arguing against any simple social or cultural transmission.     

Morbidity risk for obsessive-compulsive spectrum disorders in first-degree relatives of patients with eating disorders

OBJECTIVE: A hypothesis that eating disorders are a phenomenological variant of obsessive-compulsive disorder (OCD) has been proposed. This study was conducted to determine whether anorexia nervosa and bulimia, the two main eating disorders, are familial and whether the risk for obsessive-compulsive spectrum disorders (OCD and tic disorders) is higher in families of patients with eating disorders. METHOD: The morbidity risk for obsessive-compulsive spectrum disorders in first-degree relatives of 136 female probands with eating disorders (84 with anorexia nervosa, 52 with bulimia) was compared to that for first-degree relatives of 72 female comparison subjects. RESULTS: The morbidity risk for obsessive-compulsive spectrum disorders was significantly higher among the 436 relatives of the eating disorder probands than among the 358 relatives of the comparison subjects (9.69% versus 0%). This finding was independent of any comorbid diagnosis of an obsessive-compulsive spectrum disorder in the eating disorder probands. The eating disorder group and the comparison group did not differ in familial risk for eating disorders and tic disorders. CONCLUSIONS: To better understand the genetic components of eating disorders, these disorders should be considered as part of the obsessive-compulsive spectrum of disorders.     

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 Tourette's 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.     

Gilles de la Tourette's syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship

Previous studies have suggested that obsessive-compulsive symptoms frequently occur among patients with Gilles de la Tourette's syndrome (TS). To examine the relationship between TS and obsessive-compulsive disorder (OCD), data from all first-degree relatives of TS probands were obtained with a semistructured interview designed to collect information on the presence of TS, other tic disorders, and neuropsychiatric illnesses during the lifetime of the individual. The rate of OCD among first-degree relatives was significantly increased over estimates from the general population and a control sample of adoptive relatives. The rates of TS, OCD, and chronic multiple tics (CMT) were virtually the same in families of probands with OCD (TS +/- OCD) when compared with families of probands without OCD (TS - OCD). Finally, the frequency of OCD without TS or CMT among first-degree relatives was significantly elevated in families of both TS + OCD and TS - OCD probands, suggesting that some forms of OCD may represent an alternative expression of the factors responsible for TS and/or CMT.     

Anxiety and major depression comorbidity in a family study of obsessive-compulsive disorder

To understand the familial relationship between obsessive-compulsive disorder (OCD), other anxiety disorders, and major depressive disorder (MDD), we examined the rates of anxiety disorders and MDD in first-degree relatives of OCD probands and controls, the association between age at onset of OCD and the occurrence of other anxiety disorders and major depressive disorder in relatives of probands, and the co-transmission of specific anxiety disorders, MDD, and OCD within families of probands. Recurrence risks were estimated from 466 first-degree relatives of 100 probands with OCD and 113 first-degree relatives of 33 non-psychiatric controls. Rates of non-OCD anxiety disorders and MDD were comparable in relatives of OCD probands and controls. Rates of anxiety disorders and MDD were higher among case relatives with OCD than among case relatives without OCD and control relatives. Fifty percent of case relatives with OCD had at least one comorbid anxiety disorder. Early age at onset (<10 years) in probands was associated with higher rates of anxiety and depression comorbidity among case relatives with OCD but not among case relatives without OCD. The occurrence of specific anxiety disorders and MDD in case relatives was independent of the same comorbid diagnosis in the OCD probands. OCD, panic disorder, generalized anxiety disorder, and MDD occurred together more often than expected by chance among individuals with OCD. Furthermore, age at onset in probands is associated with specific anxiety and affective comorbidity among case relatives. These findings support the hypothesis that early- and late-onset OCD represent different etiologic variants.     

A family study of juvenile obsessive-compulsive disorder.

OBJECTIVES: To determine whether juvenile obsessive-compulsive disorder (OCD) is familial and whether the rate of Tourette syndrome (TS) and tic disorders is higher among relatives of patients with OCD than among relatives of controls subjects. METHOD: We assessed first-degree relatives of 35 juvenile OCD probands (aged 16 years or less) and 34 matched, psychiatrically unaffected control subjects, using the Diagnostic Interview for Children and Adolescents-Revised (DICA-R) (unpublished), a Questionnaire for tic disorders, the Children's Version of Leyton's Obsessional Inventory (CV-LOI), and the Children's Version of the Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Similarly, we assessed adult relatives, using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Leyton's Obsessional Inventory (LOI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and a Questionnaire for tic disorders. The diagnoses were determined by consensus, using DSM-III-R criteria. We calculated age-corrected morbid risk, using Weinberg's method. RESULTS: The morbid risk for OCD among the relatives of OCD probands was 4.96%, while none of the relatives of unaffected control subjects had OCD. We did not diagnose TS in any of the relatives of either OCD probands or control subjects. We diagnosed chronic motor tic disorders in only 1 of the relatives of OCD probands, while none of the relatives of control subjects had any tic disorder. CONCLUSION: Most juvenile cases of OCD are nonfamilial and unrelated to tic disorders, while only a few are familial. There is a need to re-examine the issue of familiality in cases of OCD, as well as its relation to TS, using larger community samples to better understand the hypotheses of familial transmission and comorbidity with tic disorders.     

The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study.

BACKGROUND: The familial relationship between obsessive-compulsive disorder (OCD) and "obsessive-compulsive spectrum" disorders is unclear. This study investigates the relationship of OCD to somatoform disorders (body dysmorphic disorder [BDD] and hypochondriasis), eating disorders (e.g., anorexia nervosa and bulimia nervosa), pathologic "grooming" conditions (e.g., nail biting, skin picking, trichotillomania), and other impulse control disorders (e.g., kleptomania, pathologic gambling, pyromania) using blinded family study methodology. METHODS: Eighty case and 73 control probands, as well as 343 case and 300 control first-degree relatives, were examined by psychiatrists or Ph.D. psychologists using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety version. Two experienced psychiatrists independently reviewed all diagnostic information and made final consensus diagnoses using DSM-IV criteria. RESULTS: Body dysmorphic disorder, hypochondriasis, any eating disorder, and any grooming condition occurred more frequently in case probands. In addition, BDD, either somatoform disorder, and any grooming condition occurred more frequently in case relatives, whether or not case probands also had the same diagnosis. CONCLUSIONS: These findings indicate that certain somatoform and pathologic grooming conditions are part of the familial OCD spectrum. Though other "spectrum" conditions may resemble OCD, they do not appear to be important parts of the familial spectrum.     

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

BACKGROUND: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD. METHODS: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education. RESULTS: In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency). CONCLUSIONS: Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.     

Mental disorders in first-degree relatives of schizophrenics

A total 215 first-degree relatives of 88 twin probands with schizophrenia, mood disorders and nonaffective psychoses were studied. The twins' parents and siblings were personally interviewed with structured diagnostic instruments and diagnosed in accordance with DSM-III-R criteria. The first-degree relatives were interviewed by interviewers who were blind to the twins' diagnoses. Schizophrenia and schizotypal personality disorder were significantly more frequent in first-degree relatives of schizophrenic twins. Respectively, anxiety and mood disorders were significantly more prevalent among the parents and siblings of probands with mood disorders. Schizophrenic spectrum disorders were significantly more common in the families of schizophrenic probands compared with relatives of mood disorder probands, thus confirming a relationship between schizophrenia and schizophrenic spectrum disorders. However, we cannot, based on our study, specify whether this relationship is caused by genetic or environmental factors.     

Childhood-onset obsessive-compulsive disorder and tic disorders: case report and literature review

A subgroup of childhood-onset obsessive-compulsive disorder (OCD) and tic disorders has been found to have a postinfectious autoimmune-mediated etiology. Clinical observations and systematic investigations have shown that a subgroup of children with OCD and/or tic disorders have the onset and subsequent exacerbations of their symptoms following infections with group A beta-hemolytic streptococci (GABHS). This subgroup has been designated by the acronym PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and the temporal association between symptom exacerbations and GABHS infections. The proposed poststreptococcal inflammatory etiology provides a unique opportunity for treatment and prevention, including immunomodulatory therapies such as plasma exchange and intravenous immunoglobulin. A placebo-controlled trial revealed that both intravenous immunoglobulin and plasma exchange were effective in reducing neuropsychiatric symptom severity (40 and 55% reductions, respectively) for a group of severely ill children in the PANDAS subgroup. Further research is required to determine why the treatments are helpful and to ascertain whether or not antibiotic prophylaxis can help prevent poststreptococcal symptom exacerbations.     

Family history of suicidal behavior and mood disorders in probands with mood disorders

OBJECTIVE: First-degree relatives of persons with mood disorder who attempt suicide are at greater risk for mood disorders and attempted or completed suicide. This study examined the shared and distinctive factors associated with familial mood disorders and familial suicidal behavior. METHOD: First-degree relatives' history of DSM-IV-defined mood disorder and suicidal behavior was recorded for 457 mood disorder probands, of whom 81% were inpatients and 62% were female. Probands' lifetime severity of aggression and impulsivity were rated, and probands' reports of childhood physical or sexual abuse, suicide attempts, and age at onset of mood disorder were recorded. Univariate and multivariate analyses were carried out to identify predictors of suicidal acts in first-degree relatives. RESULTS: A total of 23.2% of the probands with mood disorder who had attempted suicide had a first-degree relative with a history of suicidal behavior, compared with 13.2% of the probands with mood disorder who had not attempted suicide (odds ratio=1.99, 95% CI=1.21-3.26). Thirty percent (30.8%) of the first-degree relatives with a diagnosis of mood disorder also manifested suicidal behavior, compared with 6.6% of the first-degree relatives with no mood disorder diagnosis (odds ratio=6.25, 95% CI=3.44-11.35). Probands with and without a history of suicide attempts did not differ in the incidence of mood disorder in first-degree relatives (50.6% versus 48.1%). Rates of reported childhood abuse and severity of lifetime aggression were higher in probands with a family history of suicidal behavior. Earlier age at onset of mood disorder in probands was associated with greater lifetime severity of aggression and higher rates of reported childhood abuse, mood disorder in first-degree relatives, and suicidal behavior in first-degree relatives. CONCLUSIONS: Risk for suicidal behavior in families of probands with mood disorders appears related to early onset of mood disorders, aggressive/impulsive traits, and reported childhood abuse in probands. Studies of such clinical features in at-risk relatives are under way to determine the relative transmission of these clinical features.     

The identification of OCD-related subgroups based on comorbidity.

BACKGROUND: Individuals with obsessive-compulsive disorder (OCD) frequently have other psychiatric disorders. This study employed latent class analysis (LCA) to explore whether there are underlying clinical constructs that distinguish "OCD-related" subgroups. METHODS: The study included 450 subjects, case and control probands and their first-degree relatives, and LCA was used to derive empirically based subgroups of 10 disorders: OCD, obsessive-compulsive personality disorder (OCPD), recurrent major depressive disorder (RMDD), separation anxiety disorder, panic disorder or agoraphobia (PD/AG), tic disorders (TD), generalized anxiety disorder (GAD), somatoform disorders (hypochondriasis or body dysmorphic disorder), pathologic skin picking or nail biting (PSP/NB), and eating disorders (EDs). The derived classes were compared on several clinical variables. RESULTS: The best fitting model is a four-class structure: minimal disorder, predominant RMDD and GAD, "highly comorbid," and PD/AG and TD. The nature and number of disorders represented suggests that the first classes are distributed ordinarily on a dimension of severity, and the fourth class is qualitatively distinct. Support for this structure is based on the number of disorders, age at onset of OCD, neuroticism, and extraversion. CONCLUSIONS: In this OCD enriched sample, LCA identified four classes of disorder. These classes appear to conform to two subgroups that may prove useful in investigating the etiology of OCD.     

DSM-III-R personality disorders in panic and obsessive-compulsive disorder: a comparison study.

Forty-eight patients with panic disorder/agoraphobia (PAD) and 30 with obsessive-compulsive disorder (OCD) were assessed for DSM-III-R axis II personality disorders (PD) and the presence of the same anxiety disorder in the relatives of probands (homotypic disorders). No specific personality disorder was present significantly more often in either of the two groups. Agoraphobia was not associated with higher rates of axis II disorders in PAD patients. Duration of illness did not influence the presence of a PD in patients of both groups. Secondary cases of the same anxiety disorder were significantly more common among first-degree relatives of PAD patients. A discriminant analysis performed on the most frequent personality traits of both groups provided a correct classification of cases of 97.4%. Our results do not support the hypothesis of PD as secondary to anxiety disorders and confirm previous findings of a lack of specificity between DSM-III-R axis II categories and OCD and PAD.     

A family study of anxiety disorders: familial transmission and relationship to mood disorder and psychoactive substance use disorder

The prevalence of mental disorders in 76 first-degree relatives (parents and nontwin siblings) of 33 subjects with anxiety disorder was compared with the prevalence of mental disorders in 45 first-degree relatives of 20 subjects with mood disorder and 13 first-degree relatives of 6 subjects with psychoactive substance use disorder. All subjects were personally interviewed with the Structured Clinical Interview for DSM-III-R Axis I (SCID I). Interrater reliability was high for most diagnoses. Significantly more first-degree relatives of subjects with anxiety disorder had panic disorder and generalized anxiety disorder compared with relatives of probands with mood disorder. Significantly more female than male relatives of anxiety subjects suffered from anxiety disorders; there were no gender differences in the prevalence of anxiety disorders in relatives of mood and psychoactive substance use disorder (PSUD) subjects. The combination of anxiety and mood disorder was overrepresented in first-degree relatives of subjects with the same type of comorbidity. In relatives of subjects with mixed anxiety and psychoactive substance use disorder, but no mood disorder, there was an overrepresentation of PSUD; mainly alcohol abuse or dependence.     

A family study of obsessive-compulsive disorder.

First-degree relatives of probands with obsessive-compulsive disorder (OCD) (n = 32) and psychiatrically normal controls (n = 33) were blindly interviewed with the use of the Diagnostic Interview Schedule. The morbidity risk for anxiety disorders was increased among the relatives of obsessional subjects compared with that for the relatives of controls, but the risk for OCD was not. Risk for a more broadly defined OCD (including relatives with obsessions and compulsions not meeting criteria for OCD) was increased among the parents of obsessional subjects but not among the parents of controls (16% vs 3%). The findings suggest that an anxiety disorder diathesis is transmitted in families with OCD, but that its expression within these families is variable. The findings also support the current practice of classifying OCD as an anxiety disorder.     

The role of clinical phenotypes in understanding the genetics of obsessive-compulsive disorder

Studies have shown that genetic factors are significant in predisposing individuals to obsessive-compulsive disorder (OCD). Family studies have demonstrated significantly higher rates of OCD in parents and siblings of OCD probands with an age-corrected morbid risk ranging from approximately 10% to 35% in first-degree relatives. Twin studies suggest that this familiality is, in part, due to genetic factors, and results from complex segregation analyses imply the existence of genes that have major effects on the transmission of OCD. However, not all cases of OCD seem to be familial. Furthermore, it appears that even in the familial form, there are clinical and genetic heterogeneities. Thus, future studies should either adjust the prevalence rates used in genetic analyses to account for nonfamilial cases or perform separate analyses of those families with a demonstrably familial form of OCD. Furthermore, in complex psychiatric disorders such as OCD, a single genetic locus may influence only a small part of phenotypic variance, and other genetic and environmental factors may interact in determining clinical phenotype. The implications of this finding on clinical and genetic heterogeneity in OCD are discussed.     

Obsessive-compulsive symptoms in parents of Tourette syndrome probands and autism spectrum disorder probands

Obsessive-compulsive symptoms (OCS) frequently occur in patients with Tourette syndrome (TS) and autism spectrum disorders (ASD). It has been suggested that genetic factors play a role in the transmission of both TS and ASD and that obsessive-compulsive disorder (OCD) may have some genetic relationship with these disorders. The objective of this study was to explore whether the OCS associated with TS and ASD were found in the parents of TS and ASD probands by comparing them with normal controls. The subjects were parents of 13 TS and 16 ASD probands. All parents underwent an examination for tic symptoms and OCD, and completed the Maudsley Obsessional Compulsive Inventory (MOCI) and State-Trait Anxiety Inventory (STAI). No significant differences were observed in the MOCI and STAI scores among all three groups. However, the MOCI total score was higher in fathers of ASD probands than in male normal controls with a marginal significance. There was a significant tendency for the mean cleaning score of MOCI in fathers of ASD probands to be higher than that in male normal controls, and the mean checking score in fathers of ASD probands was fourfold higher than that in male normal controls, although there was no significant difference. No significant relationship was observed between OCS in TS or ASD probands and OCS of their parents. Further studies on OCD and OCS including a dimensional approach within ASD families are needed.     

The link between autoimmune diseases and obsessive-compulsive and tic disorders: A systematic review

Immunological factors are increasingly recognized as being important in a range of neuropsychiatric disorders. We aimed to summarize the disperse and often conflicting literature on the potential association between autoimmune diseases (ADs) and obsessive-compulsive disorder (OCD) and tic disorders. We searched PubMed, EMBASE, and PsycINFO for original studies evaluating the relationship between ADs and OCD/tic disorders until July, 13th 2016. Seventy-four studies met inclusion criteria. Overall, the studies were of limited methodological quality. Rates of OCD were higher in rheumatic fever patients who were also affected by its neurological manifestation, Sydenham’s chorea. The literature on other ADs was scarce and the findings inconclusive. Few studies examined the association between ADs and tic disorders. A handful of family studies reported elevated rates of ADs in first-degree relatives of individuals with OCD/tic disorders, and vice versa, potentially suggesting shared genetic and/or environmental mechanisms. In conclusion, at present, there is modest evidence for a possible association and familial co-aggregation between ADs and OCD/tic disorders. We offer some suggestions for future research.     

Is parental report of upper respiratory infection at the onset of obsessive-compulsive disorder suggestive of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection?

The diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) requires a prospectively determined association between group A beta-hemolytic streptococcal (GABHS) infection and obsessive-compulsive disorder (OCD) or tic disorder. Screening for GABHS infection imposes a significant burden on both patient and clinician. To heighten the index of suspicion for PANDAS, it would be useful to know if parent-reported upper respiratory infection (URI) is associated with PANDAS symptoms or associated characteristics. Eighty-three consecutive, clinically referred patients aged 6 to 17 years with a primary diagnosis of OCD and their primary caregivers were asked about URI signs and symptoms at the time of OCD onset, PANDAS symptoms, OCD and tic symptoms, comorbidity, and putative PANDAS risk factors. Specific inquiry regarding URI symptoms proved more informative than general inquiry. In the URI present versus URI absent group, more patients experienced a sudden rather than insidious onset of symptoms. Additionally, more patients with a URI plus sudden onset exhibited a comorbid tic disorder. Until validated biomarkers permit retrospective diagnosis, a history that OCD began around the time of a URI should clue the clinician to look prospectively for PANDAS. Additional research is required to define the boundaries of PANDAS and to develop psychometrically reliable and valid diagnostic strategies.     

Infection-triggered anorexia nervosa in children: clinical description of four cases

BACKGROUND: Anorexia nervosa (AN) is a serious illness with no definitive treatment. Clinical and research evidence led to the hypothesis that some children with AN may have a pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), similar in pathogenesis to other hypothesized PANDAS disorders. METHODS: Four youngsters (ages, 11-15 years) with PANDAS AN were treated with an open trial of antibiotics, in addition to conventional treatment. They were evaluated for eating disorder and obsessive-compulsive symptoms, and for weight gain. Evidence of streptococcal infection came from clinical evaluation, throat cultures, and two serological tests: anti-deoxyribonuclease B (anti-DNase B) and anti-streptolysin O (ASO) titers. The "rheumatic" marker D8/17 was also measured. This B-cell alloantigen is associated, in several publications, with poststreptococcal autoimmunity: Rheumatic fever (RF), Sydenham's chorea (SC), and possibly PANDAS obsessive compulsive disorder (OCD) and tic disorders. RESULTS: There was clinical evidence of possible antecedent streptococcal infection in all four patients, two of whom had comorbid OCD, with possible infection-triggered AN. All four had the rheumatic marker: A percentage of D8/17-positive B cells of 28-38%, with a mean of 33% (12% or more is considered positive for the marker). The patients responded to conventional treatment plus antibiotics with weight restoration and decreased eating disorder and obsessive-compulsive symptoms. Three needed to gain weight and did so. CONCLUSIONS: There may be a link between infectious disease and some cases of AN, which raises the possibility of new treatment.