Obsessive-Compulsive Disorder and Autism Spectrum Disorders: Longitudinal and Offspring Risk

<div><p>Background</p><p>Despite substantial similarities and overlaps in the pathophysiology of obsessive-compulsive disorders (OCD) and autism spectrum disorders, little is known about the clinical and etiologic cohesion of these two disorders. We therefore aimed to determine the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders.</p><p>Methods</p><p>In a prospective study design we explored the effect of a prior diagnosis of OCD in patients and parents on the susceptibility to autism spectrum disorders and vice versa. Analyses were adjusted for sex, age, calendar year, parental age and place at residence at time of birth. As measures of relative risk incidence rate ratios (IRR) and accompanying 95% confidence intervals (CIs) were employed.</p><p>Results</p><p>The risk of a comorbid diagnosis of OCD in individuals with autism spectrum disorder and aggregation of autism spectrum disorders in offspring of parents with OCD were increased. Individuals first diagnosed with autism spectrum disorders had a 2-fold higher risk of a later diagnosis of OCD (IRR = 2.18, 95% CI = 1.91–2.48), whereas individuals diagnosed with OCD displayed a nearly 4-fold higher risk to be diagnosed with autism spectrum disorders (IRR = 3.91, 95% CI = 3.46–4.40) later in life. The observed associations were somewhat stronger for less severe types of autism spectrum disorders without a comorbid diagnosis of mental disabilities.</p><p>Conclusions</p><p>The high comorbidity, sequential risk, and shared familial risks between OCD and autism spectrum disorders are suggestive of partially shared etiological mechanisms. The results have implications for current gene-searching efforts and for clinical practice.</p></div

Incidence Rate Ratio of Obsessive-Compulsive Disorder in Persons with a Diagnosis of Autism Spectrum Disorders (ASD; 1994–2012).

<p>^aEstimates of relative risk were adjusted for calendar year, age, maternal and paternal age, sex, parental history of psychiatric illness, place of residence at time of birth and the interaction of age with sex</p><p>^bEstimates of relative risk were adjusted for calendar year, age, maternal and paternal age, sex, parental history of psychiatric illness, first psychiatric hospital contact for any other disorder, place of residence at time of birth and the interaction of age with sex</p><p>Incidence Rate Ratio of Obsessive-Compulsive Disorder in Persons with a Diagnosis of Autism Spectrum Disorders (ASD; 1994–2012).</p

Incidence Rate Ratio of Autism Spectrum Disorders in Persons with a Diagnosis of Obsessive-compulsive Disorder (OCD; 1994–2012).

<p>^aEstimates of relative risk were adjusted for calendar year, age, maternal and paternal age, sex, parental history of psychiatric illness, place of residence at time of birth and the interaction of age with sex</p><p>^bEstimates of relative risk were adjusted for calendar year, age, maternal and paternal age, sex, parental history of psychiatric illness, first psychiatric hospital contact for any other disorder, place of residence at time of birth and the interaction of age with sex</p><p>Incidence Rate Ratio of Autism Spectrum Disorders in Persons with a Diagnosis of Obsessive-compulsive Disorder (OCD; 1994–2012).</p

Incidence rate ratios, with 95% CIs (error bars), of Autism Spectrum Disorders in Offspring of Parents with an Obsessive Compulsive Disorder, 1995–2012.

<p>Incidence rate ratios, with 95% CIs (error bars), of Autism Spectrum Disorders in Offspring of Parents with an Obsessive Compulsive Disorder, 1995–2012.</p

Incidence Risk Ratio of Specific Diagnoses of Autism Spectrum Disorders in Relation to Individual and Parental Diagnosis of Obsessive-compulsive Disorder (OCD; 1994–2012).

<p>^aMaternal or paternal diagnoses were categorized hierarchically as having a history of OCD, autism spectrum disorders or other psychiatric disorders. Estimates of relative risk were adjusted for calendar year, age, maternal and paternal age, sex, place of residence at time of birth and the interaction of age with sex</p><p>^bEstimates of relative risk were adjusted for calendar year, age, maternal and paternal age, sex, parental history of psychiatric illness, first psychiatric hospital contact for any other disorder, place of residence at time of birth and the interaction of age with sex</p><p>Incidence Risk Ratio of Specific Diagnoses of Autism Spectrum Disorders in Relation to Individual and Parental Diagnosis of Obsessive-compulsive Disorder (OCD; 1994–2012).</p

Ideogram of chromosome 18 displaying positions of the functional genes along the linkage interval (Chr18p11.32-p11.31 on GRCH37/hg19 assembly) of 3.03 Mb identified in the family.

<p>Ideogram of chromosome 18 displaying positions of the functional genes along the linkage interval (Chr18p11.32-p11.31 on GRCH37/hg19 assembly) of 3.03 Mb identified in the family.</p

Two-point LOD score between ED syndrome and SNP markers on chromosome 18p11.32-p11.31.

<p><b>a</b> Physical positions of the SNPs are according to the dbSNP132 (<a href="http://genome.ucsc.edu/cgi-bin/hgGateway" target="_blank">http://genome.ucsc.edu/cgi-bin/hgGateway</a>)</p><p><b>b</b> Recombination fraction.</p><p>Two-point LOD score between ED syndrome and SNP markers on chromosome 18p11.32-p11.31.</p

Pedigree of a consanguineous Pakistani family segregating an autosomal recessive form of a novel type of ectodermal dysplasia.

<p>Circles and squares represent females and males, respectively. Clear symbols represent unaffected individuals while filled symbols represent affected individuals. Symbols with asterisk represent DNA samples available for the molecular analysis.</p

Results of the sensitivity analyses: a comparison of different nominal p-values.

<p><i>Note</i>. Results for variations of the method for the 32 Mbp width region on chromosome 5, 128–160 bp. Nom 0.01: the analysis was performed using p = 0.01 as the cutoff for nominal SNP-wise significance. Nom 0.11: the analysis was performed using p = 0.1 as the cutoff for nominal SNP-wise significance. EIGENSTRAT: the analysis was performed on data corrected for population stratification using the EIGENSTRAT procedure.</p

“Manhattan plot of the top segment located at chromosome 5 (128–136

<p> <b>Mbp)”.</b> This figure shows at the y–axis the p-values of the SNPs located at chromosome 5 (128–136 Mbp). The chromosomes are shown at the x-axis. The red line indicates a p-value of 10-7, the blue line indicates a p-value of 10-5 and the green line indicates a p-value of .05.</p