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Moya PR, Wendland JR et al.
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Supplementary Figure 1: Family pedigree of the male OCD proband with CDH2 variant
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N706S not found in any healthy volunteers. Individuals with OCD or OCPD are marked by
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blue plus red. Individuals with other neuropsychiatric disorders or specific symptoms are
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indicated by blue circles. Other family individuals besides the proband were not available
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for genotyping.
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Supplementary Figure 2: Prediction of a functional protein association network for CDH2
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by STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), version 8.3 33.
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Among the molecules most closely associated with CDH2 are CTNNA1 (catenin alpha 1),
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CTNNB1 (catenin beta 1), CTTND1 (catenin delta 1) and JUP (junction plakoglobin, catenin
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gamma). Stronger associations are represented by thicker lines.
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Moya PR, Wendland JR et al.
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SUPPLEMENTARY MATERIAL: N706S
N706S was found only in one OCD proband, one TD proband and one unrelated TD
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relative, and not in any of the controls. The OCD male proband with the non-synonymous
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N706S variant had OCD symptom impairment beginning at age 14. At the time of the
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interviews, he experienced both obsessions “all day” and compulsions “all day”. His
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obsessions center on exactness, lucky/unlucky numbers and fear of harm to self and others.
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He does not leave the house and fears that the mail will bring bad news. When he is
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speaking, writing, or eating, he wants his actions to be “just right.” In addition, his
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compulsions include “rereading, rewriting, erasing, a need to perform certain activities in a
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special way, collecting silly things, difficulty throwing things out, rituals involving blinking
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and staring, and other repetitive behaviors.”
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At age 18, he was in the Navy for 3 months, but was discharged from service with
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severe depression with suicidal ideation and was diagnosed with bipolar disorder and OCD.
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At the age of 33, when the study interviews were conducted, the patient had severe OC
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symptoms, was described as very circumstantial, with pressured speech. He was found to
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meet present criteria for bipolar I disorder (rapid cycling), with many past manic episodes,
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some spontaneous and others possibly related to medications, as well as major depressive
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episodes. Of note, rapid cycling bipolar disorder is a relatively rare diagnosis, being found in
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0.3% of an epidemiologic community sample of >54,000 individuals 66.
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The patient reported one psychotic symptom of a grandiose delusion, in which he was
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called to be a prophet. Additionally, the patient met current criteria for panic disorder,
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posttraumatic stress disorder (PTSD), and does not feel comfortable in public because of his
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perceived flaws.
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He was hospitalized twice during the course of multiple interview assessments. On
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the global assessment of functioning scale, the patient scored 50/100 for current functioning,
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and 31/100 for the worst ever functioning during his lifetime. He is educated at the high
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school level and his income comes from part-time occasional work and social security
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disability income. His family included four generations of individuals with multiple
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neuropsychiatric symptoms disorders: both parents had obsessive-compulsive disorders, his
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siblings had obsessive-compulsive symptoms and alcohol/substance abuse, and a deceased
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uncle had been diagnosed with schizophrenia (Supplementary Figure 1). These other family
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members declined DNA donations.
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The other two individuals with CDH2 variant N706S were both female. One, a TD
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proband with subclinical OCD and probable ADHD, spontaneously described to the
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interviewer that she had vivid hypnogogic and hynopomic experiences during sleep such as
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hearing tapping noises that waked her and were interpreted as messages from her mother
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about burglars. These had been acted upon on some occasions by her arming herself with a
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knife to go downstairs to check. The third was the sister of a different, unrelated TD proband
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(who also had OCD); this individual had motor and phonic tics but did not meet full criteria
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for TD.
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