Post-partum obsessive-compulsive disorder associated with 9q33.1 deletion

To the Editor

According to the Diagnostic and Statistical Manual of Mental Disorders–Fifth Edition (DSM-5) (American Psychiatric Association, 2013) obsessive-compulsive disorder (OCD) is characterized by recurrent thoughts, impulses, images (obsessions) or repetitive behaviour or mental acts in response to a mental obsession (compulsions), interfering with everyday living. Pregnancy and puerperium can precipitate pre-existing OCD or trigger OCD onset, negatively affecting the new-born care and mother–child relationship (Williams and Koran, 1997). The prevalence of OCD is reported to be approximately 2–3% in the general population, although some studies have found higher rates among women in the post-partum period.

A 40-year-old woman showing aggressive obsessions, fear of harming her child and related compulsions (avoidance of being alone with her child) was sent to our post-partum psychiatric service. She had never presented psychiatric symptoms before. According to DSM-5 criteria, she received an OCD diagnosis, and treatment with fluvoxamine (titrated till 150 mg/day) was prescribed. Due to a partial response, after 4 weeks, risperidone 0.5 mg/day was added. Due to the new-born clinical presentation (bilateral twisted feet, minor facial alterations, muscle hypertonia, pylore stenosis) a genetic evaluation by array-based Comparative Genomic Hybridization (CGH) was performed, in order to detect DNA copy number variations as a consequence of amplifications/duplications or deletions. The analysis reported a deletion of 229 Kb copies of DNA in 9q33.1, involving pregnancy-associated plasma protein A (PAPPA) gene and 3′ portion of astrotactin 2 (ASTN2) gene (Table 1). Our patient presented the same genetic alterations of her son. When asked, she agreed in publishing this report.

Table 1.

Summary of PAPPA/ASTN2 gene features.

Genes	Encoded proteins	Functions	Associated diseases
PAPPA	PAPP1_HUMAN, Q13219	Encodes a metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs), involved in local proliferative processes. Low plasma level of this protein has been suggested as a biochemical marker for pregnancies with aneuploid foetuses.	Limb-girdle muscular dystrophy type 2h Tricuspid valve insufficiency.
ASTN2	ASTN2_HUMAN, O75129	Encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia. Multiple transcript variants encoding different proteins have been found for this locus.	Schizophrenia

PAPPA: pregnancy-associated plasma protein A.

A 9q33.1 deletion was incidentally found after a post-partum OCD onset, and authors’ opinion is that hormonal and immunological changes could have unmasked an OCD genetic predisposition. Actually, no associations are reported between PAPPA gene and psychiatric disorders; however, increased levels of PAPPA have been found in patients with high risk for cardiovascular diseases, causing systemic inflammation and immunological abnormalities, known as possible bio-markers of psychiatric illnesses. 9q33.1 deletion involves ASTN2 gene encoding a protein associated to glial-guided neuronal migration, a key step in the development of cortical regions and a prerequisite for physiological brain neurodevelopment. In the current literature, 9q33.1 deletions, completely or partially involving gene ASTN1/2, have been associated with psychomotor retardation, autism disorders, attention deficit hyperactivity disorder (ADHD), language disorders, anxiety and OCD (Lionel et al., 2014). This letter is the first to report 9q33.1 deletion in a post-partum OCD; future studies are needed to confirm or exclude this association.