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Letters to the Editor   |    
Gender Identity Disorders and Bipolar Disorder Associated With the Ring Y Chromosome
FAYCAL MOUAFFAK; THIERRY GALLARDA; NICOLAS BAUP; JEAN-PIERRE OLIÉ; MARIE-ODILE KREBS
Am J Psychiatry 2007;164:1122-1123. doi:10.1176/appi.ajp.164.7.1122

To The Editor: Gender identity disorder is a rare condition of atypical gender development in which there is a subjective perception of self in opposition to an individual’s gender. The lifetime prevalence of mood disorders comorbidity with gender identity disorder is approximately 45% (1). We report the case of a patient carrying a Y chromosomal abnormality associated with gender identity disorder and comorbid bipolar II disorder.

“Mr. G” was a 31-year-old, single, bank manager who was first referred in May 2000 for depressive symptoms and suicidal thoughts precipitated by the accidental death of his sister and the failure of a heterosexual relationship. His personal history was marked by delayed language acquisition and virtually no social or familial interactions during his school years and after, except for a symbiotic relationship with his sister. His limited social abilities contrasted with his remarkable skills in mathematics and an early inclination for electronics. During the interview, Mr. G revealed his desire since childhood to be a woman, and he asked for a sex change operation. Gender identity disorder was diagnosed. After a few months, Mr G experienced a hypomanic episode with mood lability and began wearing eccentric women’s clothing in public and insisted on receiving female sex steroid hormones and sex change surgery.

At admission, the patient met criteria for bipolar II disorder. His physical examination did not reveal any abnormality: his genitalia were normal, and he did not have gynecomastia. A biological examination revealed a disturbed hormonal profile with an elevated follicle stimulating hormone level; a normal testosterone level; and an abnormal karyotype with a mosaicism (45, X[2]/ 46, X, r(Y)[23]), which showed one cell line presenting the ring Y chromosome. This chromosomal formula provided to the patient an argument to claim his sex change. During a 6-year follow-up, the patient was admitted eight times and developed impulsive behavior such as suicidal and self-injurious attempts. A broad range of antidepressants, mood stabilizers, and antipsychotic treatments were unsuccessful until clozapine (75 mg daily) and lithium carbonate (1000 mg daily) permitted a sustained remission. Subsequently, the patient relinquished his demands for a sex change.

Our case shows a possible interaction between transsexualism and bipolar disorder, where both depression and mania exacerbate the demands for sex change, as reported and discussed in the literature (2).

The ring Y chromosome is usually associated with deletions in telomeric regions. It often provokes the loss of the ring chromosome during mitosis, resulting in a mosaic. Several genes on the Y chromosome could account for this complex developmental phenotype that associates gender identity disorder and bipolar disorders with schizoid-like personality and speech delay. The SRY gene (Yp11.3), which is involved in gender determination, is located close to the telomeric region. Its accessibility and regulation could be disturbed by the ring conformation. The SYBL1 and NLGN4Y genes both map to the Yq pseudoautosomal region and encode proteins that are essential for functional synapses. Variants of those genes have been found to be associated with bipolar (3) and autism spectrum disorders (4), respectively.

Concerning our case study, further genetic explorations are warranted in order to determine the extent of genetic anomalies associated with the ring Y chromosome, which could help to establish the possible genetic, predisposing factors to gender identity disorder.

1.Hepp U, Kraemer B, Schnyder U, Miller N, Delsignore A: Psychiatric comorbidity in gender identity disorder. J Psychosom Res 2005; 58:259–261
 
2.Habermeyer E, Kamps I, Kawohl W: A case of bipolar psychosis and transsexualism. Psychopathology 2003; 36:168–170
 
3.Muller DJ, Schulze TG, Jahnes E, Cichon S, Krauss H, Kesper K, Held T, Maier W, Propping P, Nothen MM, Rietschel M: Association between a polymorphism in the pseudoautosomal X-linked gene SYBL1 and bipolar affective disorder. Am J Med Genet 2002; 114:74–78
 
4.Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T: Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 2003; 34:27–29
 
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References

+The authors report no competing interests.

+Reprints are not available; however, Letters to the Editor can be downloaded at http://ajp.psychiatryonline.org.

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References

1.Hepp U, Kraemer B, Schnyder U, Miller N, Delsignore A: Psychiatric comorbidity in gender identity disorder. J Psychosom Res 2005; 58:259–261
 
2.Habermeyer E, Kamps I, Kawohl W: A case of bipolar psychosis and transsexualism. Psychopathology 2003; 36:168–170
 
3.Muller DJ, Schulze TG, Jahnes E, Cichon S, Krauss H, Kesper K, Held T, Maier W, Propping P, Nothen MM, Rietschel M: Association between a polymorphism in the pseudoautosomal X-linked gene SYBL1 and bipolar affective disorder. Am J Med Genet 2002; 114:74–78
 
4.Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T: Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 2003; 34:27–29
 
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