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tions, including physical examination and laboratory stud-ies, revealed no abnormality outside of an elevated pro-lactin level of 39.7 ng/ml. It was thought that this wasrelated to the effect of venlafaxine on serotonin elevatingprolactin, and thus bupropion extended release was in-creased to 450 mg daily, which resolved her depression.Venlafaxine was decreased over several weeks, and drymouth, constipation, and vaginal spotting were elimi-nated. The patients breast discharge persisted, although

her prolactin level was normalized at 12.5 ng/ml. Becauseher mood worsened, venlafaxine was discontinued andreplaced with duloxetine 60 mg daily. Her mood re-mained impaired, but her breast discharge increased andher prolactin level rose from 10.8 ng/ml to 28.2 ng/mlwithin 1 month. Duloxetine was discontinued and re-placed with modafinil to address the patients complaintof fatigue, with subsequent remission of her depression.Over the next 7 weeks, her breast discharge discontinuedand her prolactin level decreased to 5.1 ng/ml. Receivinga combination of bupropion extended release (450 mgdaily) and modafinil (100 mg daily), the patients depres-sion has been under control for 1 year.

To our knowledge, this is the first report of SNRI-induced,dose dependent, nonmenstrual, vaginal spotting and galact-orrhea accompanied by prolactin elevation. It is not likely that bupropion extended release caused these problems inour patient, since symptoms and prolactin levels changed with the dose adjustment of venlafaxine and duloxetine whileholding the bupropion dose steady. Although there did notappear to be any interaction of bupropion with venlafaxineand duloxetine by way of inhibition of cytochrome p450 2D6,it is unfortunate that drug levels were not obtained. Potentialmechanisms for the patients side effects were a direct effectof serotonin on prolactin or an indirect effect through seroto-nin agonism producing dopamine antagonism, possibly by way of 5-HT2c inhibition of mesocortical/mesolimbicdopamine (2). There are reports of older serotonin enhancing antidepressants that have caused elevations of prolactin andgalactorrhea (3). Surprisingly, our patients prior selective se-rotonin reuptake inhibitor courses did not cause similar sideeffects, but perhaps this was because they were dosed too low.

Although these findings are unusual, physicians should beaware that patients taking SNRIs could experience hyperpro-lactinemia, galactorrhea, and nonmenstrual vaginal spotting.Heightened surveillance might increase reporting and aclearer risk could be delineated.

References1. Sternbach H: Venlafaxine-induced galactorrhea. J Clin Psycho-

pharmacol 2003; 23:1091102. Barnes NM, Sharp T: A review of central 5-HT receptors and

their function. Neuropharmacology, 1999; 38:10831152

3. Egberts AC, Meyboom RH, De Koning, FH, Bakker A, LeufkensHG: Non-puerperal lactation associated with antidepressantdrug use. Br J Clin Pharmacol 1997; 44: 277281

ADAM KELLER ASHTON, M.D.MARLENE C. LONGDON, M.Sc.N., N.P.

Williamsville, N.Y.

Dr. Ashton has served on the speakers bureaus for the following: Eli Lilly, Pfizer, GlaxoSmithKline, Wyeth, Cephalon, Sepracor, Bristol- Myers Squibb, Abbott Laboratories, Forest Laboratories, Zeneca,Takeda, Cyberonics, and Sanofi-Aventis. Ms. Longdon reports nocompeting interests.

Gender Identity Disorders and Bipolar DisorderAssociated With the Ring Y Chromosome

TO THE EDITOR : Gender identity disorder is a rare conditionof atypical gender development in which there is a subjectiveperception of self in opposition to an individuals gender. Thelifetime prevalence of mood disorders comorbidity with gen-der identity disorder is approximately 45% (1). We report the

case of a patient carrying a Y chromosomal abnormality asso-ciated with gender identity disorder and comorbid bipolar IIdisorder.

Mr. G was a 31-year-old, single, bank manager who wasfirst referred in May 2000 for depressive symptoms and sui-cidal thoughts precipitated by the accidental death of hissister and the failure of a heterosexual relationship. His per-sonal history was marked by delayed language acquisitionand virtually no social or familial interactions during hisschool years and after, except for a symbiotic relationshipwith his sister. His limited social abilities contrasted with hisremarkable skills in mathematics and an early inclinationfor electronics. During the interview, Mr. G revealed his de-sire since childhood to be a woman, and he asked for a sexchange operation. Gender identity disorder was diagnosed.After a few months, Mr G experienced a hypomanic epi-sode with mood lability and began wearing eccentricwomens clothing in public and insisted on receiving fe-male sex steroid hormones and sex change surgery.

At admission, the patient met criteria for bipolar II disor-der. His physical examination did not reveal any abnormal-ity: his genitalia were normal, and he did not have gyneco-mastia. A biological examination revealed a disturbedhormonal profile with an elevated follicle stimulating hor-mone level; a normal testosterone level; and an abnormalkaryotype with a mosaicism (45, X[2]/ 46, X, r(Y)[23]),which showed one cell line presenting the ring Y chromo-some. This chromosomal formula provided to the patientan argument to claim his sex change. During a 6-year fol-

low-up, the patient was admitted eight times and devel-oped impulsive behavior such as suicidal and self-injuriousattempts. A broad range of antidepressants, mood stabiliz-ers, and antipsychotic treatments were unsuccessful untilclozapine (75 mg daily) and lithium carbonate (1000 mgdaily) permitted a sustained remission. Subsequently, thepatient relinquished his demands for a sex change.

Our case shows a possible interaction between transsexual-ism and bipolar disorder, where both depression and maniaexacerbate the demands for sex change, as reported and dis-cussed in the literature (2).

The ring Y chromosome is usually associated with dele-tions in telomeric regions. It often provokes the loss of thering chromosome during mitosis, resulting in a mosaic. Sev-eral genes on the Y chromosome could account for this com-plex developmental phenotype that associates gender iden-tity disorder and bipolar disorders with schizoid-likepersonality and speech delay. The SRY gene (Yp11.3), which isinvolved in gender determination, is located close to the telo-meric region. Its accessibility and regulation could be dis-turbed by the ring conformation. The SYBL1 and NLGN4Y genes both map to the Yq pseudoautosomal region and en-code proteins that are essential for functional synapses. Vari-ants of those genes have been found to be associated with bi-polar (3) and autism spectrum disorders (4), respectively.

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Concerning our case study, further genetic explorations are warranted in order to determine the extent of genetic anoma-lies associated with the ring Y chromosome, which could helpto establish the possible genetic, predisposing factors to gen-der identity disorder.

References1. Hepp U, Kraemer B, Schnyder U, Miller N, Delsignore A: Psychi-

atric comorbidity in gender identity disorder. J Psychosom Res

2005; 58:2592612. Habermeyer E, Kamps I, Kawohl W: A case of bipolar psychosis

and transsexualism. Psychopathology 2003; 36:1681703. Muller DJ, Schulze TG, Jahnes E, Cichon S, Krauss H, Kesper K,

Held T, Maier W, Propping P, Nothen MM, Rietschel M: Associa-tion between a polymorphism in the pseudoautosomal X-

linked gene SYBL1 and bipolar affective disorder. Am J MedGenet 2002; 114:7478

4. Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gill-berg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourg-eron T: Mutations of the X-linked genes encoding neuroliginsNLGN3 and NLGN4 are associated with autism. Nat Genet2003; 34:2729

FAYCAL MOUAFFAK, M.D.THIERRY GALLARDA, M.D.

NICOLAS BAUP, M.D. JEAN-PIERRE OLI, M.D.

MARIE-ODILE KREBS, M.D., P.H.D.Paris, France

The authors report no competing interests.

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

Corrections

In the article A Randomized Controlled Clinical Trial of Psychoanalytic Psychotherapy for Panic Disorder(Am J Psychiatry 2007; 164:265272), the fourth sentence in the Introduction section of the article contains anincorrect statement. The sentence Patients with panic disorder account for 20% of emergency room visits

and are 12.6 times as likely to visit emergency rooms as the general population. should have read In studiesof patients with PD, it has been shown that 21% had visited an emergency room (2) and patients with PD are12.6 times as likely to visit emergency rooms as the general population (3).

In the article titled Medical Treatment of Opiate Dependence: Expanding Treatment Options (Am J Psy-chiatry 2007; 164:702704) by Kathleen Brady, M.D., Ph.D., an error appeared. When buprenorphine naltrex-one combination appears, it should actually read buprenorphine-naloxone combination.

In the article titled The Homocysteine Hypothesis of Depression (Am J Psychiatry 2007; 164:861867) by Folstein et al., one of the authors names was incorrect. It should be Jennifer Buell, M.S.

In the article title Aberrant Default Mode Functional Connectivity in Schizophrenia (Am J Psychiatry 2007; 164:450457) by Garrity et al., a production error caused a mislabeling of the y axis of Figure 2. Below ishow the figure should have appeared:

M e a n

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l t M o

d e

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l i t u

d e

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Comparisonsubjects (N=22)

Target Novel

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Schizophreniapatients (N=21)