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CLINICAL SYNTHESIS   |    
Gender Issues in Psychiatry
Mary V. Seeman, M.D., F.R.C.P.C.
FOCUS 2006;4:3-5.
View Author and Article Information

CME Financial Disclosure
Mary V. Seeman, M.D., Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

No disclosure of financial interests or affiliations to report.

Copyright 2006 American Psychiatric Association

Regardless of specific diagnosis, females almost always express psychological distress somewhat differently from males. Age is a key factor in differences between the two. In child mental health services, the patients are preponderantly male (1). Boys suffer more than girls from autism, hyperactivity syndromes, learning disabilities, conduct disorders, and depressive and anxiety syndromes, especially phobias. School phobia is much more common in boys than girls. Parents have more difficulties with their sons at early ages, and teachers have more difficulties with the boys in their classes. Boys learn to talk later than girls; they have more problems with stuttering and dyslexia, with psychosomatic disorders like stress headaches and stomachaches, and with asthma, muscular tics, and spasms; and they do not do as well academically as girls. They have more accidents, are more aggressive with each other, and get into more trouble with the law.

This all changes around the time of puberty (2). Girls begin puberty, which extends over a number of years, earlier than boys, and they become physiologically and psychologically mature earlier. Around this time, rates of psychiatric illness suddenly change. After adolescence, virtually all the major psychiatric disorders (the exceptions are substance abuse, schizophrenia, and impulse control disorders) become substantially more prevalent in females than in males.

Depression and anxiety are twice as common in women as in men, and this fact cannot be explained by women’s greater readiness to acknowledge and seek help for psychological symptoms. It has been argued that conflicting and additive responsibilities at home and at work may contribute to today’s high prevalence of anxiety, depression, and psychosomatic disorders in women (3). The economic disadvantage of women in relation to men is undoubtedly contributory, since the rate of all mental illnesses rises sharply in the context of poverty and economic hardship (4).

Friendship networks are larger among women than men, and in theory such networks buffer stress. On the other hand, women more than men pay the "price of caring," as their extended social circles position them in proximity to large numbers of individuals with whom they identify and whose personal problems become their own (5). As a subset of social agents, family members have long been suspect in their role as both triggers and buffers of psychiatric symptoms. Family ties are perceived and experienced differently by men and women. Marriage, for instance, has repeatedly been found to shield men against psychiatric illness; intriguingly, the opposite is true for women (6). Marriage puts women’s mental health at risk. Women, in general, act as caretakers of spouses, children, and aging parents, so the emotional burdens of family life probably weigh more heavily on their shoulders.

Although women and men are genetically different, genes alone do not explain sex differences in vulnerability to illness. The interaction of genes and environment is complex; genetic endowment elicits individual environments (the nature of nurture), and experience modulates gene expression (the nurturing of nature) (7). Exposure to overwhelmingly stressful life events has been postulated as the vehicle by which genetically vulnerable individuals succumb to psychiatric disease. Stressful life events may result from the misfortune of being born into economic disadvantage or social upheaval, or, alternatively, the misfortune of having a difficult temperament shaped by genes and early experience. It is thought that physical and sexual abuse in children (sexual abuse being more prevalent in girls) are important risk factors for adult emotional impairment (8).

Gender-specific hormonal effects play a role in gender differences in psychiatric illness, and perhaps an important one. During development (and also during adult life), gonadal steroid receptors are expressed in areas of the cerebral cortex that mediate cognition and affect. The female hormone estrogen is known to regulate neuronal function in a number of important ways, essentially to prevent cell death and to promote the growth of cell connections and thus to enhance neural communication (9).

To better understand male-female differences in psychiatry, it is important to appreciate what happens in the brain at times of hormonal flux. Puberty marks the turning point in the female-to-male ratio in psychiatric vulnerability. Neurons undergo active growth and/or drastic pruning during this stage of life. It is thought that the pace of these events and the steady state that is finally achieved are profoundly influenced by the differential action of male and female hormones, whose concentration in the brain rises sharply during this period. In women, the monthly fluctuation in gonadal hormone levels may no longer protect them as effectively as before against the potentially harmful effects of stress axis hormones (10). In other words, puberty may result in women’s brains becoming more vulnerable than men’s to the effects of stress. After suffering trauma, women are twice as likely as men to develop a posttraumatic stress syndrome. Anatomically, women’s strong inter-hemispheric brain connections may facilitate the generalization of past stressors and the invocation of traumatic memories more easily than the less well connected hemispheres in men’s brains (11).

Optimal treatment of psychiatric illness is known to differ by sex. As an example, interpersonal interventions tend to be more significant to women. Safety during the provision of psychiatric service is an issue of concern to women (12). Because they are perceived as subjugated and unlikely to press legal charges or even to be believed should they complain, psychiatrically ill women too often experience aggressive acts at the hands of male patients (and sometimes staff) in psychiatric settings.

As for pharmacological interventions, the optimal dose range of a therapeutic medication may not be the same for women as for men. The side effect profile often differs (13). "Standard" treatment, when applied to women, works less well than for men because it has largely been tested on male animals in the laboratory and on male research subjects in the clinic.

Women’s bodies contain more adipose tissue than men’s per unit of body weight, which is importantly linked to the response to psychotherapeutic drugs. Since antipsychotics, antidepressants, and anxiolytics are all lipophilic, these drugs will be retained longer in women’s bodies after drug discontinuation; they can also be released unexpectedly from fat stores during rapid weight loss, causing untoward side effects. Blood flow to the brain (taking the drugs along with it) is, to a large extent, under hormonal control. It is swifter in women than in men, which means that psychotropic agents reach their brain targets faster in women, although the actual speed varies during the menstrual cycle.

Sex differences exist in the activity of liver enzymes that degrade drugs and turn them into other molecules (sometimes chemically active, sometimes not) before they are eliminated from the body. The female liver, for instance, detoxifies alcohol much less efficiently than does the male liver, so the same initial concentration of blood alcohol is more toxic for women than it is for men. Clinicians are becoming increasingly aware that the prescription of psychopharmacological agents is complicated by the induction of enzymes by one agent that may enhance or reduce the activity of a second agent prescribed for a comorbid condition (drug interactions). Women with psychiatric problems are more likely than men to be receiving several medications because they more often suffer from concomitant allergies, thyroid conditions, arthritic conditions, pain, and insomnia. They may also be taking contraceptives or hormone replacement therapies. Thus, drug interactions are more frequently encountered in women and, correspondingly, so are adverse drug reactions (14).

Men and women differ in the side effects they find tolerable. Since appearance is of importance to most women, drugs that induce weight gain (as most psychotropics do) are especially problematic. Sedating drugs that interfere with parental responsibilities are a particular problem for women, and drugs that cause hypotension are dangerous for elderly women at risk of osteoporosis and bone fractures.

The greatest impact of psychiatric disease in women, in human terms, is the effect it has on their children (15). For instance, psychiatric disorders are known to be associated with teenage parenthood. The consequences for infants are many and varied: teenage mothers are less responsive to their infants’ needs than are older mothers, they display less positive attitudes toward motherhood, their expectations of their children are unrealistic, and they are more likely than more mature mothers to abuse their children. Children born to young mothers weigh less at birth, show a delay in cognition, and experience a multitude of school and conduct problems.

This overview has addressed general factors that impinge on the experience of psychiatric disease in men and women without sufficiently emphasizing that specific factors are probably uniquely relevant to specific diseases. Such differences as do exist between the sexes may offer clues to the origin and perpetuation of specific psychiatric diseases, and for that reason, it is important to identify them. Beyond the need to better understand psychiatric disease is the clinical responsibility to provide individualized, optimally effective, gender-specific care to all patients (16).

Gardner W, Pajer KA, Kelleher KJ, Scholle SH, Wasserman RC: Child sex differences in primary care clinicians’ mental health care of children and adolescents. Arch Pediatr Adolesc Med  2002; 156:454—459
[PubMed]
 
Sweeting H, West P: Sex differences in health at ages 11, 13, and 15. Soc Sci Med  2003; 56:31—39
[CrossRef] | [PubMed]
 
Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, de Girolamo G, Graaf R, Demyttenaere K, Gasquet I, Haro JM, Katz SJ, Kessler RC, Kovess V, Lepine JP, Ormel J, Polidori G, Russo LJ, Vilagut G, Almansa J, Arbabzadeh-Bouchez S, Autonell J, Bernal M, Buist-Bouwman MA, Codony M, Domingo-Salvany A, Ferrer M, Joo SS, Martinez-Alonso M, Matschinger H, Mazzi F, Morgan Z, Morosini P, Palacin C, Romera B, Taub N, Vollebergh WA (ESEMeD/MHEDEA 2000 Investigators), European Study of the Epidemiology of Mental Disorders (ESEMeD) Project: Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl  2004; 420:21—27
[PubMed]
 
Miller G. Poor countries, added perils for women. Science  2005; 308(5728):1576
[CrossRef] | [PubMed]
 
Schuster TL, Kessler RC, Aseltine RH Jr: Supportive interactions, negative interactions, and depressed mood. Am J Community Psychol  1990; 18:423—438
[CrossRef] | [PubMed]
 
Williams K: Has the future of marriage arrived? A contemporary examination of gender, marriage, and psychological well-being. J Health Soc Behav  2003; 44:470—487
[CrossRef] | [PubMed]
 
Wyman RJ: Experimental analysis of nature-nurture interactions. J Exp Zoolog A Comp Exp Biol  2005; 303:415—421
 
Thompson MP, Kingree JB, Desai S: Gender differences in long-term health consequences of physical abuse of children: data from a nationally representative survey. Am J Public Health  2004; 94:599—604
[CrossRef] | [PubMed]
 
Marin R, Guerra B, Alonso R, Ramirez CM, Diaz M: Estrogen activates classical and alternative mechanisms to orchestrate neuroprotection. Curr Neurovasc Res  2005; 2:287—301
[CrossRef] | [PubMed]
 
De Bellis MD, Keshavan MS, Beers SR, Hall J, Frustaci K, Masalehdan A, Noll J, Boring AM: Sex differences in brain maturation during childhood and adolescence. Cereb Cortex  2001; 11:552—557
[CrossRef] | [PubMed]
 
Piefke M, Fink GR: Recollections of one’s own past: the effects of aging and gender on the neural mechanisms of episodic autobiographical memory. Anat Embryol (Berl)  2005; 20:1—16
 
Seeman MV: Single-sex psychiatric services to protect women. Medscape Women’s Health eJournal 7(4),  2002. Available at
 
Fankhauser MP: Psychiatric disorders in women: psychopharmacologic treatments. J Am Pharm Assoc (Wash)  1997; NS37(6):667—678
[PubMed]
 
Seeman MV: Gender differences in the prescribing of antipsychotic drugs. Am J Psychiatry  2004; 161:1324—1333
[CrossRef] | [PubMed]
 
Leiferman JA, Ollendick TH, Kunkel D, Christie IC: Mothers’ mental distress and parenting practices with infants and toddlers. Arch Women Ment Health  2005; 8:243—247
[CrossRef]
 
Andreasen NC: Vulnerability to mental illnesses: gender makes a difference, and so does providing good psychiatric care. Am J Psychiatry  2005; 162:211—213
[CrossRef]  | [PubMed]
 
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References

Gardner W, Pajer KA, Kelleher KJ, Scholle SH, Wasserman RC: Child sex differences in primary care clinicians’ mental health care of children and adolescents. Arch Pediatr Adolesc Med  2002; 156:454—459
[PubMed]
 
Sweeting H, West P: Sex differences in health at ages 11, 13, and 15. Soc Sci Med  2003; 56:31—39
[CrossRef] | [PubMed]
 
Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, de Girolamo G, Graaf R, Demyttenaere K, Gasquet I, Haro JM, Katz SJ, Kessler RC, Kovess V, Lepine JP, Ormel J, Polidori G, Russo LJ, Vilagut G, Almansa J, Arbabzadeh-Bouchez S, Autonell J, Bernal M, Buist-Bouwman MA, Codony M, Domingo-Salvany A, Ferrer M, Joo SS, Martinez-Alonso M, Matschinger H, Mazzi F, Morgan Z, Morosini P, Palacin C, Romera B, Taub N, Vollebergh WA (ESEMeD/MHEDEA 2000 Investigators), European Study of the Epidemiology of Mental Disorders (ESEMeD) Project: Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl  2004; 420:21—27
[PubMed]
 
Miller G. Poor countries, added perils for women. Science  2005; 308(5728):1576
[CrossRef] | [PubMed]
 
Schuster TL, Kessler RC, Aseltine RH Jr: Supportive interactions, negative interactions, and depressed mood. Am J Community Psychol  1990; 18:423—438
[CrossRef] | [PubMed]
 
Williams K: Has the future of marriage arrived? A contemporary examination of gender, marriage, and psychological well-being. J Health Soc Behav  2003; 44:470—487
[CrossRef] | [PubMed]
 
Wyman RJ: Experimental analysis of nature-nurture interactions. J Exp Zoolog A Comp Exp Biol  2005; 303:415—421
 
Thompson MP, Kingree JB, Desai S: Gender differences in long-term health consequences of physical abuse of children: data from a nationally representative survey. Am J Public Health  2004; 94:599—604
[CrossRef] | [PubMed]
 
Marin R, Guerra B, Alonso R, Ramirez CM, Diaz M: Estrogen activates classical and alternative mechanisms to orchestrate neuroprotection. Curr Neurovasc Res  2005; 2:287—301
[CrossRef] | [PubMed]
 
De Bellis MD, Keshavan MS, Beers SR, Hall J, Frustaci K, Masalehdan A, Noll J, Boring AM: Sex differences in brain maturation during childhood and adolescence. Cereb Cortex  2001; 11:552—557
[CrossRef] | [PubMed]
 
Piefke M, Fink GR: Recollections of one’s own past: the effects of aging and gender on the neural mechanisms of episodic autobiographical memory. Anat Embryol (Berl)  2005; 20:1—16
 
Seeman MV: Single-sex psychiatric services to protect women. Medscape Women’s Health eJournal 7(4),  2002. Available at
 
Fankhauser MP: Psychiatric disorders in women: psychopharmacologic treatments. J Am Pharm Assoc (Wash)  1997; NS37(6):667—678
[PubMed]
 
Seeman MV: Gender differences in the prescribing of antipsychotic drugs. Am J Psychiatry  2004; 161:1324—1333
[CrossRef] | [PubMed]
 
Leiferman JA, Ollendick TH, Kunkel D, Christie IC: Mothers’ mental distress and parenting practices with infants and toddlers. Arch Women Ment Health  2005; 8:243—247
[CrossRef]
 
Andreasen NC: Vulnerability to mental illnesses: gender makes a difference, and so does providing good psychiatric care. Am J Psychiatry  2005; 162:211—213
[CrossRef]  | [PubMed]
 
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