Comment
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2 Purcell SM, Wray NR, Stone JL, et al, for the International Schizophrenia
Consortium. Common polygenic variation contributes to risk of
schizophrenia and bipolar disorder. Nature 2009; 460: 748–52.
3 Manolio TA. Genomewide association studies and assessment of the risk
of disease. N Engl J Med 2010; 363: 166–76.
4 Schizophrenia Working Group of the Psychiatric Genomics Consortium.
Biological insights from 108 schizophrenia-associated genetic loci.
Nature 2014; 511: 421–27.
5 Insel TR. The NIMH Research Domain Criteria (RDoC) Project: precision
medicine for psychiatry. Am J Psychiatry 2014; 171: 395–97.
6 Vilhjalmsson BJ, Nordborg M. The nature of confounding in
genome-wide association studies. Nat Rev Genet 2013; 14: 1–2.
Sex and gender differences in mental disorders
Sex and gender differences in mental disorders are among
the most intriguing and stable findings in psychiatry.
For example, differences exist regarding prevalence,
symptomatology, risk factors and influencing factors, or
Caia Image/Science Photo Library
course.1 Thus, it is well known that women have a higher
lifetime prevalence of mood or anxiety disorders than
men1–4 or a later onset of schizophrenic psychoses.5
But we still do not really understand the causes of these
differences, and comparatively little research has been
Published Online done to explain them. This lack of research is more than
November 14, 2016
http://dx.doi.org/10.1016/
surprising since explanations of these findings could give
S2215-0366(16)30348-0 us important insights into aetiological and pathogenetic
See Series pages 63, 73 mechanisms of these mental disorders in general. At
See Online/Series
the same time, they would most likely improve our
http://dx.doi.org/10.1016/
S2215-0366(16)30379-0, therapeutic approaches for both women and men.
http://dx.doi.org/10.1016/
S2215-0366(16)30358-3
This Lancet Psychiatry Women’s Mental Health Series
tries to meet this challenge. It offers four papers5–8 on
gender-specific issues relevant to mental disorders and
an accompanying comment9 on the lack of studies in
this area.
The gender gap in depression has been reviewed by
Christine Kuehner.6 She identifies potential risk factors
such as the influence of sex hormones, women’s
blunted hypothalamic–pituitary–adrenal axis response
to stress, girls’ and women’s lower self-esteem and
higher tendency for body shame and rumination,
higher rates of interpersonal stressors, experienced
violence, childhood sexual abuse, and—on a societal
level—lack of gender equality and discrimination. All
in all, it seems striking that many factors that are well
known to increase the risk for depression are more
prevalent in women and might therefore contribute to
their higher depression rate.
A similar gender gap exists in the prevalence of
anxiety, trauma-related and stress-related disorders.
8 www.thelancet.com/psychiatry Vol 4 January 2017
7 Reich DE, Cargill M, Bolk S, et al. Linkage disequilibrium in the human
genome. Nature 2001; 411: 199–204.
8 Beckman L, Janson S, von Kobyletzki L. Associations between
neurodevelopmental disorders and factors related to school, health, and
social interaction in schoolchildren: Results from a Swedish
population-based survey. Disabil Health J 2016; 9: 663–72.
9 Turkheimer E, Haley A, Waldron M, D’Onofrio B, Gottesman, II.
Socioeconomic status modifies heritability of IQ in young children.
Psychol Sci 2003; 14: 623–28.
In their review, Li and colleagues7 tried to find
explanations for this gap, focusing on the potential
role of the sex hormones oestradiol and progesterone.
They proposed that women might be more vulnerable
to these disorders because of their greater monthly
and life-span fluctuations of these hormones, which
obviously cannot only modify neurotransmitters
and neurosteroids, but also influence cognition and
behavioural processes for the gender gap in these
disorders. A further review should discuss potential
psychosocial explanations.
One of the most important psychosocial risk factors
for mental disorders in women, namely gender-
based violence, is covered in a review by Oram and
colleagues.8 They clearly show that women, much
more often than men, experience different forms
of gender-based violence, and that this experience
is associated with an increased prevalence of post-
traumatic stress, anxiety, and depressive disorders.
It seems obvious that violence must be taken much
more seriously in diagnosis and treatment of women
with mental illness. Oram and colleagues focus on
domestic and sexual violence but also discuss human
trafficking, female genital mutilation, forced and early
marriage, and honour crimes.
Domestic violence and abuse is recognised as an
expression of power inequalities between men and
women.8 Many more of these inequalities exist
and can most likely also influence women’s mental
health, such as gender role traditionality3 and gender
harassment, or simple discrimination in the workplace
or during professional careers,10 and would certainly
justify their own review.
My paper in this Series discussed schizophrenic
psychoses with a focus on the potential influence

of the hypothalamic-pituitary-gonadal axis.2 Also
in these disorders, an increased incidence has been
shown in periods of low oestradiol concentrations.
Many women with schizophrenia, even in the
untreated prodromal phase, experience oestradiol
deficiency and gonadal dysfunction, which might have
put them at increased risk and might be due to stress-
induced hyperprolactinaemia.
As stated in all the papers in this Series, mental health
research often ignores sex and gender differences as
well as the different risk factors and protective factors
of both women and men. Howard and colleagues9
expand on this problem and its consequences. Not to
investigate potentially differing causal pathways and
treatment responses of women and men not only
undermines scientific validity, but also results in a
failure to deliver gender-sensitive treatments.
In conclusion, it is high time for a shift in practice and
research. Research, psychiatric training, and practice
should consider sex and gender aspects much more
strongly. Population-based, representative cohorts of
patients should be examined longitudinally to draw
more valid conclusions on true gender differences
(which cannot be assessed in selected populations) and
causal pathways (which cannot be drawn from cross-
sectional studies). More multilevel, interdisciplinary
research investigating sex (biology) and gender
(psychosocial influencing factors) should be done.
More research is needed on gender differences in illness
behaviour, coping, help-seeking, and compliance, as
well as on sex-specific aspects of psychopharmacology,
hormonal therapies, or gender-sensitive psychotherapy.
Also, a quite neglected issue is the abuse of women
Gender-neutral mental health research is sex and gender biased
Few would disagree that sex is of relevance in
understanding and treating mental disorders, but
there seems to be less consensus on the extent to
which researchers should consider sex and gender
in study design, analysis, and interpretation. The
Institute of Medicine defines sex as “the classification
of living things, generally as male or female according
to their reproductive organs and functions assigned
by chromosomal complement”.1 Gender is defined as
“a person’s self-representation as male or female, or
www.thelancet.com/psychiatry Vol 4 January 2017
Comment
in therapeutic relationships.11 Last but not least, the
outlined research should be published in the form of
regular articles in widely read journals and not only in
special Series on women’s mental health.
Anita Riecher-Rössler
Center for Gender Research and Early Detection, University of
Basel Psychiatric Hospital, CH-4051 Basel, Switzerland
anita.riecher@upkbs.ch
I declare no competing interests.
1 Riecher-Rössler A. Prospects for the classification of mental disorders in
women. Eur Psychiatry 2010; 25: 189–96.
2 Boyd A, Van de Velde S, Vilagut G, et al. Gender differences in mental
disorders and suicidality in Europe: results from a large cross-sectional
population-based study. J Affect Disord 2015; 173: 245–54.
3 Seedat S, Scott KM, Angermeyer MC, et al. Cross-national associations
between gender and mental disorders in the World Health Organization
World Mental Health Surveys. Arch Gen Psychiatry 2009; 66: 785–95.
4 Wittchen HU, Jacobi F, Rehm J, et al. The size and burden of mental
disorders and other disorders of the brain in Europe 2010.
Eur Neuropsychopharmacol 2011; 21: 655–79.
5 Riecher-Rössler A. Oestrogens, prolactin, hypothalamic-pituitary-gonadal
axis, and schizophrenic psychoses. Lancet Psychiatry 2016; published
online Nov 14. http://dx.doi.org/10.1016/S2215-0366(16)30379-0.
6 Kuehner C. Why is depression more common among women than
among men? Lancet Psychiatry 2016; published online Nov 14.
http://dx.doi.org/10.1016/S2215-0366(16)30263-2.
7 Li SH, Bronwyn M, Graham B. Why are women so vulnerable to anxiety,
trauma-related and stress-related disorders? The potential role of sex
hormones. Lancet Psychiatry 2016; published online Nov 14.
http://dx.doi.org/10.1016/S2215-0366(16)30358-3.
8 Oram S, Khalifeh H, Howard L. Violence against women and mental
health. Lancet Psychiatry 2016; published online Nov 14.
http://dx.doi.org/10.1016/S2215-0366(16)30261-9.
9 Howard L, Ehrlich A, Gamlen F, Oram S. Gender-neutral mental health
research is sex and gender biased. Lancet Psychiatry 2016; published
online Nov 14. http://dx.doi.org/10.1016/S2215-0366(16)30209-7.
10 Cortina L, EA L. Workplace harassment based on sex: a risk factor for
women’s mental health problems. In: García-Moreno C,
Riecher-Rössler A, eds. Violence against women and mental health. Basel:
Karger, 2013: 139–47.
11 Tschan W. Abuse in doctor-patient relationships. In: García-Moreno C,
Riecher-Rössler A, eds. Violence against women and mental health.
Basel: Karger, 2013: 129–38.
how that person is responded to by social institutions Published Online
November 14, 2016
based on the individual’s gender presentation. http://dx.doi.org/10.1016/
Gender is shaped by environment and experience”.1 S2215-0366(16)30209-7
These definitions have been criticised, particularly See Online/Series
http://dx.doi.org/10.1016/
for treating sex and gender as dichotomous variables S2215-0366(16)30261-9
(whereas many of the sex-related and gender-related
differences in function and disease are more usefully
conceptualised as continuous variables), and focusing
on the individual (which neglects the multidimensional
relational nature of gender);2 however, we use the
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