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Implications of sex-Distribution of mental disorders for gender Models in psychiatry exemplified by the Lesch-Nyhan syndrome and depressive disorders
Bernd Rüdiger Brüggemann, Petra Garlipp
Department of Social Psychiatry and Psychotherapy
Hannover Medical School, Germany
Background: There are sex differences in lifetime prevalence for some mental disorders.
Objective: The significance of the sex distribution of mental disorders concerning the understanding of gender in psychiatry will be pronounced using the example of Lesch-Nyhan syndrome and depressive disorders.
Methods: The MEDLINE and PsycINFO database were searched for articles from 1967 to 2006 including the following medical subject heading terms: affective disorder, depressive disorder, depression, Lesch-Nyhan syndrome combined with sex, sex differences, gender, gender differences, and gender role. The search was extended by using the bibliographies of selected articles.
Results: The sex distribution of the Lesch-Nyhan syndrome is caused by the biological, especially by the chromosomal sex. The essential etiopathogenetic factor is the lack of the enzyme hypoxanthine-guanine-phosphoribosyltransferase (HPRT). The connection to the sex of the patient is caused by the HPRT coding gene lying on the x-chromosome. Depressive disorders have a multifactoral etiopathogenesis with important roles of both biological and psychosocial factors. Psychosocial and cultural factors have proven to be very helpful in understanding the epidemiological findings concerning the sex distribution.
Conclusions: In the Lesch-Nyhan syndrome psychological as well as social gender models can not give any explanation for the syndrome. In this rare case a simple biological model of sex may be adequate. In depressive disorders a complex model of human gender that includes the biological, psychological and social level, has proved to be effective.
Gender, gender-role, sex, Lesch-Nyhan syndrome, depressive disorders
Women suffer more often from depressive, anxiety, eating and somatoform disorders than men, whereas alcohol- and drug-related disorders as well as antisocial personality disorders can be seen more often in men. Sex differences of lifetime prevalence could not be found in relation to obsessive-compulsive disorders, manias and schizophrenic psychoses (Bijl et al, 1998; Kessler et al, 1994; Meyer et al, 2000; Robins et al, 2005; Wittchen et al, 1992).
Looking at the influence of the sex defining the beginning and the course of a psychiatric disorder, it is of central importance to reflect which level of human gender it is related to and which theoretical model of gender development it is based upon. Favouring biological theories of the etiology of mental disorders they can be best related to biological models of human sex. Favouring a psychosocial understanding of gender psychosocial influences on psychiatric disorders are consequently favoured. The significance of the sex distribution of mental disorders concerning the understanding of gender in psychiatry will be pronounced using the example of the Lesch-Nyhan syndrome and the depressive disorders.
The MEDLINE and PsycINFO database were searched for articles from 1967 to 2006 that including the following medical subject heading terms: affective disorder, depressive disorder, depression, Lesch-Nyhan syndrome combined with sex, sex differences, gender, gender differences, and gender role. Articles were screened for relevance based on title, key words, and abstracts. The search was extended by using the bibliographies of selected articles.
The Lesch-Nyhan syndrome is a good example showing that the sex distribution of a neurological-psychiatric syndrome can be explained on a genetic base. The Lesch-Nyhan syndrome is a rare x-chromosome related recessive hereditary disease (Lesch et al, 1964). The disease is characterized by the lack of the enzyme hypoxanthine guanine-phosphoribosyltransferase (HPRT). A recessive gene being responsible, heterocygote female carriers do not fall ill. Newborn and babies do not show any clinical symptoms. Up to the 8th month the babies go through a normal development. Between the 8th and the 24th month first neurological signs can be seen. Between the 4th and the 10th year most children show the whole Lesch-Nyhan syndrome. They show behavioural disturbances like self-mutilations or aggressive bevaviour against others. The neurological symptomatology is characterized by an extended spastic syndrome, dystonias, choreoathetosis, articulation disturbances because of diaphragm dyskinesias and a pseudo-bulbar palsy (Matthews et al, 1995). Whereas in older publications an extended intelligence deficit was assumed, newer works show that the patients showed a minimal mental retardation but could alos reach medium intelligence (Matthews et al, 1995).
As can be expected because of the x-chromosomal recessive hereditary pathway the Lesch-Nyhan syndrome is nearly only seen in men. Up to now only single cases of the syndrome could be found concerning the female sex (Aral et al, 1996; DeGregorio et al, 2000; Hara et al, 1982; Ogasawara et al, 1989; vanBogaert et al, 1992; Yamada et al, 1994; Yukawa et al, 1992). The sex distribution of the Lesch-Nyhan syndrome can clearly be explained by its genetic cause. Psychological and social factors may play a certain role in relation to the behavioural and cognitive disturbances but they do not influence the sex distribution.
Sex distribution of depressive disorders
Looking at the sex distribution of depressive disorders hypotheses with biological, neurocognitive, psychoanalytical, psychodynamical, behavioural, cognitive psychological, and sociocultural emphasis as well as the so-called artefact hypothesis were promoted, which correlate with the corresponding gender models (Table 1). The hypotheses cited must prove themselves in relation to the empirical data.
Several prevalence and incidence studies of depressive disorders of population samples in the USA, Canada, Europe, Australia and New Zealand (Angst et al, 1984; Bijl et al, 1998; Bland et al, 1988; Canino et al, 1987; Joyce et al, 1990; Kessler et al, 1994; Lee et al, 1990; Lepine et al, 1997; Weissman et al, 1988; Weissman et al, 1996) show – with some exceptions (Loewenthal et al, 1995; Murphy et al, 1984; Young et al, 1990) - a clear dominance of women. This can be said for major depression and dysthymia whereas in minor depression the sex distribution is nearly equal (Angst et al, 2002).
Interestingly enough epidemiological studies in some cultures or religious communities found an equal sex distribution of depressive disorders, the distribution depends on age and has changed in the last decades.
Looking at the theory that the vulnerability of women to become depressive may be represented in alcohol and drug abuse in men (Angst et al, 2002; Loewenthal et al, 2003), the Old Order Amish, an ultraconservative protestant sect in the USA, is interesting. In a study of the epidemiology of affective disorders among 8186 Amish people in Pennsylvania only 20 men and 21 women were diagnosed to suffer from a major depression related to a 5-year-timespan from 1976 till 1980 (Egeland et al, 1983). Thinking of the base population it means a nearly balanced distribution. As men in the Amish population cannot chose the way of alcohol and drug abuse, the even prevalence of depressive disorders might have been caused by higher rates of depression in men.
A similar conclusion shows a reanalysis of data of the ECA-Study which investigated the sex distribution of depressive disorders according to the religious orientation (Levav et al, 1997). Jewish people showed in total a higher yet sex balanced prevalence. This finding was deducted from a higher depression rate in men and related to the significantly lesser number of alcohol abusing men. The association between religious involvement and depression differs substantially between men and women (Norton et al, 2006).
Surveys of the sex distribution of depressive disorders in childhood and youth (Angold et al, 1993; Bebbington, 1996; Essau et al, 1995; Fleming et al, 1990; Jorm, 1987; Nolen-Hoeksema, 1990) show on the one hand that depressive symptoms can extremely rarely be found in preschool children, in later childhood and youth the numbers strongly rise. On the other hand it can be shown that before puberty – if at all – boys suffer more often from depressive syndromes than girls and from 14 to 15 years on, women fall ill more often. From the age of 55 on, the rates of depression get balanced again between the sexes.
Epidemiological studies extending across the second half of the 20th Century could show changes of the sex distribution of depressive disorders (Fichter, 1990; Hagnell et al, 1982; Mattisson et al, 2005; Murphy et al, 1984; Sturt et al, 1984) and mostly showed an approximation between the sexes. Together with the finding that in younger age cohorts in the USA, Puerto Rico, Western Europe, the Middle East, the Pacific region and in Asia an increase of major depression can be seen (Cross-National Collaborative Group, 1992) in our opinion the cited epidemiological data hint at the sociocultural factors in the etiopathogenesis of depressive disorders.
Main sociocultural factors being related to gender are (for literature see (Brüggemann et al, 2002)):
Marriage and family: A „good“ marriage means a higher protection for men from a depressive disorder whereas a „bad“ marriage increases the risk of depression in women. Mother role can be protective as well as depression inducing because of stress being induced by the child care. Caring for a relative, especially parent, mostly done by women, increases the depression risk.
Occupation and housework: Whereas housework has more depression inducing effects, occupation is a mostly positive influence but it depends on the kind of work and role dependent strains must be considered.
Violence and discrimination: Bodily and sexual harm against women can contribute to depressive disorders as well as material or other disadvantages.
Depression rates of males and females have come closer in the last decades. This could be connected to an adjustment of gender roles and a change in gender typical coping in modern societies. The different sex distribution in depressive disorders in different cultures or religious communities can be understood by different judgements and expectations of gender, family and professional roles. Furthermore culture and religion dependent patterns of gender specific conflict coping mechanisms can be shown. Reliable partnership needs of younger girls that cannot be satisfied because of other factors (insecure attachment, fearful avoidant personality, no real instrumental coping-style, hormonal changes) could be the reason for a dominance of depressive disorders in young girls. Another factor could be traumatization often related to this age span.
Yet sociological theories without including psychological and biological theories cannot explain, why only a small percentage of persons that lives in depression inducing circumstances will indeed suffer from depressive disorders and why other people will suffer from depressive disorders without living in these circumstances. A certain depression inducing effect of certain situations needs a special individual predisposition. This may be special personality traits or the physical constitution. To sum up sociological explanations cannot show why people suffer from depressive illness but it can be explained which circumstances form predispositions.
The terms „gender“, respectively „femininity“ and „masculinity“, are based on different meanings in biology, psychology and sociology. Table 1 shows how the gender-models correspond with hypotheses of etiopathology in sex distribution by the example of depressive disorders.
Table 1 Corresponding gender models and hypotheses of etiopathology in sex distribution of depressive disorders (Brüggemann et al, 2002; Halpern, 2000; Kestemberg et al, 2003; Nolen-Hoeksema, 1990; Nopoulos et al, 1999)
|Human gender models||Hypotheses of etiopathology in sex/gender distribution of depressive disorders|
|Biological and neurocognitive models||
|Psychoanalytic and psychodynamic models||
|Behavioural and cognitive models||
|Androgyny and constructivistic models||
Artefact hypothesis (variations of classification systems and diagnostical instruments, gender typical behaviour in looking for help, gender typical social interactions between patient and therapist)
Biological and neurocognitive gender models
In biology the genetical, chromosomal, gonadal and somatic sex is distinguished. Looking at the molecular biological level the differentiation between male and female is relatively simple as the chromosome pair XX means the chromosomal sex female and XY the male chromosomale sex. Difficulties of this pattern appear when chromosomal aberrations exist, e. g. the Klinefelter-Syndrome which shows the combination XXY (Sadler et al, 2003; Tobach, 2001). Furthermore genetical variations exist showing a female chromosomal XX pair but a male phenotype, e.g. the adrenogenital syndrome. The opposite is the androgen insensitivity-syndrome with a female phenotype but a XY chromosomal pair.
Depending on the chromosomal sex the gonadal sex will develop. Meanwhile the gene inducing the development of the male phenotype, the testis-determinating factor, could be identified on the Y-chromosome (Le Vay, 1994). The somatic sex – the male or female phenotype – is mainly determined by hormonal effects on different somatic tissues.
Studies showed neurocognitive differences between boys and girls already in the newborn stage. This is an age in which social and environmental factors cannot have influenced the brain and the behaviour that much (Nopoulos et al, 1999). Sexual hormones` influence on the developing brain could be proved in studies of mammals. Experimental studies showed the sexual hormones` influence on brain volumina, the morphology of single neurons and the type and number of synapses (MacLusky et al, 1981; Pilgrim et al, 1994). Influence of androgenes in the critical phase of early development can change behaviour that is not directly connected with the reproductive circle. Rhesus monkeys having received androgenes in the critical period, showed a wilder playing behaviour, a more aggressive contact with males and less imitating behaviour related to the mother (Kelly et al, 1996) in the prepubertal age when relatively few hormones influence the brain. Similar behaviour could be registered in humans. Girls being exposed to a higher level of androgenes in their embryonic and fetal development because of an illness of their mother, were described as especially wild and aggressive during their childhood and showed a boy-typical toy preference (Kimura, 1992). Estrogene and androgene sensitive cell systems could be found in the area of the hypothalamus and the limbic system in the adult mammal brain (Birbaumer et al, 2002).The growth of neural structures of these cells under the influence of sex specific hormone concentrations could lead to structural differences of the male and female brain even in adult life.
The adult female and male brain show several structural and functional differences in spite of a predominant similarity. The less controversially discussed area is that one that is connected with reproduction – the neuroendocrinium. Newer imaging procedures (MRI, fMRI, PET, SPECT) could show morphological and functional differences between the female and male brain (Altemus et al, 1999; Breedlove, 1994; Nopoulos et al, 2000; Nopoulos et al, 1999). Autopsy studies and imaging could prove, that the male brain is 10-15% bigger and heavier (Kimura, 1999) than the female one and that the difference also persisted when body height and mass (Breedlove, 1994) as well as age (Nopoulos et al, 1999) were considered. The size and weight difference does not exist for the whole brain. The cerebellum does not significantly differ in relation to the size yet the male cerebrum is bigger. Women do have proportionally more grey matter in the area of the right parietal lobe(Nopoulos et al, 2000). Sex differences of the structural lateralization of the brain which had been postulated for years could not be confirmed with newer imaging procedures (Nopoulos et al, 1999). Contradictory findings were described concerning morphological sex differences in the area of hippocampus, hypothalamus and corpus callosum (Breedlove, 1994; Halpern, 2000; Kimura, 1999; Nopoulos et al, 1999).
Neurocognitive examinations – e.g. in patients after a cerebral infarction – give hints for a more pronounced bilateralization and function of the female brain. Although there are some contradictory findings, most studies demonstrated a stronger lateralization of verbal (Hausmann et al, 1998; Shaywitz et al, 1995) and visual spatial processes (Chiarello et al, 1989; Corballis et al, 1993; Halpern, 2000; Voyer, 1996) in men (Hausmann, 2001). Gonadale steroid hormones seem to be responsible for sex typical differences of the grade of asymmetry as well as for the stronger variations in women. Especially progesterone seems to have a great significance because of its neuropharmacological traits (Hausmann, 2001). Intrahemispheric differences between male and female brains are described with a stronger focussing of functions in women (Halpern, 2000).
Biological concepts concerning the developmental history of gender differences in morphology, cognition, emotion and behaviour favour evolution theoretical models – e.g. the „hunters and collectors hypothesis“ (Halpern, 2000).
To sum up it can be stated, that different studies hint at the assumption that the brain in early developmental phases is influenced by sexual hormones and hereby a sex typical variation of the microstructure and functional modifications of the brain result. Furthermore there are hints that even the adult brain is influenced by sex typical hormone concentrations in microstructure and function.
Sociological and psychological models
In sociology the topic of human gender is focussed in the phrase „gender role“.
To answer the question, how the gender role is acquired by the individual one has to look at psychological models.
Psychoanalytical concepts of gender
Freud assumed a biological and psychic bisexuality in humans. He opposed the biological bisexuality to the psychological bisexuality (Freud, 1989b). The “pure masculinity and femininity” became theoretical constructs to him, as all human individuals combine male and female characters because of their bisexual base and crossed hereditary pathways.
Freud assumed a different sexual development in males and females. Early phases of libido development – like oral, sadistic-anal and phallic phase – are similar in both sexes (Freud, 1989c). The mother forms the primary object for boys as well as for girls during these phases. The different psychosexual development of boys and girls was induced by the discovery of the “anatomical sex difference” which resulted in a gender typical solution of the Ödipus complex. This is a phase when the child is tenderly affected by the opposite parent and hostility concerning the other parent dominates. The boy takes his mother as his first loving object and takes his father as his rival. The castration complex resolves the Ödipus complex in boys. The boy`s narcissistic interest in his penis which is threatened to be taken away is in conflict with the libidinal image of his mother. If the Ödipus complex is successfully resolved the construction of the Über-Ich (superego) is induced.
In girls the realization of her penislessness results in an inferiority feeling. Freud proclaims three possible development directions for girls in this situation: 1) shying away from sexuality in general, 2) the “masculinity complex” – a self-demonstration of the threatened masculinity in females, and 3) the “normal” female development when the girl`s father becomes the object (Freud, 1989d). Castration complex induces the Ödipus complex in girls. Therefore the girl lacks an important motive for the solution of the Ödipus complex and an incomplete development of the Über-Ich may result. The gender typical personality development and a higher grade of narcissism in women is based in different solutions of the Ödipus complex which is induced by the penis envy in women.
Freud`s concept of gender has always been controversially discussed. Even when Freud was still alive and especially in today`s feministic literature the phallocentric view of the world, where the male seems to be the prototype of the human, has strongly been criticised. Already in 1926 Karen Horney took a critical position concerning Freud`s concept of the female personality development (Horney, 1926). She interpreted the idea of the phallic monism and the assumed female penis-envy an attempt to repulse the male envy in relation to the reproduction capability of the female. Freud`s concept of female personality development can be understood as a male concept of femininity in a paternalistic society. The female is just the substitute of a self-anticipated male domination in the gender struggle of a paternalistic society (Simmel, 1985). Those traits excluded and repulsed by the male self definition are directed to the female gender. Rohde-Dachser names this process the “containment function” of the female for the male (Rohde-Dachser, 1992). Besides the lack of social criteria in Freud`s concept has to be seen critically. Lerner notes that women have good reasons to envy the men`s positions in society caused by other reasons than the “valuable penis” (Lerner, 1991). It could be asked if the penis envy does not mean the envy concerning political and social male power and the advantages for men in many areas of the professional and private field.
Freud`s well-known saying: “Anatomy forms fate” (Freud, 1989a), trying to reason the postulated differences in male and female personality development, forms a problematic begin of discussion. Gender roles applied by the society are based upon the biological sex. Yet they clearly vary in different cultures and eras. Thus to reduce the gender roles to their anatomical difference does not seem legitimate to us. Freud mostly neglected sociocultural factors that participate in the development of female personality. Fromm therefore criticized Freud`s image of the female gender as a “slightly rationalized variant of paternalistic prejudices” (Fromm, 1961). To claim a higher degree of narcissism as connected to her anatomy strengthens the ideology of inherited femininity – a concept of biological and psychological inferiority of women.
Like Psychoanalysis as a whole also the psychoanalytical gender concepts have been further developed in the 20th century. Taking into account the Ich-psychology, the object relation theory, the self psychology and the current newborn research a significant change and differentiation of the psychoanalytical gender concepts has taken place that we cannot comment on in this paper. Important steps on this way are connected with Stoller (Stoller, 1968), Mahler (Mahler et al, 1993), Galenson and Roiphe (Galenson et al, 1974) and Stern (Stern, 2003). Newer psychoanalytical gender concepts can be found in the review paper of Callan (Callan, 2001).
Behavioural and cognitive psychological concepts of gender
Behavioural psychology assumes two basic learning processes which can be used to explain gender typical personality development: learning by direct reinforcement of behaviour and model learning (Lott et al, 2001).
If a boy`s active, independent, self-assertive behaviour is often positively reinforced and passive, dependent, emotional behaviour is punished, the first behaviour will be more frequently shown. By using reinforcement and punishment of different behaviour in boys and girls the child is socialised in gender roles.
Model learning is the other basic learning experience which transports gender typical behaviour. “Representative reinforcement” of behaviour forms the centre of this theory (Schuster, 1984).
To deal with our subject in question it is decisive which model is really imitated reflecting the numerous choice of models in the child`s environment. Hypotheses are: A model is imitated because love withdrawal is feared. The model is imitated because punishment is expected otherwise. A person is chosen as model because this person earns rewards from others. A model is chosen that seems similar to own traits and social roles (Schuster, 1984).
All these theories can explain why girls prefer to chose models of the same gender and especially those that fit the gender role taken as a model. The girl fears love withdrawal and punishment if she does not chose the mother as model; the little girl experiences that women are rewarded for gender typical role behaviour and punished for non conformist behaviour. Model learning is not restricted to the child`s environment. Stereotypically presented gender roles in media and literature can serve as the child`s role model.
Whereas no sex differences in intelligence often differences in cognitive capabilities could be found (Halpern, 2001; Kestemberg et al, 2003).
Dominating cognitive theories of femininity and masculinity is the phrase of the cognitive scheme (Martin et al, 2001). One of the first and most influencing schemes built up by the child is the sexual scheme. The child characterizes itself and others into the categories male and female and develops more and more differentiated concepts on appearance, capabilities, psychological traits and occupations of men and women dependent on dominating gender models. By finding itself into a certain gender role the child`s self scheme corresponds to the common gender scheme. The self scheme, having a gender compound, influences the perception and behaviour of the individual.
To sum up it can be stated that different psychological theories concur that psychic gender is not something primarily genuine. The psychological concepts emphasize the developmental aspect of gender. A critical aspect of the traditional concepts is that the psychic femininity and masculinity form two poles of one dimension. High femininity means low masculinity and vice versa. Reacting to this some alternative concepts were developed looking at femininity and masculinity as independent variables or in a constructivistic sense. These concepts implicate a criticism versus the described biological and psychological gender concepts.
Androgyny and constructivistic gender concepts
Androgyny unifies femininity and masculinity – usually being defined as two opposite traits of human existence – in one person. The first half of the 20th century was dominated by an unidimensional model of psychic gender (Terman et al, 1936). This model implied that individuals could not integrate male and female traits in their self image at once (Strauss et al, 1999). In the Seventies authors like Bem (Bem, 1974) and Spence and Helmreich (Spence et al, 1978) developed gender concepts with masculinity and femininity as two independent dimensions of gender role identities. Following these concepts the individual is able to integrate male and female traits in the self. In this model persons, showing male and female traits to a similar extent, are called androgyn. Empirical studies confirmed these twodimensional models instead of the older onedimensional one (Strauss et al, 1999). The problems of empirical measuring of male and female traits are discussed by Halpern (Halpern, 2000).
Advantages of androgyn persons compared to those seeming masculine, feminine or undifferentiated, lie in a broader spectrum of action possibilities and a higher grade of flexibility and coping with different situations as well as a higher level of emotional well-being (Bock, 2004). A higher self-esteem and a better mental health are deducted from the male identity compound (Sieverding et al, 1992).
The androgyny concept was not just agreed upon. Looking back at the last thirty years especially the feministic discussion named the following criticisms: concerning the grammar already “der Androgyn” (in German) signifies a male connotation. The traditional understanding of femininity and masculinity persists and with it the hierarchy of genders. Furthermore the androgyny concept seems a bit paradoxical trying to gain a tendency of overcoming the stereotypes of gender while using them as the base of the concept. Androgyny is seen as a step on the way to an individual and social development overcoming the limited gender role identities (Bock et al, 1999).
The common sense postulates two and just two sexes. Each human has one sex or the other. Sex is stated by birth and does not change anymore. Sex can undoubtedly be identified by the genitals and therefore forms a natural, biological and uniquely defined fact which cannot be influenced by humans. In constructivistic concepts the social gender reality is the result of a historical process and a perpetuating social practice which always renews the common sense of gender. This is not just assumed for gender but also for sex. Even the biological sex – the reproductive organs – is seen as historically influenced and does not form the base but the effect of social practice (Wetterer, 2004). A natural, free of the social dimension, perception and reflection of the body is denied (Douglas, 1974).
Ethnological studies could show that not all societies differentiate between two sexes. Not all cultures apply one gender role for the whole life span. The reproductive organs do not always cause the gender role (Ortner et al, 1981; Pomata, 1983).
West and Zimmerman developed the concept of “doing gender” in contrast to the more common “sex-gender-differentiation” (West et al, 1987). The sex-gender-concept implicates a “natural difference” between the sexes and the cultural constructs of gender are interpreted as a social reflex of nature (Gildemeister, 2004). “Doing gender” assumes to recognize sex not only as an individual trait but to look at those social processes that have developed gender as a social differentiation and reproduce it. Gender role specific occupations and work have shown a great relevance – “doing gender while doing work” (Leidner, 1991; Williams, 1989).
Buttler managed to develop an analytical (de)construction of gender (Buttler, 1991). The mode of gender construction is located by her in the field of language and discourse (Villa, 2004). Gender discourse hereby defines the area of thinkable and livable aspects. Gender as the material sex is also seen as an effect of discourse and a practice that permanently repeats and cites itself (Buttler, 1995).
The sex distribution of mental disorders results in focussing of different levels of human sex or gender in order to understand the etiopathogenesis.
Epidemiological findings hint at the etiopathogenetic significance of sex or gender in relation to many mental disorders. The Lesch-Nyhan syndrome is an example for an x-chromosomale recessive hereditary pathway which results in nearly affecting male patients only. The sex distribution is caused by the biological, especially by the chromosomal sex. The essential etiopathogenetic factor is the lack of the enzyme hypoxanthine-guanine-phosphoribosyltransferase (HPRT). The connection to the sex of the patient is caused by the HPRT coding gene lying on the x-chromosome. The gonadale and somatic sex on the biological level, and psychological as well as social gender models can not give any explanation for the syndrome. In this rare case a simple biological model of sex may be adequate.
Depressive disorders have a multifactoral etiopathogenesis with important roles of both biological as well as psychosocial factors. Psychosocial and cultural factors have proven to be very helpful in understanding the epidemiological findings concerning the sex distribution. The sociological concept of gender as well as the psychological models of acquiring the gender role, are the focus in understanding why women suffer more often from depressive disorders than men.
Biological studies hint at the findings that the brain is influenced by sexual hormones from an early developmental phase on and that a sex typical modification of microstructure and functions results. Even the adult brain is influenced by it in the same context. As psychosocial factors influence those areas as well gender typical behavioural and perceptive modes cannot be just reduced to be induced by hormonal influences. A direct effect of social influences on the brain cannot be assumed. Only physical factors can directly influence the brain. To gain an understanding of the mode of influence of social factors on the brain those factors would have to be “translated” into physical “language” which is nearly impossible because of their complexity. Morphology and function of the brain influence how the individual perceives its world, which environment, persons and experiences it chooses. These are reciprocal processes which do not make sense in the question if biological or psychosocial factors are primarily responsible for gender differences (Halpern, 2000). Sociological theories cannot work without psychological and biological theories in explaining why only a small percentage of people that live in pathogene circumstances develop a mental disorders and why others without those circumstances do fall ill. A special predisposition forms the ground for special situations resulting in a mental disorder.
To understand the sex and gender distribution in depressive disorders and in most other mental disorders a complex model of human gender that includes the biological, psychological and social level – as mentioned in the discussion – has proved to be effective.
Altemus M, Arleo E. (1999) Modulation of anxiety by reproductive hormones. In: Leibenluft E (ed) Gender differences in mood and anxiety disorders – From bench to bedside. American Psychiatric Press, New York: 53-89
Angold A, Worthman CW. (1993) Puberty onset of gender differences in rates of depression: a developmental, epidemiologic and neuroendocrine perspective. Journal of Affective Disorders. 29, 145-158.
Angst J, Dobler-Mikola A. (1984) The Zurich study. III. Diagnosis of depression. Eur Arch Psychiatry Neurol Sci. 234, 30-37.
Angst J, Gamma A, Gastpar M, Lepine JP, Mendlewicz J, Tylee A, Depression Research in European Society. (2002) Gender differences in depression. Epidemiological findings from the European DEPRES I and II studies. Eur Arch Psychiatry Clin Neurosci. 252, 201-209.
Aral B, de S, Al-Garawi S, Kamoun P, Ceballos-Picot I. (1996) Novel nonsense mutation in the hypoxanthine guanine phosphoribosyltransferase gene and nonrandom X-inactivation causing Lesch-Nyhan syndrome in a female patient. Hum Mutat. 7, 52-58.
Bebbington P. (1996) The origins of sex differences in depressive disorder: Bridging the gap. Int Rev Psychiatry. 8, 295-332.
Beck AT, Rush AJ, Shaw BF, Emery G, Hautzinger M. (2001) Kognitive Therapie der Depression. Beltz, Weinheim
Bem SL. (1974) The measurement of psychological androgyny. J Consult Clin Psychol. 42, 155-162.
Bijl RV, Ravelli A, van Zessen G. (1998) Prevalence of psychiatric disorder in the general population: results of The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Soc Psychiatry Psychiatr Epidemiol. 33, 587-595.
Birbaumer N, Schmidt R. (2002) Biologische Psychologie. Springer, Berlin
Bland RC, Orn H, Newman SC. (1988) Lifetime prevalence of psychiatric disorders in Edmonton. Acta Psychiatr Neurol Scand. 338, 24-32.
Bock U. (2004) Androgynie: Von Einheit und Vollkommenheit zu Vielfalt und Differenz. In: Becker R, Kortendiek B (eds) Handbuch Frauen- und Geschlechter-Forschung. Theorie, Methoden, Empirie. Verlag für Sozialwissenschaften, Wiesbaden: 99-103
Bock U, Alfermann D. (1999) Androgynie in der Diskussion: Auflösung der Geschlechterrollengrenzen oder Verschwinden der Geschlechter? – Eine Einleitung. In: Bock U, Alfermann D (eds) Querelles - Jahrbuch für Frauenforschung 1999 - Androgynie, Vielfalt der Möglichkeiten. Metzler, Stuttgart: 11-34
Breedlove SM. (1994) Sexual differentiation of the human nervous system. (Review) (155 refs). Annu Rev Psychol. 45, 389-418.
Brüggemann BR, Haltenhof H. (2002) Der Beitrag soziokultureller Faktoren zum Verständnis der Geschlechterverteilung depressiver Störungen. Z Klin Psychol Psychiatr Psychother. 50, 101-132.
Buttler R. (1991) Das Unbehagen der Geschlechter. Suhrkamp, Frankfurt am Main
Buttler R. (1995) Körper von Gewicht. Die diskursiven Grenzen des Geschlechts. Berlin Verlag, Berlin
Callan JE. (2001) Gender development. Psychoanalytic perspectives. In: Worell J (ed) Encyclopedia of women and gender. Sex similarities and differences and the impact of society on gender. Academic Press, San Diego: 523-536
Canino GJ, Bird HR, Shrout PE, Rubio-Stipec M, Bravo M, Martinez R, Sesman M, Guevara LM. (1987) The prevalence of specific psychiatric disorders in Puerto Rico. Arch Gen Psychiatry. 44, 727-735.
Chiarello C, McMahon MA, Schaefer K. (1989) Visual cerebral lateralization over phases of the menstrual cycle: a preliminary investigation. Brain Cogn. 11, 18-36.
Corballis MC, Sidey S. (1993) Effects of concurrent memory load on visual-field differences in mental rotation. Neuropsychologia. 31, 183-197.
Cross-National Collaborative Group. (1992) The Changing Rate of Major Depression. JAMA. 268, 3098-3105.
DeGregorio L, Nyhan WL, Serafin E, Chamoles NA. (2000) An unexpected affected female patient in a classical Lesch-Nyhan family. Mol Genet Metab. 69, 263-268.
Douglas M. (1974) Ritual, Tabu und Körpersymbolik. Suhrkamp, Frankfurt am Main
Egeland JA, Hostetter AM. (1983) Amish Study, I: Affective disorders among the Amish, 1976-1980. Am J Psychiatry. 140, 56-61.
Essau CA, Petermann U. (1995) Depression in children and adolescents. (German). Z Klin Psychol Psychiatr Psychother. 43, 18-33.
Fichter MM. (1990) Verlauf psychischer Erkrankungen in der Bevölkerung. Springer, Berlin
Fleming JE, Offord DR. (1990) Epidemiology of childhood depressive disorders: A critical review. J Am Acad Child Adolesc Psychiatry. 29, 571-580.
Freud S. (1989b) Drei Abhandlungen zur Sexualtheorie. In: Mitscherlich A, Richards A, Strachey J (eds) Sigmund Freud Studienausgabe Band V: Sexualleben. Fischer, Frankfurt am Main
Freud S. (1989a) Der Untergang des Ödipuskomplexes. In: Mitscherlich A, Richards A, Strachey J (eds) Sigmund Freud Studienausgabe Band V: Sexualleben. Fischer, Frankfurt am Main
Freud S. (1989c) Neue Folge der Vorlesungen zur Einführung in die Psychoanalyse. Die Weiblichkeit. In: Mitscherlich A, Richards A, Strachey J (eds) Sigmund Freud Studienausgabe Band I: Vorlesungen zur Einführung in die Psychoanalyse und Neue Folge. Fischer, Frankfurt am Main
Freud S. (1989d) Über die weibliche Sexualität. In: Mitscherlich A, Richards A, Strachey J (eds) Sigmund Freud Studienausgabe Band V: Sexualleben. Fischer, Frankfurt am Main
Fromm E. (1961) Sigmund Freuds Sendung. Ullstein, Frankfurt am Main
Galenson E, Roiphe H. (1974) The emergence of genital awareness during the second year of life. In: Friedman RC, Richart RM, van de Wiele RL (eds) Sex differences in behavior. Wiley, New York: 223-231
Gildemeister R. (2004) Doing Gender: Soziale Praktiken der Geschlechterunterscheidung. In: Becker R, Kortendiek B (eds) Handbuch Frauen- und Geschlechter-Forschung. Theorie, Methoden, Empirie. Verlag für Sozialwissenschaften, Wiesbaden: 132-140
Hagnell O, Lanke J, Rorsman B, Ojesjo L. (1982) Are we entering an age of melancholy? Depressive illnesses in a prospective epidemiological study over 25 years: the Lundby Study, Sweden. Psychol Med. 12, 279-289.
Halpern DF. (2000) Sex differences in cognitive abilities. LEA Publishers, Mahwah, New Jersey, London
Halpern DF. (2001) Sex difference research: cognitive abilities. In: Worell J (ed) Encyclopedia of women and gender. Sex similarities and differences and the impact of society on gender. Academic Press, San Diego: 963-972
Hara K, Kashiwamata S, Ogasawara N, Ohishi H, Natsume R, Yamanaka T, Hakamada S, Miyazaki S, Watanabe K. (1982) A female case of the Lesch-Nyhan syndrome. Tohoku J Exp Med. 137, 275-282.
Hausmann M. (2001) Geschlechtsspezifische Aspekte der funktionellen zerebralen Asymmetrie und deren Relevanz für die Psychiatrie. In: Riecher-Rössler A, Rohde A (eds) Psychische Erkrankungen bei Frauen - Für eine geschlechtersensible Psychiatrie und Psychotherapie. Karger, Basel: 124-137
Hausmann M, Behrendt-Korbitz S, Kautz H, Lamm C, Radelt F, Gunturkun O. (1998) Sex differences in oral asymmetries during wordrepetition. Neuropsychologia. 36, 1397-1402.
Horney K. (1926) Flucht aus der Weiblichkeit. Der Männlichkeitskomplex der Frau im Spiegel männlicher und weiblicher Betrachtung. Internationale Zeitschrift für Psychoanalyse, 360-374.
Jorm AF. (1987) Sex and age differences in depression: a quantitative synthesis of published research. Australian & New Zealand Journal of Psychiatry. 21, 46-53.
Joyce PR, Oakley-Browne MA, Wells JE, Bushnell JA, Hornblow AR. (1990) Birth cohort trends in major depression: increasing rates and earlier onset in New Zealand. J Affect Disord. 18, 83-89.
Kelly D, Jessel T. (1996) Geschlecht und Gehirn. In: Kandel ER, Schwartz JH, Jessel TM (eds) Neurowissenschaften. Spektrum Akademischer Verlag, Heidelberg: 591-606
Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 51, 8-19.
Kestemberg LB, Tarnofsky Silverman MB, Santandreu NG. (2003) Gender differences in neuropsychological functioning. In: Kapala M, Keitel M (eds) Handbook of Counseling Women. Sage Publications, London: 86-105
Kimura D. (1992) Weibliches und männliches Gehirn. Spektrum der Wissenschaften. 11, 104-113.
Kimura D. (1999) Sex and Cognition. MIT Press, Cambridge
Le Vay S. (1994) Keimzellen der Lust. Die Natur der menschlichen Sexualität. Spektrum Akademischer Verlag, Heidelberg
Lee CK, Kwak YS, Yamamoto J, Rhee H, Kim YS, Han JH, Choi JO, Lee YH. (1990) Psychiatric epidemiology in Korea. Part I: Gender and age differences in Seoul. J Nerv Ment Dis. 178, 242-246.
Leidner R. (1991) Serving Hamburgers and selling insurances: Gender, work and identity in interactive service jobs. Gender and society. 52, 177.
Lepine JP, Gastpar M, Mendlewicz J, Tylee A. (1997) Depression in the community: the first pan-European study DEPRES (Depression Research in European Society). Int J Clin Pharmacol Ther Toxicol. 12, 19-29.
Lerner HG. (1991) Das mißdeutete Geschlecht: Falsche Bilder der Weiblichkeit in Psychoanalyse und Therapie. Kreuz, Zürich
Lesch M, Nyhan WL. (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med. 36, 561-570.
Levav I, Kohn R, Golding JM, Weissman MM. (1997) Vulnerability of Jews to affective disorders. Am J Psychiatry. 154, 941-947.
Loewenthal K, Goldblatt V, Gorton T, Lubitsch G, Bicknell H, Fellowes D, Sowden A. (1995) Gender and depression in Anglo-Jewry. Psychol Med. 25, 1051-1063.
Loewenthal KM, MacLeod AK, Cook S, Lee M, Goldblatt V. (2003) Beliefs about alcohol among UK Jews and Protestants: do they fit the alcohol-depression hypothesis? Soc Psychiatry Psychiatr Epidemiol. 38, 122-127.
Lott B, Maluso D. (2001) Gender development. Social learning. In: Worell J (ed) Encyclopedia of women and gender. Sex similarities and differences and the impact of society on gender. Academic Press, San Diego: 537-570
MacLusky NJ, Naftolin F. (1981) Sexual differentiation of the central nervous system. Science. 211, 1294-1302.
Mahler MS, Pine F, Bergmann A. (1993) Die psychische Geburt des Menschen. Symbiose und Individuation. Fischer, Frankfurt am Main
Martin CL, Dinella LM. (2001) Gender development: Gender schema theory. In: Worell J (ed) Encyclopedia of women and gender. Sex similarities and differences and the impact of society on gender. Academic Press, San Diego: 507-522
Matthews WS, Solan A, Barabas G. (1995) Cognitive functioning in Lesch-Nyhan syndrome. Dev Med Child Neurol. 37, 715-722.
Mattisson C, Bogren M, Nettelbladt P, Munk-Jorgensen P, Bhugra D. (2005) First incidence depression in the Lundby Study: a comparison of the two time periods 1947-1972 and 1972-1997. Journal of Affective Disorders. 87, 151-160.
Meyer C, Rumpf HJ, Hapke U, Dilling H, John U. (2000) Lifetime prevalence of mental disorders in the adult general population: Findings from the TACOS study. (German). (References). Nervenarzt. 71, 535-542.
Murphy JM, Sobol AM, Neff RK, Olivier DC, Leighton AH. (1984) Stability of prevalence. Depression and anxiety disorders. Arch Gen Psychiatry. 41, 990-997.
Nolen-Hoeksema S. (1990) Sex differences in depression. University Press, Stanford
Nopoulos P, Flaum M, O'Leary D, Andreasen NC. (2000) Sexual dimorphism in the human brain: evaluation of tissue volume, tissue composition and surface anatomy using magnetic resonance imaging. Psychiatry Res. 98, 1-13.
Nopoulos PC, Andreasen NC. (1999) Gender differences in neuroimaging findings. In: Leibenluft E (ed) Gender differences in mood and anxiety disorders – From bench to bedside. American Psychiatric Press, Washington: 1-30
Norton MC, Skoog I, Franklin LM, Corcoran C, Tschanz JT, Zandi PP, Breitner JC, Welsh-Bohmer KA, Steffens DC, Cache C, I. (2006) Gender differences in the association between religious involvement and depression: the Cache County (Utah) study. Journals of Gerontology Series B-Psychological Sciences & Social Sciences. 61, 129-136.
Ogasawara N, Stout JT, Goto H, Sonta S, Matsumoto A, Caskey CT. (1989) Molecular analysis of a female Lesch-Nyhan patient. J Clin Invest. 84, 1024-1027.
Ortner SB, Whitehead H. (1981) Sexual meanings, the cultural construction of gender and sexuality. Cambridge University Press, Cambridge
Pilgrim C, Hutchison JB. (1994) Developmental regulation of sex differences in the brain: can the role of gonadal steroids be redefined? Neuroscience. 60, 843-855.
Pomata G. (1983) Die Geschichte der Frauen zwischen Anthropologie und Biologie. Feministische Studien. 2, 113-127.
Robins LN, Regier DA. (2005) Psychiatric disorders in America. The Epidemiologic Catchment Area Study. Free Press, New York
Rohde-Dachser C. (1992) Expedition in den dunklen Kontinent: Weiblichkeit im Diskurs der Psychoanalyse. Berlin,
Sadler TW, Langman J. (2003) Medizinische Embryologie. Thieme, Stuttgart
Schuster M. (1984) Modelllernen. In: Angermeier W (ed) Lerndpsychologie. Reinhardt, München
Seligman MEP. (1981) Gelernte Hilflosigkeit. In: Blöschl L (ed) Verhaltenstherapie depressiver Reaktionen. Huber, Bern
Shaywitz BA, Shaywitz SE, Pugh KR, Constable RT, Skudlarski P, Fulbright RK, Bronen RA, Fletcher JM, Shankweiler DP, Katz L, . (1995) Sex differences in the functional organization of the brain for language. Nature. 373, 607-609.
Sieverding M, Alfermann D. (1992) Instrumentelles (maskulines) und expressives (feminines) Selbstkonzept: ihre Bedeutung für die Geschlechtsrollenforschung. Zeitschrift für Sozialpsychologie. 1, 6-15.
Simmel G. (1985) Schriften zur Philosophie und Soziologie der Geschlechter. Suhrkamp, Frankfurt am Main
Spence JT, Helmreich RL. (1978) Masculinity and femininity. Their psychological dimension, correlates and antecedents. University of Texas Press, Austin
Stern D. (2003) Die Lebenserfahrung des Säuglings. Stuttgart. Klett-Cotta, Stuttgart
Stoller J. (1968) Sex and gender. Hogarth, London
Strauss B, Möller J. (1999) Androgynie: Typ oder Trait? -. In: Bock U, Alfermann D (eds) Querelles. Jahrbuch für Frauenforschung 1999. Metzler, Stuttgart: 200-209
Sturt E, Kumakura N, Der G. (1984) How depressing life is--life-long morbidity risk for depressive disorder in the general population. J Affect Disord. 7, 109-122.
Terman LM, Miles CC. (1936) Sex and personality - studies in masculinity and feminity. McGraw-Hill, New York
Tobach E. (2001) Development of sex and gender: Biochemistry, physiology, and experience. In: Worell J (ed) Encyclopedia of women and gender - sex similarities and differences and the impact of society on gender. Academic Press, San Diego, Calif: 315-332
vanBogaert P, Ceballos I, Desguerre I, Telvi L, Kamoun P, Ponsot G. (1992) Lesch-Nyhan syndrome in a girl. J Inherit Metab Dis. 15, 790-791.
Villa PI. (2004) (De)Konstruktion und Diskurs-Genealogie: Zur Position und Rezeption von Judith Butler. In: Becker R, Kortendiek B (eds) Handbuch Frauen- und Geschlechter-Forschung. Theorie, Methoden, Empirie. Verlag für Sozialwissenschaften, Wiesbaden
Voyer D. (1996) On the magnitude of laterality effects and sex differences in functional lateralities. Laterality. 1, 51-83.
Weissman MM, Bland RC, Canino GJ, Faravelli C, Greenwald S, Hwu HG, Joyce PR, Karam EG, Lee CK, Lellouch J, Lepine JP, Newman SC, Rubio-Stipec M, Wells JE, Wickramaratne PJ, Wittchen H, Yeh EK. (1996) Cross-national epidemiology of major depression and bipolar disorder. JAMA. 276, 293-299.
Weissman MM, Leaf PJ, Tischler GL, Blazer DG, Karno M, Bruce ML, Florio LP. (1988) Affective disorders in five United States communities. Psychol Med. 18, 141-153.
West C, Zimmerman D. (1987) Doing gender. Gender and society. 1, 125-151.
Wetterer A. (2004) Konstruktion von Geschlecht: Reproduktionsweisen der Zweigeschlechtlichkeit. In: Becker R, Kortendiek B (eds) Handbuch Frauen- und Geschlechter-Forschung. Theorie, Methoden, Empirie. Verlag für Sozialwissenschaften, Wiesbaden: 122-131
Williams CL. (1989) Gender differences at work - women and men in nontraditional occupations. University of California Press, Berkeley
Wittchen HU, Essau CA, von Z, Krieg JC, Zaudig M. (1992) Lifetime and six-month prevalence of mental disorders in the Munich Follow-Up Study. Eur Arch Psychiatry Clin Neurosci. 241, 247-258.
Yamada Y, Goto H, Yukawa T, Akazawa H, Ogasawara N. (1994) Molecular mechanisms of the second female Lesch-Nyhan patient. Adv Exp Med Biol. 370, 337-340.
Young MA, Scheftner WA, Fawcett J, Klerman GL. (1990) Gender differences in the clinical features of unipolar major depressive disorder. J Nerv Ment Dis. 178, 200-203.
Yukawa T, Akazawa H, Miyake Y, Takahashi Y, Nagao H, Takeda E. (1992) A female patient with Lesch-Nyhan syndrome. Dev Med Child Neurol. 34, 543-546.
Dr. med. Bernd Rüdiger Brüggemann M.A.
Department of Social Psychiatry and Psychotherapy
Hannover Medical School
Received August 2007. Accepted November 2007
Copyright November 2007 Priory Lodge Education Limited