Stress and Gender Gender related differences in a changing society

1. Stress and GenderGender related differences in a changing society Maria S Kopp MD, PhD, Árpád Skrabski, PhD, Csilla Csoboth, MD, PhD. Gender Medicine Working Group, Institute of Behavioural sciences, Budapest, Hungary www.behsci.sote.hu Gender-Specific Medicine Conference February 23-26,2006, Berlin

2. Gender differences: • Although men and women share the same socio-economic circumstances, there are significant gender differences in worsening mortality rates in Hungary • Socioeconomic differences are more closely connected with male premature mortality rates • What is the explanation for the increased vulnerability of middle aged men during this period of rapid economic change?

3. Aggregate mortality according to low versus high education(Mackenbach et al, 1999)

4. Mortality rates of middle aged (45-64) men and women in Hungary (2001)

5. Special experimental model • The paradoxical features of gender related premature mortality and morbidity rates in Central-Eastern-European countries might be regarded as • a special experimental model to understand better the human consequences of chronic stress and • gender differences in this respect

6. What can explain the opposite changes in gender differences in life expectancy? • In the 1970s no differences in Austrian and Hungarian life expectancy • Life expectancy in Hungary today: • Male 68.2, female 76.5 years-8.3 years differences in Hungary, 2.3 years lost • In neighbouring Austria: • Male 75.9- they live 7.7 years longer, • Female 81.7- they live 5.2 years longer 5.8 years differences in Austria

7. Growing polarization of the socio-economic situation between 1960 and 2002 • Until 1960, practically no income inequality, there were no mortality differences between socio-economic strata and there were smaller gender differences • Since that time increasing disparities in socio-economic conditions have been accompanied by a widening socio-economic gradient in mortality, but much more among men.

8. Mortality rate in 1000 men in corresponding age groups in the Hungarian population(Demographic Yearbook, 2004)

9. Possible explanations: • This deterioration cannot be ascribed to defficiencies in health care,because • during these years there was a significant decrease in infant and old age mortality and improvements in other dimensions of health care. • Between 1960 and 1989 there was a constant increase in the gross domestic product in Hungary. Worsening material situation cannot be the explanation • Genetic causes- sudden changes, not probable, possible changes in genetic expression

10. General adaptation Theory of János Selye: • The three phases of stress: • alarm reaction, • resistance phase and, • the third, physiologically most harmful phase, exhaustion, chronic stress • What type of chronic stress level is higher among men than among women in Hungary?

11. Gender differences • There are no fundamental gender differences in physiological adaptation processes • Although male and female hormones influence it in both respect • Estrogenes decrease the stress reactivity • According to animal studies, males appear to be more vulnerable to long-lasting stress-induced hippocampal damage than females (Uno et al, J. Neurosci,9,1705-1711,1989), the decline of circulating testosterone levels resulting from uncontrollable stress seems to play an additional role. • Perinatal processes might result in dysregulation- post-natal depression

12. Early life chronic stress: • Phases of disruption of mother-infant or peer bonding: • 1. "protest" behaviour (acute and resistance phases of stress). • 2.“despair”: locomotor inactivity and a disinterst in motivationally salient external stimuli. • 3."detachment""hardwired" in the brain of many social mammals and results in high stress vulnerability

13. Attachment theory (Bowlby, Imre Hermann) • Physiological, psychological and developmental importance of the early childhood affective mother-child bond and the negative consequences of the disruption of this relationship. • According to follow up studies, insecure attachment predicts later emotional instability and health deterioration. Maltreatment at an early age can have enduring negative effects on a child’s brain development and function, and on his or her vulnerability to stress.

14. Special gender roles, crucial effect of maternal care • Maternal neglect behaviour results in attachment disturbances • Animal experiments: influence of „caring” and „non-caring” mothers on development of offsprings • Naturally occuring variations in maternal care alter the expression of genes that regulate behavioral and endocrine responses to stress, as well as hippocampal synaptic development – related to oxytocin receptor gene expression (M.J.Meaney: Ann Rev Neurosci2001, 24,1161-1192) • Intergenerational transmission- importance of maternal care- in low socioeconomic groups more maternal neglect

15. Learned helplessness as result of chronic stress • A condition of loss of control created by subjecting animals or humans to an unavoidable, emotionally negative life situation (such as unavoidable shocks, relative deprivation, role conflict, etc). Being unable to avoid or escape (flight or fight) an aversive situation for a long period of time produces a feeling of helplessness that generalises to subsequent situations.

16. Brain consequences of learned helplessness: • The hippocampus is primarily affected by the long-lasting elevations of circulating corticosteroids resulting from uncontrollable stress. Severe stress for a prolonged period causes damage in hippocampal pyramidal neurons, especially in the CA 3 and CA4 region and reductions in the length and arborization of their dendrites.

17. Main biological pathways of chronic stress: • - Dysregulation of the hypothalamus-hypophysis-adrenocortical (HPA) axis and the sympathetic-adrenal-medullary system (SAM) resulting in elevations in serum catecholamin and cortisol levels. • Sympathoadrenal hyperactivity contributes to the development of CVD through effects of catecholamines upon the heart, blood vessels and platelets. • Sympathoadrenal activation modifies the function of circulating platelets

18. Human learned helplessness: • expectancy that responses and outcomes are uncontrollable and might result in only emotionally negative consequences. • refers to the motivational, cognitive and emotional components of the interpretation of the environmental stimuli • Central importance: values, self-ideal, expectations, attitudes • Gender differences in this respect.

19. Gender differences? • Differences in environmental, cultural and gender role requirements • Masculine versus feminine societies ( Geert Hofstede, 2001:Cultures consequences ) Hungary is extremely masculine society- different gender roles • Socioeconomic status seems to be more important for men, • Family affairs for women • Differences according to education level

20. Effect of sex „nonconformity” • Girls who are more „masculine” according to attitude scores • and boys who are more „feminine” tend to do better in intellectual giftednes measured by National Merit test score • This nonconforming seems to be more important among girls • Bem Sex-Role Inventory (BSRI) – masculine, feminine adjective checklists (Lippa,R, 1998, in Males, Females and Behavior, eds:Ellis L, Ebertz, L,Praeger, pp.177-194.)

21. Gender differences: • Anxiety and depression is significantly higher among women according to most of the studies • In Hungary male depression rate is relatively higher, similar to female depression rates • Anxiety rates are twofold of male anxiety rates • Alcohol and drog abuse, smoking is much more prevalent among men • Depression seems to influence cardiovascular risk more among men than among women according to follow up studies. (Pennix et al, 2001, Arch.Gen.Psych,58,221-227) • Despite similar free cortisol responses of men and women (studied in the luteal phase) to psychosocial stress, gender may exert differential effects on the immune system by modulating glucocorticoid sensitivity of proinflammatory cytokine production.(Rohleider et al,2001,Psychosom Med 63,966-972)

22. Objectives of our behavioral medicine studies in Hungary: • To reveal those social, mental and behavioural factors in their inter-relatedness with biological processes that lead to health deterioration in the Hungarian middle-aged population, • Analyse gender related differences in this respect, • introduce effective preventive strategies that are based on research findings

23. National representative surveys in the Hungarian population • The samples represent the Hungarian population above age 16 according to gender, age and county • Hungarostudy 1983 more than 6000 persons • Hungarostudy 1988 20.902 persons • Hungarostudy 1995 12.463 persons

24. Latest surveys: Hungarostudy 2002 and follow up in progress • 12,643 persons were interviewed in their homes, they represented the population above age 18 according to age and sex and counties • The refusal rate was 17,7% for the full sample, although there were significant differences, depending on settlements • About 6.500 persons agreed to participate in a follow up study- now in progress

25. Education, Income, Subjective socioeconomic status (Nancy Adler) Acces to car Employment Marital status Housing environment Family environment Childhood experiences Self-rated socioeconomic changes Socio-economic factors:

26. Shortened Beck Depression Score Hospital Anxiety Score WHO Wellbeing Questionnaire Self-efficacy score Vital exhaustion score Hostility Score Type D Personality Questionnaire Hopelessness Score Hungarostudy indicators, mental health:

27. Social support questionnaire (Caldwell) Marital stress questionnaire Social capital measures: trust, civic associations Chicago collective efficacy Stress and coping Ways of coping questionnaire Purposes in Life Meaning (R.Rahe) Anomie score TCI shortened cooperativeness and sensation seeking Dysfunctional attitude score Life events Further mental health indicators:

28. Work stress variables: • Control at work • Social support at work • Working hours per week days • and weekend days • Income as job related reward • Job security • Unemployment

29. Smoking Alcohol (AUDIT) Drug consumption Physical activity Body weight and height- BMI Sleep complaints Religious involvement Suicidal behaviour Womens health- factors related to pregnancy and birth ethnical factors Health behaviour, lifestyle and other confounding factors:

30. Depression severity categories in 1988, 1995 and 2002 in the Hungarian adult population (above 18)

31. Clinical depression (BDI: 18-), men Hungarostudy 2002

32. Clinical depression (BDI: 18-), female Hungarostudy 2002

33. Mean Beck depression score according to age among Hungarian men and women (Hungarostudy 2002)

34. Significance of chronic stress-depressive symptomatology • Based on the data of our national representative surveys, we found that the worse socioeconomic situation is linked to higher morbidity and mortality rates in Hungary as well, • however, higher morbidity rates are connected to relatively poor socioeconomic situations mainly through the mediation of depressive symptoms, • in broader sense through chronic stress

36. Low income, depression and morbidity • In 1988 depression mediated between low income and self-rated morbidity among men, • while among women low income was not significantly connected neither to depression, nor with self reported morbidity. • In 1995 low income became directly connected to morbidity both in men and women, • but the mediating effect of depression between low income and morbidity remained more important among men than among women.

37. Why are men more susceptible to relative income inequality? • 1.Income inequality is much higher among men. • 2. Men are more susceptible to loss of status than women. Animal experiments have shown males to be more sensitive than females to loss of dominance position, that is loss of position in hierarchy. In animal studies social rank is the best predictor of quality of life and health among males.

38. Depression and chronic stress: • A self-destructive circle develops from the enduring relatively disadvantageous socioeconomic situation and depressive symptoms, • This circle resulting in chronic stress, might play a significant role in the increase of morbidity and mortality rates in the lower socioeconomic groups of the population. • Kopp MS, Réthelyi J (2004) Where psychology meets physiology:chronic stress and premature mortality- the Central-Eastern-European health paradox, Brain Research Bulletin ,62,351-367.

39. Ecological level analyses:determinants of mid-aged mortality differences based onnational representative survey data and national statistical mortality data for 150 Hungarian subregions

40. Mortality rates of middle aged men and depression scores in 2002

41. Ecological studies on determinants of chronic stress in the Hungarian population • Socio-economic status (education and income), social capital and collective efficacy (neigborhood cohesion) explained a considerable part of the sub-regional variance in middle aged mortality rates, • Competitive attitude was a significant predictor of mortality only among men, while religious involvement was a significant protective factor only among women. • Skrabski Á, Kopp MS, Kawachi I (2004) Social capital and collective efficacy in Hungary:cross-sectional associations with middle aged female and male mortality rates, J Epidemiology and Community Health ,30, 65-70.

42. Interaction between male and female health: • It is an interesting finding that the most important social capital variables of the opposite sex seem to influence the mortality for the other sex: • Civic support perceived by men is a protective factor for women, while the amount of reciprocity perceived by women seems to be a significant predictor of male health. • Skrabski ,Á, Kopp MS, Kawachi I.(2003) Social capital in a changing society:cross sectional associations with middle aged female and male mortality rates, J Epidemiology and Community Health 57, 2, 114-119.

43. Which are the protective factors for women? • Relative economic deprivation, rival attitude and social distrust are all less important risk factors for women • The socio-economic differences are less important regarding the middle aged female mortality differences. • Neighborhood cohesion, religious involvement and reciprocity were not so much influenced by sudden socio-economic changes, therefore the protective network of women remained relatively unchanged.

44. Gender paradox of subjective social status: • Female subjective social status influenced highly significantly the male mid-aged mortality: • r (female SSS and male mid-aged mortality)= -.597 p=.000 • That is, the subjective evaluation of the relative social deprivation by women might be an important risk factor for men as well • Kopp MS, Skrabski Á, Kawachi I, Adler NE (2005) Low socioeconomic staus of the opposite gender is a risk factor for middle aged mortality, J. Epidemiology and Community Health59,675-678.

45. Correlations of male and female social status and male mid aged mortality Korrelációs együtthatók, középkoró férfiak halálozása

46. Education -.599 Income -.512 Unemployment .465 Social support from friends -.372 Subjective social status .353 Depression .352 Weekend work hours .344 Anomie .340 Non stop alcohol .288 Morning alcohol .266 Hostility .257 Control at work -.255 Self-blame because of alcohol .250 Job security -.220 Social support at work -.197 Smoking (cigarettes pro day) .188 Significant correlations of total mid-aged CV mortality rates among men (n=150):

47. Education -.527 Income -.402 Unemployment .378 Social support from friends -.345 Depression .331 Non stop alcohol .313 Job security -.304 Subjective social status .303 Anomie .287 Hostility .229 Control at work -.275 Weekend work hours .225 Morning alcohol .224 Social support at work -.179 Smoking (cigarettes pro day) .151 Significant correlations of total mid-aged CV mortality rates among women:

48. Work stress variables in relation to total mid-aged CV mortality rates: Total male mid-aged CV mortality: Explained variance - weekend work hours 11.2 % - social support at work 14.7 % Total female mid-aged CV mortality - job security 8.7 % - weekend work hours 10.9 %

49. Work stress variables in relation to mid-aged ischemic heart disease mortality rates: Male mid-aged IHD mortality: Explained variance - social support at work 3.9 % - weekend work hours 7.6 % Female mid-aged IHD mortality - control at work 10.6 %

50. Work stress variables in relation to mid-aged cerebrovascular mortality rates: Male mid-aged cerebrovascular mortality: Explained variance - weekend work hours 11.7 % - control at work 14.4 % Female mid-aged cerebrovascular mortality - job security 4.8 % - week day work hours 7.2 %