Adherence to long-term therapy for chronic illnesses in developed countries averages 50%. In developing countries, the rates are even lower. Noncommunicable diseases (cancer, hypertension, diabetes,etc) Mental disorders, human immunodeficiency virus/acquired immunodeficiency syndrome and tuberculosis, together represented 54% of the burden of all diseases worldwide in 2001 and will exceed 65% worldwide in 2020. Trasmissibili

La Depressione : definizione La depressione come fenomeno appare di non facile definizione, in quanto legata indissolubilmente al concetto di umore. L’umore è una dimensione complessa della vita psichica dell’uomo, nella quale confluiscono aspetti emozionali, affettivo/sentimentali, cognitivi, temporali, motivazionali e motori che, se così si può dire, “colora di sé” tutta la vita dell’individuo, costituendo una sorta di griglia percettiva ed elaborativa con cui si dà significato alla realtà. (Vella, Siracusano1994)

La Depressione : definizione Esiste una linea di continuità che collega la depressione sia alla tristezza, esperienza comune e fisiologica, sia al dolore, che rappresenta a sua volta uno dei nulei centrali della depressione. La qualità che fa traghettare dolore e tristezza nella depressione può essere riconosciuta nella loro pervasività, nell’interessare psiche e soma allo stesso modo, nella loro fissità, nel non essere più modificabili dalle situazioni esterne, tristi o liete, nell’intensità del dolore, che tende a congelare vissuti psichici e somatici in un unico blocco privo di spinta evolutiva.

Depressione e suicidio 10-15% dei pazienti depressi si suicida I due terzi tra i pazienti depressi hanno idee suicide I pazienti depressi con aspetti psicotici considerano talvolta l’uccisione di persone coinvolte nei loro sistemi deliranti

Population projection of US adults with lifetime experience of depressive disorder by age and sex from year 2005 to 2050 (I). In year 2006 the (weighted) prevalence of lifetime experience of depressive disorder was 15.7% among 188,292 respondents aged 18 years or older. Female prevalence was 20.6%, which was about twice as high as the prevalence among males (11%). Heo M,, Murphy CF ET AL.Int J Geriatr Psychiatry. 2008 May 23. [Epub ahead of print]

Population projection of US adults with lifetime experience of depressive disorder by age and sex from year 2005 to 2050 (II). From year 2005-2050, the total number of US adults with depressive disorder will increase from 33.9 million to 45.8 million, a 35% increase. The increase is projected to be greater in the elderly population aged >/= 65 years (3.8-8.2, a 117% increase???) than in the young population aged < 65 years (30.1-37.7, a 25% increase). Heo M,, Murphy CF ET AL.Int J Geriatr Psychiatry. 2008 May 23. [Epub ahead of print]

Depressione e suicidio 10-15% dei pazienti depressi si suicida I due terzi tra i pazienti depressi hanno idee suicide I pazienti depressi con aspetti psicotici considerano talvolta l’uccisione di persone coinvolte nei loro sistemi deliranti

Gender differences in health status In industrialized countries males tend to die earlier than females and females tend to have greater longevity but higher rates of morbidity (Okojie, 1994; Stein, 1997; Lewis, 1998) This female advantage is a relatively recent phenomenon and female excess mortality, which defined many western societies prior to the industrial revolution, still pertains in many less developed countries today ( Annandale, 1998)

Prevalenza della depressione (National Comorbidity Survey)

Prevalence of Depression: Women compared to Men Major depression is a TREATABLE major public health problem in women Annual Lifetime Women 13% 21% Men 8% 12% The rate of MD for women rises dramatically above that for men during and after puberty (with two peaks - childbearing years and perimenopausal transition) and then actually falls after menopause

Gender Differences in Prevalence of Major Depression Women: 1.5-2.5 X rate relative to men during ages 15-54 Women are approximately 1.7 times as likely as men to report a lifetime history of MDE. Sex difference begins in early adolescence (age 10) and persists through the mid-50s. The sharp divergence in the 50’s is based upon a small sample size and not thought to be reliable. Sex difference in depression is most pronounces among early adolescents, with the highest relative hazard of first onset (OR=2.3) in the age range 10-14. This is a consistent finding throughout the world, regardless of how depression is diagnosed. Since women are no more likely than men to be chronically depressed or to have ana acute recurrence in the past year – therefore higher prevalence is due to higher risk of 1st onset. The NCS was a congressionally mandated survey with the specific goal of studying the comorbidity of psychiatric disorders. 8000 individuals, ages 15-54 interviewed. Used a supplemental nonresponse survey, with financial incentive, based on previous evidence that survey nonresponders tend to have higher rates of psychiatric d/o. A structured psychiatric interview (DIS-diagnositc interiew schedule – can be administered by trained interviewers who are not clinicians) was administered to a representative US sample. Based on results that respondents underreport stem questions once they recognize that positive responses lead to more detailed questions, they used a life review section before probing any positive stem responses and to facilitate active memory search for lifetime episodes. Anxiety d/o have an approximately 5% 1-yr prevalence form the same study Kessler et al (1993) Journal of Affective Disorders

The rate of MD for women rises dramatically above that for men during and after puberty (with two peaks - childbearing years and perimenopausal transition) and then actually falls after menopause New, hormonally driven needs for affiliation, difficulties with the transition to adolescence  negative life events (Cyranowski) Puberal status, puberal timing,age, hormonal mechanisms (Angold) Difficulties with self-image, temperament and early sexuality (Stattin and Magnusson) Genetic loading  negative life events (Silberg, Pickles, Rutter) Women are approximately 1.7 times as likely as men to report a lifetime history of MDE. Sex difference begins in early adolescence (age 10) and persists through the mid-50s. The sharp divergence in the 50’s is based upon a small sample size and not thought to be reliable. Sex difference in depression is most pronounces among early adolescents, with the highest relative hazard of first onset (OR=2.3) in the age range 10-14. This is a consistent finding throughout the world, regardless of how depression is diagnosed. Since women are no more likely than men to be chronically depressed or to have ana acute recurrence in the past year – therefore higher prevalence is due to higher risk of 1st onset. The NCS was a congressionally mandated survey with the specific goal of studying the comorbidity of psychiatric disorders. 8000 individuals, ages 15-54 interviewed. Used a supplemental nonresponse survey, with financial incentive, based on previous evidence that survey nonresponders tend to have higher rates of psychiatric d/o. A structured psychiatric interview (DIS-diagnositc interiew schedule – can be administered by trained interviewers who are not clinicians) was administered to a representative US sample. Based on results that respondents underreport stem questions once they recognize that positive responses lead to more detailed questions, they used a life review section before probing any positive stem responses and to facilitate active memory search for lifetime episodes. Anxiety d/o have an approximately 5% 1-yr prevalence form the same study History of MD, traumatic experiences, genetic factors, temperament (Kendler) Girls who lack healthy parental attachmentsanxious or inhibited temperament failed to develop good coping skills (Cyranowski)

Reproductive Hormones and Neurotransmitters Effects of Estrogen Synapse formation Activates mature neuronal cells Increases sensory perception Increases cerebral perfusion Augments central nervous system glucose use Alters pain pathways

Differences between Males and Females in Rates of Serotonin Synthesis in Human Brain Nishizawa S, Benkelfat C, Young SN, et al. Proc Natl Acad Sci USA 1997; 94 (10): 5308-13

DEPRESSIONE NELLA DONNA Fasi Vita IPOTESI TEORICHE Fasi vita FASI VITA Problemi Collegati Concentrazioni basse o fluttuanti di ormoni serici Developmental Life Events-Stress-Trauma Ambiente Familiare Temperamento Cambiamenti Ormonali Predisposizione Genetica Contraccettivi Fecondazione Assistita Aborto Terapia Ormonale Sosti. Gravi. Multi. Pubertà-Fase Premestruale Gravidanza-Post Partum Menopausa Pathways Depressione

Gender Differences in The Rates of Exposure to Stressful Life Events and Sensitivity to Their Depressogenic Effects Stressful Life Events Assault Divorce or separation Financial problems Housing problems Illness Job loss Legal problems Loss of confidant Marital problems Robbery Work problems Proximal network event: Problems in getting alone Crisis Death Illness Distal network event: Kendler KS, et al., 2001

Gender Differences in The Rates of Exposure to Stressful Life Events and Sensitivity to Their Depressogenic Effects Conclusion Women reported more interpersonal whereas Men reported more legal and work -related stressful life events. Most life event categories influenced the risk for major depression similarly in the two sexes The greater prevalence of major depression in women versus men is due neither to differences in the rates of reported stressful life events nor to differential sensitivity to their pathogenic effect. Kendler KS, et al., 2001

Gender and the Frequency of Stressful Life Events Male preponderant: Female preponderant: Housing problems, Loss of confidant, Problems getting along with and crises involving individuals in their proximal network Illness of an individual in their distal network  Job loss, Legal problems, Robbery Work problems No or inconsistent gender difference: financial or marital problems, illness, illness of individual in in one’s proximal network, and problems getting along with and death of an individual in one’s distal network Kendler KS, et al., 2001

Depressogenic Effect of Stressful Life Events Gender and Sensitivity to Depressogenic Effect of Stressful Life Events Male-sensitive: Female-sensitive: problems getting along with and death of an individual in their proximal network divorce or separation work problem No or inconsistent gender difference across samples, no consistent and significant gender differences were seen in the sensitivity to the remaining 15 event categories Kendler KS, et al., 2001

 Vulnerability/Exposure to Stressful Life Events  Genetic Loading  PREVALENCE OF MD IN WOMEN  Vulnerability/Exposure to Stressful Life Events  Genetic Loading Life Cycle in Women Reproductive HPG Axis Neuromodulators Modulation Of The Neuroendocrine System by Fluctuating Gonadal Hormones Psychological Puberty Menopause Adolescence, Sexuality, Maternity, Lifestyle, “Empty-nest syndrome”

Longitudinal View of Depressive Illnesses Across Women’s Lives Menarche Premenstruum Pregnancy Postpartum Menopause

Depression as a function of reproductive related transitions in women Condition Reproductive Transition Premestrual syndrome Luteal phase of the menstrual cycle Premestrual dysphoric disorder Luteal phase of the menstrual cycle Depression in pregnancy Antepartum months Postpartun “blues” First 2 postpartum weeks Postpartum depression First postpartum month (up to first 3 pp. month) First postpartum month, especially first 2 pp. weeks Postpartum psychosis Perimenopausal depression 5-7 years prior to menopause

POSTPARTUM DEPRESSION

Depression as a function of reproductive related transitions in women Condition Frequency Premestrual syndrome Up to 80% of naturally menstruating women Premestrual dysphoric disorder 3%-8% of naturally menstruating women No altered risks for MD. 20% of pregnant women may have minor depressive symptoms Depression in pregnancy Postpartun “blues” 50%-80% of postpartum women Postpartum depression 10%-22% of postpartum women Postpartum psychosis 0.1 % of postpartum women exact frequency unknown due to sources of inconsistency across studies (i.e.definition of menopause status) Perimenopausal depression

Postpartum Depression: what it’s not Postpartum depression has been used as a catchall phrase for many disorders, but it’s important to differentiate it from other postpartum disorders: Maternity Blues Postpartum panic disorder Postpartum obsessive-compulsive disorder Postpartum bipolar II disorder Postpartum posttraumatic stress disorder Postpartum psychosis (Beck, Cheryl Tatano DNSc, CNM, FAAN, American Journal of Nursing, 2006; 106 (5) 40-50)

Postpartum Depression: what it is Postpartum Depression is a major depressive disorder. It strikes about 1 in 10 women. Depressed Mood or Loss of Interest or Pleasure with 5 or more of the following symptoms for at least two week: 1) insomnia or hypersomnia, 2) psychomotor agitation or retardation, 3) fatigue, 4) changes in appetite, 5) feelings of worthlessness or guilt, 6) decreased concentration and suicidality. Although the DSM-IV-TR states that the depressive episode begins within four weeks of birth, many clinicians and researchers agree that this description is too limiting, as it’s thought that postpartum depression can occur up to a year after childbirth.

RISK FACTORS Associated With The Development of Postpartum Mood Disorders Were found to be significant risk factors for postpartum mood disorders: Premenstrual Dysphoric Disorder (PMDD) Mood symptoms during past oral contraceptive use A past history of depression Mood symptoms during the first 2-4 days postpartum Bloch M et al. J Affect Disord. 2005; 88 (1): 9-18.

Two recent metaanalyses have identified significant risk factors for Postpartum Depression Prenatal depression Low self-esteem Difficulties with child care Prenatal anxiety A high stress level A low level of social support Poor marital relationship A history of depression Difficult infant temperament Maternity blues Single marital status Low socioeconomic status Unplanned or unwanted pregnancy Beck, Cheryl Tatano DNSc, CNM, FAAN, American Journal of Nursing, 2006

A History of Depression PMDD Mood Symptoms During Past Oral Contraceptive Use Single marital status-Poor marital relationship Low a low level of social support-socioeconomic status Unplanned or unwanted pregnancy Multiple Birth Cesarean Surgery Assisted Conception Maternity blues POST PARTUM DEPRESSION

Population projection of US adults with lifetime experience of depressive disorder by age and sex from year 2005 to 2050 (III). CONCLUSIONS By year 2050, approximately 46 million US adults aged 18 years Or older will be diagnosed with a depressive disorder. The increase will be more pronounced in adults aged 65 or older. Prevention, detection, and treatment of depressive disorders might attenuate the magnitude of this estimate. Heo M,, Murphy CF ET AL.Int J Geriatr Psychiatry. 2008 May 23. [Epub ahead of print]

Classificazione dei Disturbi dell’Umore secondo il DSM-IV TR Il problema della diagnosi : Esiste una “Depressione dell’anziano” ? Classificazione dei Disturbi dell’Umore secondo il DSM-IV TR 296.xx Disturbo Depressivo Maggiore .2x Episodio Singolo .3x Ricorrente 300.4 Disturbo Distimico 311 Disturbo Depressivo NAS ?

Most common clinical features LA PRESENTAZIONE CLINICA DELLA DEPRESSIONE NELL’ANZIANO Most common clinical features 1. Una restrizione di competenze e abilità sociali, in seguito ad una crescente multi-morbidità, isolamento sociale, solitudine, perdita del partner e dei parenti, nelle sindromi depressive reattive” (Müller-Spahn et al, Gerontology 1994) 2. “Diffuse e mutevoli lamentele somatiche, ansia e agitazione psicomotoria nelle sindromi depressive endogene ” (Müller-Spahn et al, Gerontology 1994) 3. Comorbidità con disturbi d’ansia : disturbo di panico, fobie specifiche, fobia sociale (Lenze et al., Am J Psychiatry 2000)

Most common clinical features LA PRESENTAZIONE CLINICA DELLA DEPRESSIONE NELL’ANZIANO Most common clinical features Hopelessness (Joiner et al, J Affect Disorder 2007) Disforia e disturbi dell’appetito: sintomi prodromici (Berger et al, Am J Psychiatry 1998) 6) Più lenta risposta agli antidepressivi (Mandelli et al, Psychiatry Res 2007)

PSEUDODEMENZA DEPRESSIVA vs ALZHEIMER DATI ANAMNESTICI Alzheimer Disease Pseudodemenza Depressiva  Evoluzione lenta e progressiva  Nessuna storia significativa di Depressione  Evoluzione piuttosto rapida Pregressi episodi di tipo depressivo