ARTICLE IN PRESS. Journal of Affective Disorders xx (2005) xxx xxx. Research report

Transcription

1 DTD 5 Journal of Affective Disorders xx (2005) xxx xxx Research report Risk factors associated with the development of postpartum mood disorders Miki Bloch a,c, *, Nivi Rotenberg b, Dan Koren c, Ehud Klein c a Psychiatric Service, Tel-Aviv Souraski Medical Center, Tel-Aviv, Israel b Shalvata Psychiatric Center, Hod Hasharon, Israel c Psychiatric Department, Rambam Medical Center, Haifa, Israel Received 7 July 2004; received in revised form 25 April 2005; accepted 25 April Abstract Background: Various factors have been reported to be associated with the development of postpartum mood disorders. The relationship between postpartum mood disorders and putatively hormone-related phenomena such as premenstrual dysphoric disorder (PMDD) is unclear. This study attempts to determine whether such mood phenomena are risk factors for postpartum mood disorders. Methods: Postpartum women (n = 1800) were assessed for risk factors for postpartum mood disorders during the first 2 4 days after parturition. Of these, 133 were defined as bhigh riskq and 109 as blow riskq according to fixed criteria. A structured phone diagnostic interview was performed at 6 8 weeks postpartum to assess for the presence of postpartum depression or the blues. Results: Premenstrual dysphoric disorder (PMDD), mood symptoms during the first 2 4 days postpartum, a past history of depression and mood symptoms during past oral contraceptive use, were found to be significant risk factors for postpartum mood disorders. Women at high risk for postpartum mood disorders had a 9.3-, 1.5-, 1.6- and 2.6-fold increase in risk for major depression, minor depression, the blues and adjustment disorder respectively compared to women at low risk. Limitations: While the study design is prospective, it is limited by the retrospective assessment of risk factors. Conclusions: This study provides preliminary evidence that putatively hormone-related phenomena such as PMDD are related to the occurrence of postpartum mood disorders. The results go some way to support the hypothesis that the etiology for postpartum mood disorders may be related to differential hormonal sensitivity. Such risk factors should be included in any assessment of the risk for these disorders. D 2005 Elsevier B.V. All rights reserved. Keywords: Postpartum depression; PMDD; Blues; Risk factors * Corresponding author. Psychiatric Service, Tel Aviv Souraski Medical Center, 6 Weizmann Str., Tel Aviv 64239, Israel. Tel./fax: address: mikib@tasmc.health.gov.il (M. Bloch). 1. Introduction While the prevalence of postpartum mood disorders reaches 10 15% for depression (major or minor) /$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi: /j.jad JAD-03016; No of Pages 10

2 2 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx and 50% for the bbluesq (O Hara and Swain, 1996), many of these cases are not diagnosed or treated. Knowledge of factors that predispose women to postpartum depression (PPD) may help identify those who are at higher risk and can benefit from early professional help. Various putative psychosocial and obstetric factors have been studied and suggested as risk factors for the development of PPD, however, these results are inconsistent and do not effectively help predict women at risk. Whereas the blues is a well-established risk factor for PPD (Pitt, 1968; Kendell, 1985; Stowe and Nemeroff, 1995), data are scarce regarding other potential risk factors that may reflect individual hormonal sensitivity (e.g., PMDD) (Pearlstein et al., 1990; Gotlib et al., 1991; Posner et al., 1997). Such specific hormonal sensitivity has been reported as a disorder such as Premenstrual Syndrome (PMS) (Schmidt et al., 1998) and PPD (Bloch et al., 2000), and has been implied as a depression occurring during the perimenopause as well. It can be hypothesized that women who show a sensitivity to the mood-destabilizing effects of hormonal changes in putatively hormone-related mood syndromes other than PPD will be at risk for developing PPD as well. Our aim was to further explore the risk factors for the development of PPD with special emphasis on factors that may reflect individual variations of hormonal sensitivity. Using a prospective design for the diagnosis of postpartum mood disorders, preand postpartum factors that may be associated with later development of PPD were identified. Subsequently, we examined the predictive value of grouping women as bhigh riskq or blow riskq for PPD according to these previously identified risk factors. 2. Methods 2.1. Population All women admitted to the Rambam Medical Center s (Haifa, Israel) two maternity wards during the years were consecutively assessed for this study. All women who were fluent in Hebrew were asked to participate in the study after signing an informed consent. Twenty eight percent of the eligible women could not be assessed for technical reasons such as early discharge, continuous guest visits, medical procedures, etc. Only 1% of the remaining women refused to participate. A total of 1800 women completed and returned the questionnaire after a complete description of the study was given to them and a written informed consent was obtained. The final sample represents 71% of all eligible women during the study period Study design All newly admitted women were approached 2 4 days after childbirth and completed a questionnaire containing information regarding potential risk factors for PPD. Present mood was assessed using the Hebrew version of the Edinburgh Postnatal Depression Scale (EPDS) (Glasser and Barell, 1999) and by selfreport questions. Based on the information collected, women were classified as either belonging to a bhighq (HR) or blowq (LR) risk group for developing postpartum mood disorders. The criteria for bhigh-risknessq were based on reported risk factors in the literature. Specifically, women were included in the HR group if they met at least one of the following: (1) A history of a major depressive episode (lasting more than 2 weeks, compromising function and necessitating treatment). (2) A history of a PPD episode (lasting more than 2 weeks, compromising function and necessitating treatment). (3) A self-report affirming all of the following four criteria for PMDD: (a) Mood lability, irritability, sadness or anxiety appearing during the days before the menstrual bleeding; (b) the symptoms appear during most cycles; (c) the symptoms always remit after menses commence; (d) symptoms were severe enough to compromise functioning. (4) A self-report indicating recent onset of mood instability, sadness or anxiety symptoms appearing during the 3rd trimester of the present pregnancy. (5) EPDS N 10. Of the 1800 women who completed the initial assessment, 209 women met our criteria for the HR group (12%). The LR group was all the other women who did not meet any of the HR criteria. All of the HR women were contacted 6 8 weeks postpartum and were asked to participate in a Structured clinical interview for Axis I DSM IV (SCID)

3 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx 3 based phone interview. Of 209 HR women, 133 (64%) agreed to participate in the interview 41 (20%) were not available, and 35 (17%) refused to participate. To assess the predictive value of the risk factors, a comparison group of 109 women was selected from the LR group and interviewed. This control group was matched to the study group by the number of days after parturition (HR 2.2 F 2.6; LR 2.4 F 2.2) and by key sociodemographic variables, such as age, ethnicity, and socioeconomic status (Table 1) Measures Risk factor questionnaire The risk factor questionnaire (administered 2 4 days postpartum) contained the following information: (1) General demographic background. (2) Description of the present and past pregnancies. (3) Personal and 1st degree family psychiatric history. This part was comprised of a direct question regarding past diagnosis of major depression (MDD), PPD, anxiety disorders and psychotic disorders and whether the participant was treated or hospitalized for any of these. Furthermore, for the diagnoses of MDD and PPD, a series of questions based on the core Table 1 Sociodemographic variables of participants by risk groups Total group (N =1800) High-risk group (N =133) Low-risk group (N =109) Age Mean (S.D.) 30.4F F F5.2 No. of children Mean (S.D.) 1.2F F F1.6 Marital Married 1415 (78.6%) 117 (87.9%) 98 (89.9%) status Divorced 30 (1.7%) 1 (0.8%) 5 (4.6%) Living with 28 (1.6%) 2 (1.5%) 2 (1.8%) partner Missing data 327 (18.1%) 13 (9.8%) 4 (3.7%) Family Europe 433 (23.1%) 39 (29.3%) 25 (22.9%) origins America Asia Africa 570 (31.7%) 50 (37.6%) 39 (35.8%) Mixed 580 (32.2%) 41 (30.8%) 41 (37.6%) Missing data 217 (12.0%) 3 (2.3%) 4 (3.7%) Economic High 316 (17.6%) 32 (24.1%) 17 (15.6%) status Average 616 (34.2%) 49 (36.8%) 49 (44.9%) Low 473 (26.3%) 34 (25.6%) 37 (33.9%) Missing data 395 (21.9%) 18 (13.5%) 6 (5.5%) No significant differences were found between studied groups. symptoms (according to the DSM-IV) were also asked. These diagnoses were considered positive only if the criteria were met including duration of symptoms for over 2 weeks and having had considerable functional impairment and having sought treatment. (4) Past putatively bhormone-relatedq mood symptoms: (a) mood instability during puberty, considered positive only if causing severe distress; (b) PMDD, based on DSM-IV criteria, considered positive only if there were severe premenstrual emotional symptoms of sadness, irritability, mood lability or anxiety which occurred during most cycles, starting in the luteal phase and ending with menses and causing considerable distress or functional impairment; (c) emotional reactivity to oral contraceptives, considered positive if women reported of sadness, irritability, mood lability or anxiety while taking oral contraceptives leading to the termination of treatment; (d) sadness, irritability, mood lability or anxiety occurring during the 3rd trimester of the present pregnancy. (5) Present mood change was assessed by self-report through a series of questions regarding present mood instability, depressive symptoms or unusual euphoric feelings during the days since parturition. This was considered positive only if the subject assessed their mood as highly unusual and disruptive Edinburgh Post Natal Depression Scale (EPDS) The EPDS is a short and popular 10-item questionnaire developed by Cox et al. (1987) to detect PPD. The sum of the EPDS has been found to correlate with the severity of depression (Appleby et al., 1994), and a score of 10 or above indicating high risk for developing PPD (Evins et al., 2000; Righetti-Veltema et al., 1998). It has been translated to and validated in many languages, including Hebrew (Glasser et al., 1998) Phone interview A phone interview based on the Hebrew version of the SCID (Shalev et al., 1994) was conducted between weeks 6 and 8 postpartum. The modules of the SCID that were administered consisted of those for mood disorders and adjustment disorder. Questions were asked regarding both the present and previous postpartum periods. The interviewers were a resident in psychiatry (NR) and a psychiatric social

4 4 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx worker, both with a good clinical background in psychiatry who were trained and supervised by a senior psychiatrist (MB) in administering the phone SCID and had a high inter-rater variability. The interviews were reviewed by a psychiatrist (MB) blinded to the grouping of the women as HR or LR, and one of the following diagnoses was made; major depression, minor depression, blues, adjustment disorder, or no evidence of mental illness. As there are no specific criteria for the blues in the SCID, structured questions based on the timing (appearing and remitting during the first postpartum week), nature (mood lability, anxiety, irritability and depression) and severity (mild and not necessitating treatment) of symptoms experienced were developed for the blues and asked in the interview Statistical analysis To ascertain that the two study and comparison groups were indeed well-matched, a set of t-tests (SAS: Proc TTEST) for continuous variables and chi-square analyses (SAS: Proc FREQ) for discrete variables was used. The relationship between the various risk factors and later development of PPD or the blues was assessed using a set of chi-square analyses. A set of one-way ANOVAs (SAS: Proc GLM) was used for the analysis of continuous variables. Finally, the predictive value of grouping women as bhighq versus blowq risk for the development of postpartum mood disorders was evaluated using a set of odds ratio analyses (SAS: Proc LOGISTIC). 3. Results 3.1. Specific risk factors for PPD Factors that may be related to hormonal changes Table 2 presents the prevalence of risk factors among the whole group of women according to diagnosis (PPD, blues, or no diagnosis). The prevalence of PMDD, mood symptoms in the early postpartum and mood symptoms secondary to OC, all psychiatric conditions that we suggest to be hormone-related, were significantly greater in women who developed PPD (defined as either major or minor) or the blues compared to women who did not develop any psychiatric morbidity. The incidence of women with PPD who scored 10 or higher on the EPDS between days 2 and 4 postpartum (a good indication for the presence of the blues) was also significantly higher than in women without PPD as was the mean EPDS score. Another way to look at the data is the incidence rates of the different diagnoses according to the presence or absence of various risk factors. From Table 3 it can be seen that the incidence rate of having either major, minor depression or the blues in women who reported PMS, past mood symptoms due to OC use, or mood symptoms in days 2 4 postpartum by subjective measures or by EPDS was 55%, 84%, 73% and 70%, respectively. This high incidence is striking when compared to women without any risk factor (LR group, Table 4) who had a total incidence rate of 26% for either major, minor depression or the blues. Table 2 Prevalence of risk factors among women (n =210) with postpartum depression (major+minor), blues, or no-diagnosis (number and valid percentage) Risk factor Depression (n =40) Blues (n =51) No diagnosis (n =119) v 2 /F df p PMDD 17 (43%) 23 (45%) 33 (28%) p =0.048 Mood symptoms on OC 5 (13%) 6 (12%) 2 (2%) 14 4 p =0.007 Mood symptoms after birth 14 (36%) 17 (34%) 12 (10%) 19 2 p =0.001 EPDSz10 13 (33%) 13 (25%) 11 (9%) 14 2 p b0.001 Mood symptoms at puberty 16 (48%) 21 (53%) 38 (32%) p =0.057 Mood symptoms at 3rd trimester 17 (43%) 23 (46%) 34 (29%) p =0.060 Past MDD 6 (15%) 10 (20%) 4 (3%) p =0.002 Mean number of pregnancies (S.D.) 2.0 (0.9) 2.4 (1.7) 2.8 (1.8) p =0.030 Mean EPDS (S.D.) 6.9 (5.6) 5.5 (5.3) 2.9 (3.3) p =0.000

5 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx 5 Table 3 Prevalence of mental illness according to different risk factors (number and percentage) PMDD Past MDD Mood symptoms following oral contraceptive use Mood symptoms after birth EPDSz10 Yes No Yes No Yes No No OC use Yes No Yes No Depression (Major and Minor) 17 (23%) 23 (17%) 6 (30%) 34 (18%) 5 (38%) 26 (17%) 9 (20%) 14 (33%) 25 (15%) 13 (35%) 28 (16%) Blues 23 (32%) 28 (20%) 10 (50%) 40 (21%) 6 (46%) 40 (26%) 5 (11%) 17 (40%) 33 (20%) 12 (34%) 39 (22%) None 33 (45%) 86 (63%) 4 (20%) 114 (61%) 2 (15%) 85 (56%) 31 (69%) 12 (27%) 105 (65%) 11 (30%) 107 (62%) Total v * 12.8** 14.0** 18.5** 14.03** * p b0.05. ** p b0.01. Two other conditions that were assessed and may be hormonally related; mood symptoms during the third trimester of pregnancy, and mood symptoms at puberty showed a strong trend for significance with a higher incidence in women with PPD or the blues Other risk factors The prevalence of a past history of depression was found to be significantly higher in women who developed PPD (major or minor) or the blues compared to women without any diagnosis. The incidence rate for either PPD or the blues in women who reported a past history of depression was 80% compared to 39% in those without such a history and 26% in women without any risk factor. Women who developed major or minor depression had fewer average lifetime pregnancies than women with the blues or no diagnosis (Table 2, p = 0.03). Thus few lifetime pregnancies were significantly associated with PPD. The following factors were not found to be associated with PPD or the blues; economical status, marital status, ethnic background, number of children, planned versus unplanned pregnancy, spontaneous pregnancy versus hormonal treatment or IVF, type of birth normal labor or cesarean section, family history of affective disorder, postpartum depression in the past and other psychiatric illness in the past Psychiatric outcome in women with HR for the development of PPD compared to LR women Of the 1800 postpartum women screened, 12% met our criteria for being at HR for postpartum mood disorders. All diagnoses were significantly higher in the HR group (Table 4). Overall, 65% of the HR women had at least one psychiatric diagnosis in the postpartum period as compared to only 34% in the LR group. Using an odds ratio estimate, the best two predictors for outcome were postpartum mood and a past history of depression. Next, in order to identify the optimal model for prediction of level of postpartum depression, we entered all the risk factors Table 4 Incidence of psychiatric diagnoses in women at high risk (n =133) for developing PPD compared with women at low risk (n =109) Major depression Minor depression Adjustment disorder Blues Any diagnosis HR a 11 (8.3%) 18 (13.5%) 24 (18%) 33 (25%) 86 (65%) LR 1 (0.9%) 10 (9%) 8 (7.3%) 18 (16.5%) 37 (34%) O.R % confidence interval for mean a Diagnosis by group effect: F =26.2, df =4, p b0.001.

6 6 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx into a stepwise regression model. The alpha for both entering and staying at the model was set at p b0.15, which is the less conservative level of significance that is commonly recommended in the literature for predictive (as opposed to explanatory) models. The most economic model for prediction of postpartum outcome included postpartum mood (standardized beta = 0.35, p =0.04), past history of depression (standardized beta = 0.39, p =0.06), history of mood symptoms due to use of oral contraceptives (standardized beta = 0.19, p =0.09), EPDS (standardized beta =0.28, p =0.12), and PMS group (standardized beta = 0.19, p = 0.13), which together accounted for 14.4% of the variance in postpartum depression ( F (5,165) =5.6, p b0.0001). Finally, in order to examine the diagnostic efficiency of this model, we used a logistic regression with a diagnosis of post-partum depression (of any kind) as the outcome dichotomous variable and the five risk factors as predictors. The overall accuracy rate of the five risk factors in correctly classifying post-partum depression was 70%, with a sensitivity of 76% but specificity of only 36% (that is, high level of false positives). 4. Discussion While a number of demographic and obstetric risk factors have been previously shown to be associated with the development of PPD (Kumar and Robson, 1984; Hannah et al., 1992), the current study screened a large number of women for risk factors and is unique in the large subgroup followed up prospectively and diagnosed for postpartum mood disorders using a structured interview Risk factors for postpartum mood disorders Existing data from uncontrolled studies give some limited support to the notion of a possible association between PMDD and the development of PPD. Pearlstein et al. (1990) reported that 29% of the parous women interviewed, who also met criteria for Premestrual Syndrome (PMS), had a prior episode of minor or major PPD. This result is compatible with the incidence rate of 23% PPD we have found in women with PMDD. In another study 68% of a group of prospectively confirmed PMS patients reported a history of PPD. Similarly, high postpartum depressive scores have been associated with a history of PMS (Sugawara et al., 1997; McGill et al., 1995). In the present study, a clear association is found between having a history of PMDD and the development of either PPD or the blues. While the present study is also limited by the retrospective report of PMDD symptoms, the prospective diagnosis of postpartum mood disorders and comparison to a control group strongly supports considering a history of PMDD as a risk factor for postpartum mood disorders. There is some evidence suggesting an association between OC use and affective (Graham et al., 1995) and anxiety syndromes in women (Pigott, 1999), however, information regarding an association between a history of mood symptoms secondary to OC use and PPD is very scarce. One study found an association between OC-related affective symptoms and PMS (Sugawara et al., 1997) and another claims that OCs may have a therapeutic role in treatment of PMS (Warner and Bancroft, 1990). Other studies claim that there is no clear evidence that OC are related to depressive illness in general (Long and Kathol, 1993) nor to PPD (Stowe and Nemeroff, 1995). In the present study almost twice as many women who reported mood symptoms while taking OC in the past developed either PPD or the blues than women without such a history. While the retrospective recall of symptoms for this risk factor limits definitive conclusions, our data do suggest that affective sensitivity to the gonadal steroids in OC is associated with subsequent PPD and that this factor should be further studied in this context. In contrast to PMDD and OC use, many welldesigned studies have looked at a possible association between the blues and PPD, resulting in mostly (yet not exclusively) positive associations (Paykel et al., 1980; Whiffen, 1988). We used two measures for assessing the blues, first, a self-report of new onset mood symptoms causing distress appearing between days 2 and 4 of the postpartum period, and second, the EPDS questionnaire. Both measures were found to be significantly more prevalent in women who subsequently developed PPD, supporting the current literature regarding early postpartum mood changes as risk factors for PPD. One limitation of this study

7 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx 7 is that we did not employ a specific blues questionnaire in our early assessment, however, this is not unlike most studies in the literature that, in the absence of an accepted diagnostic tool for the blues, use the EPDS questionnaire to assess the syndrome. Pregnancy has traditionally been conceptualized as a period of increased well-being and emotional stability (Paffenbarger, 1982). More recently, a number of prospective studies have shown that the rate of depression may be similar during pregnancy and the postpartum period and that the presence of anxiety or depression during pregnancy is associated with depressive illness during the puerperium (O Hara et al., 1990; Hamilton et al., 1985; Dean et al., 1989). O Hara et al. (1991) also reported that depressive symptoms during pregnancy predicted the onset of postpartum blues. In the present study we see a strong trend for a significant effect of mood symptoms during the 3rd trimester and the development of PPD. In this case also, despite the definite limitation of relying on women s retrospective recollection of symptoms, our results agree with the literature. Very little information exists regarding an association between mood instability at puberty and PPD. Some researchers have suggested that women are prone to develop depressive episodes during all times of reproductive hormonal changes including puberty (Parry and Newton, 2001; Steiner, 1992; Kessler et al., 2001). Schraufnagel et al. (2001) reported that the presentation of affective illness changes with age, with manic features predominating in younger children, and depressive symptomatology being more evident with pubertal maturation. In the present study a strong trend was found for an association between mood instability at puberty and PPD. While recall bias could certainly be a factor, this association should be further explored, preferably using prospective methods. Past depression has been consistently found to be a strong risk factor for PPD (Stowe and Nemeroff, 1995). Women with a history of an affective disorder have a chance of 1:3 to develop PPD (Appleby et al., 1994). We have also found a 30% incidence rate of PPD in women with a past history of depression (significantly greater than in women without such history). This risk factor was found to be one of the two strongest predictors for PPD. It is of interest that also the blues was significantly more prevalent in these women than in women without a history of depression. The negative results for family history of affective disorder, postpartum depression in the past and other psychiatric illness in the past are somewhat surprising, and may be due both to a reporting bias and also to the small number of women who reported on these items. Studies looking at the possible effect of pregnancy number on PPD are controversial. Some studies show a possible association between 1st childbirth and PPD (Tamaki et al., 1997). Kendell (1985) reported on a two-fold increase in the incidence of postpartum psychosis in primipara compared to multipara women, with no age correlation, but no difference in PPD. Other studies did not find an association between number of deliveries and PPD (Posner et al., 1997) or, alternatively, that high parity is associated with PPD (Righetti-Veltema et al., 1998). In our work we found that in the order of pregnancies, earlier ones entail a higher risk of PPD. This result may reflect the possibility that women who develop PPD are less inclined to become pregnant again after experiencing depression, and thus women with multiple pregnancies may represent a group of women with a relatively lower vulnerability for PPD. Alternatively, it is possible that the vulnerability to PPD diminishes with multiple deliveries due to a nonspecific decrease in stress associated with the pregnancy and delivery, or for other yet unexplained reasons. Economical and marital status, ethnic background, number of children, planned versus unplanned pregnancy, spontaneous pregnancy versus hormonal treatment or IVF, normal labor or cesarean section were all not found to be associated with PPD. While there are few reports in the literature associating some of these with PPD, for most there are conflicting results. It is of interest that all of the parameters assessed in this study, that were not presumably hormone-dependent or related to personal psychiatric history, were not found to be associated with postpartum mood disorders (with the possible exception of bnumber of pregnanciesq which is an obstetric parameter, yet was found to be associated with postpartum mood disorders). These results strengthen the positive results which were mainly found for factors that may have a hormonal etiology.

8 8 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx 4.2. Incidence of postpartum depressive syndromes in high- and low-risk groups The LR group of our sample should represent the general population, albeit more conservatively, as women with any known risk factors were excluded from this sample. Indeed, the incidence of PPD in this sample (major + minor depression) was found to be about 10% which is compatible with the literature. The incidence of the blues in this group was 16.5%, a somewhat lower figure than usually reported. Highrisk women developed a depressive syndrome during the postpartum period at an incidence of almost twice that of women at LR. While all diagnoses we examined were higher in the HR group, the most impressive difference was a 10-fold increase in the incidence of major depression. This result is quite similar to the data reported recently by Verkerk et al. (2003) who showed significantly higher rates of depression in high-risk compared to low-risk women 3 months postpartum. As our HR group was selected according to factors that are presumably of biological significance, the very high incidence of postpartum major depression suggests that this disorder may be selectively more responsive to hormonal triggers that characterize the postpartum period. Of interest also is the 2.6-fold increase in the diagnosis of badjustment disorderq. This finding may suggest that during the puerperium, women with a history of hormone-related mood symptoms or of depression may have difficulties coping with this stressful life situation, perhaps due to subclinical symptoms not meeting criteria for major or minor depression. The present study focuses mostly on the assessment of risk factors that are putatively hormone-related and on the well-established risk factors of past depressive disorders. Our positive results suggest that a history of psychological sequela to events related to hormonal fluctuations (e.g., menstrual cycle, pregnancy, use of OC) may be of greater relevance to the development of PPD than psychosocial or obstetric risk factors. This conclusion is supported by the fact that in the present study all but one obstetric (number of past pregnancies) and one psychosocial (past depression) factors we examined were not significant risk factors. Our findings suggest that future attempts to create tools for predicting PPD should incorporate hormone-related risk factors that seem to have a relatively high predictive value. It can further be contended that the differences found between groups in depressive syndrome incidence are an underestimation. This is so because the HR group represented all of the HR women from the initial screening group of 1800 women while the control LR group was only a representative subset of the group. Had we included all 1800 women we would have had many more btrue negativesq (another 1485\1500 assuming the same 0.9% major depression rate and no risk factors) and very few false negatives (15\1500), thus further strengthening the statistical significance Biological implications In another study we have shown in the past that women with a history of PPD have a differential vulnerability to gonadal steroids compared to women without a history of PPD (Bloch et al., 2000). This was the first direct evidence for a vulnerability to the development of depression in the postpartum period as a consequence of hormonal changes. While the biological basis for this differential sensitivity is unknown, it may represent the effect of genetic polymorphism in genes that regulate reproductive hormone signaling or that are regulated by reproductive hormones, predisposing some women to detrimental effects of gonadal steroids. The results of the present study expectedly show that a past history of major depression may be the strongest predictor of PPD. Furthermore, they also strongly support existing epidemiologic data linking postpartum depressed mood, which may, or may not be hormone-related, but also PMS and sensitivity to OC, which are likely to be hormone-related phenomena, and predisposition for PPD. This association is suggestive of an increased vulnerability to the mood-destabilizing effects of reproductive hormones in a subgroup of women, a phenomenon consistent with the onset of mood disorders during either pregnancy or the postpartum. Obvious hormonal candidates that may be of importance in mediating such a bvulnerabilityq are the gonadal steroids estrogen and progesterone. These hormones have been implied in the etiology of syndromes such as PMDD, PPD and perimenopausal depression. The present study results, linking PMDD and other putatively hormone-related phenomena with the onset of postpartum mood disorders, go some way

9 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx 9 to suggest that these phenomena may have, at least in part, a common sensitivity to gonadal steroid changes. Furthermore, this association emphasizes the importance of biological factors in the etiology of postpartum mood disorders, an area that should be further explored. Acknowledgement This study was supported by a grant from the National Institute for Psychobiology in Israel. Our thanks to Dr. E.Z. Zimmer, director of the maternity wards, Rambam Medical Center, Haifa, Israel, for his cooperation. References Appleby, L., Gregoire, A., Platz, C., Prince, M., Kumar, R., Screening women for HR of postnatal depression. Journal of Psychosomatic Research 38, Bloch, M., Schmidt, P.J., Danaceau, M., Murphy, J., Nieman, L., Rubinow, D.R., The role of gonadal steroid in postpartum depression. American Journal of Psychiatry 157 (6), Cox, J.L., Holden, J.M., Sagovsky, R., Detection of postnatal depression. Development of the 10-item Edinburgh postnatal depression scale. British Journal of Psychiatry 150, Dean, C., Williams, R.J., Brockington, I.F., Is puerperal psychosis the same as bipolar manic-depressive disorder? A family study. Psychological Medicine 19, Evins, G.G., Theofrastous, J.P., Galvin, S.L., Postpartum depression: a comparison of screening and routine clinical evaluation. American Journal of Obstetrics and Gynecology 182 (5), Glasser, S., Barell, V., Depression scale for research in and identification of postpartum depression. Harefuah 136, Glasser, S., Barell, V., Shoham, A., Ziv, A., Boyko, V., Lusky, A., Hart, S., Prospective study of postpartum depression in an Israeli cohort: prevalence, incidence and demographic risk factors. Journal of Psychosomatic Obstetrics and Gynaecology 19 (3), Gotlib, I.H., Whiffen, V.E., Wallace, P.M., Mount, J.H., Prospective investigation of postpartum depression: factors involved in onset and recovery. Journal of Abnormal Psychology 100, Graham, C.A., Ramos, R., Bancrof, J., Maglaya, C., Farley, T.M., The effects of steroidal contraceptives on the well-being and sexuality of women: a double-blind, placebo-controlled, two center study of combined and progesterone-only methods. Contraception 52 (6), Hamilton, J.A., Parry, B.L., Blumenthal, S.J., The menstrual cycle in context. I: affective syndromes associated with reproductive hormonal changes. Journal of Clinical Psychiatry 49, Hannah, P., Adams, D., Lee, A., Glover, V., Sandler, M., Links between early post-partum mood and post-natal depression. British Journal of Psychiatry 160, Kendell, R.E., Emotional and physical factors in the genesis of puerperal mental disorders. Journal of Psychosomatic Research 29, Kessler, R.C., Avenevoli, S., Merikangas, K., Mood disorders in children and adolescents: an epidemiologic perspective. Biological Psychiatry 49 (12), Kumar, R., Robson, K.M., A prospective study of emotional disorders in childbearing women. British Journal of Psychiatry 144, Long, T.D., Kathol, R.G., Critical review of data supporting affective disorder caused by nonpsychotropic medication. Annals of Clinical Psychiatry 5 (4), McGill, H., Burrows, V.L., Holland, L.A., Langer, H.G., Sweet, M.A., Postnatal depression: a Christchurch study. New Zealand Medical Journal 108, O Hara, M.W., Swain, A.M., Rates and risk of postpartum depression a meta-analysis. International Review of Psychiatry 8, O Hara, M.W., Zekowski, E.M., Philipps, L.H., Wright, E.J., Controlled prospective study of postpartum mood disorders: comparison of childbearing and nonchildbearing women. Journal of Abnormal Psychology 99, O Hara, M.W., Schlechte, J.A., Lewis, D.A., Varner, M.W., Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables. Journal of Abnormal Psychology 100, Paffenbarger, R.S., Epidemiological aspects of mental illness associated with childbearing. In: Brockington, I.F., Kumar, R. (Eds.), Motherhood and Mental Illness. Academic Press, London, pp Parry, B.L., Newton, R.P., Chronobiological basis of femalespecific mood disorders. Neuropsychopharmacology 25 (5 Suppl.), S102 S108. Paykel, E.S., Emms, E.M., Fletcher, J., Rassaby, E.S., Life events and social support in puerperal depression. British Journal of Psychiatry 136, Pearlstein, T.B., Frank, E., Tovar, A.R., Thoft, J.S., Jacobs, E., Mieczkowski, T.A., Prevalence of axis I and axis II disorders in women with late luteal phase dysphoric disorder. Journal of Affective Disorders 20, Pigott, T.A., Gender differences in the epidemiology and treatment of anxiety disorders. Journal of Clinical Psychiatry 60, Pitt, B., batypicalq depression following childbirth. British Journal of Psychiatry 114, Posner, N.A., Unterman, R.R., Williams, K.N., Williams, G.H., Screening for postpartum depression, an antepartum questionnaire. Journal of Reproductive Medicine 42, Righetti-Veltema, M., Conne-Perreard, E., Bousquet, A., Manzano, J., Risk factors and predictive signs of post-

10 10 M. Bloch et al. / Journal of Affective Disorders xx (2005) xxx xxx partum depression. Journal of Affective Disorders 49 (3), Schmidt, P.J., Nieman, L.K., Danaceau, M.A., Adams, L.F., Rubinow, D.R., Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. New England Journal of Medicine 338, Schraufnagel, C.D., Brumback, R.A., Harper, C.R., Weinberg, W.A., Affective illness in children and adolescents: patterns of presentation in relation to pubertal maturation and family history. Journal of Child Neurology 6 (8), Shalev, A.Y., Abramowitz, M.Z.Kaplan DeNour, A., Structured clinical interview for Axis I DSM IV patient edition (Hebrew). Jerusalem Center for Traumatic Stress, Dept of Psychiatry, Hadassah University Hospital. Stowe, Z.N., Nemeroff, C.H., Women at risk for postpartum onset major depression. American Journal of Obstetrics and Gynecology 173, Sugawara, M., Toda, M.A., Shima, S., Mukai, T., Sakakura, K., Kitamura, T., Premenstrual mood changes and maternal mental health in pregnancy and the postpartum period. Journal of Clinical Psychology 53, Steiner, M., Female-specific mood disorders. Clinical Obstetrics and Gynecology 35 (3), Tamaki, R., Murata, M., Okano, T., Risk factors for postpartum depression in Japan. Psychiatry and Clinical Neuroscience 51 (3), Verkerk, G.J., Pop, V.J., Van Son, M.J., Van Heck, G.L., Prediction of depression in the postpartum period: a longitudinal follow-up study in high-risk and low-risk women. Journal of Affective Disorders 77 (2), Warner, P., Bancroft, J., Factors related to self reporting of the pre menstrual syndrome. British Journal of Psychiatry 157, Whiffen, V.E., Vulnerability of postpartum depression: a prospective multivariate study. Journal of Abnormal Psychology 97,