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  <front>
    <journal-meta><journal-id journal-id-type="nlm-ta">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><!--===== Grouping journal title elements =====--><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher>
        <publisher-name>Public Library of Science</publisher-name>
        <publisher-loc>San Francisco, USA</publisher-loc>
      </publisher></journal-meta>
    <article-meta><article-id pub-id-type="publisher-id">PONE-D-11-15785</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0030719</article-id><article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Article</subject>
        </subj-group>
        <subj-group subj-group-type="Discipline-v2">
          <subject>Biology</subject>
          <subj-group>
            <subject>Population biology</subject>
            <subj-group>
              <subject>Epidemiology</subject>
            </subj-group>
          </subj-group>
        </subj-group>
        <subj-group subj-group-type="Discipline-v2">
          <subject>Medicine</subject>
          <subj-group>
            <subject>Epidemiology</subject>
          </subj-group>
          <subj-group>
            <subject>Mental health</subject>
            <subj-group>
              <subject>Psychiatry</subject>
            </subj-group>
            <subj-group>
              <subject>Psychology</subject>
            </subj-group>
          </subj-group>
          <subj-group>
            <subject>Public health</subject>
          </subj-group>
        </subj-group>
        <subj-group subj-group-type="Discipline-v2">
          <subject>Social and behavioral sciences</subject>
          <subj-group>
            <subject>Psychology</subject>
          </subj-group>
        </subj-group>
        <subj-group subj-group-type="Discipline">
          <subject>Public Health and Epidemiology</subject>
          <subject>Mental Health</subject>
        </subj-group>
      </article-categories><title-group><article-title>Overtime Work as a Predictor of Major Depressive Episode: A 5-Year Follow-Up of the Whitehall II Study</article-title><alt-title alt-title-type="running-head">Overtime Work and Depression</alt-title></title-group><contrib-group>
        <contrib contrib-type="author" xlink:type="simple">
          <name name-style="western">
            <surname>Virtanen</surname>
            <given-names>Marianna</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="cor1">
            <sup>*</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author" xlink:type="simple">
          <name name-style="western">
            <surname>Stansfeld</surname>
            <given-names>Stephen A.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author" xlink:type="simple">
          <name name-style="western">
            <surname>Fuhrer</surname>
            <given-names>Rebecca</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author" xlink:type="simple">
          <name name-style="western">
            <surname>Ferrie</surname>
            <given-names>Jane E.</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>5</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author" xlink:type="simple">
          <name name-style="western">
            <surname>Kivimäki</surname>
            <given-names>Mika</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
        </contrib>
      </contrib-group><aff id="aff1"><label>1</label><addr-line>Finnish Institute of Occupational Health, Helsinki, Finland</addr-line>       </aff><aff id="aff2"><label>2</label><addr-line>Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom</addr-line>       </aff><aff id="aff3"><label>3</label><addr-line>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada</addr-line>       </aff><aff id="aff4"><label>4</label><addr-line>Department of Epidemiology and Public Health, University College London, London, United Kingdom</addr-line>       </aff><aff id="aff5"><label>5</label><addr-line>School of Community and Social Medicine, University of Bristol, Bristol, United Kingdom</addr-line>       </aff><contrib-group>
        <contrib contrib-type="editor" xlink:type="simple">
          <name name-style="western">
            <surname>Mazza</surname>
            <given-names>Marianna</given-names>
          </name>
          <role>Editor</role>
          <xref ref-type="aff" rid="edit1"/>
        </contrib>
      </contrib-group><aff id="edit1">Catholic University of Sacred Heart of Rome, Italy</aff><author-notes>
        <corresp id="cor1">* E-mail: <email xlink:type="simple">marianna.virtanen@ttl.fi</email></corresp>
        <fn fn-type="con">
          <p>Conceived and designed the experiments: JEF MK RF MV SAS. Performed the experiments: JEF MK RF MV. Analyzed the data: MV. Contributed reagents/materials/analysis tools: RF JEF SAS. Wrote the paper: MV SAS RF JEF MK.</p>
        </fn>
      <fn fn-type="conflict">
        <p>The authors have declared that no competing interests exist.</p>
      </fn></author-notes><pub-date pub-type="collection">
        <year>2012</year>
      </pub-date><pub-date pub-type="epub">
        <day>25</day>
        <month>1</month>
        <year>2012</year>
      </pub-date><volume>7</volume><issue>1</issue><elocation-id>e30719</elocation-id><history>
        <date date-type="received">
          <day>11</day>
          <month>8</month>
          <year>2011</year>
        </date>
        <date date-type="accepted">
          <day>20</day>
          <month>12</month>
          <year>2011</year>
        </date>
      </history><!--===== Grouping copyright info into permissions =====--><permissions><copyright-year>2012</copyright-year><copyright-holder>Virtanen et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract>
        <sec>
          <title>Background</title>
          <p>The association between overtime work and depression is still unclear. This study examined the association between overtime work and the onset of a major depressive episode (MDE).</p>
        </sec>
        <sec>
          <title>Methodology/Principal Findings</title>
          <p>Prospective cohort study with a baseline examination of working hours, psychological morbidity (an indicator of baseline depression) and depression risk factors in 1991–1993 and a follow-up of major depressive episode in 1997–1999 (mean follow-up 5.8 years) among British civil servants (the Whitehall II study; 1626 men, 497 women, mean age 47 years at baseline). Onset of 12-month MDE was assessed by the Composite International Diagnostic Interview (CIDI) at follow-up. In prospective analysis of participants with no psychological morbidity at baseline, the odds ratio for a subsequent major depressive episode was 2.43 (95% confidence interval 1.11 to 5.30) times higher for those working 11+ hours a day compared to employees working 7–8 hours a day, when adjusted for socio-demographic factors at baseline. Further adjustment for chronic physical disease, smoking, alcohol use, job strain and work-related social support had little effect on this association (odds ratio 2.52; 95% confidence interval 1.12 to 5.65).</p>
        </sec>
        <sec>
          <title>Conclusions/Significance</title>
          <p>Data from middle-aged civil servants suggest that working long hours of overtime may predispose to major depressive episodes.</p>
        </sec>
      </abstract><funding-group><funding-statement>The Whitehall II study has been supported by grants from the Medical Research Council, <ext-link ext-link-type="uri" xlink:href="http://www.mrc.ac.uk/" xlink:type="simple">www.mrc.ac.uk/</ext-link>, British Heart Foundation <ext-link ext-link-type="uri" xlink:href="http://www.bhf.org.uk/" xlink:type="simple">www.bhf.org.uk/</ext-link>, Stroke Association, <ext-link ext-link-type="uri" xlink:href="http://www.stroke.org.uk/" xlink:type="simple">http://www.stroke.org.uk/</ext-link>, National Heart Lung and Blood Institute, <ext-link ext-link-type="uri" xlink:href="http://www.nhlbi.nih.gov/" xlink:type="simple">http://www.nhlbi.nih.gov/</ext-link> (HL36310), National Institute on Aging, <ext-link ext-link-type="uri" xlink:href="http://www.nia.nih.gov/" xlink:type="simple">http://www.nia.nih.gov/</ext-link> (AG13196). Dr. Kivimäki is supported by the Academy of Finland, <ext-link ext-link-type="uri" xlink:href="http://www.aka.fi/en-GB/A/" xlink:type="simple">http://www.aka.fi/en-GB/A/</ext-link> (124271, 124322, 129264 and 132944), the EU New OSH ERA Programme, <ext-link ext-link-type="uri" xlink:href="http://www.newoshera.eu/en/index_html" xlink:type="simple">http://www.newoshera.eu/en/index_html</ext-link>, and the BUPA Foundation, UK, <ext-link ext-link-type="uri" xlink:href="http://www.bupafoundation.com/" xlink:type="simple">http://www.bupafoundation.com/</ext-link>; Dr. Ferrie is supported by the National Institute of Aging, <ext-link ext-link-type="uri" xlink:href="http://www.nia.nih.gov/" xlink:type="simple">http://www.nia.nih.gov/</ext-link>. Dr. Fuhrer holds the CIHR Canada; <ext-link ext-link-type="uri" xlink:href="http://www.cihr-irsc.gc.ca/e/193.html" xlink:type="simple">http://www.cihr-irsc.gc.ca/e/193.html</ext-link> Research Chair in Psychosocial Epidemiology. The funders have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts>
        <page-count count="5"/>
      </counts></article-meta>
  </front>
  <body>
    <sec id="s1">
      <title>Introduction</title>
      <p>Common mental disorders, such as depression, are an important public health concern <xref ref-type="bibr" rid="pone.0030719-Mathers1">[1]</xref>, <xref ref-type="bibr" rid="pone.0030719-Eaton1">[2]</xref>. According to projections by the World Health Organisation, depressive disorders will be the leading cause of disease burden in high-income countries by 2030 <xref ref-type="bibr" rid="pone.0030719-Mathers1">[1]</xref>. In addition to human misery, mental disorders often result in substantial work impairment and lost work days <xref ref-type="bibr" rid="pone.0030719-Eaton1">[2]</xref>, <xref ref-type="bibr" rid="pone.0030719-Adler1">[3]</xref>–<xref ref-type="bibr" rid="pone.0030719-Demyttenaere1">[5]</xref>.</p>
      <p>Recent prospective studies, although not entirely consistent <xref ref-type="bibr" rid="pone.0030719-vanderHulst1">[6]</xref>–<xref ref-type="bibr" rid="pone.0030719-Virtanen3">[11]</xref> suggest that long working hours may increase the risk of various adverse outcomes, including psychological distress and symptoms of depression and anxiety <xref ref-type="bibr" rid="pone.0030719-Virtanen1">[8]</xref>, <xref ref-type="bibr" rid="pone.0030719-Suwazono1">[9]</xref>, decline in cognitive function <xref ref-type="bibr" rid="pone.0030719-Virtanen2">[10]</xref>, and new-onset sleep disturbances <xref ref-type="bibr" rid="pone.0030719-Virtanen3">[11]</xref>. However, to date, little is known about the relationship between long working hours and clinical depression. In a follow-up of Canadians over 1–2 years <xref ref-type="bibr" rid="pone.0030719-Shields1">[12]</xref>, working 41 hours or more per week compared to 35–40 hours was associated with a higher rate of new-onset major depressive episode (MDE) among women but not among men. Another study with a 24-year follow-up did not find any association between “overtime work” and incidence of depressive disorder which included also cases of subclinical depression <xref ref-type="bibr" rid="pone.0030719-Michelsen1">[13]</xref>. A Japanese study that used employee insurance company records found no association between long working hours and mental disorders <xref ref-type="bibr" rid="pone.0030719-Tarumi1">[14]</xref>. Several factors in previous studies may have contributed to the mixed evidence, including the dichotomisation of working hours, use of retrospective reports of hours worked, and clinically non-validated disease outcome measures, as well as extensive follow-up periods potentially introducing effect dilution bias.</p>
      <p>In this study, we examined the association between overtime work and the onset of a major depressive episode in a sample of British civil servants who were free from psychological morbidity at baseline. We used the Composite International Diagnostic Interview (CIDI) <xref ref-type="bibr" rid="pone.0030719-Wittchen1">[15]</xref>, <xref ref-type="bibr" rid="pone.0030719-Kessler1">[16]</xref> to assess the onset of 12-month DSM-III-R-defined MDE <xref ref-type="bibr" rid="pone.0030719-American1">[17]</xref>, as this instrument is considered as the gold standard for large epidemiologic studies.</p>
    </sec>
    <sec id="s2" sec-type="methods">
      <title>Methods</title>
      <sec id="s2a">
        <title>Ethics statement</title>
        <p>Informed consent was obtained from all participants and the University College London Medical School Committee on the Ethics of Human Research approved the protocol.</p>
      </sec>
      <sec id="s2b">
        <title>Participants and Procedure</title>
        <p>Recruitment to the Whitehall II study (phase 1) took place between late 1985 and early 1988 among all office staff, aged 35 to 55 years, from 20 London-based Civil Service departments <xref ref-type="bibr" rid="pone.0030719-Marmot1">[18]</xref>. The response rate was 73% (6895 men and 3413 women).</p>
        <p>The data for exposure and outcome measures for the present study are drawn from two survey phases; phase 3 (1991–3), the baseline for the present analyses when working hours were measured for the first time; and phase 5 (1997–99), follow-up, when DSM-III-R MDE was evaluated for the first and only time. The number of participants who worked full time (≥7 hours per day) at phase 3 baseline was 7287 and a further 7024 (96%) had complete data on covariates at baseline, 6251 responded at follow-up, and 4366 were still employed at follow-up. We selected those who were employed to reduce misclassification of working hours during the follow-up. In this sub-sample, 2724 had also completed the CIDI-interview at follow-up. Finally, we excluded 601 participants with psychiatric morbidity at baseline defined as caseness on the 30-item General Health Questionnaire (GHQ-30 total score ≥5) <xref ref-type="bibr" rid="pone.0030719-Goldberg1">[19]</xref>. In relation to diagnosed mental disorders, especially mood and anxiety disorders, the GHQ has shown good clinical validity as a screening instrument <xref ref-type="bibr" rid="pone.0030719-Goldberg1">[19]</xref>–<xref ref-type="bibr" rid="pone.0030719-Stansfeld1">[21]</xref>. The GHQ-30 has been validated specifically against the Clinical Interview Schedule in Whitehall II data, giving a cut-off point 4/5 for dividing ‘non-cases’ from ‘cases’ <xref ref-type="bibr" rid="pone.0030719-Stansfeld1">[21]</xref>. The final analytic sample consisted of 2123 employees followed for a mean of 5.8 (S.D. = 0.4, range 3.8 to 7.2) years.</p>
        <p>Presence of an MDE in the preceding 12 months was ascertained during the clinical health examination using the University of Michigan version of the Composite International Diagnostic Interview (UM-CIDI) adapted for self-administered computerised interview <xref ref-type="bibr" rid="pone.0030719-Wittchen1">[15]</xref>, <xref ref-type="bibr" rid="pone.0030719-Kessler1">[16]</xref>. The program used operationalized criteria for diagnoses in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) <xref ref-type="bibr" rid="pone.0030719-American1">[17]</xref>. In addition to the criteria for the presence and duration of the DSM-III-R symptoms, the definition of a MDE required that the episode also fulfilled criteria for impairment and change in function, and was not due to organic conditions, bereavement, or mania. The CIDI interview was commenced after the beginning of screening at phase 5: all participants attending the screening clinic after the CIDI was introduced were invited to complete the interview.</p>
        <p>We determined working hours at baseline with the following question: “On an average weekday, approximately how many hours do you spend on the following activities (if applicable): Work (daytime and work brought home)?” Response categories covered working hours from 1 hour to 12 hours. As previously <xref ref-type="bibr" rid="pone.0030719-Virtanen4">[22]</xref>, we divided the participants into the following groups: 7–8 working hours/day (the Civil service standard, i.e. no overtime work); 9 hours/day (1 hour of overtime work a day); 10 hours/day (2 hours of overtime work); 11–12 hours/day (3–4 hours of overtime work).</p>
        <p>Data on socio-demographic factors, health-related behaviours, and physical health at baseline were used as covariates in the analyses. Socio-demographic factors included sex, age, marital status (married/cohabiting vs not), and socioeconomic position, SES (as indicated by occupational grade grouped into six levels). Alcohol consumption was classified as 0, &gt;0 to 14 units/week for women and 0, &gt;0 to 21 units/week for men (alcohol consumption within the recommended limits); and &gt;14 units for women and &gt;21 units for men (alcohol consumption over the recommended limits) <xref ref-type="bibr" rid="pone.0030719-White1">[23]</xref>. Smoking was assessed by questions on whether the respondent was a current, past, or never-smoker. Poor physical health was indicated by the presence of at least one of the following conditions: report of longstanding illness, disease, or medical condition for which the participant had sought treatment in the 12 months before the baseline survey; presence of coronary heart disease (for details <xref ref-type="bibr" rid="pone.0030719-Kivimki1">[24]</xref>). Work stress was operationalised as self-reported job demands, job control, and social support at work <xref ref-type="bibr" rid="pone.0030719-Karasek1">[25]</xref>, <xref ref-type="bibr" rid="pone.0030719-Karasek2">[26]</xref>. As an indicator of job strain we formulated a variable in which the demand and control scales were dichotomized based on their median scores, and participants were assigned to 1 of 4 categories according to scores on each dimension: low strain (low demand and high control), passive (low demand and low control), active (high demand and high control), or high strain (high demand and low control) – this variable corresponds the original definition of job strain by Karasek <xref ref-type="bibr" rid="pone.0030719-Karasek1">[25]</xref>. Social support was low when the respondent was in the lowest third of work social support. Employment status at follow-up (employed vs not) was derived from the follow-up survey.</p>
      </sec>
      <sec id="s2c">
        <title>Statistical analysis</title>
        <p>Descriptive statistics were carried out using χ<sup>2</sup> and general linear modeling to examine heterogeneity across study variables. The association between working hours and new-onset MDE was examined with binary logistic regression analysis sequentially adjusting for sociodemographic variables, chronic conditions, health behaviours, and job characteristics. As a sensitivity analysis, we examined the associations between working hours and MDE in a sample also including those who were no longer employed at follow-up (total n = 2881) and adjusted for follow-up employment status (employed vs not). All analyses were performed using SAS 9.2 statistical software for Windows (Cary, Texas, USA).</p>
      </sec>
    </sec>
    <sec id="s3">
      <title>Results</title>
      <sec id="s3a">
        <title>Characteristics of the baseline, follow-up and analytic samples</title>
        <p>The three left columns of <xref ref-type="supplementary-material" rid="pone.0030719.s001">Table S1</xref> present descriptive statistics for all the baseline participants (n = 7024) and the selected study samples (n = 6251 before and n = 2123 after exclusions of GHQ-30 cases, non-employed, and CIDI non-respondents). The participants in the analytic study sample were younger, more likely to be male, married or cohabiting, from higher occupational grades, less likely to have a chronic disease or to be a smoker and more likely to be in low strain or active jobs than the baseline sample including all baseline respondents. Some of these differences seemed to develop after the exclusion of GHQ-30 psychological morbidity cases which is as expected given that many of these characteristics are known correlates of psychological morbidity. Furthermore (not shown in the table), 54% of the original sample (vs. 52% in the study sample) worked standard 7–8 hours, 21% (vs. 21%) worked 9 hours, 15% (vs. 16%) worked 10 hours, and 10% (vs. 11%) worked 11–12 hours a day. Thus, any differences in working hours between the participants and the total baseline population were small.</p>
        <p>As shown in <xref ref-type="supplementary-material" rid="pone.0030719.s001">Table S1</xref> right-hand side columns, employees with long working hours were more likely to be men, married or cohabiting, from the higher occupational grades, those who had active jobs and high social support at work, and less often passive jobs or low strain jobs, than employees with standard working hours. They also tended to drink alcohol above the recommended limits, and were more likely to be ex-smokers and less likely to be never-smokers. Age and prevalence of chronic physical disease did not differ between categories of working hours.</p>
      </sec>
      <sec id="s3b">
        <title>Predictors of major depressive episode</title>
        <p>Sixty-six cases of MDE were identified at follow-up, resulting in a rate of 3.1% (<xref ref-type="table" rid="pone-0030719-t001">Table 1</xref>). Predictors of the onset of depression were younger age, female sex, lower occupational grade, chronic physical disease, and moderate alcohol use (the odds ratio for depression for participants with alcohol use beyond the recommended limits was 2.19; in the expected direction but not statistically significant at conventional levels). We found no robust associations between marital status, smoking, job strain, or work social support and the onset of depression.</p>
        <table-wrap id="pone-0030719-t001" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0030719.t001</object-id><label>Table 1</label><caption>
            <title>Age- and sex-adjusted associations between baseline covariates and a major depressive episode at follow-up, the Whitehall II study, 1991–9.</title>
          </caption><!--===== Grouping alternate versions of objects =====--><alternatives><graphic id="pone-0030719-t001-1" mimetype="image" position="float" xlink:href="info:doi/10.1371/journal.pone.0030719.t001" xlink:type="simple"/><table>
            <colgroup span="1">
              <col align="left" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
            </colgroup>
            <thead>
              <tr>
                <td align="left" colspan="1" rowspan="1">Characteristic</td>
                <td align="left" colspan="1" rowspan="1">N</td>
                <td align="left" colspan="1" rowspan="1">N of cases</td>
                <td align="left" colspan="1" rowspan="1">Odds ratio (95% CI)</td>
                <td align="left" colspan="1" rowspan="1"><italic>P-v</italic>alue</td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" colspan="1" rowspan="1">Age</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1">0.94 (0.89–0.99)</td>
                <td align="left" colspan="1" rowspan="1">0.029</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Sex</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Male</td>
                <td align="left" colspan="1" rowspan="1">1626</td>
                <td align="left" colspan="1" rowspan="1">41</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Female</td>
                <td align="left" colspan="1" rowspan="1">497</td>
                <td align="left" colspan="1" rowspan="1">25</td>
                <td align="left" colspan="1" rowspan="1">2.08 (1.25–3.46)</td>
                <td align="left" colspan="1" rowspan="1">0.005</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Marital status</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Married/cohabiting</td>
                <td align="left" colspan="1" rowspan="1">1717</td>
                <td align="left" colspan="1" rowspan="1">49</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Non-married/-cohabiting</td>
                <td align="left" colspan="1" rowspan="1">406</td>
                <td align="left" colspan="1" rowspan="1">17</td>
                <td align="left" colspan="1" rowspan="1">1.21 (0.68–2.16)</td>
                <td align="left" colspan="1" rowspan="1">0.51</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Occupational grade</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">1 (highest)</td>
                <td align="left" colspan="1" rowspan="1">385</td>
                <td align="left" colspan="1" rowspan="1">4</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">2</td>
                <td align="left" colspan="1" rowspan="1">527</td>
                <td align="left" colspan="1" rowspan="1">15</td>
                <td align="left" colspan="1" rowspan="1">2.51 (0.82–7.67)</td>
                <td align="left" colspan="1" rowspan="1">0.11</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">3</td>
                <td align="left" colspan="1" rowspan="1">349</td>
                <td align="left" colspan="1" rowspan="1">9</td>
                <td align="left" colspan="1" rowspan="1">2.17 (0.66–7.15)</td>
                <td align="left" colspan="1" rowspan="1">0.20</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">4</td>
                <td align="left" colspan="1" rowspan="1">332</td>
                <td align="left" colspan="1" rowspan="1">13</td>
                <td align="left" colspan="1" rowspan="1">3.19 (1.02–9.99)</td>
                <td align="left" colspan="1" rowspan="1">0.047</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">5</td>
                <td align="left" colspan="1" rowspan="1">279</td>
                <td align="left" colspan="1" rowspan="1">16</td>
                <td align="left" colspan="1" rowspan="1">4.53 (1.47–13.90)</td>
                <td align="left" colspan="1" rowspan="1">0.008</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">6 (lowest)</td>
                <td align="left" colspan="1" rowspan="1">251</td>
                <td align="left" colspan="1" rowspan="1">9</td>
                <td align="left" colspan="1" rowspan="1">2.54 (0.74–8.69)</td>
                <td align="left" colspan="1" rowspan="1">0.139</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Chronic physical disease</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">No</td>
                <td align="left" colspan="1" rowspan="1">1454</td>
                <td align="left" colspan="1" rowspan="1">33</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Yes</td>
                <td align="left" colspan="1" rowspan="1">669</td>
                <td align="left" colspan="1" rowspan="1">33</td>
                <td align="left" colspan="1" rowspan="1">2.30 (1.41–3.78)</td>
                <td align="left" colspan="1" rowspan="1">0.001</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Alcohol use</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">No</td>
                <td align="left" colspan="1" rowspan="1">333</td>
                <td align="left" colspan="1" rowspan="1">5</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Moderate</td>
                <td align="left" colspan="1" rowspan="1">1432</td>
                <td align="left" colspan="1" rowspan="1">51</td>
                <td align="left" colspan="1" rowspan="1">2.68 (1.05–6.82)</td>
                <td align="left" colspan="1" rowspan="1">0.038</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">High</td>
                <td align="left" colspan="1" rowspan="1">358</td>
                <td align="left" colspan="1" rowspan="1">10</td>
                <td align="left" colspan="1" rowspan="1">2.19 (0.73–6.55)</td>
                <td align="left" colspan="1" rowspan="1">0.16</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Smoking</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Never</td>
                <td align="left" colspan="1" rowspan="1">1105</td>
                <td align="left" colspan="1" rowspan="1">28</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Ex</td>
                <td align="left" colspan="1" rowspan="1">758</td>
                <td align="left" colspan="1" rowspan="1">28</td>
                <td align="left" colspan="1" rowspan="1">1.65 (0.96–2.83)</td>
                <td align="left" colspan="1" rowspan="1">0.07</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Current</td>
                <td align="left" colspan="1" rowspan="1">260</td>
                <td align="left" colspan="1" rowspan="1">10</td>
                <td align="left" colspan="1" rowspan="1">1.46 (0.70–3.06)</td>
                <td align="left" colspan="1" rowspan="1">0.31</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Job strain</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Low strain</td>
                <td align="left" colspan="1" rowspan="1">494</td>
                <td align="left" colspan="1" rowspan="1">14</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Active</td>
                <td align="left" colspan="1" rowspan="1">720</td>
                <td align="left" colspan="1" rowspan="1">16</td>
                <td align="left" colspan="1" rowspan="1">0.77 (0.37–1.59)</td>
                <td align="left" colspan="1" rowspan="1">0.47</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Passive</td>
                <td align="left" colspan="1" rowspan="1">597</td>
                <td align="left" colspan="1" rowspan="1">26</td>
                <td align="left" colspan="1" rowspan="1">1.39 (0.71–2.71)</td>
                <td align="left" colspan="1" rowspan="1">0.34</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">High strain</td>
                <td align="left" colspan="1" rowspan="1">312</td>
                <td align="left" colspan="1" rowspan="1">10</td>
                <td align="left" colspan="1" rowspan="1">1.04 (0.46–2.39)</td>
                <td align="left" colspan="1" rowspan="1">0.92</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Social support at work</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">High</td>
                <td align="left" colspan="1" rowspan="1">699</td>
                <td align="left" colspan="1" rowspan="1">21</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Intermediate</td>
                <td align="left" colspan="1" rowspan="1">648</td>
                <td align="left" colspan="1" rowspan="1">24</td>
                <td align="left" colspan="1" rowspan="1">1.41 (0.77–2.56)</td>
                <td align="left" colspan="1" rowspan="1">0.26</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">Low</td>
                <td align="left" colspan="1" rowspan="1">776</td>
                <td align="left" colspan="1" rowspan="1">21</td>
                <td align="left" colspan="1" rowspan="1">1.11 (0.60–2.06)</td>
                <td align="left" colspan="1" rowspan="1">0.73</td>
              </tr>
            </tbody>
          </table></alternatives><table-wrap-foot>
            <fn id="nt101">
              <label/>
              <p>CI = Confidence interval.</p>
            </fn>
          </table-wrap-foot></table-wrap>
        <p>Working 11+ hours a day was related to a 2.43-fold odds of MDE compared to working 7 to 8 hours a day in an analysis adjusted for socio-demographic characteristics (<xref ref-type="table" rid="pone-0030719-t002">Table 2</xref>). However, this effect was not seen until SES was introduced into the models (Model 3), suggesting that unadjusted associations are suppressed by SES. This is because high SES was related to an increased likelihood of working long hours (<xref ref-type="supplementary-material" rid="pone.0030719.s001">Table S1</xref>), but high SES is associated with a reduced risk of MDE (<xref ref-type="table" rid="pone-0030719-t001">Table 1</xref>). Further adjustment for health and health behaviours made little change to the association (2.30). It was also robust to additional adjustment for work characteristics (job strain and social support at work), the odds ratio of MDE being 2.52-fold for 11+ working hours in the final model.</p>
        <table-wrap id="pone-0030719-t002" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0030719.t002</object-id><label>Table 2</label><caption>
            <title>Association between working hours at baseline and a major depressive episode at follow-up, the Whitehall II study, 1991-9.</title>
          </caption><!--===== Grouping alternate versions of objects =====--><alternatives><graphic id="pone-0030719-t002-2" mimetype="image" position="float" xlink:href="info:doi/10.1371/journal.pone.0030719.t002" xlink:type="simple"/><table>
            <colgroup span="1">
              <col align="left" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
            </colgroup>
            <thead>
              <tr>
                <td align="left" colspan="1" rowspan="1">Working Hours at Baseline</td>
                <td align="left" colspan="1" rowspan="1">N</td>
                <td align="left" colspan="1" rowspan="1">N of cases</td>
                <td align="left" colspan="1" rowspan="1">Odds ratio (95% CI)<xref ref-type="table-fn" rid="nt102">*</xref></td>
                <td align="left" colspan="1" rowspan="1"><italic>P-v</italic>alue</td>
                <td align="left" colspan="1" rowspan="1">Odds ratio (95% CI)<xref ref-type="table-fn" rid="nt103">†</xref></td>
                <td align="left" colspan="1" rowspan="1"><italic>P-v</italic>alue</td>
                <td align="left" colspan="1" rowspan="1">Odds ratio (95% CI)<xref ref-type="table-fn" rid="nt104">‡</xref></td>
                <td align="left" colspan="1" rowspan="1"><italic>P-v</italic>alue</td>
                <td align="left" colspan="1" rowspan="1">Odds ratio (95% CI)<xref ref-type="table-fn" rid="nt105">§</xref></td>
                <td align="left" colspan="1" rowspan="1"><italic>P-v</italic>alue</td>
                <td align="left" colspan="1" rowspan="1">Odds ratio (95% CI)<xref ref-type="table-fn" rid="nt106">¶</xref></td>
                <td align="left" colspan="1" rowspan="1"><italic>P-v</italic>alue</td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" colspan="1" rowspan="1">7–8 hours</td>
                <td align="left" colspan="1" rowspan="1">1105</td>
                <td align="left" colspan="1" rowspan="1">38</td>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
                <td align="left" colspan="1" rowspan="1">1.00</td>
                <td align="left" colspan="1" rowspan="1"/>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">9 hours</td>
                <td align="left" colspan="1" rowspan="1">445</td>
                <td align="left" colspan="1" rowspan="1">8</td>
                <td align="left" colspan="1" rowspan="1">0.51 (0.24–1.11)</td>
                <td align="left" colspan="1" rowspan="1">0.09</td>
                <td align="left" colspan="1" rowspan="1">0.57 (0.26–1.23)</td>
                <td align="left" colspan="1" rowspan="1">0.15</td>
                <td align="left" colspan="1" rowspan="1">0.68 (0.31–1.49)</td>
                <td align="left" colspan="1" rowspan="1">0.33</td>
                <td align="left" colspan="1" rowspan="1">0.62 (0.28–1.38)</td>
                <td align="left" colspan="1" rowspan="1">0.24</td>
                <td align="left" colspan="1" rowspan="1">0.66 (0.29–1.48)</td>
                <td align="left" colspan="1" rowspan="1">0.31</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">10 hours</td>
                <td align="left" colspan="1" rowspan="1">346</td>
                <td align="left" colspan="1" rowspan="1">10</td>
                <td align="left" colspan="1" rowspan="1">0.84 (0.41–1.70)</td>
                <td align="left" colspan="1" rowspan="1">0.62</td>
                <td align="left" colspan="1" rowspan="1">0.92 (0.45–1.88)</td>
                <td align="left" colspan="1" rowspan="1">0.83</td>
                <td align="left" colspan="1" rowspan="1">1.23 (0.59–2.58)</td>
                <td align="left" colspan="1" rowspan="1">0.58</td>
                <td align="left" colspan="1" rowspan="1">1.18 (0.56–2.51)</td>
                <td align="left" colspan="1" rowspan="1">0.66</td>
                <td align="left" colspan="1" rowspan="1">1.27 (0.59–2.72)</td>
                <td align="left" colspan="1" rowspan="1">0.54</td>
              </tr>
              <tr>
                <td align="left" colspan="1" rowspan="1">11–12 hours</td>
                <td align="left" colspan="1" rowspan="1">227</td>
                <td align="left" colspan="1" rowspan="1">10</td>
                <td align="left" colspan="1" rowspan="1">1.29 (0.64–2.64)</td>
                <td align="left" colspan="1" rowspan="1">0.48</td>
                <td align="left" colspan="1" rowspan="1">1.55 (0.75–3.20)</td>
                <td align="left" colspan="1" rowspan="1">0.24</td>
                <td align="left" colspan="1" rowspan="1">2.43 (1.11–5.30)</td>
                <td align="left" colspan="1" rowspan="1">0.026</td>
                <td align="left" colspan="1" rowspan="1">2.30 (1.05–5.06)</td>
                <td align="left" colspan="1" rowspan="1">0.038</td>
                <td align="left" colspan="1" rowspan="1">2.52 (1.12–5.65)</td>
                <td align="left" colspan="1" rowspan="1">0.025</td>
              </tr>
            </tbody>
          </table></alternatives><table-wrap-foot>
            <fn id="nt102">
              <label/>
              <p>*Unadjusted.</p>
            </fn>
            <fn id="nt103">
              <label>†</label>
              <p>Adjusted for age and sex.</p>
            </fn>
            <fn id="nt104">
              <label>‡</label>
              <p>As previous model but additionally adjusted for occupational grade and marital status.</p>
            </fn>
            <fn id="nt105">
              <label>§</label>
              <p>As previous model but additionally adjusted for chronic physical disease, smoking, and alcohol use.</p>
            </fn>
            <fn id="nt106">
              <label>¶</label>
              <p>As previous model but additionally adjusted for job strain and social support at work.</p>
            </fn>
            <fn id="nt107">
              <label/>
              <p>CI = Confidence interval.</p>
            </fn>
          </table-wrap-foot></table-wrap>
      </sec>
      <sec id="s3c">
        <title>Sensitivity analysis</title>
        <p>As a sensitivity analysis, we examined the associations between working hours and MDE in a sample also including those who were no longer employed at follow-up (n = 2881). Working 11 hours or more at baseline was associated with a 1.89 odds (95% CI 0.92–3.86) of MDE at follow-up when compared to standard 7–8 hours. Further adjustment for employment status (employed vs. retired/other) made little change to the association (OR 1.87, 95% CI 0.91–3.84).</p>
      </sec>
    </sec>
    <sec id="s4">
      <title>Discussion</title>
      <p>Working overtime predicted the onset of a major depressive episode in a middle-aged cohort of British civil servants, followed for an average of 5.8 years. Working 11 or more hours a day was associated with a 2.3- to 2.5-fold risk of an MDE when compared with working a standard 7–8 hours a day. This association was robust to adjustment for a range of socio-demographic, life-style, and work-related factors at baseline.</p>
      <p>The main strengths of our study are its relatively large sample size, the prospective design and the use of the standardized CIDI interview which has been shown to be a valid measure of DSM-III-R non-psychotic disorders <xref ref-type="bibr" rid="pone.0030719-Wittchen1">[15]</xref>. However, some limitations are noteworthy. First, the CIDI interview was only available at follow-up so baseline cases had to be excluded based on GHQ-30 caseness. However, the GHQ is a well-established scale for the evaluation of psychological morbidity in general population samples. In relation to diagnosed mental disorders, especially mood and anxiety disorders, the GHQ has shown good clinical validity <xref ref-type="bibr" rid="pone.0030719-Goldberg1">[19]</xref>–<xref ref-type="bibr" rid="pone.0030719-Stansfeld1">[21]</xref>. As the GHQ-30 also detects a range of minor psychiatric disorders, such as subclinical depression, it is possible that our baseline exclusion of GHQ-30 cases is over zealous.</p>
      <p>Second, being based on observational data, this investigation cannot rule out the possibility of residual confounding by other, unmeasured or imprecisely measured predictors of new-onset depression. We also found that the statistically significant association between 11+ weekly hours of work and the onset of depression was hidden in models not adjusted for individual SES. As SES was inversely associated with depression and positively associated with working hours, its effect can be considered as suppression, ‘a situation in which the magnitude of the relationship between an independent variable and a dependent variable becomes larger when a third variable is included’ <xref ref-type="bibr" rid="pone.0030719-Tselgov1">[27]</xref>–<xref ref-type="bibr" rid="pone.0030719-MacKinnon1">[28]</xref>. In terms of prevention, revealing the relevance of long working hours as a risk factor among high-SES employees who otherwise have lower risk of depression seems important.</p>
      <p>A further limitation relates to our inability to assess interaction effects due to the relatively small numbers of new-onset cases of MDE. For example, it is possible there are sex differences in the association between long working hours and mental health <xref ref-type="bibr" rid="pone.0030719-Virtanen1">[8]</xref>, <xref ref-type="bibr" rid="pone.0030719-Shields1">[12]</xref>. Some positive work characteristics, such as high control or high rewards at work, may buffer an employee against the adverse health effects of long working hours <xref ref-type="bibr" rid="pone.0030719-Virtanen4">[22]</xref>, <xref ref-type="bibr" rid="pone.0030719-Stansfeld2">[29]</xref>–<xref ref-type="bibr" rid="pone.0030719-Harris1">[35]</xref>. On the other hand, working long hours may also mean higher exposure to adverse working conditions. Further studies with larger sample sizes are needed to examine possible interaction effects in relation to clinical depression.</p>
      <p>The rate of depression at follow-up was 3.1%. The median 1-year prevalence of depression across studies in general populations has been higher, approximately 5% <xref ref-type="bibr" rid="pone.0030719-Eaton1">[2]</xref>. This might be because only participants free of psychological distress at baseline were selected for follow-up. Furthermore, the Whitehall II study comprised a working population which has previously been shown to be healthier than the general population <xref ref-type="bibr" rid="pone.0030719-Honkonen1">[36]</xref>. As all civil servants are white collar workers, it remains to be investigated whether our findings are generalizable to blue-collar workers and employees in the private sector.</p>
      <p>Predictors of the onset of depression in our study were younger age, female sex, lower occupational grade, chronic physical disease, and moderate alcohol use (the odds ratio for depression in participants who used alcohol beyond the recommended limits was 2.19; in the expected direction but not statistically significant at conventional levels). We found no robust associations between marital status, smoking, job strain, or work social support and the onset of depression. Earlier literature suggests quite strong evidence for age (early or mid-adulthood), female sex, chronic physical disease such as CHD, binge drinking, smoking, low SES, and negative stressful life events as predictors of depression <xref ref-type="bibr" rid="pone.0030719-Harris1">[35]</xref>, <xref ref-type="bibr" rid="pone.0030719-Kendler1">[37]</xref>–<xref ref-type="bibr" rid="pone.0030719-Isomets1">[41]</xref>. Smoking intensity in white-collar employees, such as those in our study, is very likely to be lower than in the general population, which may be one explanation for the lack of an association with depression. Work stress and work social support have been suggested to be associated with depression <xref ref-type="bibr" rid="pone.0030719-Stansfeld2">[29]</xref>–<xref ref-type="bibr" rid="pone.0030719-Stansfeld4">[34]</xref>, but a recent review focusing on clinical disorders <xref ref-type="bibr" rid="pone.0030719-Bonde1">[32]</xref> suggested that the association is inconclusive. However, in other analyses in this cohort we have found associations between job strain and depression, especially when the exposure to job strain was repeated <xref ref-type="bibr" rid="pone.0030719-Stansfeld4">[34]</xref>.</p>
      <p>Our sensitivity analysis of all follow-up participants irrespective of employment status revealed similar, although a weaker association between overtime work and depression compared to findings from analyses restricted to those employed at follow-up. These slightly weaker associations were expected given the possible misclassification of working hours during follow-up among those who were no longer employed. Some of those not employed may have stopped working several years before the onset of depression.</p>
      <p>Our findings are in accordance with some observations from previous studies showing a positive association between long working hours and depression <xref ref-type="bibr" rid="pone.0030719-Shields1">[12]</xref> but contrast with other reports of null findings <xref ref-type="bibr" rid="pone.0030719-Shields1">[12]</xref>–<xref ref-type="bibr" rid="pone.0030719-Tarumi1">[14]</xref>. Mixed findings in this field of research may relate to various operationalisations of long working hours, that is, in some studies the cut-point has been 40 <xref ref-type="bibr" rid="pone.0030719-Shields1">[12]</xref> or 45 hours <xref ref-type="bibr" rid="pone.0030719-Tarumi1">[14]</xref> or “more than one hour weekly overtime work” versus less <xref ref-type="bibr" rid="pone.0030719-Michelsen1">[13]</xref> and possibly to the different work cultures in which these studies were carried out. Furthermore, some studies included part-time workers in the reference group although it is known that people with pre-existing health problems may choose part-time jobs <xref ref-type="bibr" rid="pone.0030719-Ettner1">[42]</xref>. For a better comparison between studies, a consistent definition for overtime and long working hours is needed in the future.</p>
      <p>Plausible explanations of why long working hours are associated with the development of depression can not be drawn directly from our study. Serial adjustment for socio-demographic factors, physical disease, smoking, alcohol use, job strain, and social support at work, had little effect on the association or even strengthened it. Long working hours may in part affect mental health through factors not measured in our study, such as work-family conflicts <xref ref-type="bibr" rid="pone.0030719-Caruso1">[7]</xref>, <xref ref-type="bibr" rid="pone.0030719-Crouter1">[43]</xref>, <xref ref-type="bibr" rid="pone.0030719-Jansen1">[44]</xref>, difficulties in unwinding after work <xref ref-type="bibr" rid="pone.0030719-Rissler1">[45]</xref> or prolonged increased cortisol levels <xref ref-type="bibr" rid="pone.0030719-Lundberg1">[46]</xref>. The effect of long working hours on mental health may also be different in women and men <xref ref-type="bibr" rid="pone.0030719-Virtanen1">[8]</xref>, <xref ref-type="bibr" rid="pone.0030719-Shields1">[12]</xref>. To date, the exact aetiology of depression is not known, but it is widely assumed that it is multifactorial involving genetic, biological, and psychosocial factors <xref ref-type="bibr" rid="pone.0030719-Harris1">[35]</xref>, <xref ref-type="bibr" rid="pone.0030719-Kendler1">[37]</xref>, <xref ref-type="bibr" rid="pone.0030719-Kessler2">[38]</xref>, <xref ref-type="bibr" rid="pone.0030719-Harkonmki1">[47]</xref>.</p>
      <p>In conclusion, this study suggests an association between long working hours and the onset of major depressive episode. Large-scale population-based cohort studies are needed to examine whether the association can be found in other contexts than Civil Service and intervention studies are needed to examine whether interventions designed to reduce working hours would alter depression risk in working populations.</p>
    </sec>
    <sec id="s5">
      <title>Supporting Information</title>
      <supplementary-material id="pone.0030719.s001" mimetype="application/msword" position="float" xlink:href="info:doi/10.1371/journal.pone.0030719.s001" xlink:type="simple">
        <label>Table S1</label>
        <caption>
          <p>
            <bold>Characteristics of the participants by daily working hours at baseline Data are N (%) or mean (S.D.), the Whitehall II study, 1991–9.</bold>
          </p>
          <p>(DOC)</p>
        </caption>
      </supplementary-material>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>References</title>
      <ref id="pone.0030719-Mathers1">
        <label>1</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Mathers</surname><given-names>CD</given-names></name><name name-style="western"><surname>Loncar</surname><given-names>D</given-names></name></person-group>             <year>2006</year>             <article-title>Projections of global mortality and burden of disease from 2002 to 2030.</article-title>             <source>PLoS Med</source>             <volume>3</volume>             <fpage>e442</fpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Eaton1">
        <label>2</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Eaton</surname><given-names>WW</given-names></name><name name-style="western"><surname>Martins</surname><given-names>SS</given-names></name><name name-style="western"><surname>Nestadt</surname><given-names>G</given-names></name><name name-style="western"><surname>Bienvenu</surname><given-names>OJ</given-names></name><name name-style="western"><surname>Clarke</surname><given-names>D</given-names></name><etal/></person-group>             <year>2008</year>             <article-title>The burden of mental disorders.</article-title>             <source>Epidemiol Rev</source>             <volume>30</volume>             <fpage>1</fpage>             <lpage>14</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Adler1">
        <label>3</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Adler</surname><given-names>DA</given-names></name><name name-style="western"><surname>McLaughlin</surname><given-names>TJ</given-names></name><name name-style="western"><surname>Rogers</surname><given-names>WH</given-names></name><name name-style="western"><surname>Chang</surname><given-names>H</given-names></name><name name-style="western"><surname>Lapitsky</surname><given-names>L</given-names></name><etal/></person-group>             <year>2006</year>             <article-title>Job performance deficits due to depression.</article-title>             <source>Am J Psychiatry</source>             <volume>163</volume>             <fpage>1569</fpage>             <lpage>1576</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Wang1">
        <label>4</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Wang</surname><given-names>PS</given-names></name><name name-style="western"><surname>Beck</surname><given-names>AL</given-names></name><name name-style="western"><surname>Berglund</surname><given-names>P</given-names></name><name name-style="western"><surname>McKenas</surname><given-names>DK</given-names></name><name name-style="western"><surname>Pronk</surname><given-names>NP</given-names></name><etal/></person-group>             <year>2004</year>             <article-title>Effects of major depression on moment-in-time work performance.</article-title>             <source>Am J Psychiatry</source>             <volume>161</volume>             <fpage>1885</fpage>             <lpage>1891</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Demyttenaere1">
        <label>5</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Demyttenaere</surname><given-names>K</given-names></name><name name-style="western"><surname>Bruffaerts</surname><given-names>R</given-names></name><name name-style="western"><surname>Posada-Villa</surname><given-names>J</given-names></name><name name-style="western"><surname>Gasquet</surname><given-names>I</given-names></name><name name-style="western"><surname>Kovess</surname><given-names>V</given-names></name><etal/></person-group>             <year>2004</year>             <article-title>WHO World Mental Health Survey Consortium. Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys.</article-title>             <source>JAMA</source>             <volume>291</volume>             <fpage>2581</fpage>             <lpage>2590</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-vanderHulst1">
        <label>6</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>van der Hulst</surname><given-names>M</given-names></name></person-group>             <year>2003</year>             <article-title>Long workhours and health.</article-title>             <source>Scand J Work Environ Health</source>             <volume>29</volume>             <fpage>171</fpage>             <lpage>188</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Caruso1">
        <label>7</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Caruso</surname><given-names>CC</given-names></name></person-group>             <year>2006</year>             <article-title>Possible broad impacts of long work hours.</article-title>             <source>Ind Health</source>             <volume>44</volume>             <fpage>531</fpage>             <lpage>536</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Virtanen1">
        <label>8</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Virtanen</surname><given-names>M</given-names></name><name name-style="western"><surname>Ferrie</surname><given-names>JE</given-names></name><name name-style="western"><surname>Singh-Manoux</surname><given-names>A</given-names></name><name name-style="western"><surname>Shipley</surname><given-names>MJ</given-names></name><name name-style="western"><surname>Stansfeld</surname><given-names>SA</given-names></name><etal/></person-group>             <year>2011</year>             <article-title>Long working hours and symptoms of anxiety and depression: a 5-year follow-up of the Whitehall II study.</article-title>             <source>Psychol Med</source>             <volume>41</volume>             <fpage>2485</fpage>             <lpage>2494</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Suwazono1">
        <label>9</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Suwazono</surname><given-names>Y</given-names></name><name name-style="western"><surname>Okubo</surname><given-names>Y</given-names></name><name name-style="western"><surname>Kobayashi</surname><given-names>E</given-names></name><name name-style="western"><surname>Kido</surname><given-names>T</given-names></name><name name-style="western"><surname>Nogawa</surname><given-names>K</given-names></name></person-group>             <year>2003</year>             <article-title>A follow-up study on the association of working conditions and lifestyles with the development of (perceived) mental symptoms in workers of a telecommunication enterprise.</article-title>             <source>Occup Med (Lond)</source>             <volume>53</volume>             <fpage>436</fpage>             <lpage>442</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Virtanen2">
        <label>10</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Virtanen</surname><given-names>M</given-names></name><name name-style="western"><surname>Singh-Manoux</surname><given-names>A</given-names></name><name name-style="western"><surname>Ferrie</surname><given-names>JE</given-names></name><name name-style="western"><surname>Gimeno</surname><given-names>D</given-names></name><name name-style="western"><surname>Marmot</surname><given-names>MG</given-names></name><etal/></person-group>             <year>2009</year>             <article-title>Long working hours and cognitive function: the Whitehall II Study.</article-title>             <source>Am J Epidemiol</source>             <volume>169</volume>             <fpage>596</fpage>             <lpage>605</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Virtanen3">
        <label>11</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Virtanen</surname><given-names>M</given-names></name><name name-style="western"><surname>Ferrie</surname><given-names>JE</given-names></name><name name-style="western"><surname>Gimeno</surname><given-names>D</given-names></name><name name-style="western"><surname>Vahtera</surname><given-names>J</given-names></name><name name-style="western"><surname>Elovainio</surname><given-names>M</given-names></name><etal/></person-group>             <year>2009</year>             <article-title>Long working hours and sleep disturbances: the Whitehall II prospective cohort study.</article-title>             <source>Sleep</source>             <volume>32</volume>             <fpage>737</fpage>             <lpage>745</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Shields1">
        <label>12</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Shields</surname><given-names>M</given-names></name></person-group>             <year>1999</year>             <article-title>Long working hours and health.</article-title>             <source>Health Rep</source>             <volume>11</volume>             <fpage>33</fpage>             <lpage>48</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Michelsen1">
        <label>13</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Michelsen</surname><given-names>H</given-names></name><name name-style="western"><surname>Bildt</surname><given-names>C</given-names></name></person-group>             <year>2003</year>             <article-title>Psychosocial conditions on and off the job and psychological ill health: depressive symptoms, impaired psychological wellbeing, heavy consumption of alcohol.</article-title>             <source>Occup Environ Med</source>             <volume>60</volume>             <fpage>489</fpage>             <lpage>496</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Tarumi1">
        <label>14</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Tarumi</surname><given-names>K</given-names></name><name name-style="western"><surname>Hagihara</surname><given-names>A</given-names></name><name name-style="western"><surname>Morimoto</surname><given-names>K</given-names></name></person-group>             <year>2003</year>             <article-title>A prospective observation of onsets of health defects associated with working hours.</article-title>             <source>Ind Health</source>             <volume>41</volume>             <fpage>101</fpage>             <lpage>108</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Wittchen1">
        <label>15</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Wittchen</surname><given-names>HU</given-names></name></person-group>             <year>1994</year>             <article-title>Reliability and validity studies of the WHO–Composite International Diagnostic Interview (CIDI): a critical review.</article-title>             <source>J Psychiatr Res</source>             <volume>28</volume>             <fpage>57</fpage>             <lpage>84</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Kessler1">
        <label>16</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Kessler</surname><given-names>RC</given-names></name><name name-style="western"><surname>McGonagle</surname><given-names>KA</given-names></name><name name-style="western"><surname>Zhao</surname><given-names>S</given-names></name><name name-style="western"><surname>Nelson</surname><given-names>CB</given-names></name><name name-style="western"><surname>Hughes</surname><given-names>M</given-names></name><etal/></person-group>             <year>1994</year>             <article-title>Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey.</article-title>             <source>Arch Gen Psychiatry</source>             <volume>51</volume>             <fpage>8</fpage>             <lpage>19</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-American1">
        <label>17</label>
        <element-citation publication-type="other" xlink:type="simple">             <collab xlink:type="simple">American Psychiatric Association</collab>             <year>1987</year>             <source>Diagnostic and Statistical Manual of Mental Disorders (DSM III-R)</source>             <publisher-loc>Washington, D.C.</publisher-loc>          </element-citation>
      </ref>
      <ref id="pone.0030719-Marmot1">
        <label>18</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Marmot</surname><given-names>MG</given-names></name><name name-style="western"><surname>Smith</surname><given-names>GD</given-names></name><name name-style="western"><surname>Stansfeld</surname><given-names>S</given-names></name><name name-style="western"><surname>Patel</surname><given-names>C</given-names></name><name name-style="western"><surname>North</surname><given-names>F</given-names></name><etal/></person-group>             <year>1991</year>             <article-title>Health inequalities among British civil servants: the Whitehall II study.</article-title>             <source>Lancet</source>             <volume>337</volume>             <fpage>1387</fpage>             <lpage>1393</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Goldberg1">
        <label>19</label>
        <element-citation publication-type="other" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Goldberg</surname><given-names>DP</given-names></name></person-group>             <year>1972</year>             <source>The detection of psychiatric illness by questionnaire</source>             <publisher-loc>London</publisher-loc>             <publisher-name>Oxford University Press</publisher-name>          </element-citation>
      </ref>
      <ref id="pone.0030719-Goldberg2">
        <label>20</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Goldberg</surname><given-names>DP</given-names></name><name name-style="western"><surname>Gater</surname><given-names>R</given-names></name><name name-style="western"><surname>Sartorius</surname><given-names>N</given-names></name><name name-style="western"><surname>Ustun</surname><given-names>TB</given-names></name><name name-style="western"><surname>Piccinelli</surname><given-names>M</given-names></name><etal/></person-group>             <year>1997</year>             <article-title>The validity of two versions of the GHQ in the WHO study of mental illness in general health care.</article-title>             <source>Psychol Med</source>             <volume>27</volume>             <fpage>191</fpage>             <lpage>197</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Stansfeld1">
        <label>21</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Stansfeld</surname><given-names>SA</given-names></name><name name-style="western"><surname>Marmot</surname><given-names>MG</given-names></name></person-group>             <year>1992</year>             <article-title>Social class and minor psychiatric disorder in the British civil servants: a validated screening survey using the General Health Questionnaire.</article-title>             <source>Psychol Med</source>             <volume>22</volume>             <fpage>739</fpage>             <lpage>749</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Virtanen4">
        <label>22</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Virtanen</surname><given-names>M</given-names></name><name name-style="western"><surname>Ferrie</surname><given-names>JE</given-names></name><name name-style="western"><surname>Singh-Manoux</surname><given-names>A</given-names></name><name name-style="western"><surname>Shipley</surname><given-names>MJ</given-names></name><name name-style="western"><surname>Vahtera</surname><given-names>J</given-names></name><etal/></person-group>             <year>2010</year>             <article-title>Overtime work and incident coronary heart disease: the Whitehall II prospective cohort study.</article-title>             <source>Eur Heart J</source>             <volume>31</volume>             <fpage>1737</fpage>             <lpage>1744</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-White1">
        <label>23</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>White</surname><given-names>IR</given-names></name><name name-style="western"><surname>Altmann</surname><given-names>DR</given-names></name><name name-style="western"><surname>Nanchahal</surname><given-names>K</given-names></name></person-group>             <year>2004</year>             <article-title>Mortality in England and Wales attributable to any drinking, drinking above sensible limits and drinking above lowest-risk level.</article-title>             <source>Addiction</source>             <volume>99</volume>             <fpage>749</fpage>             <lpage>756</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Kivimki1">
        <label>24</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Kivimäki</surname><given-names>M</given-names></name><name name-style="western"><surname>Head</surname><given-names>J</given-names></name><name name-style="western"><surname>Ferrie</surname><given-names>JE</given-names></name><name name-style="western"><surname>Shipley</surname><given-names>MJ</given-names></name><name name-style="western"><surname>Steptoe</surname><given-names>A</given-names></name><etal/></person-group>             <year>2007</year>             <article-title>Hypertension is not the link between job strain and coronary heart disease in the Whitehall II study.</article-title>             <source>Am J Hypertens</source>             <volume>20</volume>             <fpage>1146</fpage>             <lpage>1153</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Karasek1">
        <label>25</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Karasek</surname><given-names>RA</given-names></name></person-group>             <year>1979</year>             <article-title>Job demands, job decision latitude and mental strain: implications for job redesign.</article-title>             <source>Admin Sci Q</source>             <volume>24</volume>             <fpage>285</fpage>             <lpage>307</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Karasek2">
        <label>26</label>
        <element-citation publication-type="other" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Karasek</surname><given-names>R</given-names></name><name name-style="western"><surname>Theorell</surname><given-names>T</given-names></name></person-group>             <year>1990</year>             <source>Healthy work: stress, productivity, and the reconstruction of working life</source>             <publisher-loc>New York (NY)</publisher-loc>             <publisher-name>Basic Books</publisher-name>          </element-citation>
      </ref>
      <ref id="pone.0030719-Tselgov1">
        <label>27</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Tselgov</surname><given-names>J</given-names></name><name name-style="western"><surname>Henik</surname><given-names>A</given-names></name></person-group>             <year>1991</year>             <article-title>Suppression situations in psychological research: Definitions implications and applications.</article-title>             <source>Psychol Bull</source>             <volume>209</volume>             <fpage>524</fpage>             <lpage>536</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-MacKinnon1">
        <label>28</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>MacKinnon</surname><given-names>DP</given-names></name><name name-style="western"><surname>Krull</surname><given-names>JL</given-names></name><name name-style="western"><surname>Lockwood</surname><given-names>CM</given-names></name></person-group>             <year>2000</year>             <article-title>Equivalence of the mediation, confounding and suppression effect.</article-title>             <source>Prev Sci</source>             <volume>1</volume>             <fpage>173</fpage>             <lpage>181</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Stansfeld2">
        <label>29</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Stansfeld</surname><given-names>SA</given-names></name></person-group>             <year>2002</year>             <article-title>Work, personality and mental health.</article-title>             <source>Brit J Psychiatry</source>             <volume>181</volume>             <fpage>96</fpage>             <lpage>98</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Paterniti1">
        <label>30</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Paterniti</surname><given-names>S</given-names></name><name name-style="western"><surname>Niedhammer</surname><given-names>I</given-names></name><name name-style="western"><surname>Lang</surname><given-names>T</given-names></name><name name-style="western"><surname>Consoli</surname><given-names>SM</given-names></name></person-group>             <year>2002</year>             <article-title>Psychosocial factors at work, personality traits and depressive symptoms. Longitudinal results from the GAZEL study.</article-title>             <source>Brit J Psychiatry</source>             <volume>181</volume>             <fpage>111</fpage>             <lpage>117</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Stansfeld3">
        <label>31</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Stansfeld</surname><given-names>SA</given-names></name><name name-style="western"><surname>Candy</surname><given-names>B</given-names></name></person-group>             <year>2006</year>             <article-title>Psychosocial work environment and mental health - a meta-analytic review.</article-title>             <source>Scand J Work Environ Health</source>             <volume>32</volume>             <fpage>443</fpage>             <lpage>462</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Bonde1">
        <label>32</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Bonde</surname><given-names>JP</given-names></name></person-group>             <year>2008</year>             <article-title>Psychosocial factors at work and risk of depression: a systematic review of the epidemiological evidence.</article-title>             <source>Occup Environ Med</source>             <volume>65</volume>             <fpage>438</fpage>             <lpage>445</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Netterstrom1">
        <label>33</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Netterstrom</surname><given-names>B</given-names></name><name name-style="western"><surname>Conrad</surname><given-names>N</given-names></name><name name-style="western"><surname>Bech</surname><given-names>P</given-names></name><name name-style="western"><surname>Fink</surname><given-names>P</given-names></name><name name-style="western"><surname>Olsen</surname><given-names>O</given-names></name><etal/></person-group>             <year>2008</year>             <article-title>The relation between work-related psychosocial factors and the development of depression.</article-title>             <source>Epidemiol Rev</source>             <volume>30</volume>             <fpage>118</fpage>             <lpage>132</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Stansfeld4">
        <label>34</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Stansfeld</surname><given-names>SA</given-names></name><name name-style="western"><surname>Shipley</surname><given-names>M</given-names></name><name name-style="western"><surname>Head</surname><given-names>J</given-names></name><name name-style="western"><surname>Fuhrer</surname><given-names>R</given-names></name></person-group>             <year>In Press</year>             <article-title>Repeated job strain and the risk of depression: longitudinal analyses from the Whitehall II Study.</article-title>             <source>Am J Public Health</source>             <comment>In press</comment>          </element-citation>
      </ref>
      <ref id="pone.0030719-Harris1">
        <label>35</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Harris</surname><given-names>T</given-names></name></person-group>             <year>2001</year>             <article-title>Recent developments in understanding the psychosocial aspects of depression.</article-title>             <source>Br Med Bull</source>             <volume>57</volume>             <fpage>17</fpage>             <lpage>32</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Honkonen1">
        <label>36</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Honkonen</surname><given-names>T</given-names></name><name name-style="western"><surname>Virtanen</surname><given-names>M</given-names></name><name name-style="western"><surname>Ahola</surname><given-names>K</given-names></name><name name-style="western"><surname>Kivimäki</surname><given-names>M</given-names></name><name name-style="western"><surname>Pirkola</surname><given-names>S</given-names></name><etal/></person-group>             <year>2007</year>             <article-title>Employment status, mental disorders and service use in the working age population.</article-title>             <source>Scand J Work Environ Health</source>             <volume>33</volume>             <fpage>29</fpage>             <lpage>36</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Kendler1">
        <label>37</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Kendler</surname><given-names>KS</given-names></name><name name-style="western"><surname>Karkowski</surname><given-names>LM</given-names></name><name name-style="western"><surname>Prescott</surname><given-names>CA</given-names></name></person-group>             <year>1999</year>             <article-title>Causal relationship between stressful life events and the onset of major depression.</article-title>             <source>Am J Psychiatry</source>             <volume>156</volume>             <fpage>837</fpage>             <lpage>841</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Kessler2">
        <label>38</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Kessler</surname><given-names>RC</given-names></name></person-group>             <year>1997</year>             <article-title>The effects of stressful life events on depression.</article-title>             <source>Annu Rev Psychol</source>             <volume>48</volume>             <fpage>191</fpage>             <lpage>214</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Kuper1">
        <label>39</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Kuper</surname><given-names>H</given-names></name><name name-style="western"><surname>Nicholson</surname><given-names>A</given-names></name><name name-style="western"><surname>Kivimäki</surname><given-names>M</given-names></name><name name-style="western"><surname>Aitsi-Selmi</surname><given-names>A</given-names></name><name name-style="western"><surname>Cavalleri</surname><given-names>G</given-names></name><etal/></person-group>             <year>2009</year>             <article-title>Evaluating the causal relevance of diverse risk markers: a horizontal systematic review.</article-title>             <source>BMJ</source>             <volume>339</volume>             <fpage>b4265</fpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Lorant1">
        <label>40</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Lorant</surname><given-names>V</given-names></name><name name-style="western"><surname>Deliege</surname><given-names>D</given-names></name><name name-style="western"><surname>Eaton</surname><given-names>W</given-names></name><name name-style="western"><surname>Robert</surname><given-names>A</given-names></name><name name-style="western"><surname>Philippot</surname><given-names>P</given-names></name><etal/></person-group>             <year>2003</year>             <article-title>Socioeconomic inequalities in depression: a meta-analysis.</article-title>             <source>Am J Epidemiol</source>             <volume>157</volume>             <fpage>98</fpage>             <lpage>112</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Isomets1">
        <label>41</label>
        <element-citation publication-type="other" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Isometsä</surname><given-names>E</given-names></name></person-group>             <year>2008</year>             <article-title>Masennushäiriöt [Depressive disorders].</article-title>             <person-group person-group-type="editor"><name name-style="western"><surname>Lönnqvist</surname><given-names>J</given-names></name><name name-style="western"><surname>Heikkinen</surname><given-names>M</given-names></name><name name-style="western"><surname>Henriksson</surname><given-names>M</given-names></name><name name-style="western"><surname>Marttunen</surname><given-names>M</given-names></name><name name-style="western"><surname>Partonen</surname><given-names>T</given-names></name></person-group>             <source>Psykiatria [Psychiatry, in Finnish]</source>             <publisher-loc>Jyväskylä</publisher-loc>             <publisher-name>Gummerus Oy, Duodecim</publisher-name>             <fpage>157</fpage>             <lpage>195</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Ettner1">
        <label>42</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Ettner</surname><given-names>SL</given-names></name><name name-style="western"><surname>Frank</surname><given-names>RG</given-names></name><name name-style="western"><surname>Kessler</surname><given-names>RC</given-names></name></person-group>             <year>1997</year>             <article-title>The impact of psychiatric disorders on labor market outcomes.</article-title>             <source>Ind Labor Rel Rev</source>             <volume>51</volume>             <fpage>64</fpage>             <lpage>81</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Crouter1">
        <label>43</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Crouter</surname><given-names>AC</given-names></name><name name-style="western"><surname>Bumpus</surname><given-names>MF</given-names></name><name name-style="western"><surname>Head</surname><given-names>MF</given-names></name><name name-style="western"><surname>McHale</surname><given-names>SM</given-names></name></person-group>             <year>2001</year>             <article-title>Implications of overwork and overload for the quality of men's family relationships.</article-title>             <source>J Marriage Family</source>             <volume>63</volume>             <fpage>404</fpage>             <lpage>416</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Jansen1">
        <label>44</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Jansen</surname><given-names>NW</given-names></name><name name-style="western"><surname>Kant</surname><given-names>I</given-names></name><name name-style="western"><surname>Nijhuis</surname><given-names>FJ</given-names></name><name name-style="western"><surname>Swaen</surname><given-names>GM</given-names></name><name name-style="western"><surname>Kristensen</surname><given-names>TS</given-names></name></person-group>             <year>2004</year>             <article-title>Impact of worktime arrangements on work-home interference among Dutch employees.</article-title>             <source>Scand J Work Environ Health</source>             <volume>30</volume>             <fpage>139</fpage>             <lpage>148</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Rissler1">
        <label>45</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Rissler</surname><given-names>A</given-names></name></person-group>             <year>1977</year>             <article-title>Stress reactions at work and after work during a period of quantitative overload.</article-title>             <source>Ergonomics</source>             <volume>20</volume>             <fpage>13</fpage>             <lpage>16</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Lundberg1">
        <label>46</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Lundberg</surname><given-names>U</given-names></name><name name-style="western"><surname>Hellström</surname><given-names>B</given-names></name></person-group>             <year>2002</year>             <article-title>Workload and morning salivary cortisol in women.</article-title>             <source>Work Stress</source>             <volume>16</volume>             <fpage>356</fpage>             <lpage>363</lpage>          </element-citation>
      </ref>
      <ref id="pone.0030719-Harkonmki1">
        <label>47</label>
        <element-citation publication-type="journal" xlink:type="simple">             <person-group person-group-type="author"><name name-style="western"><surname>Harkonmäki</surname><given-names>K</given-names></name><name name-style="western"><surname>Silventoinen</surname><given-names>K</given-names></name><name name-style="western"><surname>Levälahti</surname><given-names>E</given-names></name><name name-style="western"><surname>Pitkäniemi</surname><given-names>J</given-names></name><name name-style="western"><surname>Huunan-Seppälä</surname><given-names>A</given-names></name><etal/></person-group>             <year>2008</year>             <article-title>The genetic kiability to disability retirement: A 30-year follow-up study of 24,000 Finnish twins.</article-title>             <source>PloS ONE</source>             <volume>3</volume>             <fpage>e3402</fpage>          </element-citation>
      </ref>
    </ref-list>
    
  </back>
</article>