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Title: Reliability and validity of the Center for Epidemiologic Studies- Depression scale in 1 screening for depression among HIV infected and uninfected pregnant women attending 2 antenatal services in northern Uganda 3 4 Authors: Barnabas K. Natamba1, 2*, Thomas O. Oyok3, Angela Arbach4, Jane Achan5, Shibani 5 Ghosh6, Saurabh Mehta1, Rebecca J. Stoltzfus1, Jeffrey K. Griffiths6, 7, Sera L. Young1 6 7 Author affiliations: 1Division of Nutritional Sciences, Cornell University, Ithaca, NY 14850, 8 USA. 2Department of Public Health, Faculty of Medicine, Gulu University. Gulu. Uganda. 9 3Department of Mental Health, Faculty of Medicine, Gulu University. Gulu. Uganda. 4Weill 10 Cornell Medical College. New York. NY 10021. USA. 5Department of Pediatrics and Child 11 Health, Makerere University. Kampala. Uganda. 6Friedman School of Nutrition Science and 12 Policy. School of Medicine, Veterinary Medicine, Nutrition and Engineering. Tufts University, 13 Boston, MA 02155. USA. 7Department of Public Health and Community Medicine. School of 14 Medicine, Veterinary Medicine, Nutrition and Engineering. Tufts University. Boston. MA 02155. 15 USA. 16 17 *Corresponding author: Division of Nutritional Sciences, Cornell University, Ithaca. N.Y. 18 14850. Email bkn6@cornell.edu; Fax: 1-607-255-1033 ; Tel: +256782415501 19 20 21 22 23 24 25

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Abstract 26 Introduction: Given the paucity of data on the burden and measurement of depression in 27 pregnant women living in high HIV burden resource poor settings, we aimed at determining the 28 reliability and validity of the Center for Epidemiologic Studies Depression (CES-D) scale as a 29 screening tool for depression among pregnant Ugandan women of mixed HIV status. 30 Methods: 123 (36 HIV-infected and 87 HIV-uninfected) pregnant women receiving antenatal 31 care at Gulu Regional Referral Hospital were recruited in their first and second trimesters and 32 underwent two consecutive interviews: (1) a screening interview using the CES-D scale and (2) 33 a diagnostic Mini-International Neuropsychiatric Interview (MINI) for current major depressive 34 disorder (MDD) performed by a psychiatrist. We employed measures of internal consistency 35 (Cronbachs alpha), criterion validity (Area Under the Receiver Operating Characteristic Curve 36 (AUROC), sensitivity (Se) and positive predictive value (PPV)) and construct validity (unadjusted 37 bivariate analyses between CES-D scores and maternal HIV status, food insecurity score, and 38 tertile of per capita household income) to evaluate the reliability and accuracy of the CES-D 39 scale. 40 Results: 35.8% of the respondents were diagnosed to be experiencing a current MDD as 41 defined by the MINI. The CES-D had high internal consistency (Cronbachs alpha=0.92), 42 demonstrated good discriminatory ability in detecting MINI-defined current MDDs 43 (AUROC=0.82) and had an optimum cut-off score for screening for current MDDs of 15 (Se= 44 84.1%, PPV=77.2%). Lastly, the CES-D showed strong construct validity with HIV infected 45 women, poorer women, or more food insecure women scoring higher on this scale than their 46 better off counterparts. 47 Conclusions: The CES-D is a suitable scale for screening for depression among pregnant 48 women attending antenatal services in Uganda. 49 Key words: pregnancy, major depression, prenatal depression, northern Uganda 50

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Introduction 51 In the two decades since the first Global Burden of Disease (GBD) report was released 52

in 1990, the impacts that HIV infection and major depressive disorders (MDDs) have had on 53 medical and public health systems have changed profoundly. The 2010 GBD report indicates 54 that HIV infection has risen from being the 33rd to the 5th contributor to the global burden of 55 disease (Murray et al. 2013). At the same time, the disease burden attributable to MDDs has 56 risen from being the 15th to the 11th. Whereas there has been a surge in information and 57 strategies for managing or preventing HIV infection, practical strategies for managing MDDs are 58 still very limited, particularly in resource poor settings. 59 60

In various settings in Sub-Saharan Africa, prevalence rates of MDDs among adults living 61 with HIV ranging from 71.3% in Zambia (Chishinga et al. 2011) to 47% in Uganda (Kaharuza et 62 al. 2006), 43.7% in South Africa (Myer et al. 2008), and 30% in Zimbabwe (Chibanda et al. 63 2010) have been documented. A number of biological factors, psychosocial variables, and 64 mental history or comorbid psychiatric illnesses may help explain why persons with HIV are at a 65 higher risk of depression (Arseniou et al. 2014). Importantly, depression has been associated 66 with increased rates of HIV disease progression and mortality (Antelman et al. 2007), inequity in 67 decision-making and relationship power among heterosexual couples (Hatcher et al. 2012), and 68 AIDS related stigma (Simbayi et al. 2007). Whereas reports indicate that as many as 30% of 69 persons living with HIV/AIDS develop depressive disorders during the course of their illness 70 (Ciesla et al. 2001; Nakimuli-Mpungu et al. 2011), most studies reporting the prevalence or 71 incidence of depressive symptoms among people living with HIV (PLHIV) have not compared 72 this to HIV negative persons. In one small cross-sectional study, where the prevalence of 73 depression in newly tested HIV positive pregnant women were compared to that of HIV negative 74 women, authors did not find an association between HIV infection status and depression 75

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(Rochat et al. 2006). Understanding the prevalence and drivers of MDDs among HIV infected 76 and uninfected persons need further clarification so as to enable mental health providers and 77 planners in resource poor settings better target appropriate care for those that are affected 78 most. 79 80

In addition to the importance of the interaction between HIV infection and MDDs in areas 81 with high HIV burden, it is important to recognize that the two diseases disproportionately affect 82 women and most likely this happens during the perinatal period (Arseniou et al. 2014; Bennet et 83 al. 2004). Research from both resource-poor (Roberts et al. 2008; Olley et al. 2004) and 84 resource-rich (Hwu et al. 1996) settings indicate that women are more likely than men to report 85 a high prevalence of depressive symptoms. Biological, sociocultural and psychological factors 86 may explain why women are at greater risk of HIV infection (Wingood & DiClemente 2000) 87 and/or depression (Nolen-Hoeksema 2006) than men. 88 89

Given the coexistence of HIV infection and MDDs in SSA, combining screening for 90 depression and HIV in primary care settings targeting women may be an efficient means to use 91 limited resources, especially if there is potential for treatment and/or referral following 92 administration of screening tests. Indeed, in 2010, the WHO developed the mental health Gap 93 Action Program (mhGAP) that recommends interventions to address mental health problems in 94 resource poor settings with limited specialist care for such problems (WHO 2010). Antenatal 95 care (ANC) clinics in regional, district, and lower level primary health care centers in resource-96 poor settings offering services to prevent the vertical transmission of HIV may also provide entry 97 points for the identification, treatment and referral of pregnant women suffering from depression. 98 99

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In order to appropriately identify participants with or at risk for depression, theres need 100 for using a reliable and valid screening tool. A review of depression screening tools used in low 101 and middle income countries did not recommend any specific instrument, as no single 102 depression screening tool was found to be superior to others (Akena et al. 2012). The Center for 103 Epidemiologic Studies-Depression (CES-D) (Radloff, 1977) is an attractive scale for screening 104 for depression because it takes a short period of time to administer, can be administered after 105 only a short training period, and covers all of the common symptoms of major depression, i.e. 106 depressive mood, feelings of guilt and worthlessness, psychomotor retardation, loss of appetite, 107 and sleep disturbance. The CES-D assesses 20 items designed to measure self-reported 108 depressive symptoms in the prior week. Each of the 20 items is assigned a value of 0-3, with 109 four items positively worded and reverse scored. The total score is computed by adding each of 110 the 20 items, such that the range is 0 to 60. A score of >16 in the general US population 111 suggests the presence of a major depressive disorder. Elsewhere, the cutoff will depend on the 112 population studied and the extent to which each of the 20 items are prevalent in such a 113 population. Thus, it is important that the scale be validated before it is used in a non-US 114 population. 115 116

Within sub-Saharan Africa, the CES-D has been validated in Zambia (Chishinga et al. 117 2011) and South Africa (Myers et al. 2008) by comparing results of the CES-D to those obtained 118 using the gold standard for depression assessment, the depression module of the Mini-119 International Neuropsychiatric Interview (MINI). The MINI is a short, structured diagnostic 120 interview that was developed in 1990 by psychiatrists and clinicians in the United States and 121 Europe for DSM-IV psychiatric disorders (Sheehan et al. 2006). Although the CES-D has been 122 used among PLHIV in Uganda (Kaharuza et al. 2006 & Nakasujja et al. 2010), it has actually not 123 been validated there. Further, all of these studies occurred among HIV-infected adults only, 124

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making it difficult to compare findings from such populations to those of HIV negative 125 populations. Therefore, we aimed at assessing the reliability, construct and criterion validity of 126 the CES-D as a measure of depression in both HIV-infected and uninfected pregnant women in 127 northern Uganda. 128 129 130 Materials and methods 131 132 Design, setting and participants 133

Data were collected between 10th October 2012 and 21st December 2012, within the 134 context of the Prenatal Nutrition and Psychosocial Health Outcomes Study (PreNAPs), a 135 longitudinal cohort study aimed at describing and comparing nutritional and psychosocial 136 exposures and outcomes among HIV infected and uninfected pregnant women attending ANC 137 services in northern Uganda. 138 139

Participants were recruited from the antenatal care (ANC) clinic of Gulu Regional 140 Referral Hospital (GRRH) in Gulu, northern Uganda, a busy primary care clinic at which more 141 than 400 initial antenatal visits occur monthly. As at other public medical facilities in Uganda, all 142 services at GRRH including medications, care for pregnant women with HIV, etc. are offered 143 free of charge. 144 145

Both HIV infected and uninfected pregnant women presenting at ANC between 10 and 146 26 weeks of gestation and who resided within 30 KM of GRRH were invited to participate. 147 Consistent with Ugandan national policy, all HIV infected women were receiving prophylactic 148 ARVs. Two women whose HIV status could not be ascertained after they were interviewed were 149 excluded. HIV infected women were oversampled to achieve a ratio of 1 HIV infected: 2 HIV 150

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uninfected participants, a proportion that is much higher than the 10.3% age adjusted 151 prevalence of HIV observed at various ANC clinics in northern Uganda (Fabian et al. 2007). 152 153 Data collection and analysis 154

Before interviews began, all study instruments were translated by local research staff 155 into Acholi and Langi, the two predominant and similar Luo languages in the study communities. 156 The questionnaires were back-translated into English by the same team and discrepancies in 157 conceptual and semantic equivalence were resolved through discussion involving all the 158 translators, the research assistants, and the GRRH psychiatrist. 159 160

The CES-D was administered by research assistants after a baseline health and 161 demographics data were collected. Then, on the same day, respondents underwent a diagnostic 162 interview by the GRRH psychiatrist (TOO) using the MINI-depression module. The MINI 163 diagnostic interview was conducted by a psychiatrist who was blinded to the results of the CES-164 D screening interview. 165 166

Study participants were categorized into cases and non-cases of depressed patients 167 based on the MINI outputs for currently experiencing a MDD. Median total scores on the CES-D 168 were then compared against the MINI-defined diagnosis of current MDD using the Wilcoxon 169 rank-sum test. We used multiple methods to determine the reliability (or internal consistence), 170 criterion and construct validity of the CES-D. Firstly we assed the reliability of the entire CES-D 171 scale using the Cronbachs test for internal consistency. Cronbachs alpha coefficients of 0.7 or 172 greater were considered to be reliable (Santos 1999). Secondly, we determined the CES-Ds 173 criterion validity i.e. the extent to which measurements obtained using the CES-D concurred with 174 those determined with an established diagnostic test or gold standard (Porta 2008 ), by 175

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comparing scores on the CES-D with psychiatrist administered MINI outputs. We used a non-176 parametric method, area under the receiver operating characteristic curve (AUROC) analysis, to 177 estimate the diagnostic accuracy of the CES-D. The optimum cut-off scores consistent with 178 current MDD were determined for this population based on the psychiatric assessment. The cut-179 off score that maximized sensitivity and positive predictive value (PPV) was selected. 180 181

Lastly, we determined the construct validity, i.e. the extent to which a given 182 measurement corresponds to theoretical concepts (constructs) concerning the phenomena 183 under study (Porta 2008 & Straus 2009), by conducting bivariate analyses to determine 184 whether, as we had hypothesized, CES-D scores were higher for HIV infected, poorer, or food 185 insecure pregnant women. Maternal HIV status was determined at the ANC clinic following 186 Government of Uganda HIV counseling and testing guidelines and prior to enrollment into this 187 study. Wealth was operationalized based on household per capita income obtained by summing 188 the estimated monthly income of all income earning household members and dividing this figure 189 by the number of all household members including the respondent. Given the non-normal 190 distribution of per capita household income data, we used tertiles of household per capita 191 income as the independent variable in the bivariate model with CESD scores as the outcome 192 variable. Individual level FI was assessed using the Individually-focused Food Insecurity Access 193 Scale (IFIAS)- a modified version of the Household Food Insecurity Access Scale (HFIAS; 194 Coates et al. 2007). Unlike the HFIAS, and given potential for intra-household differences in the 195 experience of food insecurity, the IFIAS assesses perceptions of inadequate access to food at 196 the level of the individual. IFIAS scores and categories were derived using the methods 197 recommended by Coates et al. (2007). 198 199

Data were analyzed using Stata 12 (College Station, Texas, USA). 200

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201 Ethical considerations 202

The study protocol was approved by Cornell University Institutional Review Board, Gulu 203 University Institutional Review Committee and the Ugandan National Council for Science and 204 Technology. Written informed consent was obtained from all study subjects before enrollment. 205 Patients identified to be severely depressed, as per psychiatric assessment using the MINI-206 Depression section, were referred for further assessment and treatment at GRRH. 207 208 Results 209 210 Characteristics of the study participants 211

One hundred and thirty pregnant women were approached to participate in the MDD 212 sub-study of Pre-NAPs, and 125 (96.2%) of them consented to participate. Nonresponse was 213 mainly due to lack of time (n=5). Of the 125 participants who agreed to take part in the study, 214 two did not complete the entire interview due to lack of time, and the rest (36 HIV-infected and 215 87 HIV-uninfected) participated in both the CES-D and MINI. 216

217 The median age of study participants was 23 years, a majority (87.8%) were married or 218

living in stable heterosexual relationships and spoke either Acholi or Langi (94.3%). Generally, 219 study participants were of low socioeconomic status, as 53.7% had only primary education or 220 less, 50.4% described their main occupation as housewives, 52.0% perceived themselves to be 221 severely food insecure and the median monthly household income per capita was 50,000 222 Uganda shillings (approximately 20 US dollars). Further, 13% (16 participants) mentioned not 223 having any household income. 224 225

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Internal consistency and validity of the CES-D scale 226 CESD scores ranged between 0 and 57 with a mean (SD) of 17.1 (13.8). On the other 227 hand, 35.8% of participants qualified for MINI diagnosed major depressive disorder. The internal 228 consistency of the CES-D was high (Cronbachs alpha =0.92). As expected, CES-D scores were 229 higher among MINI-defined current MDD cases than non-MDD cases (Figure 1, P

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Criterion and construct validity. The AUROC, a measure of the accuracy of 251 discriminating between two groups, was 0.82 for differentiating women with current MDDs from 252 those without based on their CES-D score. Our result is similar to AUROC values reported from 253 validation studies conducted among HIV infected persons in South Africa (Myers et al 2008; 254 AUROC=0.76) and TB and HIV patients in Zambia (Chishinga et al 2011; AUROC=0.78). Per 255 our expectations, we observed higher scores on CES-D by women who were HIV infected, in 256 the lower tertile of per capita household income, or perceived themselves to be more food 257 insecure (with higher IFIAS scores) than their better off counterparts. 258

A highly sensitive test is needed for screening examinations in routine clinical care to 259 identify potential cases, while a highly specific test is preferred for confirmatory purposes. Good 260 screening tests are expected to minimize the number and proportion of false positive results, 261 and as such have a high positive predictive value, or PPV. A test with high PPV is in part valued 262 because it reduces the expense and risks related to further evaluation of false positive tests 263 especially in settings with limited resources (Patel et al. 2008). In this study, we found that the 264 CES-D with a cut-off score of 15 achieved the goal of suitably high sensitivity and moderate to 265 high PPV for the detection of MDD (Sensitivity 84.1%, PPV 77.2%). The cut-off score of 15 is 266 comparable to the cut-off score of 16 suggested by Radloff for the general US population 267 (Radloff 1977). In lower lever primary care settings with limited access to specialized mental 268 health workers capable of diagnosing prenatal depression, a cut-off score of 15 that maxims 269 both sensitivity and positive predictive value is recommended. However, for higher-level hospital 270 settings with fully equipped mental health departments and potential for referral to specialized 271 depression care, a CES-D score of 16 may be used during the screening stage, provided the 272 resultant large number of false positive results are reviewed by qualified mental health 273 providers. 274

275

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Our study has some limitations. The generalizability of our findings may be limited. First, 276 we oversampled HIV infected women, and it is possible that the CES-D performs differently 277 among HIV infected and HIV uninfected pregnant women. However, the numbers of HIV-278 infected women (n=36) compared to HIV-uninfected participants (n=87) in this study was too 279 small to separately analyze the diagnostic accuracy of the CES-D by womens HIV status. 280 Further, the study was done at a higher-level health facility, and pregnant women attending Gulu 281 Regional Referral Hospital may differ in terms of education, rural vs. urban residence, and 282 access to information from those in the general northern Uganda population, such that our 283 findings arent more widely generalizable. 284

In spite of the above stated limitations, our larger PreNAPs study cohort is designed to 285 have strong internal validity for comparing differences in psychosocial health variables between 286 HIV infected and uninfected pregnant women. To achieve strong external validity, future studies 287 could aim to assess the diagnostic accuracy of the CES-D in the general northern Uganda 288 population, taking a relatively large sample that can permit separate assessment of this 289 screening tools validity when used in HIV infected and uninfected pregnant women. In the short 290 term, interventions to mitigate prenatal depression in this vulnerable pregnant population are 291 needed given the high prevalence and potential impacts of depression on pregnant women and 292 their infants. 293

Given the high prevalence of psychiatrist-diagnosed depression in this population 294 (35.8%) it is worthwhile contemplate interventions or modifications to current mental health 295 screening policies to mitigate this disorder. Most Ugandan health facilities at regional referral 296 hospital level have mental health departments but many opportunities for screening, referral and 297 follow-up of affected patients are usually missed due to limited staffing, remuneration, and other 298 incentives to motivate and retain skilled health workers. It is likely that screening of pregnant 299 women with the CES-D may help to identify women who will benefit from treatment for 300

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depression and the CESD is a brief, valid and simple screening tool to adopt. Although the 301 current national antenatal care guidelines are silent about integrating screening for mental 302 health problems such as depression into pregnancy care, the high prevalence of MDDs 303 observed in this study may require revision of existing ANC guidelines to incorporate screening 304 for depression at least at the first of, if not all, the four antenatal care visits. The WHO focused 305 antenatal care guidelines (WHO 2001) recognize the importance of integrating mental health 306 activities into ANC programs and if used together with the WHO mhGAP (WHO, 2010) for 307 resource poor settings, a number of primary care mental health interventions targeting pregnant 308 women could be undertaken. 309 310 Conclusions 311

The CES-D scale administered by non-psychiatrists, when compared to a psychiatrist 312 administered structured MINI interview for prenatal depression, was found to be a reliable and 313 valid screening tool in a population of women with and without HIV attending an antenatal clinic. 314 The CES-D can easily be administered by nurses and midwives employed by ANC clinics and 315 given the high prevalence (35.8%) of psychiatrist diagnosed depression in this population, the 316 CES-D could be used to screen this population for the treatment of depressive disorders. 317 However, further research is needed to assess the time demands and overall programmatic 318 experience of integrating care for depression into current ANC service delivery platforms. 319 320 Acknowledgements 321

The authors would like to acknowledge the support of the Gulu Regional Referral 322 Hospital administration in allowing us to conduct the study at their hospitals ANC clinic and 323 providing space for the research team within the hospital buildings. We would also like to thank 324 the mental health staff at the Mental Health Unit of Gulu Regional Referral Hospital, especially 325

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Ms. Mary Grace Lanyero, for their willingness to provide appropriate care for pregnant women 326 diagnosed with current MDD in this study. We also thank Ms. Sophie Becky Ajok, the 327 coordinator for prevention of mother to child transmission of HIV (PMTCT) services at GRRH 328 antenatal clinic for helping us recruit both HIV infected and uninfected pregnant women for this 329 study. The research assistants involved in data collection including Stella Adoch, Hillary Kilama, 330 Gladys Akello, and Eunice Asiimwe are also highly appreciated. Lastly, we warmly thank the 331 mothers for the time they generously gave to the study. 332 333 Funding 334

Funding was provided by the USAID Feed the Future Innovation Laboratory for 335 Collaborative Research in Nutrition for Africa (Award Number AID-OAA-L-10-00006 to Tufts 336 University). The content of this paper is solely the responsibility of the authors and does not 337 necessarily represent the official views of USAID. SLY was supported by K01 MH098902 from 338 the National Institute of Mental Health. The content is solely the responsibility of the authors and 339 does not necessarily represent the official views of the National Institute of Mental Health or the 340 National Institutes of Health. 341 342 Author contributions 343

BKN, SLY, JA, SM, RJS, and JKG conceived and designed study. TOO conducted MINI 344 Depression diagnostic interviews. BKN and AA supervised data collection. BKN, JA, SM, JKG, 345 and SLY did the data analysis. BKN wrote the first draft of the manuscript. All authors 346 contributed to the interpretation of data, revising the manuscript critically for important 347 intellectual content; and final approval of the version to be published. Lastly, we gratefully 348 acknowledge Patsy Brannon for comments on earlier drafts. 349 350

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Competing interests 351 The authors declare that they have no conflict of interest. 352

353 References 354 Akena D, Joska J, Obuku EA, Amos T, Musisi S, Stein DJ: Comparing the accuracy of brief 355 versus long depression screening instruments which have been validated in low and middle 356 income countries: a systematic review. BMC Psychiatry 2012, 12:187. 357 358 Antelman, G., Kaaya, S., Wei, R., Mbwambo, J., Msamanga, G. I., Fawzi, W. W., & Fawzi, M. C. 359 S. (2007). Depressive symptoms increase risk of HIV disease progression and mortality among 360 women in Tanzania. JAIDS Journal of Acquired Immune Deficiency Syndromes, 44(4), 470-477. 361 362 Arseniou, S., Arvaniti, A. and Samakouri, M. (2014), HIV infection and depression. Psychiatry 363 and Clinical Neurosciences, 68: 96109. doi: 10.1111/pcn.12097 364 365 Bennett, H. A., Einarson, A., Taddio, A., Koren, G., & Einarson, T. R. (2004). Prevalence of 366 depression during pregnancy: systematic review. Obstetrics & Gynecology, 103(4), 698-709. 367 368 Chibanda D, Mangezi W, Tshimanga M, Woelk G, Rusakaniko P, Stranix-Chibanda L, Midzi S, 369 Maldonado Y, Shetty AK: Validation of the Edinburgh Postnatal Depression Scale among 370 women in a high HIV prevalence area in Urban Zimbabwe. Archives of Womens Mental Heath 371 2010, 13: 201-206. 372 373

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Chishinga N, Kinyanda E, Weiss HA, Patel V, Ayles H, Seedat S: Validation of brief screening 374 tools for depressive and alcohol use disorders among TB and HIV patients in primary care in 375 Zambia. BMC Psychiatry 2011, 11(1):75. 376 377 Ciesla JA, Roberts JE. Meta-analysis of the relationship between HIV infection and the risk for 378 depressive disorders. Am J. Psychiatry 2001, 158: 725-730 379 380 Coates, J., Swindale, A., & Bilinsky, P. (2007). Household Food Insecurity Access Scale 381 (HFIAS) for measurement of food access: indicator guide.Washington, DC: Food and Nutrition 382 Technical Assistance Project, Academy for Educational Development. 383 384 Fabiani M, Nattabi B, Pierotti C, Ciantia F, Opio AA, Musinguzi J, et al. HIV-1 prevalence and 385 factors associated with infection in the conflict-affected region of North Uganda. Confl Health. 386 2007; 1:3. 387 388 Hatcher, Abigail M., Alexander C. Tsai, Elias Kumbakumba, Shari L. Dworkin, Peter W. Hunt, 389 Jeffrey N. Martin, Gina Clark, David R. Bangsberg, and Sheri D. Weiser. "Sexual Relationship 390 Power and Depression among HIV-Infected Women in Rural Uganda." PloS one 7, no. 12 391 (2012): e49821. 392 393 Hwu HG, Joyce PR, Karam EG, Lee CK, Lellouch J, Wickramaratne PJ, ... & Yeh EK. Cross-394 national epidemiology of major depression and bipolar disorder. JAMA 1996, 276(0): 293-299 395 396

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Sheehan DV, Lecrubier Y, Harnett-Sheehan K: The Mini International Neuropsychiatric Interview 446 (M.I.N.I.): The Development and Validation of a Structured Diagnostic Psychiatric Interview. J 447 Clin Psychiatry 1998, 20:2233. 448 449 Simbayi, L. C., Kalichman, S., Strebel, A., Cloete, A., Henda, N., & Mqeketo, A. (2007). 450 Internalized stigma, discrimination, and depression among men and women living with 451 HIV/AIDS in Cape Town, South Africa. Social science & medicine, 64(9), 1823-1831. 452 453 Strauss ME, Smith GT. Construct Validity: Advances in Theory and Methodology. Annu. Rev. 454 Clin. Psychol. NIH Public Access; 2009 Apr;5(1):125 455 456 World Health Organisation (WHO). 2001. WHO Antenatal Care Randomized Trial: Manual for 457 the Implementation of the New Model. Geneva. WHO. WHO/RHR/01.30. 458 459 World Health Organisation (WHO): mhGAP intervention guide for mental, neurological and 460 substance use disordered in non-specialised health settings. Geneva, Switzerland. WHO Press 461 2010 462 463 Wingood GM, & DiClemente RJ. Application of the theory of gender and power to examine HIV-464 related exposures, risk factors, and effective interventions for women. Health education & 465 behavior, 2000, 27(5): 539-565. 466 467 468 469

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Table 1. Characteristics of 123 pregnant participants in the study to validate the Center for 470 Epidemiologic Studies-Depression (CES-D) scale 471 Variable Parameter/category Total (N=123) Socio-demographics Participants age, years Median (IQR) 23 (20-27) Marital status, (%) Single 6.5

Married/cohabiting 87.8 Widowed 2.4 Separated 3.3

Education, (%) No education 4.1 Primary 49.6 O level only 31.7 A levels or higher 14.6

Occupation, (%) Housewife 50.4 Farmer 8.9 Trader 22.8 Formally employed 13.0 Other 4.9

Language, (%) Acholi 90.2 Langi 4.1 Other 5.

Gestational age at interview, weeks Median (IQR) 19 (15-21) HIV-infected, (%) Positive 29.3 Monthly household income per capita (in Uganda Shillings (UGX) and US dollars (USD)

Median (IQR) UGX, 50,000 (25,000-120,000); USD, 20 (10-48)

IFIAS score Median (IQR) 9 (5-13) IFIAS category, (%) Food secure 3.3

Mild food insecure 20.3 Moderate food insecure 24.4 Severe food insecure 52.0

CES-D Score Mean (SD) 17.1(13.8) Range (Min-Max) 55 (0-55)

MINI-defined current major depressive disorder (%)

Yes 35.8

472 473 474 475

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Table 2. Unadjusted bivariate associations between CES-D scores and selected variables 476 (N=123) 477 Factor Category Unadjusted coefficient P value

HIV status HIV negative Reference

HIV positive 8.64272 0.001

IFIAS score N/A 1.029777 0.000

Per capita monthly income First tertile Reference

Second tertile -5.585366 0.066

Third tertile -6.644512 0.030

478 479 480 481 482 483 484 485 486 487 488 489 490 491 492

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Figure 1. Median CES-D Scores by Psychiatric Diagnosis using the MINI 493

CES-

D Sc

ore

05

1015

20p 5

0 of c

esds

core

No Yes

Current MDD diagnosis by MINI depression derived outputs

494 495 496 497 498 499 500 501 502 503 504

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Figure 2. Receiver Operating Characteristic Curve for the CES-D total scores for diagnosis of 505 current MDD 506

507 508 509 510 511 512 513 514 515 516 517 518 519 520

521 522 523 524 525 526 527 528

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0.75

0.751.00

1.00

1.001 - Specificity

1 - Specificity

1 - SpecificityArea under ROC curve = 0.8277

Area under ROC curve = 0.8277

Area under ROC curve = 0.8277

Feb 6 24

Figure 3. Sensitivities and positive predictive values for the CES-D by cut-off scores for 529 diagnosis of current MDD 530 531

Se/P

PV

TOTAL CES-D SCORES

532