Symptoms of depression and rates of neurocognitive impairment in HIV positive patients in Beijing, China

Journal of Affective Disorders 162 (2014) 89–95

Contents lists available at ScienceDirect

Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad

Research report

Symptoms of depression and rates of neurocognitive impairment in HIV positive patients in Beijing, China R. Dwyer a,n, L. Wenhui b, L. Cysique c, B.J. Brew d, L. Lal e, P. Bain f, S. Wesselingh g, E.J. Wright e,h,i a

School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, 99 Commercial Road, Melbourne 3004, Australia Ditan Hospital, Beijing, China c University of New South Wales and Neuroscience Research Australia, Sydney, Australia d University of New South Wales and Department of Neurology, St. Vincent's Hospital and St. Vincent's Centre for Applied Medical Research, Sydney, Australia e The Burnet Institute, Melbourne, Australia f Department of Neurology, St. Vincent's Hospital, Sydney, NSW, Australia g South Australia Health and Medical Research Institute, Adelaide, Australia h Department of Infectious Diseases, Monash University, Melbourne, Australia i Department of Infectious Diseases, The Alfred Hospital, Melbourne, Australia b

art ic l e i nf o

a b s t r a c t

Article history: Received 1 July 2013 Received in revised form 15 March 2014 Accepted 17 March 2014 Available online 31 March 2014

Background: In China an estimated 780,000 people are living with HIV (PLWH). In high-income countries PLWH are at increased risk of depression, with subsequent adverse consequences for quality of life, and HIV-related morbidity and mortality. There are few data from low-and middle-income countries. The aims of this country-specific investigation of the Asia Pacific NeuroAIDS Consortium (APNAC) study were to establish the point prevalence, severity and HIV-related and non-HIV related correlates of depressive symptoms in PLWH, in Beijing, China. Method: PLWH attending an outpatient clinic at Ditan Hospital, Beijing were recruited consecutively. Data sources were: study-specific questions about demographic characteristics, and health behaviours, the Centre for Epidemiological Studies Depression Scale (CES-D), the World Health Organisation SelfReporting Questionnaire (SRQ-20) translated into Mandarin and administered as structured individual interviews, and a screen battery of four standard neuropsychological tests. Results: In total 50/51 (98%) eligible patients agreed to participate. Overall 28% scored CES-D Z16 or SRQ20 Z 10 and 18% in these clinical ranges on both measures; 69% were classified as being neuropsychologically impaired (scoring below 1 SD of the control value on at least two tests). Higher depressive symptom scores were associated with lower education, alcohol overuse and diminished motor ability (all po0.05), but not neuropsychological impairment Conclusion: Clinically significant depressive symptoms among this cohort of PLWH in Beijing occurred at 5 times the rate reported among a general Chinese urban population. No participants had been assessed for depression prior to the study and none were treated, indicating that consideration of psychological morbidity and its consequences for health behaviours should be incorporated into routine HIV care in China. & 2014 Elsevier B.V. All rights reserved.

Keywords: Depression People living with HIV Neurocognitive impairment China

1. Background Infection with the Human Immunodeficiency Virus (HIV) incurs a significant health and economic burden to individuals and their countries at a global level. In Asia and the Pacific region there are approximately 4.8 million people living with HIV infection (PLWH) and although several countries in this region have halved their HIV incidence rates over the past decade there are still approximately

n

Corresponding author. Tel.: þ 61 3 9903 0555. E-mail address: [email protected] (R. Dwyer).

http://dx.doi.org/10.1016/j.jad.2014.03.038 0165-0327/& 2014 Elsevier B.V. All rights reserved.

300,000 regional people newly infected with HIV annually (Unaids, 2013). In high income countries depression occurs in approximately 20– 30% of HIV positive (HIVþ) populations (Pence et al., 2012) and is associated with higher mortality (Ickovics et al., 2001; Cook et al., 2004), poorer adherence to antiretroviral regimens (Ammassari et al., 2004; Kleeberger et al., 2004; Gordillo et al., 1999), reduced day-to-day functional capacities (Sherbourne et al., 2000) and may lead to an increase in risk-taking behaviour (Nyamathi et al., 1995; Rogers et al., 2003; Hutton et al., 2004; Williams and Latkin, 2005). Hence in HIVþ populations untreated depression carries the attendant risks of increased HIV transmission and HIV disease burden within the

90

R. Dwyer et al. / Journal of Affective Disorders 162 (2014) 89–95

community. However in HIVþ populations depression can be treated and managed well (Markowitz et al., 1998; Treisman et al., 2001; Hu, 2004) which is in turn associated significantly with achieving HIV virological suppression, presumably through greater medication adherence (Tsai et al., 2010). Most research on depression in HIVþ populations has been undertaken in high-income countries and there are relatively few data on the mental health of HIV positive people in lowand lower-middle income countries including China. Jin et al. interviewed 28 people living with HIV in either Beijing or a rural province of China and reported a lifetime prevalence of Major Depression of 79% of whom only 2 participants (9%) were being treated. More recently Su et al. (2013) examined 258 people living with HIV recruited from methadone and HIV clinics and the CDC registries in two Chinese cities, Henyang and Shenzhen. They also found a high lifetime prevalence of depression among participants (71.9%). There has also been some sampling of subgroups of HIV infected Chinese populations such as HIV infected blood donors where lifetime incidence of major depression was found to be 14% (Atkinson et al., 2011). These findings compare to rates of depression as low as 1.8–3.2% in the general Chinese population (Shen et al., 2006; Lee et al., 2009; Ma et al., 2009). These rates are much lower than those reported in highincome countries. This discrepancy has been attributed to two factors. First, the stigma associated with a diagnosis of depression which may lead to reporting of somatic rather than emotional symptoms of psychological distress (Parker et al., 2001). Second, low reported rates of mental disorder may reflect low actual rates of this condition in a population which may have particular cultural protective factors including a tradition of stoicism, greater family support systems and lower levels of urbanisation than in high-income countries (Parker et al., 2001). However with the social and political changes associated with globalisation such as smaller family size, reduced social support associated with rural to urban migration, more industrialised employment and broader attitudes and ideals, these traditional protective factors might be becoming less effective (Chen et al., 1999). Thus there is some indication that psychological morbidity is becoming more prevalent among the general Chinese community (Chen et al., 1999; Parker et al., 2001; Hu, 2004). Increased risk of depression in HIV-positive people in highincome countries has been attributed to low education level (Morrison et al., 2002; Cook et al., 2004), low income (Cook et al., 2004), unemployment (Zinkernagel et al., 2001; Cook et al., 2004) and inadequate perceived support from family and friends (Serovich et al., 2001; Yoshikawa et al., 2004). These have been found to be equally important across different ethnic groups (Chen et al., 1999). In China access to health, educational and economic resources may be more limited than in high income countries. In addition HIV infection remains highly stigmatised, which may also increase risk of depression symptoms (Rao et al., 2012). The Asia Pacific NeuroAIDS Consortium (APNAC) Study was undertaken in 2006 to establish the prevalence of neuropsychological complications of HIV infection across eight countries of the AsiaPacific (AP) region, including China (Wright et al., 2008). In the China APNAC substudy we sought to investigate the prevalence of depression and neurocognitive impairment and any associations between them in people living with HIV in Beijing China.

2. Methods

2.2. Participants and recruitment All patients attending the clinic for routine review and meeting the inclusion criteria of having serostatus confirmed by Elisa, Western Blot or Rapid Testing, being over 18 years of age and capable of providing informed consent, in a one-month period were eligible to participate. 2.3. Data sources Data were collected by several means. 2.4. Demographic and HIV health-related characteristics Study-specific structured questions were used to assess educational status, source of HIV infection and interval since diagnosis. HIV-related morbidity and treatment regimen were extracted from the medical record using a structured data extraction form. 2.5. Depressive symptoms Self-reported symptoms of depression were assessed by two widely used psychometric measures which were available in Chinese. The Centre for Epidemiological Studies Depression Scale (CES-D) is a 20-item self report instrument (Radloff, 1977). Scores on this scale have been found to correlate highly with those on other depression scales and cut-off scores validated against clinical diagnoses of depression (Radloff, 1977). Although it had not been used to assess Chinese PLWH, Lin (1989) in an investigation of 1000 Chinese people established that it was meaningful and acceptable to them. In a comparison of Chinese and American samples (Tally and Dong, 2000) the CES-D was found to have high internal consistency and a Cronbach alpha of 0.89 in the US and 0.85 in the Chinese sample. The WHO SRQ-20 is a 20-item self-report questionnaire developed by the World Health Organisation (WHO) as a screening tool for depressive symptoms in low-income settings where it has been used as a diagnostic aid in primary health and to determine prevalence of psychiatric morbidity (Harding et al., 1980; Harpham et al., 2003). The SRQ-20 has not previously been used for research with Chinese PLWH. However the tool has been used in a Hong Kong Study on a non-HIV positive population and was found to correlate with the General Health Questionnaire (GHQ), 0.49 (p o0.001) (Chan and Chan, 1983). No single set cut-off point has been established and a range of different scores (3–12) have been used to indicate presence of depression in different settings (WHO, 1994). In this study a higher cut-off point of 10 was chosen to reduce the risk of false positives and maximise specificity. 2.6. Screen neuropsychological test battery The tests included in the battery were (1) Finger Tapping test (non- dominant hand); (2) Lafayette Grooved Pegboard Test (dominant hand), (3) the Semantic Fluency (category animal) and the Timed Gait test. These tests were selected to form a screening battery that has been shown to be highly sensitive to HIV-related brain injury (Van Gorp et al., 1989; Miller et al., 1990; American Academy of Neurology AIDS Task Force, 1991; Selnes et al., 1995; Brew, 2001), and can be easily adapted in cross-cultural context (Wright et al., 2008).

2.1. Setting 2.7. Procedures Ditan Hospital is a large, specialist infectious diseases hospital in Northern Beijing, China. There is a daily HIV and STD outpatient clinic for PLWH.

Eligible participants were informed of the study by WL and given a participant information and consent form. Participants

R. Dwyer et al. / Journal of Affective Disorders 162 (2014) 89–95

who consented were assessed individually in a private room at the clinic. All assessments were conducted jointly by RD and WL.

91

Table 1 Sociodemographic characteristics and health behaviours of HIV positive participants in Beijing, China.

2.8. Ethics approval This study was approved by the Research and Ethics Committees of the Alfred Hospital and Ditan Hospital 2.9. Data management and analysis As local Chinese cut-off scores were not available the CESD and WHO SRQ-20 were scored using published criteria. Participants scoring above clinical cut-offs on either scale were classified as meeting the case definition criteria for that scale. To classify neuropsychological impairment across the test battery, each raw test score was transformed into a z-score based on the 161 self-reported HIV negative controls obtained in the APNAC study (Wright et al., 2008). Gender, age, and education were obtained from 161 control participants who were recruited from hospitals' domiciliary, nursing, and medical staff. No family members of the study subjects were recruited. Controls were administered the four-test neuropsychological battery to provide local normative data to control for any possible cultural and ethnic differences in the study subjects' neuropsychological test performance. Controls were not assessed for alcohol/substance use, depression, or clinical disease states as this was not a case-control study. Results of neuropsychological test performance for control participants from all sites were pooled to provide mean performance scores and standard deviations against which the study participants were compared. Study participants were compared to the controls' mean performance score rather than to the individual results of each control. Using the definition of neurocognitive impairment that we employed for the APNAC study subjects, we found that 1/161 controls (0.6%) was neurocognitively impaired (Wright et al., 2008). The results of the individual tests from the APNAC controls were as follows: (i) Grooved Pegboard (seconds): mean: 66.01, standard deviation (SD): 12.01, (ii) Verbal Fluency (number of animals): mean: 20.56, SD: 5.65, (iii) Timed gait (mean seconds): mean 10.31, SD 1.35 and (iv) Finger tapper (mean number of taps): mean: 41.21, SD: 7.51 (Wright et al., 2008). We then used the following definition to classify each case as impaired (or unimpaired) 4  1 SD below the control mean on 2 tests or, 4  2 SD below the control mean on one test. Data were analysed by descriptive statistics and univariate comparisons made using chi-squared or independent samples t-tests and Pearson correlation coefficients with significance set at 0.05. All data were entered into a SPSS (SPSS Inc, 2005) database and analysed using SPSS.

3. Results Of the 51 outpatients who attended the clinic one was not approached because he was known to be unaware of his HIV status, and all others agreed to participate. Eighty-four per cent of participants were male, the average age of the study group was 35 years (SD ¼7.3) and men and women did not differ significantly in age. There was a high smoking rate in this sample however no participant reported past or current use of injecting drugs (see Table 1). Study participants were relatively well educated, only 6 (12%) participants had not completed secondary school and 21 (42%) people had completed tertiary education. Females were significantly less well-educated than males and people who had

Age (mean 7SD) Education (years) (mean7 SD) Height (cm) (mean 7 SD) Weight (kg) (mean7 SD) Ever smoked (% [N]) Current smoker (% [N]) Alcohol use in last 6 months (% [N])

Female n¼ 8

Male n¼ 42

P value

34.4 75.5 11.8 7 2.5 161.6 7 8.2 51.0 77.7 37.5 [3] 25.0 [2] 12.5 [1]

35.1 77.7 13.7 7 2.5 174.9 7 6.1 65.5 7 7.5 59.5 [25] 54.8 [23] 42.9 [18]

0.79 0.04 o 0.001 o 0.001 0.22 0.12 0.11

Table 2 Current ARV therapy for HIV þ study participants. Total all participants [50] (% [N])

Female [8] (% [N])

Currently taking HAART

68.0 [34]

Currently using ARVs

70.0 [35]

Didanosine (ddI) Stavudine (d4T) Lamivudine (3TC) Zidovudine (ZDV)

20.0 48.0 34.0 10.0

Efavirenz Nevirapine Other NNRTI Indinavir

Male [42] (% [N])

P value

100.0 [8]

61.9 [27]

0.04

100.0 [8]

64.3 [27]

0.04

[10] [24] [17] [5]

50.0 [4] 75.0 [6] 37.5 [3] 12.5 [1]

14.3 42.9 33.3 9.5

[6] [18] [14] [4]

– – – –

26.0 [13] 40.0 [20] 2.0 [1]

25.0 [2] 75.0 [6] 0

26.2 [11] 33.3 [14] 2.4 [1]

– – –

2.4 [1]

–

2.0 [1]

0

completed post-secondary education were younger (32.6 years) than those who had not (36.8 years) (p ¼0.04). 3.1. HIV-related health findings The mean reported interval since diagnosis for both women and men was three years. The median nadir CD4 cell count for the group was 111 cells  106/L (IQR ¼29–209), median current CD4 þ cell count was 288 cells  106/L (IQR ¼171–385) and there were no significant differences between males and females. Approximately one third of participants (30%) had experienced a past AIDS defining illness (ADI), of which the most common were P. jirovecii pneumonia (PCP) and oesophageal candidiasis. Information concerning HIV transmission was obtained by asking participants to describe mode of infection if known. For women the predominant mode of transmission was heterosexual contact with their spouse and for men it was same sex sexual contact. However, perhaps due to social stigmatisation a high proportion (26%) described method of transmission as unknown. Current anti-retroviral therapy use of participants is summarised in Table 2 and, of note, women were significantly less likely to be receiving highly active antiretroviral therapy (HAART). 3.2. Symptoms of depression Participants were asked about past personal history of episodes of depression. Only one reported a past diagnosis of Major Depression, and none were taking anti-depressant medications at time of study evaluation. In total 28% (14) of participants scored above the cut-off on at least one scale (CES-D Z16 ¼24% (12/50) and SRQ-20 Z10¼ 22%

92

R. Dwyer et al. / Journal of Affective Disorders 162 (2014) 89–95

Table 3 Comparison between participants classified as cases and non-cases using the CES-D and SRQ-20. CES-D

Age (mean7 SD) Male Any tertiary education Alcohol use in last 6 months Current smoker

SRQ-20

ScoreZ 16 [n ¼12]

Scoreo 16 [n¼ 38]

P value

ScoreZ 10 [n¼ 11]

Scoreo 10 [n¼39]

P value

36.3 7 8.7 91.7% 8.3% 66.7% 58.3%

34.6 7 6.9 81.6% 52.6% 28.9% 47.4%

0.51 0.37 0.006 0.02 0.37

34.7 7 7.1 100% 9.1% 63.6% 63.3%

35.1 78.3 79.5% 53.3% 30.8% 46.2%

0.88 0.12 0.02 0.05 0.25

Table 4 HIV-related health and depressive symptoms. Reported past ADI Yes

No

P value

Yes

No

P value

13.9 7 8.7 6.3 7 4.2

10.7 7 6.2 4.6 7 3.9

0.15 0.19

13.8 7 8.7 6.7 7 3.9

10.4 7 5.8 4.2 7 3.9

0.10 0.03

(11/50) and 18% (9) participants scored above the clinical cut-off point on both scales. The median score on the CES-D was 11 (IQR ¼6.7–15.2) and for the SRQ 4 (IQR ¼ 1.75–7). Scores on the two measures were highly correlated (r ¼ 0.68 and p o0.01). Individuals scoring in the clinical range on one scale were highly likely to score in the clinical range on the other (χ 21 ¼25.85, p o0.01) indicating high construct validity (Table 3). Age was unrelated to the likelihood of scoring above the cut-off on either scale and men were as likely as women to score in the clinical range on both measures. Participants who had only completed up to secondary education had higher rates of clinically significant symptoms than those with post-secondary qualifications. Only one person who was classified as a case on either scale had proceeded to any post-secondary education. Smoking in the cohort was prevalent (50%). There was no relationship between smoking and scoring above the cut off on depression scales, however smokers were significantly more likely to have used alcohol in the previous six months. Those participants who had experienced a past ADI or who were currently experiencing symptoms of peripheral neuropathy had a higher mean score on both depression scales however, overall these differences were minor with only the relationship between the SRQ-20 score and symptoms of peripheral neuropathy reaching statistical significance (see Table 4).

30

Men (n=42) Women (n=8)

25 Number of participants

CES-D Score (mean 7SD) SQR-20 Score (mean 7SD)

Current symptoms of peripheral neuropathy

20 15 10 5 0

Above -1 SD on all four tests

Below 1 SD on 1 test

Below 1 SD on 2 Greater than -4SD tests, OR below 2 in total SD on 1 test or up to -4SD total

Results of neuropsychological 4-test battery (n=50) Fig. 1. Results of neuropsychological 4-test battery among 50 PLWH at Ditan Hospital, Beijing China.

on either depression scale and the presence of cognitive impairment on testing (CES-D, χ 21 ¼0.24, p ¼0.63) (SRQ-20, χ 21 ¼0.07, p¼ 0.79).

3.3. Neurocognitive impairment 4. Discussion Using the brief test battery a significant number of participants were found, by comparison with HIV negative controls, to have cognitive impairment, with only 12% of people scoring within 1 SD of the control mean on all four tests. Over half (69.4%) of patients had a degree of cognitive impairment by scoring below 1 SD of the control value on at least two tests. A total of 10 participants (20%) demonstrated more substantial impairment as defined by a total of four standard deviations below the control mean accrued across four tests (see Fig. 1). 3.4. Neurocognitive impairment and depression Participants meeting case definition on both depression scales had significantly poorer results on the grooved pegboard test (t47 ¼  2.93, p ¼ 0.005) but not on the other three neurocognitive tests. There was no correlation between scoring above the cut-off

This study has established, in a consecutively recruited cohort of PLWH attending an outpatient clinic in urban China that at least 28% of patients have scores which indicate clinically significant depressive symptoms. In addition it was found that over half these patients had impairment on neurocognitive testing that was commensurate with the impairment observed in patients with either asymptomatic neurocognitive impairment (ANI) or minor neurocognitive disorder (MND) (Antinori et al., 2007). However without assessment of daily functioning it was not possible to classify participants according to the Frascati criteria (Antinori et al., 2007). It is however possible that the majority of patients in this study had ANI as opposed to MND. This may still be clinically relevant given the findings of the CHARTER study, which suggest that even patients with ANI may be at greater risk of progressing to more severe, symptomatic impairment compared with people

R. Dwyer et al. / Journal of Affective Disorders 162 (2014) 89–95

without neurocognitive impairment (Antinori et al., 2007; Heaton et al., 2012). In comparing the findings of this study with those conducted in high-income countries it is important to acknowledge the impact of differences in access to antiretroviral therapy. Reduced access to antiretroviral regimens that offer less toxicity and lower pill burden may be associated with increased toxicity and poorer adherence which may be associated with increased rates of impairment or depression in this population compared to a group living in a high income, highly resourced setting. In China the background prevalence of depression has been reported as 0.3–4% (Chiu, 2004; Shen et al., 2006; Lee et al., 2009, Ma et al., 2009), but in this study group of PLWH the prevalence of current depression is at least five times higher. Our findings provide an indication of an increased prevalence of depression in this group of people infected with HIV, but any, direct comparison to the general population should be interpreted with caution given the inability to accurately match for confounders such as drug and alcohol use, age and education. These findings are however, consistent with other studies of HIV infected populations where reported prevalence estimates of clinically significant depressive symptoms are high ranging from 14% to 79% (Jin et al., 2006; Atkinson et al., 2011; Su et al., 2013). Future research involving adequately matched controls will be important in further characterising the true impact of HIV infection on the mental health of PLWH in China. It is important to note that this population may differ significantly from other groups of PLWH in China. In contrast to Su et al. this study group was on average, well educated with limited rates of injecting drug use (Su et al., 2013). Most female participants reported mode of infection as heterosexual contact mostly from their marital partners and the majority of male participants believed they had contracted HIV through homosexual contact. Thus, we cannot generalise findings from this cohort to people who live in rural areas, are poorly educated or who inject drugs. Lower level of education was associated with higher odds of depression, a finding which is consistent with the substantial existing evidence that education is protective of mental health, in particular depression (Cook et al., 2004). It supports the findings of Chen et al. (1999) who found in the general Chinese population that both less education and the experience of chronic disease were significant risk factors for depression. The findings of this study also suggest that there is an association between complications of HIV such as current experience of symptoms of peripheral neuropathy or a prior ADI and depression, although it was only possible to describe a significant relationship between current symptoms of peripheral neuropathy and higher score on the SRQ-20. This is consistent with the findings of the larger APNAC study which described a significant association between peripheral neuropathy and symptoms of depression (Wright et al., 2008). In high-income countries studies have indicated that greater disease progression is associated with increased risk of depression and these data suggest a similar relationship within Chinese HIV positive populations but this requires further investigation. PLWH who are depressed have a reduced quality of life, increased risk taking behaviours leading to onward transmission of the virus and increased risk of mortality (Nyamathi et al., 1995; Sherbourne et al., 2000; Ickovics et al., 2001; Murphy et al., 2002; Rogers et al., 2003; Cook et al., 2004; Hutton et al., 2004; Williams and Latkin, 2005). It is therefore of great concern that the mental health needs of this group were not known to their treating clinicians. None of these participants was currently receiving either pharmacological or non-pharmacological treatment. Previous investigators have identified injecting drug use (Sun et al., 1994) as the predominant mode of transmission of HIV in

93

China, but sexual transmission is becoming more common in particular male to male sexual contact (Ministry of Health of the People's Republic of China, 2012). Same sex relationships are strongly socially proscribed in China and may be associated with stigma, and social isolation which might contribute to depression. Lower levels of education (Morrison et al., 2002; Cook et al., 2004) and drug abuse (Judd and Mijch, 1996; Komiti et al., 2003; Cook et al., 2004) have been identified as independent risk factors for depression in HIV positive people. These factors may differ significantly between our study group and the broader population of PLWH in China and hence the prevalence of depression may differ significantly also in other sub-groups of the Chinese HIV positive population. This is consistent with reports of higher prevalence of depression in HIV infected male sex workers at 68% and prevalence of suicidality in a rural population of 34.1%. This study has several strengths. First, it was conducted at a major general hospital in Beijing, China's capital city that provides care for large numbers of PLWH and the near complete consecutive cohort may therefore provide reasonable representation of the population treated at this hospital. Local researchers (also clinicians at the study site) felt participants recruited were representative of their clinic population as a whole. The use of two independent psychometric measures provided internal validity of the prevalence of depression within the sample. The study also sought to obtain a history on the intercurrent use of antidepressants which is a surrogate marker for clinical recognition of depression. Together these suggest that the results can be generalised with some confidence. However, we acknowledge some methodological limitations. First, the APNAC study design required that participants be recruited over a four-week period at the site and therefore the actual sample size was relatively small and the short recruitment period may have introduced unknown seasonal selection biases. Second, in order to take the social determinants of health status into account, it would have been preferrable to collect more detailed sociodemographic data, in particular current occupation and marital status. It would also have been relevant to investigate HIV management policies at the hospital and thereby gain better understanding of the level of adherence to recommended treatment regimens and compliance with medication use. These factors would have provided a more comprehensive view of the participant group and allowed more detailed description of the impact of depression on quality of life, in particular reduced ability to participate in paid employment and reduced medication adherence. Psychological morbidity was assessed only by self-report screening scales and not a formal structured clinical diagnostic interview, which might have led to overestimates of severity. However, both the CES-D and SRQ-20 have good reliability and validity when used previously in Chinese populations (Chan and Chan, 1983; Lin, 1989; Who, 1994; Tally and Dong, 2000). We acknowledge the limitation that we were only able to administer a brief, albeit highly sensitive neurocognitive test battery and that we were not able formally assess participants' everyday functioning. Thus without information on the prevalence of symptomatic neurocognitive impairment we have not been able to categorise patients according to the Frascati Criteria (Antinori et al., 2007). Finally, the lead investigator RD was from a different country, culture and language setting than the study participants. It was therefore necessary to communicate with them through an interpreter and to use translated materials. However, WL a senior clinician at Ditan Hospital co-completed the assessments and endorsed their accuracy. In conclusion this study adds to the evidence that clinically significant symptoms of depression and rates of measurable neurocognitive impairment are prevalent in PLWH in Beijing, China. Although there is growing awareness of psychological morbidity, in

94

R. Dwyer et al. / Journal of Affective Disorders 162 (2014) 89–95

this population symptoms of depression were significantly under recognised and undertreated. Future research should focus on further characterisation of clinical and functional impact of these conditions and development of interventions to combat these debilitating conditions and address the needs of this group of people.

Role of funding source This study was supported as a student research project and Monash University had no part in decisions regarding study design, data collection or publication.

Conflict of interest The authors declare that they have no conflicts of interest.

Acknowledgements Funding from this study came from the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health and was a Supplemental Grant to R01 NS44807. RD was supported by a Monash University Bachelor of Medical Science Scholarship. The authors are grateful for the support of the Asia-Pacific Neuro-AIDS Consortium, and the Substantial In-Kind Contribution of Ditan Hospital, Beijing.

References American Academy of Neurology Aids Task Force, 1991. Nomenclaure and research case definitions for neurological manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Neurology 41, 778–785. Ammassari, A., Antinori, A., Aloisi, M., Trotta, M., Murri, R., Bartoli, L., D'arminio Monforte, A., Wu, A., Starace, F., 2004. Depressive symptoms, neurocognitive impairment, and adherence to highly activ. Psychosomatics 45, 394–402. Antinori, A., Arendt, G., Becker, J., Brew, B., Byrd, A., Cherner, M., Clifford, D., Cinque, P., Epstein, L., Goodkin, K., Gisslen, M., Grant, I., Heaton, R., Joseph, J., Marder, K., Marra, C., Mcarthur, J., Nunn, M., Price, R., Pulliam, L., Robertson, K., Sacktor, N., Valcour, V., Wojna, V., 2007. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69, 1789–1799. Atkinson, J., Jin, H., Shi, C., Yu, X., Duarte, N., Casey, C., Franklin, D., Vigil, O., Cysique, L., Wolfson, T., Riggs, K., Gupta, S., Letendre, S., Marcotte, T., Grant, I., Wu, Z., Heaton, R., 2011. Psychiatric context of human immunodeficiency virus infection among former plasma donors in rural China. J. Affect. Disord. 130, 421–428. Brew, B., 2001. HIV Neurology. Oxford University Press, New York. Chan, D., Chan, T., 1983. Reliability, validity and the structure of the General Health Questionnaire in a Chinese context. Psychol. Med. 13, 363–371. Chen, R., Copeland, J., Wei, L., 1999. A meta-analysis of epidemiological studies in depression of older people in the People's Republic of China. Int. J. Geriatr. Psychiatry 14, 821–830. Chiu, E., 2004. Epidemiology of depression in the Asia Pacific region. Australas. Psychiatry 12, S4–S10. Cook, J., Grey, D., Burke, J., Cohen, M., Gurtman, A., Richardson, J., Wilson, T., Young, M., Hessol, N., 2004. Depressive symptoms and AIDS-related mortality among a multisite cohort of HIV-positive women. Am. J. Public Health 94, 1133–1140. Gordillo, V., Del Amo, J., Soriano, V., González-Lahoz, J., 1999. Sociodemographic and psychological variables influencing adherence to antiretroviral therapy. AIDS 13, 1763–1769. Harding, T., De Arango, M., Baltazar, J., Climent, C., Ibrahim, H., Ladrido-Ignacio, L., Srinivasa Murthy, R., Wig, N., 1980. Mental disorders in primary health care: a study of their frequency and diagnosis in four developing countries. Psychol. Med. 10, 231–241. Harpham, T., Reichenheim, M., Oser, R., Thomas, E., Hamid, N., Jaswal, S., Ludermir, A., Aidoo, M., 2003. Measuring mental health in a cost-effective manner. Health Policy Plan. 18, 344–349. Heaton R., Franklin D., Woods S. et al., 2012. Asymptomatic mild HIV-associated neurocognitive disorder increases risk for future symptomatic decline: a CHARTER longitudinal study. Abstract number 77. In: Proceedings of the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, March 5–8, 2012. Hu, T.-W., 2004. The economic burden of depression and reimbursement policy in the Asia Pacific region. Australas. Psychiatry 12, S11–S15. Hutton, H., Lyketsos, C., Zenilman, J., Thompson, R., Erbelding, E., 2004. Depression and HIV risk behaviors among patients in a sexually transmitted disease clinic. Am. J. Psychiatry 161, 912–914. Ickovics, J., Hamburger, M., Vlahov, D., Schoenbaum, E., Schuman, P., Boland, R., Moore, J., 2001. Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women. JAMA 285, 1466–1474. Jin, H., Hampton Atkinson, J., Yu, X., Heaton, R., Shi, C., Marcotte, T., Young, C., Sadek, J., Wu, Z., Grant, I., 2006. Depression and suicidality in HIV/AIDS in China. J. Affect. Disord. 94, 269–275. Judd, F., Mijch, A., 1996. Depressive symptoms in patients with HIV infection. Aust. N. Z. J. Psychiatry 30, 104–109.

Kleeberger, C., Buechner, J., Palella, F., Detels, R., Riddlerd, R., Godfrey, R., Jacobson, L., 2004. Changes in adherence to highly active antiretroviral therapy medications in the multicenter AIDS cohort study. AIDS 18, 683–688. Komiti, A., Judd, F., Grech, P., Mijch, A., Hoy, J., Williams, B., Street, A., Lloyd, J., 2003. Depression in people living with HIV/AIDS attending primary care and outpatient clinics. Aust. N. Z. J. Psychiatry 37, 70–77. Lee, S., Tsang, A., Huang, Y., He, Y., Liu, Z., Zhang, M., Shen, Y., Kessler, R., 2009. The epidemiology of depression in metropolitan China. Psychol. Med. 39, 735–747. Lin, N., 1989. Measuring depressive symptomatology in China. J. Nerv. Ment. Dis. 177, 121–131. Markowitz, J., Kocsis, J., Fishman, B., Spielman, L., Jacobsberg, L., Francis, A., Klerman, G., Perry, S., 1998. Treatment of depressive symptoms in human immunodeficiency virus-positive patients. Arch. Gen. Psychiatry 55, 452–457. Ma, X., Xiang, Y., Cai, Z., Li, S., Xiang, S., Guo, H., Hou, Y., Li, Z.-B., Li, Z.-J., Tao, Y., Dang, W., Wu, X., Deng, J., Wang, C., Lai, K., Ungvari, G., 2009. Prevalence and socio-economic correlates of major depressive episode in rural and urban areas of Beijing, China. J. Affect. Disord. 115, 323–330. Miller, E., Selnes, O., Mcarthur, J., Satz, P., Becker, J., Cohen, B., Sheridan, K., Machado, A., Van Gorp, W., Visscher, B., 1990. Neuropsychological performance in HIV-1-infected homosexual men: the multicentre AIDS cohort study. Neurology 40, 197–203. Ministry of Health of the People's Republic of China, 2012. China AIDS Response Progress Report. Morrison, M., Petitto, J., Have, T., Gettes, D., Chiappini, M., Weber, A., BrinkerSpence, P., Bauer, R., Douglas, S., Evans, D., 2002. Depressive and anxiety disorders in women with HIV infection. Am. J. Psychiatry 159, 789–796. Murphy, D., Marelich, W., Dello Stritto, M., Swendeman, D., Witkin, A., 2002. Mothers living with HIV/AIDS: mental, physical, and family functioning. AIDS Care 14, 633–644. Nyamathi, A., Bennett, C., Leake, B., 1995. Predictors of maintained high-risk behaviours among impoverished women. Public Health Rep. 110, 600–606. Parker, G., Gladstone, G., Chee, K., 2001. Depression in the planet's largest ethnic group: the Chinese. Am. J. Psychiatry 158, 857–864. Pence, B., O'donnell, J., Gaynes, B., 2012. Falling between the cracks: the gaps between depression prevalence, diagnosis, treatment and response in HIV care. AIDS 26, 656–658. Radloff, L., 1977. The CES-D scale: a self-report depression scale for research in the general population. Appl. Psychol. Meas. 1, 385–401. Rao, D., Chen, W., Pearson, C., Simoni, J., Fredriksen-Goldsen, K., Nelson, K., Zhao, H., Zhang, F., 2012. Social support mediates the relationship between HIV stigma and depression/quality of life among people living with HIV in Beijing, China. Int. J. STD, AIDS 23 (7), 481–484. Rogers, G., Curry, M., Oddy, J., Pratt, N., Beilby, J., Wilkinson, D., 2003. Depressive disorders and unprotected casual anal sex among Australian homosexually active men in primary care. HIV Med. 4, 271–275. Selnes, O., Galai, N., Bacellar, H., Miller, E., Becker, J., Wesch, J., Van Gorp, W., Mcarthur, J., 1995. Cognitive performance after progression to AIDS: a longitudinal study from the multicentre AIDS cohort study. Neurology 45, 267–275. Serovich, J., Kimberly, J., Mosack, K., Lewis, T., 2001. The role of family and friend social support in reducing emotional distress among HIV-positive women. AIDS Care 13, 335–341. Sherbourne, C., Hays, R., Fleishman, J., Vitiello, B., Magruder, K., Bing, E., Mccaffrey, D., Burnam, A., Longshore, D., Eggan, F., Bozzette, S., Shapiro, M., 2000. Impact of psychiatric conditions on health-related quality of life in persons with HIV infection. Am. J. Psychiatry 157, 248–254. Shen, Y., Zhang, M., Huang, Y., He, Y., Liu, Z., Cheng, H., Tsang, A., Lee, S., Kessler, R., 2006. Twelve-month prevalence, severity, and unmet need for treatment of mental disorders in metropolitan China. Psychol. Med. 36, 257–267. SPSS INC, 2005. SPSS. 12.0.1, Chicago. Su, X., Lau, J., Mak, W., Choi, K., Chen, L., Song, J., Zhang, Y., Zhao, G., Feng, T., Chen, X., Liu, C., Liu, J., Liu, D., Cheng, J., 2013. Prevalence and Associated factors of depression among people living with HIV in two cities of China. J. Affect. Disord. Sun, X., Nan, J., Guo, Q., 1994. AIDS and HIV infection in China. AIDS 8, S55–S59. Tally, S., Dong, Q., 2000. Family, peer and individual correlates of depressive symptomatology among US and Chinese adolescents. J. Consult. Clin. Psychol. 68, 209–219. Tsai, A., Weiser, S., Peterson, M., 2010. A marginal sturctural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally joiused persons with HIV. Arch. Gen. Psychiatry 67, 1282–1290. Treisman, G., Angelino, A., Hutton, H., 2001. Psychiatric issues in the management of patients with HIV infection. JAMA 286, 2857–2864. Unaids, 2013. HIV in the Asia and the Pacific, UNAIDS Report. Van Gorp, W., Satz, P., Hinkin, C., Evans, D., Miller, E., 1989. The neuropsychological aspects of HIV-1 spectrum disease. Psychiatr. Med. 7, 59–78. WHO, 1994. User's Guide to the Self-Reporting Questionnaire (SRQ). World Health Organisation, Geneva Williams, C., Latkin, C., 2005. The role of depressive symptoms in predicting sex with multiple and high-risk partners. J. Acquir. Immune Defic. Syndr. 38, 69–73. Wright, E., Brew, B., Arayawichanont, A., Robertson, K., Samintharapanya, K., Kongsaengdao, S., Lim, M., Vonthanak, S., Lal, L., Sarim, C., Huffam, S., Li, P., Imran, D., Lewis, J., Lun, W.H., Kamarulzaman, A., Tau, G., Ali, S.T., Kishore, K., Bain, M.P., Dwyer, R., Mccormack, G., Hellard, M., Cherry, C., Mcarthur, J., Wesselingh, S., 2008. Neurologic disorders are prevalent in HIV-positive outpatients in the Asia-Pacific region. Neurology 71 (1), 50–56.

R. Dwyer et al. / Journal of Affective Disorders 162 (2014) 89–95

Yoshikawa, H., Wilson, P.-D., Chae, D., Cheng, J.-F., 2004. Do family and friendship networks protect against the influence of discriminations on mental health and HIV risk among Asian and Pacific Islander Gay Men. AIDS Educ. Prev. 16, 84–100.

95

Zinkernagel, C., Taffe, P., Rickenbach, M., Amiet, R., Ledergerber, B., Volkart, A.-C., Rauchfleisch, U., Kiss, A., Werder, V., Vernazza, P., Battegay, M., 2001. Importance of mental health assessment in HIV-infected outpatients. J. Acquir. Immune Defic. Syndr. 28, 240–249.