Vele mensen zullen het gevoel wel kennen, ze zitten aan de antibiotica, maar hebben dan een feestje amoxicilline kopen zonder recept Antibiotica zijn medicijnen die alleen op recept te krijgen zijn.
Pone.0044415 1.5
Cognitive Dysfunction among HIV Positive and HIVNegative Patients with Psychosis in Uganda
Noeline Nakasujja1,2*, Peter Allebeck2, Hans Agren3, Seggane Musisi1, Elly Katabira4
1 Department of Psychiatry, College of Health Sciences, Makerere University, Kampala, Uganda, 2 Department of Public Health Sciences, Karolinska Institute, Stockholm,
Sweden, 3 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden, 4 Department of
Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
Background: Cognitive impairment is an established phenomenon in HIV infected individuals and patients that havepsychosis. However there is need to establish the severity of the impairment if patients are co morbid with both conditions.
Aim: To compare cognitive function among HIV positive individuals and HIV negative individuals with psychosis.
Methods: We recruited patients with psychosis at two national referral hospitals. A standardized demographicsquestionnaire and psychiatric, physical, and laboratory assessments were conducted. Types of psychosis were diagnosedusing the Mini International Neuropsychiatric Inventory-PLUS while cognitive functioning was determined using the Minimental state examination (MMSE) and a neuropsychological test battery. Follow-up assessments on cognitive function andseverity of psychiatric illness were performed at 3 and 6 months. Pairwise comparison and multivariable logistic regressionanalysis were used to determine the differences between the HIV positive and HIV negative individuals.
Results: There were 156 HIV positive and 322 HIV negative participants. The mean age was 33 years for the HIV positivegroup and 29 years for the HIV negative group (p,0.001). The HIV positive individuals were almost three times (OR = 2.62 CI95% 1.69–4.06) more likely to be cognitively impaired on the MMSE as well as the following cognitive tests:- WHO-UCLAAuditory Verbal Learning Test (OR 1.79, 95% CI 1.09–2.92), Verbal Fluency (OR 3.42, 95% CI 2.24–5.24), Color Trails 1 (OR 2.03,95% CI 1.29–3.02) and Color Trails 2 (OR 3.50 95% 2.00–6.10) all p = 0.01. There was improvement in cognitive function atfollow up; however the impairment remained higher for the HIV positive group (p,0.001).
Conclusion: Cognitive impairment in psychosis was worsened by HIV infection. Care plans to minimize the effect of thisimpairment should be structured for the management of individuals with HIV and psychosis.
Citation: Nakasujja N, Allebeck P, Agren H, Musisi S, Katabira E (2012) Cognitive Dysfunction among HIV Positive and HIV Negative Patients with Psychosis inUganda. PLoS ONE 7(9): e44415. doi:10.1371/journal.pone.0044415
Editor: Kenji Hashimoto, Chiba University Center for Forensic Mental Health, Japan
Received January 9, 2011; Accepted August 7, 2012; Published September 6, 2012
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone forany lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Funding: Source of funding: Makerere University-Swedish International Development Cooperation Agency/Department for Research Cooperation cooperationgrant. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
CD4 count and were of older age [11]. While the severity ofimpairment may decrease with antiretroviral therapy (ART), the
Cognitive dysfunction in patients having primary psychiatric
prevalence of any degree of cognitive impairment even after the
illness like schizophrenia has been well documented [1,2]. The
use this medication remains as high as 40–70-% [12,13].
cognitive functioning of an individual with psychosis is affected by
The debilitation that occurs in HIV positive individuals who are
a number of factors including the severity of psychosis and anti
cognitively impaired hinders their management as they may fail to
psychotic medication being taken [3]. In many patients the
adhere to their treatment regimen, the situation being further
cognitive impairment is not secondary to delusions or effects of
worsened if the person has a psychotic condition. In resource
hallucinations but may rise from the lack of motivation the patients
constrained settings, lack of clear guidelines at primary care
experience [4]. Though cognitive dysfunction does not occur in all
centers and the scarcity of ART results in delayed treatment [14]
patients with psychosis [5], the dysfunction is common among
creating a dilemma in the management of HIV and related
patients with HIV associated psychosis, [6,7].
conditions like psychosis, even when there is evidence that ART
The prevalence of HIV dementia among HIV positive
improves the symptoms of psychosis and cognitive impairment
individuals has decreased from 30–40% before the introduction
[12,15]. Understanding the level of cognitive function in patients
of highly active antiretroviral therapy to 10–15% in settings with
that develop psychosis would create insight into ways of managing
adequate access to the medication [8,9,10]. In Uganda, ambulant
them. This study set out to compare the cognitive deficits among
patients attending an HIV outpatient clinic were found to have an
psychotic HIV positive and psychotic HIV negative individuals.
HIV dementia prevalence rate of 31% especially if they had low
September 2012 | Volume 7 | Issue 9 | e44415
Cognitive Dysfunction in HIV Associated Psychosis
cryptococcal antigen, toxo titers and Venereal Disease ResearchLaboratory (VDRL).
We consecutively recruited 478 patients who were admitted at
The study interviews were carried out in the locally spoken
Mulago and Butabika national referral hospitals in Kampala,
language Luganda or English. The patients continued to receive
Uganda between February 2008 and April 2009. Ethical approval
routine psychiatric care in the hospital even after being enrolled
for conduction of the study was received from the Uganda
into the study. Three hundred seventy eight (79%) patients
National Council for Science and Technology as well as the
returned for the 3 month and 302 (63%) returned for the 6 months
Makerere University Research and Ethics Committee.
visit. The loss to follow up at 6 months was 36.8%.
Individuals were included in the study if they had features of
psychosis, were aged 18–59 years old, were resident within a
radius of 30 km of the city centre, and gave written informed
The data was analysized using STATA version 10, (StataCorp,
consent to participate in the study. We excluded individuals who
College Station, TX USA). Chi square test and Fishers exact test
had any known medical condition other than HIV and its
were used to determine the difference in type of psychiatric illness,
complications e.g. syphilis that could be related to the manic
MMSE scores and to evaluate differences on neuropsychological
episode, a recent onset of severe headache or substance
performance for the HIV positive and HIV negative groups. The
dependency. The participants received a standardized demo-
level of cognitive function was determined by the presence or
graphics questionnaire, psychiatric, physical, and laboratory
absence of impairment on specific cognitive domains. The
likelihood of cognitive impairment was determined using logisticregression using a stepwise approach while controlling for age,
gender, HIV status and educational level.
The Mini International Neuropsychiatric Inventory-PLUS
(MINI-PLUS) instrument was used to diagnose psychiatric
illnesses: mania, depression, schizophrenia and psychosis nototherwise specified (PSY NOS) [16]. The severity of the different
The HIV positive individuals were older, mean (SD), 33 years
disorders was determined at baseline, 3 and 6 months using the
(8.24) than the HIV negative individuals 29 years (8.07);
Young Mania Rating Scale (YMRS) [17], the Brief Psychiatric
(p,0.001). Most individuals 372 (77.82%) had more than 7 years
Rating Scale (BPRS) [18] and the Patient Health Questionnaire
of education and there was no statistical difference between the
(PHQ-9) [19]. The participants’ consent to continue in the study
HIV positive and HIV negative groups p = 0.424. The average
was again sought when the patients came for the follow up
CD4 count in the HIV positive group was 305 cell/uL. Only
7(4%) of the HIV positive individuals were at WHO clinical stage4 i.e. AIDS. Only 43 (27.5%) HIV positive individuals were on
ART at baseline and 52 (33.3%) were on it by the 6 month. Allpatients were taking antipsychotic medication that included
The cognitive function for the HIV positive individuals was
chlorpromazine, haloperidol stelazine and or an antidepressant
tested using the International HIV Dementia Scale (IHDS) [20].
like a tricyclic antidepressant or fluoxetine depending on the
Both HIV positive and HIV negative groups received a battery of
disorder they were being treated for. We found that 67 (43%) of
neuropsychological tests for evaluating the different cognitive
the HIV positive individuals did not have a prior episode of mental
domains. The tests included: WHO UCLA Auditory Verbal
illness and pair wise comparison with the HIV negatives 88 (27%)
Learning Test for verbal memory, learning and recall; Symbol
who had no prior episodes was statistically significant, p,0.001.
Digit Modalities Test for visual motor coordination; Animal Recall
The mean score on the MMSE was 20.32 (5.13) for the HIV
for verbal fluency; the Digit Span backward (WAIS III) for
positive and 22.87(4.79) for the HIV negative group. The mean
working memory; Digit Span forwards(WAIS III) for attention;
IHDS score was 5.8(2.3). The psychiatric diagnoses by gender are
Color Trails 1 and Color Trails 2 for abstraction/executive and
presented in table 1; mania was the commonest type of psychosis
speed of information processing. Each test score was standardized
for both males and females. Psy NOS occurred more in the HIV
to normal, 1 or 2 standard deviations (sd) from the mean in
positive group (p,0.001). There was no history of prior episodes of
comparison to normative values of the general non HIV, non
psychiatric illness in 10 (62.5%) of the HIV positive individuals
psychotic population [21]. The three following categories of
who had Psy NOS. At the baseline MMSE evaluation, there were
cognitive impairment were created; normal if scores were not
more cognitively impaired individuals within the HIV positive
deviating from the mean; mild if an individual had 1.0 sd in any of
group 64.7%vs 35.3% than in the HIV negative group 49.4% vs
the tests up to a maximum of 6 tests and severe if an individual had
50.6%, (p,0.000). The HIV positive individuals were almost three
I.0 sd in any of the tests and in addition had 2.0 sd in one or more
times (OR = 2.62 CI 95% 1.69–4.06) as likely to be cognitively
tests. The neuropsychological tests were repeated at 3 and 6
impaired. The females 270 (58.82%) were more impaired than the
males 189 (41.18%), p = 0.018. All tested cognitive tests apart fromdigit span were more likely to be impaired in the HIV positive
group (table 2). The odds of impairment on each of the tests are
The HIV testing was done using DETERMINE I/II (Abbot
presented in table 3. Adjusted odds revealed female gender (OR
Japan Cp. Ltd, Minato-ku, Tokyo, Japan), it was validated using
2.89, 95% 1.05–7.92), p = 0.038 and older age (OR 1.62, 95%
STAT PAK (ChemiBio Diagnostics System, Inc., Medford, USA)
0.59–4.45), p = 0.34 to be associated with cognitive impairment
and UNIGOLD (Trinity Biotech Plc, Bray Co Wicklow, Ireland)
(table 4). At the 3 months follow up, the mean MMSE score was
test kits. HIV pre and post-test counseling was done for all
22.93 in the HIV positive group and 24.41 for the HIV negative
patients. For individuals who were found to be HIV positive and
group while at 6 months it was 22.15 and 24.25 respectively. The
met criteria for starting ART, this treatment was initiated at the
categories for the levels of cognitive impairment at follow up are
HIV treatment clinics at Mulago or Butabika hospitals. Other
summarized in table 5. There was also improvement in psychiatric
laboratory evaluations included a full blood count, CD 4 count,
September 2012 | Volume 7 | Issue 9 | e44415
Cognitive Dysfunction in HIV Associated Psychosis
Table 1. Type of psychosis by gender.
*Major Dep: represents Major depressive disorder,{Psy NOS: represents Psychosis not otherwise specified. doi:10.1371/journal.pone.0044415.t001
signifying a difference in the manifestation of psychosis for theHIV positive individual.
Cognitive impairment was found to be worse among HIV
Cognitive impairment for both psychotic and non psychotic
positive individuals with psychosis in comparison to HIV negative
individuals occurs more often among HIV positive older patients
individuals with psychosis. The impairment was worse among
and more so in individuals of female gender [24,26] similar to
To our knowledge this is the first study to use a standardized
Our study had a higher representation of females compared to
neuropsychological battery of tests to compare cognitive function
males in the HIV positive group by almost three thirds, reflecting
in HIV positive and HIV negative patients with psychosis. Most of
what is seen in most African HIV clinic settings. Females are eager
the studies have used only the MMSE to assess the level ofcognitive function, however this test does not specify the cognitivedomains that may be affected [22]. Even though previous studies
Table 3. Estimated odds ratios of being impaired in specific
have shown that individuals with primary psychosis can have
cognitive impairment [23], we found that the severity of theimpairment is worse in HIV positive individuals even after thesymptoms of psychiatric illness decrease during follow up.
As has been observed in other studies in our setting [7,24]
mania, was the commonest presentation of psychosis. Among
individuals with depression, the statistical difference observed inthe HIV positive males and HIV negative males could be
explained by the very low numbers of individual with the disorder.
However this significance was not observed when comparing the
HIV positive and HIV negative groups without stratification for
Males with a diagnosis of schizophrenia were more among HIV
negative individuals. It has been shown that the prevalence of
schizophrenia is more and also occurs earlier among males
compared to females [25]. Psychosis NOS occurred more for the
HIV positive population and the majority of the individuals who
presented with the disorder had no prior episode of mental illness
Table 2. Neuropsychological test performance among HIV
positive and HIV negative individuals at baseline.
VLT RAI; Verbal Learning Test recall after interference. *statistically significant.
Adjusted for all other covariates for each cognitive domain.
September 2012 | Volume 7 | Issue 9 | e44415
Cognitive Dysfunction in HIV Associated Psychosis
Table 4. Odds ratios for cognitive impairment in patients with psychosis.
*Only gender, age and education level entered into the regression model for the different types of the psychosis. doi:10.1371/journal.pone.0044415.t004
in seeking care and maintaining follow up compared to their male
the participants experience interview fatigue more so if they have
counter parts [27], in addition they are more affected by the HIV
been started on antipsychotic treatments. However the evaluations
scourge and hence tend to be more afflicted by the complications
were carried out when the patients were usually calm enough and
that arise from the infection [24]. However it remains important to
on lower medication dosage, indeed in some situations if a
look into other factors that may predispose females to the
participant expressed a desire to rest, the interview would be
development of HIV associated psychosis and co- occurring
postponed to a time when they would feel comfortable to complete
cognitive impairment. For instance, theories on the neurotoxin
the evaluation. The improvement observed in performance could
production, specifically kynurenic acid that has been found to be
be a result of practice effects however the HIV positive group still
higher in HIV individuals with psychosis [28,29], have not
performed worse than the HIV negative group. The selection of
highlighted any differences between males and females.
the study participants was cumulative and when the HIV negative
A number of earlier studies emphasised that cognitive impair-
group reached saturation, we continued with the recruitment of
ment and psychosis were late manifestations of HIV disease [6,30].
the HIV positive group till the total sample size was achieved. This
The onset of psychosis primarily resulting from the HIV virus
may have affected the randomness of the sample selected.
attack of the brain tissue or through opportunistic infections
However this occurred only in the last two months of the study.
[31,32,33,34]. Recent studies including the findings of this study
We also did not test for motor performance since the patients were
show that the two conditions can sometimes occur early as
on antipsychotic medication whose side effects would have
evidenced by the moderate level of CD4 count and the
introduced bias in the observations made. We had an advantage
intermediate WHO stages of disease manifestation [35]. Further-
of having a large sample size which could cater for some of these
more the cognitive impairment persists even when the symptoms
individual differences. There was a considerable loss to follow up
of psychosis improved. This finding underscores the importance of
by 6 months but the large sample size allowed for statistical
early initiation of antiretroviral therapy for HIV positive individual
significance to be inferred from the number that came back for re
who develop cognitive impairment or psychosis or both conditions
since there is evidence that the situation can be alleviated by this
In summary this study compared cognitive function in HIV
positive and HIV negative individuals in a cohort of individuals
There were some limitations to this study. Conduction of the
with psychosis. The cognitive impairment was more pronounced
neuropsychological assessments is usually elaborate and sometimes
among the HIV positive individuals and especially so for the
Table 5. Cognitive function in HIV positive and HIV negative patients at 3 and 6 months of follow up.
September 2012 | Volume 7 | Issue 9 | e44415
Cognitive Dysfunction in HIV Associated Psychosis
females. Whereas there are explanations for the higher impair-
ment in the HIV positive group there is a need for future research
We wish to acknowledge the research assistants and the patients who
to focus on the mechanism that brings about this difference with
gender. Strategies that include measures for the early detection ofHIV in patients with psychosis, use of non sedating antipsychotics
or the early initiation of ART treatment should be in place forimproved mental health care.
Conceived and designed the experiments: NN SM HA EK. Performed theexperiments: NN. Analyzed the data: NN. Wrote the paper: NN PA HASM EK.
1. Goldberg TE, Berman KF, Weinberger DR (1995) Neuropsychology and
19. Kroenke K, Spitzer RL, Williams JB (2001) The PHQ-9: Validity of a brief
neurophysiology of schizophrenia. Current Opinion in Psychiatry 8: 34–40.
depression severity measure. J Gen Intern Med 16: 606–613.
2. Fitzgerald D, Lucas S, Redoblado MA, Winter V, Brennan J, et al. (2004)
20. Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, et al. (2005) The
Cognitive functioning in young people with first episode psychosis: Relationship
International HIV Dementia Scale: a new rapid screening test for HIV
to diagnosis and clinical characteristics. Aust N Z J Psychiatry 38: 501–510.
3. Hori H, Noguchi H, Hashimoto R, Nakabayashi T, Omori M, et al. (2006)
21. Robertson KR, Nakasujja N, Wong M, Musisi S, Katabira E, et al. (2007)
Antipsychotic medication and cognitive function in schizophrenia. Shizophr Res
Pattern of neuropsychological performance among HIV positive patients in
4. Schmand B, Kuipers T, Van der Gaag M, Bosveld J, Bulthuis, et al. (1993)
22. Folstein MF, Folstein SE, McHugh PR (1975) ‘‘Mini-Mental State’’: A Practical
Cognitive disorders and negative symptoms as correlates of motivational deficits
method for grading the cognitive state of patients for the clinician. Journal of
in psychotic patients. Psychological Medicine 24: 869–884.
5. Bora E, Yu¨ce M, Pantelis C (2010) Cognitive Impairment in Schizophrenia and
23. Hill K, Reilly J, Harris M, Rosen C, Marvin R, et al. (2009 ) A comparison of
Affective Psychoses: Implications for DSM-V Criteria and Beyond. Schizophr
neuropsychological dysfunction in first-episode psychosis patients with unipolar
depression, bipolar disorder, and schizophrenia. Schizophrenia Research 113:
6. Sewell DD, Jeste DV, Atkinson JH, Heaton RH, Hesselink JR, et al. (1994) HIV
associated psychosis: a study of 20 cases. Am J of Psychiatry 151: 237–242.
24. Maling S, Todd J, Van der Paal L, Grosskurth H, Kinyanda E (2011) HIV-1
7. Nakimuli-Mpungu E, Musisi S, Mpungu SK, Katabira E (2006) Primary mania
seroprevalence and risk factors for HIV infection among first-time psychiatric
versus HIV-related secondary mania in Uganda. Am J Psychiatry 163: 1349–
admissions in Uganda. AIDS Care 23: 171–178.
25. Iacono W, Beiser M (1992) Are males more likely than females to develop
schizophrenia? Am J Psychiatry 149: 1070–1074.
8. Starace F, Bartoli L, Aloisi M, Antinori A, Narciso P, et al. (2002) Cognitive and
26. McArthur JC (2004) HIV dementia: an evolving disease. J Neuroimmunol 157:
affective disorders associated to HIV infection in the HAART era: findings from
the NeuroICONA study. Cognitive impairment and depression in HIV/AIDS.
27. Kipp W, Alibhai A, Saunders L, Senthilselvan A, Kaler A, et al. (2010) Gender
The NeuroICONA study. Acta Psychiatr Scand 106: 20–26.
differences in antiretroviral treatment outcomes of HIV patients in rural
9. Sacktor N, Nakasujja N, Skolasky R, Robertson K, Wong M, et al. (2006)
Uganda. AIDS Care-Psychological and socio-medical aspects of AIDS/HIV 22:
Antiretroviral therapy improves cognitive impairment in HIV+ individuals in
sub-Saharan Africa. Neurology 67: 311–314.
28. Baran H, Hainfellner JA, Kepplinger B, Mazal PR, Schmid H, et al. (2000)
10. Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, et al. (2008)
Kynurenic acid metabolism in the brain of HIV-1 infected patients. J Neural
Evolution of HIV dementia with HIV infection. International Review of
29. Atlas A, Gisslen M, Nordin C, Lindstrom L, Schweiler L (2007) Acute psychotic
11. Wong MH, Robertson K, Nakasujja N, Skolasky R, Musisi S, et al. (2007)
symptoms in HIV-1 infected patients are associated with increased levels of
Frequency of and risk factors for HIV dementia in an HIV clinic in sub-Saharan
kynurenic acid in cerebrospinal fluid. Brain Behav Immun 21: 86–91.
30. el-Mallakh RS (1992) HIV-related psychosis. J Clin Psychiatry 53: 293–294.
12. Robertson K, Smurzynski M, Parsons TD, Wu K, Bosch R, et al. (2007) The
31. Horwah E (2002) Psychiatric and neuropsychiatric manifestations of HIV
prevalence and incidence of neurocognitive impairment in the HAART era
infection. Journal of the International Association of Physicians in AIDS Care 1:
13. Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, et al. (2010) HIV-
32. Dolder CR, Patterson TL, Jeste PT (2004) HIV Psychosis and ageing: past,
associated neurocognitive disorders persist in the era of potent antiretroviral
present and future. AIDS 18: 35–82.
therapy: CHARTER Study. Neurology 75: 2087–2096.
33. Dube´ B, Benoit T, Cruess DG, Evans DL (2005) Neuropsychiatric manifesta-
14. Kapiriri L, Sofaer N, Atuyambe L, Otolok-Tanga E, Norheim OF (2009)
tions of HIV infection and AIDS. J Psychiatry Neurosci 30: 237–246.
Criteria used for selecting patients for antiretroviral therapy in Uganda: A
34. Nilsson L, Linderholm K, Engberg G, Paulson L, Blennow K, et al. (2005)
qualitative study. Journal of AIDS and HIV Research 1 034–043.
Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with
15. Shapshak P, Kangueane P, Fujimura RK, Commins D, Chiappelli F, et al.
schizophrenia. Schizophr Res 80: 315–322.
(2011) Editorial NeuroAIDS review. AIDS 25: 123.
35. Nakimuli-Mpungu E, Musisi S, Kiwuwa S, Katabira E (2008) Early-Onset
16. Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, et al. (1998) The
Versus Late-Onset HIV-Related Secondary Mania in Uganda. Psychosomatics
Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and
validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-
36. Sacktor N, Skolasky RL, Lyles RH, Esposito D, Selnes OA, et al. (2000)
Improvement in HIV-associated motor slowing after antiretroviral therapy
17. Young R, Biggs J, Ziegler V, Meyer D (1978) A rating scale for mania: reliability,
including protease inhibitors. Journal of Neurovirology 6: 84–88.
validity, and sensitivity. Br J Psychiatry 133: 429–435.
37. De Ronchi D, Faranca I, Forti P, Ravagalia G, Borderi M, et al. (2000)
18. Overall J, Gorham D (1962) The brief psychiatric rating scale. Psychological
Development of acute psychotic disorders in HIV infection. International
Journal of Psychiatry and Medicine 30: 173–183.
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