Rates, types and co-occurrence of emotional and behavioural disorders among perinatally HIV-infected youth in Uganda: the CHAKA study.

PURPOSE: To describe the rates, types and comorbidity of emotional and behavioural disorders among perinatally HIV-infected children and adolescents attending care at five HIV youth clinics in Central and Southwestern Uganda. METHODS: 1339 CA-HIV attending care at HIV youth clinics in Uganda were interviewed using the DSM-5-based Child and Adolescent Symptom Inventory-5 (CASI-5; caregiver reported) and the Youth Inventory-4R (YI-4R; youth reported). Prevalence, risk factors and comorbidity for psychiatric disorders were estimated using logistic regression models. RESULTS: According to caregiver or youth report, the prevalence of 'any DSM-5 psychiatric disorder' was 17.4% (95% CI 15.4-19.5%), while that of 'any behavioural disorder' was 9.6% (95% CI 8.1-11.2%) and that of 'any emotional disorder' was 11.5% (95% CI 9.9-13.3%). The most prevalent behavioural disorder was attention deficit hyperactivity disorder (5.3%), while the most prevalent emotional disorder was separation anxiety disorder (4.6%). The statistically significant risk factors were: for behavioural disorders, sex (more among males than females) and age group (more among adolescents than among children); for emotional disorders, age group (more among adolescents than among children) and the caregiver's highest educational attainment (more among CA-HIV with caregivers with secondary education and higher, than among CA-HIV with caregivers with no formal education or only primary level education). About a quarter (24.5%) of CA-HIV with at least one emotional disorder and about a third (33.5%) of the CA-HIV with at least one behavioural disorder had a comorbid psychiatric disorder. CONCLUSION: There was a considerable burden of psychiatric disorders among CA-HIV that spanned a broad spectrum and showed considerable comorbidity.

Apolipoprotein E-ε4 deficiency and cognitive function in hepatitis C virus-infected patients.

Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.

Intra-individual neurocognitive variability confers risk of dependence in activities of daily living among HIV-seropositive individuals without HIV-associated neurocognitive disorders.

Although HIV-associated neurocognitive disorders (HAND) are the strong predictors of everyday functioning difficulties, approximately half of all functionally impaired individuals are labeled "neurocognitively normal" according to the standard neuropsychological measures, suggesting that novel predictors of functional problems in this prevalent subgroup are needed. The present study hypothesized that increased neurocognitive intra-individual variability as indexed by dispersion would be associated with poor daily functioning among 82 persons with HIV infection who did not meet research criteria for HAND. An intra-individual standard deviation was calculated across the demographically adjusted T-scores of 13 standard neuropsychological tests to represent dispersion, and functional outcomes included self-reported declines in basic and instrumental activities of daily functioning (basic activity of daily living [BADL] and instrumental activity of daily living [IADL], respectively) and medication management. Dispersion was a significant predictor of medication adherence and dependence in both BADL and IADL, even when other known predictors of functional status (i.e., age, affective distress, and indices of disease severity) were included in the models. As a significant and unique predictor of a performance on the range of daily functioning activities, neurocognitive dispersion may be indicative of deficient cognitive control expressed as inefficient regulation of neurocognitive resources in the context of competing functional demands. As such, dispersion may have clinical utility in detecting risk for functional problems among HIV-infected individuals without HAND.

Disruption of emotion and conflict processing in HIV infection with and without alcoholism comorbidity.

Alcoholism and HIV-1 infection each affect components of selective attention and cognitive control that may contribute to deficits in emotion processing based on closely interacting fronto-parietal attention and frontal-subcortical emotion systems. Here, we investigated whether patients with alcoholism, HIV-1 infection, or both diseases have greater difficulty than healthy controls in resolving conflict from emotional words with different valences. Accordingly, patients with alcoholism (ALC, n = 20), HIV-1 infection (HIV, n = 20), ALC + HIV comorbidity (n = 22), and controls (CTL, n = 16) performed an emotional Stroop Match-to-Sample task, which assessed the contribution of emotion (happy, angry) to cognitive control (Stroop conflict processing). ALC + HIV showed greater Stroop effects than HIV, ALC, or CTL for negative (ANGRY) but not for positive (HAPPY) words, and also when the cue color did not match the Stroop stimulus color; the comorbid group performed similarly to the others when cue and word colors matched. Furthermore, emotionally salient face cues prolonged color-matching responses in all groups. HIV alone, compared with the other three groups, showed disproportionately slowed color-matching time when trials featured angry faces. The enhanced Stroop effects prominent in ALC + HIV suggest difficulty in exercising attentional top-down control on processes that consume attentional capacity, especially when cognitive effort is required to ignore negative emotions.

Association of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts.

BACKGROUND: Anecdotal reports of mood disorder following infection with common respiratory viruses with neurotropic potential have been in existence since the last century. Nevertheless, systematic studies on the association between these viruses and mood disorders are lacking. METHODS: Influenza A, B and coronavirus antibody titers were measured in 257 subjects with recurrent unipolar and bipolar disorder and healthy controls, by SCID. Pearson's χ² tests and logistic regression models were used to analyze associations between seropositivity for coronaviruses, influenza A and B viruses and the following: a) history of recurrent mood disorders b) having attempted suicide in the past c) uni- vs. bi-polarity and d) presence of psychotic symptoms during mood episodes. RESULTS: Seropositivity for influenza A (p=0.004), B (p<0.0001) and coronaviruses (p<0.0001) were associated with history of mood disorders but not with the specific diagnosis of unipolar or bipolar depression. Seropositivity for influenza B was significantly associated with a history of suicide attempt (p=0.001) and history of psychotic symptoms (p=0.005). LIMITATIONS: The design was cross-sectional. Socioeconomic factors, inflammatory markers, and axis II psychopathology were not assessed. CONCLUSIONS: The association of seropositivity for influenza and coronaviruses with a history of mood disorders, and influenza B with suicidal behavior require replication in larger longitudinal samples. The need for these studies is additionally supported by the high incidence of these viral infections, the high prevalence of mood disorders, and resilience of suicide epidemics.

Borna disease virus circulating immunocomplex positivity and psychopathology in psychiatric patients in the Czech Republic.

OBJECTIVES: Borna disease virus (BDV) is an RNA virus belonging to the family Bornaviridae. BDV is a neurotropic virus that causes changes in mood, behaviour and cognition. Patients with psychiatric disorders have a higher incidence of BDV positivity than healthy individuals. METHODS: We examined the seropositivity of BDV circulating immunocomplexes (CIC) in psychiatric patients and healthy individuals (blood donors). We examined 39 psychiatric inpatients for the presence of BDV CIC in the serum by ELISA on day 0, 28 and 56. During the same period psychopathology was measured using psychiatric scales (CGI, CGI-I, MADRS, SDS, PANSS). This is the first such study performed in the Czech Republic. RESULTS: BDV CIC positivity was detected in 66.7% of psychiatric patients (26/39) on day 0, in 53.9% (14/26) on day 28 and in 52.9% on day 56 (9/17). The control group was 22.2% (28/126) positive. The incidence of BDV CIC was significantly higher in psychiatric patients than in healthy individuals (p=0.001). The significantly higher level of BDV CIC was associated with the higher severity of psychopathology in comparison with patients with mild or moderate psychopathology (p=0.03). We did not find any association between BDV CIC positivity and other characteristics (age, diagnosis, family, personal history, the history of infectious diseases, contact with animals). CONCLUSION: In our study psychiatric patients had significantly higher levels of BDV CIC than the control group. The highest levels of BDV CIC were detected in patients with more severe psychopathology.

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C.

BACKGROUND: The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC). AIM: To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC. METHODS: Ninety-eight consecutive treatment-naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM-IV, at baseline and both during and after treatment. RESULTS: Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti-viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one). CONCLUSION: Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy.

Affective disorders in patients with HIV infection: impact of antiretroviral therapy.

At the beginning of the AIDS pandemic, affective disorders (such as depressed mood) were seen in a considerable number of HIV-1-infected individuals. These disorders were a result of the poor physical condition of the patients, brain involvement by the virus (e.g. encephalopathy) or a reaction to disadvantageous living conditions (losing friends, jobs, etc.). In the era of highly active antiretroviral therapy (HAART), mental illness related to physical weakness is declining, as is the incidence of HIV-1-associated encephalopathy. However, depressed mood and fatigue caused by efavirenz (a standard component of HAART) is becoming increasingly important, particularly in individuals who are infected long-term with HIV-1. Whatever the cause of affective disorders, their presence has been shown to negatively influence adherence to HAART and HIV-1 disease progression. Specialist knowledge of HIV-1 infection, and HAART and its psychiatric complications (particularly in subgroups of patients such as drug abusers and older people), is needed to care adequately for patients. Furthermore, prospective studies are needed to more fully differentiate between the various aetiologies of affective disorders seen in individuals living with HIV/AIDS and to determine their incidence and prevalence. Such information is important to ensure that affective disorders are recognised and adequately treated, which will in turn improve the efficacy of HAART.

Detection of Borna disease virus p24 RNA in peripheral blood cells from Brazilian mood and psychotic disorder patients.

BACKGROUND: Borna disease virus (BDV) is a virus that naturally infects a broad range of warm-blooded animals. BDV is an enveloped virus, non-segmented, negative-stranded RNA genome and has an organization characteristic of a member of Bornaviridae in the order of Mononegavirale. In the present work we investigated the presence of BDV p24 RNA in peripheral blood cells from 30 psychiatric patients (19 with mood disorder and 11 with psychotic disorder) and 30 healthy volunteers as the control group. METHODS: All subjects were interviewed by structured diagnostic criteria categorized according to the DSM-IV, Axis I (SCID-V). The presence of BDV p24 RNA was investigated by nested reverse transcriptase PCR (RT-PCR) using specific primers to p24 from BDV. The specificity of the detection was analyzed by the sequencing of PCR products. RESULTS: The mean duration of illness in mood and psychotic patients with p24 RNA of BDV was 25 (+/-12.3) years and the median age was 43.77 (+/-15.2) years. There were no significant differences in gender and age among patients and control group, neither duration of illness among patients with mood and psychotic disorders in the presence or absence of p24 RNA of BDV. We found a frequency of 33.33% (10/30) of BDV-RNA on patient's group and 13.33% (4/30) on control group. The given sequences revealed identity with GenBank database sequence for BDV. CONCLUSION: The detection of a higher level of BDV-RNA in the peripheral blood cells of patients than on control group should help our understanding of the pathogenesis in the disease.

Detection by radioligand assay of antibodies against Borna disease virus in patients with various psychiatric disorders.

Using a radioligand assay, which preserves the natural form of the antigen, antibodies against Borna disease virus nucleoprotein and phosphoprotein were detected in 11 and 19 sera of 171 psychiatric patients, respectively. Compared with results by Western blotting, three and nine sera were concordantly positive, respectively. The four sera showing the highest levels of antibodies by radioligand assay were all negative by Western blotting; however, dilution and inhibition tests supported the positive results. Our results suggest the importance of conformational structure to detect human anti-Borna disease virus antibodies.

Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients.

Herpes simplex virus (HSV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus-6 (HHV-6) are viruses capable of establishing latency. All of these infect the CNS and have been detected in human postmortem brains. Toxoplasma gondii is a protozoan organism which can reactivate in the brains of previously infected immunocompromised individuals. To screen for the presence of herpesviruses and T. gondii in postmortem orbital frontal brain samples from patients with schizophrenia, affective disorders, and controls, we used nested-polymerase chain reaction (n-PCR)/sequencing. We identified HHV-6B sequences in 2/51 postmortem brain samples but no sequences from other herpesviruses. We did not detect sequences of T. gondii in the postmortem brains. Additional studies including ones directed at the sensitive detection of viral nucleic acids in multiple brain regions should be directed at confirming or excluding a role for viruses and protozoa in the etiology of these disorders.

Psychiatric complications in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) infection is associated with psychiatric complications, including cognitive impairment, affective disorders, and psychosis. These psychiatric complications impair quality of life, affect disease prognosis, and impede treatment by compromising medication adherence. They also increase the likelihood of HIV transmission, either directly or via their high prevalence rate among drug abusers. In this article, the authors provide a brief overview of the most common psychiatric complications associated with HIV infection and discuss the role of dopamine as a link between psychiatric manifestations and the progression of immunodeficiency infection.

Immunological and PCR analyses for Borna disease virus in psychiatric patients and blood donors in Japan.

The involvement of Borna disease virus (BDV) in psychiatric diseases in humans remains controversial. T-cell memory response and seroprevalence of BDV in patients with psychiatric disorders and blood donors in Japan were evaluated collectively by Western blot (WB) analysis with inhibition test, electrochemiluminescence immunoassay, immunofluorescence assay, and T-cell proliferative response as well as detection of BDV p24 RNA in peripheral blood mononuclear cells (PBMCs). Positive proliferative responses to both BDV p40 and p24 proteins were detected in 9% of patients with mood disorders (4 of 45), 4% of schizophrenic patients (2 of 45), and 2% of blood donors (1 of 45). By WB analysis, the antibody to BDV p40 was detected only in 2% of patients with mood disorders (1 of 45). The BDV p24 antibody was detected in 2% of patients with mood disorders (1 of 45) and 9% of schizophrenic patients. (4 of 45) No plasma reacted with both BDV proteins. The finding of a lower seroprevalence than previously reported suggests the presence of false-positive cases in the previous report. BDV RNA was detected only in 2% of patients with mood disorders (1 of 45). In these three serological assays, T-cell responses, and PCR analysis, there was no significant difference in the prevalence among the three groups. However, we found three psychiatric patients who were positive for both BDV antibodies and T-cell proliferative responses and one patient who was positive for BDV RNA in PBMCs. These findings suggest the usefulness of the proliferative T-cell response and that certain individuals are infected with BDV or a BDV-related virus.

Self-esteem and optimism in men and women infected with HIV.

BACKGROUND: Self-esteem and optimism have been associated with appraisal and outcomes in a variety of situations. The degree to which the contribution of self-esteem and optimism to outcomes over time is accounted for by the differences in threat (primary) or resource (secondary) appraisal has not been established in persons with human immunodeficiency virus (HIV). OBJECTIVES: To examine the longitudinal relationship of personality (self-esteem and optimism) on primary and secondary appraisal and outcomes of well-being, mood, CD4+ T-lymphocyte count, and selected activities. METHODS: Men (n = 56) and women (n = 42) infected with HIV completed eight self-report measures twice over 18 months. Hierarchical Multiple Regressions were used to examine the relationship of personality variables on appraisals and outcomes. The mediating effects of primary and secondary appraisals were explored. RESULTS: Self-esteem uniquely accounted for 6% of the variance in primary appraisal and 5% in secondary appraisal. Optimism accounted for 8% of the unique variance in secondary appraisal. Primary and secondary appraisal mediated differently between personality and outcome variables. A strong predictor of well-being, mood disturbance, and activity disruption at Time 2 was participants' initial level of these variables. Socioeconomic status was a strong predictor of mood. CONCLUSIONS: Self-esteem and optimism are important but different resources for adapting to HIV disease. Strategies for reducing threats and increasing resources associated with HIV may improve an individual's mood and sense of well-being.

Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay.

The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia. Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant. The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors. Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders.

[Transmission of Borna disease virus as etiopathogenetic factor in schizophrenia and affective disorders]. / Zakazenia wirusem choroby Borna jako czynnik etiopatogenetyczny w schizofrenii oraz w chorobach afektywnych.

Borna Disease Virus (BDV) is a negative single-stranded ribonucleic acid (RNA) virus, showing strong neurotropism. BDV may infect many different warm-blooded animal species, causing neurological and behavioral disorders. Seroepidemiological studies suggest the existence of human infections with BDV and their higher prevalence in psychiatric patients. Using different serological assays, anti-BDV antibodies were found in about 10%-20% of patients with schizophrenia, and in 1%-2% of the control group of healthy subjects. There are also reports on BDV antigens and BDV RNA in peripheral blood mononuclear cells of human subjects, and in the brain tissue examined during the autopsy in patients with psychiatric disorders. Higher prevalence of BDV infection markers was also found in the group of patients with affective illness. A hypothesis was put forward on the activation of BDV-infection in patients with affective illness during acute episode. There are also reports on higher BDV-seropositivity in various psychiatric disorders compared with healthy control subjects. It also would be purposeful to study a possibility of BDV infections in patients with psychiatric disturbances, having their onset in childhood or adolescence.

Detection and sequence analysis of borna disease virus p24 RNA from peripheral blood mononuclear cells of patients with mood disorders or schizophrenia and of blood donors.

Borna disease virus (BDV) p24 RNA was detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patients and blood donors by nested reverse transcriptase PCR (RT-PCR). The prevalences of BDV p24 RNA in patients with mood disorders (4%) and schizophrenia (4%) were not significantly different from that in blood donors (2%). This finding was inconsistent with previous reports that showed either a high prevalence or absence of BDV p24 RNA in patients with psychiatric disorders. The differences in BDV p24 RNA prevalence in these studies may be due to differences in the criteria for positivity, the number of PBMCs used for RNA extraction, or the amount of RNA tested for nested RT-PCR or to laboratory contamination. Sequence analysis of BDV p24 RNA from the PBMCs of patients and blood donors showed a high nucleotide sequence conservation but definite nucleotide mutations compared with horse BDV p24 RNA sequences. In comparison with human BDV p24 RNA sequences previously reported from Japan and Germany, there were several positions with silent nucleotide mutations among these clones.