Does Acute Propranolol Treatment Prevent Posttraumatic Stress Disorder, Anxiety, and Depression in Children with Burns?

OBJECTIVE: This study examined whether acute propranolol treatment prevented posttraumatic stress disorder (PTSD), anxiety, and depression in children hospitalized in the pediatric intensive care unit for large burns. We hypothesized that the prevalence of PTSD, anxiety, and depression would be significantly less in the propranolol than nonpropranolol groups. METHODS: Children who had previously participated in a randomized controlled clinical trial of acute propranolol and nonpropranolol controls were invited to participate in long-term follow-up interviews. Eligible participants from 1997 to 2008 were identified from the electronic medical records, and data were collected in 2010-2011. Measures included the Missouri Assessment of Genetics Interview for Children to assess lifetime PTSD, Revised Children's Manifest Anxiety Scale to assess anxiety, and two depression inventories Children's Depression Inventory and Beck Depression Inventory-II. RESULTS: Of 202 participants, 89 were in the propranolol group and 113 were nonpropranolol controls. Children were an average of 7 years postburn. The average total body surface area burned was 56.4 + 15.1% (range = 24%-99%). The mean dose of propranolol was 3.64 ± 3.19 mg/kg per day (range = 0.36-12.12). The duration of propranolol inpatient treatment days varied, mean days 26.5 ± 19.8. The prevalence of lifetime PTSD in the propranolol group was 3.5% and controls 7.2%, but this difference was not statistically significant. We controlled for administration of pain medications, anxiolytics, and antidepressants overall and no significant differences were detected in the rates of PTSD, anxiety, or depression. CONCLUSIONS: The prevalence of PTSD, anxiety, and depression was similar in children who received propranolol acutely and those who did not. This may be influenced by the standard of care that all children received timely pharmacotherapy for pain and anxiety management and psychotherapy beginning in their acute phase of treatment.

Does acute stress disorder predict subsequent posttraumatic stress disorder in pediatric burn survivors?

OBJECTIVE: This study examined the prevalence of posttraumatic stress disorder (PTSD) in pediatric burn survivors who had been treated for acute stress disorder (ASD) symptoms during their initial hospitalization and compared them to patients who had been asymptomatic for ASD symptoms. METHOD: Participants were identified from electronic medical records from 1995 to 2008 and data were collected from 2006 to 2008. Participants were primarily matched on total body surface area burned and gender, and as close as possible on age at time of burn and number of years postburn. Pediatric burn survivors completed a semistructured clinical interview, the Missouri Assessment of Genetics Interview for Children-PTSD section, which is based on criteria from the DSM-IV for evaluating lifetime PTSD. RESULTS: There were 183 participants in the study, and from this sample 85 matched pairs were identified. Most were 5 years postburn. The prevalence of PTSD at the time of follow-up was 8.24% (7 of 85) for the ASD group and 4.71% (4 of 85) for the non-ASD comparison group. No significant differences were found between these groups at P value ≥ .05. A logistic regression analysis was conducted to determine if prior ASD diagnosis, burn size, gender, ethnicity, age at time of study participation, and number of years postburn predicted subsequent PTSD. None of the variables were significant predictors. CONCLUSION: The prevalence of PTSD was similar in children who had ASD symptoms and those without ASD symptoms. The lifetime prevalence of PTSD was lower than reported in other studies. A possible explanation for this finding is that children received timely pharmacotherapy and psychotherapy during their acute hospitalization.

Quality of Life of Young Adult Survivors of Pediatric Burns Using World Health Organization Disability Assessment Scale II and Burn Specific Health Scale-Brief: A Comparison.

The objective was to determine long-term psychological distress and quality of life (QOL) in young adult survivors of pediatric burns using the World Health Organization Disability Assessment Scale II (WHODAS) and the Burn Specific Health Scale-Brief (BSHS-B). Fifty burn survivors 2.5 to 12.5 years postburn (16-21.5 years old; 56% male, 82% Hispanic) completed the WHODAS and BSHS-B. The WHODAS measures health and disability and the BSHS-B measures psychosocial and physical difficulties. Scores were calculated for each instrument, and then grouped by years postburn, TBSA, sex, burn age, and survey age to compare the effects of each. Next, the instruments were compared with each other. The WHODAS disability score mean was 14.4 ± 2.1. BSHS-B domain scores ranged from 3 to 3.7. In general, as TBSA burned increased, QOL decreased. Female burn survivors, survivors burned prior to school entry, and adolescents who had yet to transition into adulthood reported better QOL than their counterparts. In all domains except Participation, the WHODAS consistently identified more individuals with lower QOL than the BSHS-B. Young adult burn survivors' QOL features more disability than their nonburned counterparts, but score in the upper 25% for QOL on the BSHS-B. This analysis revealed the need for long-term psychosocial intervention for survivors with larger TBSA, males, those burned after school entry, and those transitioning into adulthood. Both instruments are useful tools for assessing burn survivors' QOL and both should be given as they discern different individuals. However, the WHODAS is more sensitive than the BSHS-B in identifying QOL issues.

Self-perceptions of young adults who survived severe childhood burn injury.

The transition of pediatric burn survivors into adulthood is accompanied by a reformulation of their self-concept. To anticipate the need for and guide development of appropriate psychosocial interventions, this study examines how young adults who were burned as children perceive themselves and how this perception might affect their self-esteem. Eighty-two young adult burn survivors (45 male, 37 female) were assessed using the Tennessee Self-Concept Scale, 2nd edition (TSCS2) to determine how the participants perceive themselves and their interaction with society. To gain insight into the possible effects of these self-concept scores, relationships were analyzed between self-concept, a behavioral assessment (Young Adult Self-Report [YASR]), and a psychiatric symptom assessment (Structured Clinical Interview for DSM-IV Axis I Disorders [SCID I]). This group of burn survivors scored significantly lower in self-concepts, reflected in TSCS2 subscale scores of physical function, appearance, and sexuality, moral conduct, personal values, academics and work, and identity, than did the reference population. Pearson correlation coefficients showed that as moral, personal, family, and social aspects of self-concept decreased, clinical problems endorsed on the YASR subscales increased, including anxiety, somatic, attention, intrusive, and aggressive. Persons with lower self-concept scores on the TSCS2 personal, family, and social scales were more withdrawn on the YASR. Similarly, those with lower TSCS2 scores on the personal and family scales endorsed significantly more thought problems on the YASR. TSCS2 total self-concept, personal, and all of the supplementary scale scores were significantly lower for the group with an affective disorder. Those whose SCID I scores were consistent with a current anxiety disorder had significantly lower scores for the TSCS2 total self-concept and personal. Lower self-concept was associated with endorsement of SCID symptoms. In summary, the significantly lower self-concept scores on the TSCS2 physical scale are consistent with the physical disfigurement and handicaps common with major burn injuries, and a strong indication of this group's perception of the first impression made when interacting with others. The survivors seem to feel worthwhile within the contexts of family and friends. Although the major limitation of this study using the TSCS2 is the lack of a matched reference population to compare the burn survivors, the TSCS2 does help in gaining insight into the self-esteem issues of the burn survivor population.

Itch assessment scale for the pediatric burn survivor.

The objective of the study is to evaluate the validity and reliability of the Itch Man Scale developed in 2000 by Blakeney and Marvin in assessing the intensity of itch in the pediatric burn patient. Forty-five patients (31 males and 14 females; average age 9.9 ± 5.0 years; and % TBSA burned 41 ± 25%) with an established itch complaint were studied. They were asked to describe the severity of their itch by two independent raters to determine test-retest reliability. Individuals aged 6 years or older were assessed using parental informants. Concurrent validity was determined by comparing three scales to quantify the level of itch: the Itch Man Scale (a 5-point Likert scale), the 5-D Itch Scale (adapted from a scale for peripheral neuropathy), and the Visual Analog Scale for itch. Itch Man Scale ratings collected from independent raters showed a strong correlation (r = .912, P < .0001). The Itch Man Scale also correlated significantly with the Visual Analog Scale, the gold standard for measurement of pruritus (r = .798, P < .0001). The total summated score of the Duration, Degree, Direction, and Disability domains from the 5-D Itch Scale had a significant correlation with the Itch Man Scale (r = .614, P < .0001). The Degree domain is the only individual component with a significant correlation (r = .757, P < .0001). The Itch Man Scale is a reliable and valid tool to assess itching in pediatric burn patients and to quantify postburn pruritus.

Personality disorders in young adult survivors of pediatric burn injury.

OBJECTIVE: Life experience shapes personality and chronic trauma in childhood has been associated with risk for development of subsequent personality disorder. The purpose of this study is to determine the prevalence and character of personality disorders and traits in young adult survivors of severe pediatric burn injury. METHOD.: SCID-II and 16PF were completed by 98 young adult survivors of pediatric burn trauma. RESULTS: 48 (49%) met criteria for one or more personality disorders. The most frequent personality disorders were Paranoid (19.4%), Passive Aggressive (18.4%), Antisocial (17.3%), Depressive (11.2%), and Borderline (9.2%). Diagnosis with a personality disorder was associated with comorbid Axis I diagnoses and strongly correlated with personality traits as measured by the 16PF. CONCLUSIONS: Pediatric burn trauma is similar to other chronic traumas of childhood in significant correlation with subsequent personality disorder.

County-level estimates of need for mental health professionals in the United States.

OBJECTIVE: The goal of this study was to develop the best current estimates of need for mental health professionals in the United States for workforce planning and to highlight major data gaps. METHODS: Need was estimated indirectly, on the basis of several steps. The 2001 National Comorbidity Survey Replication (NCS-R) (N=9,282) was used to model the probability of having serious mental illness, given demographic predictors. Synthetic estimation was then used to construct national and county-level prevalence estimates for adults in households. Provider time needed by these adults was estimated from NCS-R respondents with serious mental illness who used mental health services (N=356); provider time needed by adults without serious mental illness was estimated from respondents to the 2000 Medical Expenditure Panel Survey (MEPS) (N=16,418). National mental health professional workforce practice patterns were used to convert need estimates to full-time equivalents (FTEs). RESULTS: Adult service users with serious mental illness typically spend 10.5 hours per year with nonprescriber mental health professionals and 4.4 hours per year with prescriber mental health professionals or primary care physicians in mental health visits; adults without serious mental illness spend about 7.8 minutes with nonprescriber mental health professionals and 12.6 minutes with prescriber mental health professionals or primary care physicians in mental health visits per year. With adjustment for mental health services provided by primary care practitioners, the estimated 218,244,402 members of the U.S. adult civilian household population in 2006 required 56,462 FTE prescribing and 68,581 FTE nonprescribing mental health professionals. CONCLUSIONS: Available data indicate that need across the United States varies by demography and geography. These estimates are limited by several issues; in particular, they are based on current provider treatment patterns and do not address how much care ideally should be provided and by whom. Improved estimates will require refined standards of care and more extensive epidemiological data.

County-level estimates of mental health professional shortage in the United States.

OBJECTIVE: This study examined shortages of mental health professionals at the county level across the United States. A goal was to motivate discussion of the data improvements and practice standards required to develop an adequate mental health professional workforce. METHODS: Shortage of mental health professionals was conceptualized as the percentage of need for mental health visits that is unmet within a county. County-level need was measured by estimating the prevalence of serious mental illness, then combining separate estimates of provider time needed by individuals with and without serious mental illness derived from National Comorbidity Survey Replication, U.S. Census, and Medical Panel Expenditure Survey data. County-level supply data were compiled from professional associations, state licensure boards, and national certification boards. Shortage was measured for prescribers, nonprescribers, and a combination of both groups in the nation's 3,140 counties. Ordinary least-squares regression identified county characteristics associated with shortage. RESULTS: Nearly one in five counties (18%) in the nation had unmet need for nonprescribers. Nearly every county (96%) had unmet need for prescribers and therefore some level of unmet need overall. Rural counties and those with low per capita income had higher levels of unmet need. CONCLUSIONS: These findings identified widespread prescriber shortage and poor distribution of nonprescribers. A caveat is that these estimates of need were extrapolated from current provider treatment patterns rather than from a normative standard of how much care should be provided and by whom. Better data would improve these estimates, but future work needs to move beyond simply describing shortages to resolving them.

Psychiatric disorders in long-term adjustment of at-risk adolescent burn survivors.

This study investigated the point prevalence of psychiatric disorders among adolescent long-term burn survivors. Psychiatric symptoms and diagnoses were assessed in 50 youth (30 males, 20 females) characterized as troubled by their parent or guardian on the Child Behavior Checklist from a sample of 93 adolescent burn survivors. Those selected for further evaluation had a mean age at time of burn injury of 4.5 +/- 3.7 years and the mean age at time of diagnostic interview was 14.9 +/- 1.6 years. The average burn injury size among participants was 42 +/- 25% total body surface area. Psychiatric diagnoses were assessed with the computerized diagnostic interview schedule for children. Just over half of these youth (52%) met criteria for one or more psychiatric disorders and many had two or more diagnoses (22%). The most common psychiatric diagnoses were anxiety disorders (36%), followed by substance use (18%) and disruptive behavior disorders (14%). In comparison to previous reports, this study found lower rates of current psychiatric disorders in adolescent burn survivors, even though the participants were considered troubled by a parent. Although there were lower rates of anxiety disorders, especially posttraumatic stress disorder, there were higher rates of substance use disorders and a shift in type of behavior disorders in contrast to previous reports. Although there are limitations in such comparisons, this may indicate changes in the risk factors encountered by adolescent survivors of burn injury.

Self-reported psychopathology among young, low-income, female ecstasy users.

This study examined the association of ecstasy (methylenedioxy-methylamphethamine) use with psychopathology among young, low-income females who sought care at university family planning clinics in Texas between December 2001 and May 2003. Participants reported drug use history and eight problem behavior syndromes by using the Young Adult Self-Report. The prevalence of ecstasy use was approximately 15%. About 90% of ecstasy users reported having used other drugs. Overall, ecstasy users were more likely to have exhibited delinquent behaviors and thought problems than exclusive marijuana users. Ecstasy users who continued to use any illicit drugs showed the most severe psychopathology. These findings indicate that elevated rates of self-reported psychopathology among ecstasy users may be partly attributable to the use of multiple drugs. Furthermore, it will also be important for future studies to assess the extent to which delinquent behaviors and thought problems mediate the transition of marijuana use to ecstasy use.

Differences in behavioral perceptions between young adult burn survivors and cross-informants.

The purpose of this study is to gain insight into the level of agreement, in terms of personal problems, between burn survivors and an informant with whom they have a close personal relationship. Participants in the study were 72 young adult burn survivors between the ages of 18 and 28 with a mean age of 20.9 +/- 2.6 years. There were 37 males and 35 females in the group. The mean total burn surface area was 55.34 +/- 19.9% with injuries occurring before the age of 18, a minimum of 2 years prior to the study with a mean of 14.3 +/- 4.9 years since burned. To assess this issue the participants completed The Young Adult Self-Report (YASR), and the informants completed The Young Adult Behavior Checklist (YABCL). In relationship to burn survivors, the informant group comprised 67% mothers, 3% fathers, and 30% domestic partners. Paired t-test and Pearson Correlations Coefficients were calculated to compare the differences and variance of the Total Problems Scale, Internalizing Scale and Externalizing Scale for the YABCL and YASR results. The family members of burn survivors reported more problems for their young adult relatives than did the informants of the reference population. In general, the YACBL scores were higher than and highly correlated to the YASR scores. Although there were not ethic differences in the YABCL and the YASR measures, the correlation between the YABCL and the YASR was excellent for Caucasian families but not good for Black and Hispanic families. This study supports concerns about the need for routine follow-up into adulthood for those individuals who were burned as children. This would seem to be especially critical for the female population.

Prevalence of major psychiatric illness in young adults who were burned as children.

OBJECTIVE: To determine the prevalence of major psychiatric illness in a group of young adults who suffered significant burn injury as children. METHOD: A total of 101 persons (58 males, 43 females), aged 21 +/- 2.6 years, 14.0 +/- 5.4 years postburn of 54% +/- 20% total body surface area, were assessed for serious past and present mental illness by using a Structured Clinical Interview (SCID) for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Axis I diagnoses. RESULTS: The SCID findings demonstrated that the prevalence of any Axis I major mental illness was 45.5% for the past month (current) and 59.4% for lifetime. These rates of overall disorder and the rates for most specific disorders were significantly higher than those found in the US population of comparable age. Logistic regression was used to examine demographic and burn characteristics as predictors of current and lifetime psychiatric disorder within the burn survivor sample. The female gender was significantly associated with higher rates of any current disorder. Other demographic and burn characteristics were not significantly related to the overall prevalence of current or lifetime disorder. Only a small number of those with disorders reported any current mental health treatment. CONCLUSIONS: Significant burn injury as a child leads to an increased risk of developing a major mental illness. Young adults who suffered major burn injury as children should be screened for these illnesses to initiate appropriate treatment.

The importance of family environment for young adults burned during childhood.

This study examined the role of family environment for young adult burn survivors making the transition from adolescence to adulthood. Ninety-three young adults who sustained large burns as children were asked to describe their families using the Family Environment Scale (FES). When examining the difference between burn survivors and the normative sample of the FES, burn survivors did not perceive their current family environment different than the normative group. However, burn survivors endorsed more items in the areas of achievement orientation and moral-religious emphasis, and less involvement in intellectual-cultural activities. We also examined the relationship between family characteristics on the FES and psychological adjustment of burn survivors as measured by the Young Adult Self-Report (YASR). Increased conflict on the FES was positively associated with YASR total problem score, internalizing behaviors, and externalizing behaviors. In addition, participation in recreational and social activities and organization both inversely correlated with YASR total problem score. In conclusion, increased family conflict was associated with decreased psychological adjustment of burn survivors as measured by the YASR total problem score.

Assessing potential suicide risk of young adults burned as children.

This study examines potential for suicide risk among young adults burned as children and examines characteristics associated with potential risk. Eighty-five young adults were administered the Suicide Probability Scale, which contains four clinical subscales: suicide ideation, hopelessness, negative self-evaluation, and hostility; the 16 Personality Factor Questionnaire; and the Family Environment Scale. Burn survivors reported more feelings of hopelessness in comparison to the reference group. High anxiety was positively associated with hopelessness, suicide ideation, hostility and negative self-evaluation whereas high extroversion was inversely related with hopelessness, negative self-evaluation, and hostility. Multiple regression analyses revealed emotional stability explained 29% of the variance, self-reliance 17% of the variance, and both 38% of the variance in relation to Suicide Probability Scale scores; and increased family conflict 12% of the variance. Results suggest that high anxiety, emotional reactivity, and family conflict correlate with increased potential suicide risk; whereas, extroversion correlates with decreased risk.

Carceral suicides--some exceptions and paradoxes.

Beginning with Daniel's findings and recommendations regarding prison suicides, this commentary extends the discussion to include jail suicides. Some paradoxes and exceptions to general trends and recommendations are highlighted to advance the discussion on demographic correlates, screening methods, and interventions intended to prevent suicide in jails and prisons.

The continuing shortage of child and adolescent psychiatrists.

OBJECTIVE: The national shortage of child and adolescent psychiatrists has prompted efforts to improve recruitment. It is uncertain whether these efforts will be sufficient to address this shortage and its impact on youth mental health services. METHOD: Data were compared from 1990 to 2001 by state, county characteristics, number of youths, and percentage of youths living in poverty to determine any changes in the number and distribution of child and adolescent psychiatrists. Trends in the number of residents and age distribution of child and adolescent psychiatrists were also analyzed. RESULTS: The number of child and adolescent psychiatrists has increased, but it still falls below estimates projected to adequately serve youth mental health needs. Disparities in child and adolescent psychiatrist distribution persist, with significantly fewer in rural counties or counties with a high percentage of children living in poverty. The age of child and adolescent psychiatrists has shifted, with fewer below age 35. The number of residents in training has not changed significantly since 1995. CONCLUSIONS: The shortage of child and adolescent psychiatrists remains and is still accentuated for those living in rural areas or in poverty. Despite the increased number of child and adolescent psychiatrists, the number of residents and changes in workforce age indicate that the shortage will continue.

Patterns and perceptions of ecstasy use among young, low-income women.

A significant number of young, low-income women experiment with ecstasy outside of club or rave settings. The current study examined patterns and risk factors of ecstasy use among this group of women. A cross-sectional survey was conducted among 696 women aged 18 to 31 who sought gynecological care from two university clinics in southeast Texas between December 1, 2001, and May 30, 2003. Fifteen percent of participants reported ever using ecstasy. Of those, over 90% used it at a friend's home. Compared with women who used only marijuana or other illicit drugs, ecstasy users were more likely to be white, use a larger number of other drugs, be willing to use drugs in the future, and have more friends who used drugs. Fewer ecstasy users strongly disapproved of adult drug use than users of other illicit drugs. Future interventional efforts should target young, low-income women to prevent future experimentation with illicit drugs.

Abnormal striatal dopaminergic synapses in National NeuroAIDS Tissue Consortium subjects with HIV encephalitis.

People with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) have neurological problems that overlap with diseases associated with abnormal dopaminergic (DAergic) synaptic transmission, including subcortical dementia, motor slowing, psychosis, and drug addiction. Previous study has suggested that DAergic tone may be decreased in HIV/AIDS, but biochemical confirmation of that tenet is still lacking. To that end, this study addresses the neurochemical interaction between HIV infection and DAergic synaptic transmission in human brain specimens. Protein markers of DAergic synapses were characterized in homogenates of the corpus striatum from individuals with HIV encephalitis (HIVE) and seronegative controls from the autopsy cohort of the National NeuroAIDS Tissue Consortium. Striatal DAergic markers were abnormal in HIVE. Abnormal presynaptic markers included decreased tyrosine hydroxylase (TH) protein and decreased phosphorylated TH. The presynaptic dopamine reuptake transporter (DAT) was increased reciprocally. Postsynaptic abnormalities included decreased dopamine receptor type 2 (D(2)R) and increased D(3)R. There was preferential loss of the alternatively spliced long isoform of D(2)R relative to the short isoform. Abnormal DAergic synapse proteins were significantly correlated with the HIV Gag mRNA transcripts amplified in striatal extracts. These synaptic changes resemble shifts that occur when DAergic tone is increased experimentally. Increased DAergic tone leads to heightened salience for drugs of abuse, increases behaviors that increase the risk of HIV transmission, and might decrease compliance with antiretroviral medication regimens.

Early treatment of acute stress disorder in children with major burn injury.

OBJECTIVE: This study examines retrospectively the response rate of pediatric burn survivors with acute stress disorder to either imipramine or fluoxetine. METHODS: On retrospective chart review, 128 intensive care unit patients (85 boys, 43 girls) with 52%+/- 20% total body surface area burn, length of stay of 32.8+/- 25.2 days, mean age of 9.1+/- 4.7 yrs, and age range of 13 months to 19 yrs met criteria for acute stress disorder after >or=2 days of symptoms and were treated with either imipramine or fluoxetine. If significant improvement did not occur within 7 days, the medication was either increased or switched to the other class. RESULTS: Initially, 104 patients were treated with imipramine and 24 with fluoxetine. A total of 84 patients responded to imipramine: seven of these patients required a higher dose. A total of 18 patients responded to initial fluoxetine treatment. Of 26 nonresponders to the initial medication, 13 imipramine failures and one fluoxetine failure refused further treatment. The other 12 responded to the second medication. Therefore, 114 of 128 treated patients (89%) responded to either fluoxetine (mean dose, 0.30+/- 0.14 mg/kg) or imipramine (mean dose, 1.30+/- 0.55 mg/kg). Response was independent of sex and age but was less for those with burns of >60% total body surface area. The side effects of each medication were not significant. Most patients continued treatment for >or=3 months; some required 6 months of treatment before successful discontinuation. CONCLUSIONS: Early treatment of acute stress disorder with either imipramine or fluoxetine is often able to reduce its symptoms. This is a review of a single hospital's experience in managing psychiatric distress in this very high-risk group of burned children. Additional clinical studies are needed before generalizing these findings.

Potential role for white matter lysosome expansion in HIV-associated dementia.

Expansion of the lysosomal apparatus occurs in subcortical white matter in brains from persons with AIDS. This study examined whether HIV-associated subcortical dementia (HAD) is significantly related to this lysosomal anomaly. Brain cortex and adjacent white matter from the middle frontal gyrus were obtained from the National NeuroAIDS Tissue Consortium. Lysosomal hydrolase activity was assayed in 57 subjects who underwent neuropsychological testing within 6 months prior to autopsy. Decedents were evaluated from 4 geographical sites in the United States: Galveston/Houston, Texas (n = 36), Los Angeles, California (n = 5), New York, New York (n = 5), and San Diego, California (n = 11). Increased beta-glucuronidase activity, a representative lysosomal glycosidase, was correlated with the amount of neurocognitive impairment. Significant correlation was present in 5 of 7 functional testing domains, including some that draw upon frontal lobe output (r = 0.419; P < 0.002). The biochemical anomaly was negligible in cerebral cortex and cerebrospinal fluid and was not correlated with brain dysfunction in those compartments. Glycosidase activation was associated significantly with increased HIV RNA concentration in brain tissue (r = 0.469; P < 0.021) and possibly with HIV RNA in cerebrospinal fluid (r = 0.266; P < 0.067). HIV RNA in blood plasma was not correlated. These results support the suggestion that abnormal metabolism in white matter glial cells contributes to cognitive slowing in persons with HAD. Because membrane turnover is routed through the endosome-lysosome apparatus, these data are in agreement with brain spectroscopic data that have suggested that there is an increase in membrane turnover in white matter glia.