Biomedical subjects

Dennis N Bourdette

Publications and source records attributed to Dennis N Bourdette.

At least 19 recordsLinked to original sources

PubMed2006

Lipopolysaccharide pretreatment modulates the disease course in experimental autoimmune encephalomyelitis.

Treatment with the bacterial product lipopolysaccharide (LPS) prior to the induction of experimental autoimmune encephalomyelitis (EAE) consistently led to a delayed onset of disease but not to a reduction in disease severity. T cell proliferation was reduced in LPS-treated mice, due at least in part to a loss in antigen presenting cell function. T cell and macrophage infiltration into the CNS was delayed and TNFalpha production was diminished in LPS pre-treated mice, consistent with the delay in disease onset. Real-time PCR analysis of gene expression in the CNS of LPS or saline pre-treated mice demonstrated an early induction of TNFalpha, TGFbeta, IFNbeta, and SOCS3 in the LPS pre-treated mice. Thus, exposure to LPS prior to EAE induction affects antigen presentation and may modulate the expression of inflammatory regulators that impact the autoimmune disease course.

Animals↗

PubMed2006

Antigen-specific therapy promotes repair of myelin and axonal damage in established EAE.

Inflammation results in CNS damage in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. It is uncertain how much repair of injured myelin and axons can occur following highly selective anti-inflammatory therapy in EAE and MS. In this study, SJL/J mice with established EAE were treated successfully with an antigen-specific recombinant T cell receptor ligand (RTL), RTL401, a mouse I-A(s)/PLP-139-151 construct, after the peak of EAE. To define the mechanisms by which late application of RTL401 inhibits EAE, we evaluated mice at different time points to assess the levels of neuroinflammation and myelin and axon damage in their spinal cords. Our results showed that RTL401 administered after the peak of acute EAE induced a marked reduction in inflammation in the CNS, associated with a significant reduction of demyelination, axonal loss and ongoing damage. Electron microscopy showed that RTL-treated mice had reduced pathology compared with mice treated with vehicle and mice at the peak of disease, as demonstrated by a decrease in continued degeneration, increase in remyelinating axons and the presence of an increased number of small, presumably regenerative axonal sprouts. These findings indicate that RTL therapy targeting encephalitogenic T cells may promote CNS neuroregenerative processes.

Animals↗

PubMed2006

Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis.

Lipoic acid (LA) suppresses and treats murine experimental autoimmune encephalomyelitis (EAE), which models multiple sclerosis. However, the mechanisms by which LA mediates its effects in EAE are only partially known. In the present study, LA (25, 50 and 100 microg/ml) inhibited upregulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha) stimulated cultured brain endothelial cells. Immunohistochemical analysis of spinal cords from SJL mice that had received LA (100 mg/kg/day) following immunization to induce EAE exhibited markedly reduced expression of ICAM-1 and VCAM-1 compared with that of EAE mice receiving saline. Co-localization analysis showed that ICAM-1 and VCAM-1 expression increased over endothelial cells (staining positive for von Willebrand factor, vWF) in EAE and that LA decreased the expression levels to that observed in naïve mice. Spinal cords from mice receiving LA had significantly reduced inflammation (decreased CD4 and CD11b staining) as compared to EAE mice that received saline. Overall, our data suggest that the anti-inflammatory effects of LA in EAE may be partly due to inhibition of ICAM-1 and VCAM-1 expression by central nervous system (CNS) endothelial cells.

Animals↗

PubMed2006

Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of p56(Lck).

Lipoic acid is an antioxidant that suppresses and treats a model of multiple sclerosis, experimental autoimmune encephalomyelitis. We now demonstrate that treatment of human PBMC and T cell lines with LA downmodulated CD4 expression in a concentration-dependent manner. LA treatment of Con A stimulated PBMC specifically removed CD4 from the T-cell surface, but not CD3. Epitope masking by LA was excluded by using monoclonal antibodies targeting different domains of CD4. Incubation on ice inhibited CD4 removal following LA treatment, suggesting that endocytosis was involved in its downmodulation. LA is in a unique category of compounds that induce CD4 downmodulation by various mechanisms (e.g., gangliosides). We hypothesized that LA might induce dissociation of p56(Lck) from CD4, thus leading to its downmodulation. Immunoblot analyses demonstrated reduced co-precipitation of p56(Lck) from Jurkat T-cells following LA treatment and precipitation of CD4. This unique immunomodulatory effect of LA warrants further investigation.

Antioxidants↗

PubMed2004

Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis.

We have demonstrated previously the ability of the antioxidant alpha lipoic acid (ALA) to suppress and treat a model of multiple sclerosis (MS), relapsing experimental autoimmune encephalomyelitis (EAE). We describe the effects of ALA and its reduced form, dihydrolipoic acid (DHLA), on the transmigration of human Jurkat T cells across a fibronectin barrier in a transwell system. ALA and DHLA inhibited migration of Jurkat cells in a dose-dependent fashion by 16-75%. ALA and DHLA reduced matrix metalloproteinase-9 (MMP-9) activity by 18-90% in Jurkat cell supernatants. GM6001, a synthetic inhibitor of MMP, reduced Jurkat cell migration, but not as effectively as ALA and DHLA did. Both ALA and DHLA downmodulated the surface expression of the alpha4beta1 integrin (very late activation-4 antigen; VLA-4), which binds fibronectin and its endothelial cell ligand vascular cell adhesion molecule-1 (VCAM-1). Moreover, ALA, but not DHLA, reduced MMP-9-specific mRNA and extracellular MMP-9 from Jurkat cells and their culture supernatants as detected by relative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. ALA and DHLA inhibited Jurkat cell migration and have different mechanisms for inhibiting MMP-9 activity. These data, coupled with its ability to treat relapsing EAE, suggest that ALA warrants investigation as a therapy for MS.

Antioxidants↗

PubMed2004

T-cell hybridoma specific for myelin oligodendrocyte glycoprotein-35-55 peptide produced from HLA-DRB1*1501-transgenic mice.

The goal of this study was to establish an unlimited and standardized source of humanized myelin peptide-specific T cells for in vitro testing of biological function. Thus, we perpetuated myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide-specific T cells obtained from immunized HLA-DRB1*1501-transgenic (Tg) mice by somatic fusions with BW5147 thymoma cells or BW5147 T-cell receptor (TCR) alpha(-)beta(-) variant (BW5147 variant) cells. The resulting T-cell hybridomas responded strongly to both mouse MOG-35-55 (42S) and human MOG-35-55 peptide (42P), regardless of which peptide was used for initial immunization, and were DRB1*1501 restricted. The MOG-35-55-reactive T-cell hybridomas were CD3(+)CD4(+)CD8(-) and expressed intracellular Th1 cytokines upon concanavalin A stimulation. Clones from either human MOG-35-55- or mouse MOG-35-55-selected hybridomas uniquely expressed the TCR BV8 gene in combination with AV17 and AV11 genes. V gene analyses confirmed the expression of TCR AV1, AV11, AV16, BV1, and BV5 gene segments in the widely used fusion partner BW5147 and demonstrated deletion of TCR AV1, AV11, and BV1 in the BW5147 variant. T-cell hybridomas were positively stained with anti-TCR beta-chain antibody on the cell surface, whereas neither BW5147 nor its variant had positive TCR surface expression. For functional application, we found that a monomeric form of the human HLA-DR2-derived recombinant T-cell receptor ligand (RTL) covalently linked to human MOG-35-55 peptide specifically inhibited proliferation of a hybridoma clone selected with human MOG-35-55 but not a different hybridoma clone selected with myelin basic protein. The RTL-induced inhibition in vitro of the human MOG-35-55 peptide-specific hybridoma reflected the ability of the RTL to inhibit experimental autoimmune encephalomyelitis induced by human MOG-35-55 peptide in HLA-DR2 transgenic mice. Thus, the MOG-35-55 peptide-specific T-cell hybridoma from DR2-Tg mice represents a novel humanized T-cell reagent useful for standardized biological screening of both DR2-restricted stimulation and RTL-dependent inhibition of response to human MOG-35-55 peptide.

Animals↗

PubMed2004

FK506 and a nonimmunosuppressant derivative reduce axonal and myelin damage in experimental autoimmune encephalomyelitis: neuroimmunophilin ligand-mediated neuroprotection in a model of multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) in which demyelination and axonal loss result in permanent neurologic disability. We examined the neuroprotective property of the immunosuppressant FK506 (tacrolimus), FK1706 (a nonimmunosuppressant FK506 derivative) and cyclosporin A (CsA) in a chronic relapsing experimental autoimmune encephalomyelitis (EAE) model of MS. Female SJL/J mice were immunized by subcutaneous (s.c.) injection with proteolipid protein 139-151 peptide in complete Freund's adjuvant. At the onset of paralysis, 12-14 days after immunization, mice received daily s.c. injections of FK506 (0.2, 1, and 5 mg/kg), FK1706 (5 mg/kg), CsA (2, 10, and 50 mg/kg), saline or vehicle (30% dimethylsulfoxide) for 30 days. FK506 (at a dose of 5 mg/kg) reduced the severity of the initial disease and suppressed relapses. FK1706 did not significantly alter the clinical course and CsA (at a dose of 50 mg/kg) lessened the severity of the initial episode of EAE but did not alter relapses. In the thoracic spinal cord, FK506 (5 mg/kg), FK1706 (5 mg/kg), and CsA (50 mg/kg) significantly (P < 0.001) reduced the extent of damage in the dorsal, lateral, and ventral white matter by a mean of up to 95, 68, and 30%, respectively. A nonimmunosuppressant dose of FK506 (0.2 mg/kg) also significantly (P < 0.001) reduced the extent of damage in the spinal cord by a mean of up to 45%. Other dosages of these compounds were ineffective. FK506 markedly protects against demyelination and axonal loss in this MS model through immunosuppression and neuroprotection.

Animals↗

PubMed2004

Specificity of regulatory CD4+CD25+ T cells for self-T cell receptor determinants.

Although the phenotypic and regulatory properties of the CD4(+)CD25(+) T cell lineage (Treg cells) have been well described, the specificities remain largely unknown. We demonstrate here that the CD4(+)CD25(+) Treg population includes the recognition of a broad spectrum of human TCR CDR2 determinants found in the germline V gene repertoire as well as that of a clonotypic nongermline-encoded CDR3beta sequence present in a recombinant soluble T cell receptor (TCR) protein. Regulatory activity was demonstrated in T cell lines responsive to TCR but not in T cell lines responsive to control antigens. Inhibitory activity of TCR-reactive T cells required cell-cell contact and involved CTLA-4, GITR, IL-10, and IL-17. Thus, the T-T regulatory network includes Treg cells with specificity directed toward self-TCR determinants.

Antibodies, Blocking↗

PubMed2004

Monomeric recombinant TCR ligand reduces relapse rate and severity of experimental autoimmune encephalomyelitis in SJL/J mice through cytokine switch.

Our previous studies demonstrated that oligomeric recombinant TCR ligands (RTL) can treat clinical signs of experimental autoimmune encephalomyelitis (EAE) and induce long-term T cell tolerance against encephalitogenic peptides. In the current study, we produced a monomeric I-A(s)/PLP 139-151 peptide construct (RTL401) suitable for use in SJL/J mice that develop relapsing disease after injection of PLP 139-151 peptide in CFA. RTL401 given i.v. or s.c. but not empty RTL400 or free PLP 139-151 peptide prevented relapses and significantly reduced clinical severity of EAE induced by PLP 139-151 peptide in SJL/J or (C57BL/6 x SJL)F(1) mice, but did not inhibit EAE induced by PLP 178-191 or MBP 84-104 peptides in SJL/J mice, or MOG 35-55 peptide in (C57BL/6 x SJL/J)F(1) mice. RTL treatment of EAE caused stable or enhanced T cell proliferation and secretion of IL-10 in the periphery, but reduced secretion of inflammatory cytokines and chemokines. In CNS, there was a modest reduction of inflammatory cells, reduced expression of very late activation Ag-4, lymphocyte function-associated Ag-1, and inflammatory cytokines, chemokines, and chemokine receptors, but enhanced expression of Th2-related factors, IL-10, TGF-beta3, and CCR3. These results suggest that monomeric RTL therapy induces a cytokine switch that curbs the encephalitogenic potential of PLP 139-151-specific T cells without fully preventing their entry into CNS, wherein they reduce the severity of inflammation. This mechanism differs from that observed using oligomeric RTL therapy in other EAE models. These results strongly support the clinical application of this novel class of peptide/MHC class II constructs in patients with multiple sclerosis who have focused T cell responses to known encephalitogenic myelin peptides.

Amino Acid Sequence↗

PubMed2004

CD4 T-cell epitopes of human alpha B-crystallin.

Of potential importance to multiple sclerosis (MS), oligodendroglial alpha B-crystallin is expressed and associated with the myelin sheath at the earliest stage of MS lesion development. We selected T-cell lines specific for human alpha B-crystallin from peripheral blood mononuclear cells (PBMC) of HLA-DR2 homozygous MS patients and found that the alpha B-crystallin-specific T-cells were CD4+ and restricted by DRB1*1501, and expressed Th1 cytokines. The CD4 T-cell epitopes of human alpha B-crystallin were determined by proliferation of alpha B-crystallin-specific T-cell lines to 17 20-mer synthetic overlapping peptides spanning the entire molecule of human alpha B-crystallin. It was found that the HLA-DR2 donor-derived alpha B-crystallin-specific T-cell lines proliferated to alpha B-crystallin peptides 21-40, 41-60, and to a lesser extent, 131-150. These T-cell proliferation responses were associated with intracellular expression of interleukin-2 (IL-2) and secretion of interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). The amino acid sequences of these peptides were compatible with predicted HLA-DR2-restricted binding motifs. PBMC of an early active MS patient proliferated to the epitope-containing peptides significantly better than did those of later stage MS patients or healthy controls. Taken together, these findings suggest that autoreactive alpha B-crystallin-specific Th1 cells may have the potential to contribute to MS pathogenesis.

Amino Acid Sequence↗

PubMed2003

Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity.

CD4+CD25+ regulatory T cells (Treg cells) prevent T cell-mediated autoimmune diseases in rodents. To develop a functional Treg assay for human blood cells, we used FACS- or bead-sorted CD4+CD25+ T cells from healthy donors to inhibit anti-CD3/CD28 activation of CD4+CD25- indicator T cells. The data clearly demonstrated classical Treg suppression of CD4+CD25- indicator cells by both CD4+CD25(+high) and CD4+CD25(+low) T cells obtained by FACS or magnetic bead sorting. Suppressive activity was found in either CD45RO- (naive) or CD45RO+ (memory) subpopulations, was independent of the TCR signal strength, required cell-cell contact, and was reversible by interleukin-2 (IL-2). Of general interest is that a wider sampling of 27 healthy donors revealed an age- but not gender-dependent loss of suppressive activity in the CD4+CD25+ population. The presence or absence of suppressive activity in CD4+CD25+ T cells from a given donor could be demonstrated consistently over time, and lack of suppression was not due to method of sorting, strength of signal, or sensitivity of indicator cells. Phenotypic markers did not differ on CD4+CD25+ T cells tested ex vivo from suppressive vs. nonsuppressive donors, although, upon activation in vitro, suppressive CD4+CD25+ T cells had significantly higher expression of both CTLA-4 and GITR than CD4+CD25- T cells from the same donors. Moreover, antibody neutralization of CTLA-4, GITR, IL-10, or IL-17 completely reversed Treg-induced suppression. Our results are highly consistent with those reported for murine Treg cells and are the first to demonstrate that suppressive activity of human CD4+CD25+ T cells declines with age.

Adult↗

PubMed2003

CNS gene expression pattern associated with spontaneous experimental autoimmune encephalomyelitis.

Transgenic mice with T-cell receptor (TCR) specific for myelin basic protein (MBP)-Ac1-11 peptide and homozygous for the RAG-1 mutation (T/R- mice) spontaneously develop acute progressive experimental autoimmune encephalomyelitis (Sp-EAE) mediated by CD4+ T cells. Microarray analysis of spinal cord tissue obtained from symptomatic versus non-symptomatic T/R- mice revealed strongly upregulated transcripts for genes involved in antigen presentation and processing, signal transduction, transcription regulation, metabolism, development, cell cycle, and many other processes involved in the induction of clinical and pathological signs of Sp-EAE. Several highly expressed genes were related directly to inflammation, including cytokines/receptors, chemokines/receptors, acute phase, complement molecules, and others. Many CNS-specific genes were also upregulated in sick mice. Abundance of message for the Tg TCR BV8S2 gene as well as several monocyte/macrophage-associated genes would suggest that both components play a crucial role in the pathogenesis of Sp-EAE. The profile of transcriptional changes found during the development of Sp-EAE provides the first description of the encephalitogenic process in the absence of purposeful immunization with myelin peptides and immune-enhancing adjuvants. This unique approach is the first to implicate molecules and pathways that contribute naturally to onset of paralysis and demyelination, and thus may provide unique insights and novel treatment strategies for human diseases such as multiple sclerosis.

Animals↗

PubMed2003

Production, characterization, and immunogenicity of a soluble rat single chain T cell receptor specific for an encephalitogenic peptide.

The encephalitogenic rat T cell clone C14 recognizes the myelin basic protein 69-89 peptide in the context of the RT1B major histocompatibility complex (MHC) class II molecule. Modeling of the C14 TCR molecule indicated that previously identified CDR3 motifs are likely to be central to interaction with MHC class II-presented peptide. Here we report the cloning and expression of C14-derived single chain TCR (scTCR) molecules in an Escherichia coli expression system. The recombinant molecule consists of the Valpha2 domain connected to the Vbeta8.2 domain via a 15-residue linker. Soluble C14 scTCR was purified using conventional chromatography techniques and refolded by a rapid dilution procedure. C14 scTCR was able to bind soluble rat MHC class II molecules bearing covalently coupled Gp-BP-(69-89) peptide, as analyzed using surface plasmon resonance. Immune recognition of the C14 scTCR protein as an antigen revealed that limited regions of the TCR may be more likely to induce responsiveness.

Amino Acid Sequence↗

PubMed2003

Dysregulation of the hypothalamic-pituitary-gonadal axis in experimental autoimmune encephalomyelitis and multiple sclerosis.

The ability of sex hormones to regulate cytokine production is well established, but the ability of cytokines to regulate sex hormone production has only begun to be investigated. We measured sex hormones in mice with passive experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS) patients with sexual dysfunction. Abnormally low serum testosterone levels were found in male mice with EAE and in male MS patients, while serum estrogen levels in female mice with EAE were normal. An inverse relationship between cytokine and testosterone levels in male mice with EAE, coupled with an increase in serum luteinizing hormone (LH) levels, suggests that inflammatory cytokines suppress testosterone production by a direct effect on testicular Leydig cells. Gender differences in the sensitivity of the hypothalamic-pituitary-gonadal (HPG) axis to inflammation may be an important factor regulating the duration and severity of central nervous system (CNS) autoimmunity.

Adult↗

PubMed2002

Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis.

Oxidative injury may be important to the pathogenesis of multiple sclerosis (MS). We tested the antioxidant alpha lipoic acid (ALA) in an experimental murine model of MS, experimental autoimmune encephalomyelitis (EAE). ALA was administered to SJL mice 7 days after immunization with proteolipid protein (PLP) 139-151 peptide. Mice that received 5-100 mg/kg/day of ALA had dose-dependent reductions in their 10-Day Cumulative Disease Scores (10-Day CDS) by 23-100%. Minimal inflammation, demyelination and axonal loss occurred in the spinal cords (SC) of ALA-suppressed mice, and there was a marked reduction in CD3+ T cells and CD11b+ monocyte/macrophage cells within the SC. Mice treated with ALA (100 mg/kg/day) commencing on the first day of clinical EAE had a significant reduction in 10-Day CDS. SC of ALA-treated mice had reduced demyelination and axonal loss and a rapid reduction in CD3+ T cells. In vitro, ALA and its reduced form, dihydrolipoic acid, inhibited the activity of matrix metalloproteinase-9 (MMP-9) in a dose-dependent fashion. ALA is highly effective at suppressing and treating EAE and does so by inhibiting T cell trafficking into the SC, perhaps by acting as a matrix metalloproteinase inhibitor.

Acute Disease↗

PubMedDate not supplied

Chronic fatigue in a population-based study of Gulf War veterans.

Fatigue has been associated with illness in veterans of the Gulf War; however, few studies have confirmed self-reported fatigue by using clinical evaluation, and symptomatic veterans have not been evaluated with established criteria for Chronic Fatigue Syndrome (CFS). The authors describe the frequency and clinical characteristics of CFS in a sample of veterans residing in the northwestern United States. The sample was selected randomly from U.S. Department of Defense databases of troops deployed to southwest Asia during the Gulf War. The selected individuals were invited to participate in a clinical case-control study of unexplained illness. Of 799 survey respondents eligible for clinical evaluation, 178 had fatigue symptoms. Of the 130 veterans who were evaluated clinically, 103 had unexplained fatigue, and 44 veterans met the 1994 U.S. Centers for Disease Control criteria for CFS. In this population, the authors estimated a minimum prevalence of any unexplained fatigue to be 5.1%, and of CFS to be 2.2%. The estimated prevalence was greater among females than among males. Cases were similar to healthy controls, as determined by laboratory tests and physical findings. In comparison to several clinical studies of CFS patients, the authors of this study found a lower proportion of veterans who reported a sudden onset of symptoms (19%) vs. a gradual onset (50%). Although it has previously been suggested that veterans of the Gulf War suffer from higher rates of chronic fatigue than the general population, the study results described herein--on the basis of clinical examination of a population-based sample of veterans-actually indicate that an increased rate may indeed exist. Gulf War veterans with unexplained fatigue should be encouraged to seek treatment so that the impact of these symptoms on overall quality of life can be reduced.

Adult↗

PubMedDate not supplied

Some effects of multiple sclerosis on speech perception in noise: Preliminary findings.

The present investigation examined speech perception in noise of adults with and without multiple sclerosis (MS). Institute of Electrical and Electronic Engineers (IEEE) sentences were presented at a constant level of 65 dBA L(eq) (equivalent continuous noise level [4 dB exchange rate]) from a loudspeaker located at 0-degree horizontal azimuth and 1.2 m from the study participant. Uncorrelated multitalker babble was presented from four loudspeakers positioned at 45-, 135-, 225-, and 315-degree azimuths and 1.7 m from the study participant. The starting presentation level for the babble was 55 dBA L(eq). The level of the babble was increased systematically in 1 dB steps until the subject obtained 0% key words correct on the IEEE sentences. Results revealed a significant difference in speech perception between the two groups at nine signal-to-noise ratios. Some clinical implications of these results are discussed.

Adult↗

PubMedDate not supplied

Correlations of Perceived Deficits Questionnaire of Multiple Sclerosis Quality of Life Inventory with Beck Depression Inventory and neuropsychological tests.

The Perceived Deficits Questionnaire (PDQ) is a part of the Multiple Sclerosis (MS) Quality of Life Inventory that assesses self-perceived cognitive difficulties. We used baseline data from 49 MS subjects participating in a clinical trial to evaluate the correlation of the PDQ with two measures of cognitive impairment, the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test, 2nd edition (CVLT-II), total score, and one measure of depression, the Beck Depression Inventory-Amended (BDI-IA). The PDQ correlated significantly (r = 0.42; 95% confidence interval [CI], 0.15 to 0.62; p = 0.003) with the BDI-IA scores but not with either the PASAT (r = -0.22; 95% CI, -0.48 to 0.06; p = 0.2) or the CVLT-II total (r = -0.17; 95% CI, -0.43 to 0.12; p = 0.25). A subset of 38 of these subjects who scored worse than 0.5 standard deviation below the mean on the PASAT or CVLT-II received a more extensive neuropsychological battery of tests. No significant correlations were found between any of these tests and the PDQ. These results suggest that self-perceived cognitive dysfunction relates more to depression than to objective cognitive dysfunction.

Adolescent↗