Knut Hestad

Raised plasma levels of tumor necrosis factor alpha in patients with depression: normalization during electroconvulsive therapy.

Objective To examine whether electroconvulsive therapy (ECT) could modulate tumor necrosis factor (TNF)&agr; levels in patients with depressive disorders. Method Plasma levels of TNF&agr; were analyzed in 23 depressed patients, mainly with severe depressive disorders, and in 15 sex- and age-matched healthy controls. Fifteen depressed patients were followed longitudinally with measurement of TNF&agr; before, during, and after repeated ECT treatment. For comparison, TNF&agr; levels were also analyzed longitudinally in the 8 depressed patients not receiving ECT. Results Patients with depressive disorders had markedly raised TNF&agr; levels compared with healthy controls. The clinical improvement during repeated ECT was accompanied by a gradual and significant decline in TNF&agr; level, reaching levels comparable with those in healthy controls at the end of the study. Such a decline was not seen in the depressed patients not receiving ECT, who instead showed raised TNF&agr; levels throughout the study period. Conclusion Our findings support an association between inflammation and TNF&agr; in particular and severe depression, and suggest that ECT may down-regulate this immune activation.

Cardiovascular disease in autoimmune rheumatic diseases

Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may play an important role in atherogenesis. Inflammation and complement depositions in the vessel wall are likely to contribute to vascular stiffness. Based on biopsy findings, also inflammation in the myocardium and small vessels may contribute to premature CVD in ARDs (cardiac ischemia and heart failure). There is an enormous need for an improved CVD prevention in ARDs. Studies examining the effect of DMARDs/biologics on vascular inflammation and CV risk are warranted.

The quantitative EEG theta/beta ratio in attention deficit/hyperactivity disorder and normal controls: Sensitivity, specificity, and behavioral correlates

The purpose of the present study was to determine if the theta/beta ratio, and theta and beta separately, correlate with behavioral parameters, and if these measures discriminate between children and adolescents with attention deficit/hyperactivity disorder (ADHD) and normal gender- and age-matched controls. Participants comprised 62 patients and 39 controls. A continuous performance test (CPT), a GO/NOGO test and two rating scales were used to measure behavior in the patient group. EEG spectra were analyzed in eyes-closed and eyes-opened conditions, and in a GO/NOGO task in both groups. Neither the theta/beta ratio at CZ, nor theta and beta separately, discriminated significantly between patients and controls. When each person was compared with the database, significant elevations of theta were found in 25.8% of the patients and in only one control subject (2.6%). In the ADHD group, theta at CZ was positively correlated with inattention and executive problems and negatively correlated with hyperactivity/impulsivity. Beta correlated with good attention level in the control group, but with ADHD symptoms in the patients. Omission errors in the GO/NOGO test discriminated between patients and controls with an accuracy of 85%. For theta at CZ, the accuracy was 62%. Significantly elevated theta characterized a subgroup of ADHD patients, and correlated with inattention and executive problems.

Cognitive Function in Type 1 Diabetic Adults With Early Exposure to Severe Hypoglycemia A 16-year follow-up study

OBJECTIVE We assessed adulthood cognition in relation to early exposure to severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS Sixteen years subsequent to a study of cognitive function in 28 diabetic children and 28 matched control subjects, we reexamined the same subjects with a 96% participation rate. Diabetic subjects were classified as with (n = 9) or without (n = 18) early (≤10 years of age) SH, which was defined as convulsions or loss of consciousness. RESULTS Overall, cognitive scores were 0.9 SDs lower in subjects with early SH compared with subjects without early SH (P = 0.003). The two diabetic groups particularly differed with respect to problem solving, verbal function, and psychomotor efficiency. Earlier age at first incident of SH was associated with poorer cognition (P for trend = 0.001). CONCLUSIONS The findings suggest that early exposure to SH may have lasting and clinically relevant effects on cognition.

Cognitive outcome in children and adolescents treated for acute lymphoblastic leukaemia with chemotherapy only

Objective: To examine cognitive outcome in children and adolescents with acute lymphoblastic leukaemia (ALL) in remission, treated with central nervous system prophylactic chemotherapy only.

Sex Differences in Neuropsychological Performance as an Effect of Human Immunodeficiency Virus Infection: A Pilot Study in Zambia, Africa

Abstract This study examined whether there are neuropsychological performance differences between human immunodeficiency virus–seropositive participants being followed at a University of Zambia clinic and demographically comparable seronegative controls being tested for infection in the same setting. All participants were administered a standardized neurocognitive test battery that has been found sensitive to HIV-associated Neurocognitive Disorder in the United States and internationally (e.g., in China, India, Romania, and Cameroon). The test battery was found to be applicable to a Zambian population. A clear HIV effect was seen with a medium to large overall effect size (Cohen d = 0.74). However, it was only the female seropositive participants who showed this HIV effect. HIV can result in neuropsychological deficits in Zambia, where clade C of the virus dominates. It is suggested that the HIV-infected women are more at risk of developing cognitive deficits than are men in this population, possibly because of sex-related social, financial, and healthcare disadvantages. However, further analyses are required regarding this conclusion because the finding was a result of an unplanned subanalysis.

Effects of Neurofeedback Versus Stimulant Medication in Attention-Deficit/Hyperactivity Disorder: A Randomized Pilot Study

OBJECTIVE The purpose of this pilot study was to compare the effects of 30 sessions of neurofeedback (NF) with stimulant medication on attention-deficit/hyperactivity disorder (ADHD) patients. METHODS Thirty-two medication-naïve ADHD patients, ages 7-16, from a neuropsychiatric clinic, were randomized to NF (n=16) or drug treatment (n=16). Other actions, such as parent management training, information, or support in school were given as needed, with no differences between the groups. All participants were assessed before treatment on two rating scales, each with parent and teacher forms. In addition, quantitative electroencephalogram (QEEG) and event-related potentials (ERPs), which included behavioral data from a go/no go test were administered. NF training took place in the clinic over a period of 7-11 months, and was followed by a repeat of the same assessment tools. The mean time interval between pre- and postassesment was not significantly different in the two groups. The 18 symptoms of ADHD (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV)) were used as the primary outcome measure. RESULTS Analysis of covariance revealed a significant difference between the groups at evaluation in favor of medication, with a large effect size. This picture was confirmed by other outcome measures. The QEEG spectral power in the theta and beta bands did not change in either group. In ERP, the P3 no go component increased significantly in 8 of 12 patients who had a clinically relevant medication effect, but did not increase in the medication nonresponders or the NF group. CONCLUSIONS Our study supports effects for stimulants, but not for NF. Effects of NF may require thorough patient selection, frequent training sessions, a system for excluding nonresponders, and active transfer training. The P3 no go ERP component may be a marker for treatment response.

Neuropsychological function in patients with anorexia nervosa or bulimia nervosa.

OBJECTIVE This study explored the neuropsychological performance of patients diagnosed with anorexia nervosa (AN) or bulimia nervosa (BN) compared with healthy controls (HCs). An additional aim was to investigate the effect of several possible mediators on the association between eating disorders (EDs) and cognitive function. METHOD Forty patients with AN, 39 patients with BN, and 40 HCs who were comparable in age and education were consecutively recruited to complete a standardized neuropsychological test battery covering the following cognitive domains: verbal learning and memory, visual learning and memory, speed of information processing, visuospatial ability, working memory, executive function, verbal fluency, attention/vigilance, and motor function. RESULTS The AN group scored significantly below the HCs on eight of the nine measured cognitive domains. The BN group also showed inferior performance on six cognitive domains. After adjusting for possible mediators, the nadir body mass index (lowest lifetime BMI) and depressive symptoms explained all findings in the BN group. Although this adjustment reduced the difference between the AN and HC groups, the AN group still performed worse than the HCs regarding verbal learning and memory, visual learning and memory, visuospatial ability, working memory, and executive functioning. DISCUSSION Patients with EDs scored below the HCs on several cognitive function measures, this difference being most pronounced for the AN group. The nadir BMI and depressive symptoms had strong mediating effects. Longitudinal studies are needed to identify the importance of weight restoration and treatment of depressive symptoms in the prevention of a possible cognitive decline.

Predicting the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder: data from quantitative electroencephalography, event-related potentials, and a go/no-go test.

Background We searched for predictors of the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder (ADHD), emphasizing variables from quantitative electroencephalography, event-related potentials (ERPs), and behavioral data from a visual go/no-go test. Methods Nineteen-channel electroencephalography (EEG) was recorded during the resting state in eyes-open and eyes-closed conditions and during performance of the cued go/no-go task in 98 medication-naïve ADHD patients aged 7–17 years and in 90 controls with the same age and sex distribution as the patients. For patients, the recording was followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the electrophysiological results independently rated the patients as responders (REs) (N=74) or non-responders (non-REs) (N=24). Using a logistic regression model, comparisons were made between REs and non-REs on the EEG spectra, ERPs (cue P3, contingent negative variation, and P3 no-go of the ERP waves and independent components [ICs] extracted from these waves), reaction time, reaction time variability, number of commission and omission errors, intelligence quotient, age, sex, ADHD subtype, and comorbidities. Results The two groups differed significantly on eight of the variables, with effect sizes (Cohen’s d) ranging from 0.49 to 0.76. In the multivariate logistic regression analysis, only three of these variables were significantly associated with clinical outcome. The amplitude of the IC cue P3, which has a parietal–occipital distribution, was normal in REs but significantly smaller in non-REs, whereas the centrally distributed IC P3 no-go early was smaller in REs than in non-REs and controls. In addition, the REs had more power in the EEG theta band. A quartile-based index was calculated using these three variables. The group with the lowest scores comprised only 36% REs; response rates in the three other groups were 83%, 86%, and 89%. Conclusion The clinical outcome of stimulant medication was best predicted by electrophysiological parameters. The brain dysfunctions of the REs appear to be primarily associated with prefrontal lobe hypoactivation. The non-REs were deviant from the controls in parietal–occipital functions.

High frequency and intensity of drinking may attenuate increased inflammatory cytokine levels of major depression in alcohol-use disorders

As major depression (MD) is often comorbid with alcohol‐use disorders (AUD) and alcohol itself modulates the immune system, we examined serum levels of interleukin (IL)‐6, IL‐10, tumor necrosis factor (TNF), and interferon (IFN)‐γ in AUD patients with and without MD. Putative interactions between alcohol variables and MD on cytokine levels were also assessed.