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Myalgic encephalomyelitis (ME) also known as ME/CFS (Chronic Fatigue Syndrome) or ME/SEID (Systemic Exertion Intolerance Disorder), is a disabling and often long-lasting disease that can drastically impair quality of life and physical/social functioning of the patients. Underlying pathological mechanisms are to a large extent unknown, but the presence of autoantibodies, cytokine pattern deviations and the presentation of cognitive and autonomic nervous system related symptoms provide evidence for ME being an immunological disorder with elements of autoimmunity. Increased levels of autoantibodies binding to adrenergic and muscarinic receptors in ME-patients have been reported. It is hypothesized that these autoantibodies have pathological significance and contribute to the ME-specific symptoms, however, these observations need to be validated. This study was designed to investigate potential differences in adrenergic and muscarinic receptor autoantibody levels in plasma and cerebrospinal fluid (CSF) samples between ME patients and gender and age-matched healthy controls, and to correlate the autoantibody levels to disease severity. We collected bodyfluids and health-related questionnaires from two Swedish ME cohorts, plasma and CSF from one of the cohorts (n ​= ​24), only plasma from the second cohort (n ​= ​24) together with plasma samples (n ​= ​24) and CSF (n ​= ​6) from healthy controls. All samples were analysed for IgG autoantibodies directed against Alpha- (α1, α2) and Beta- (β1-3) adrenergic receptors and Muscarinic (M) 1–5 acetylcholine receptors using an ELISA technique. The questionnaires were used as measures of disease severity. Significant increases in autoantibody levels in ME patients compared to controls were found for M3 and M4 -receptors in both cohorts and β1, β2, M3 and M4-receptors in one cohort. No significant correlations were found between autoantibody levels and disease severity. No significant levels of autoantibodies were detected in the CSF samples. These findings support previous findings that there exists a general pattern of increased antibody levels to adrenergic and muscarinic receptors within the ME patient group. However, the role of increased adrenergic and muscarinic receptor autoantibodies in the pathogenesis of ME is still uncertain and further research is needed to evaluate the clinical significance of these findings., Highlights • Myalgic Encephalomyelitis (ME) is a devastating disorder (with millions of patients worldwide) with unclear aetiology and no clear diagnostic biomarker available. • This study support the existance of a general pattern of increased antibody levels to adrenergic and muscarinic receptors within the ME patient group. • No evidence for intrathecal antibody production was found in cerebrospinal fluid. The role of increased autoantibodies in the pathogenesis of ME is still uncertain and further research is needed to evaluate their clinical significance.

Fluid collected during sweating is enriched with amino acids derived from the skin’s natural moisturising factors and has been termed “faux” sweat. Little is known about sex differences in sweat amino acid composition or whether faux sweat amino acid losses affect nitrogen balance. Faux sweat collected by healthy adults (n = 47) after exercise, and at rest by chronic fatigue patients, was analysed for amino acid composition. Healthy females had higher total amino acid concentrations in sweat (10.5 ± 1.2 mM) compared with healthy males (6.9 ± 0.9 mM). Females had higher levels of 13 amino acids in sweat including serine, alanine and glycine. Higher hydroxyproline and proline levels suggested greater collagen turnover in females. Modelling indicated that with conservative levels of exercise, amino acid losses in females via faux sweat were triple than those predicted for urine, whereas in males they were double. It was concluded that females were more susceptible to key amino acid loss during exercise and/or hot conditions. Females reporting chronic fatigue had higher levels of methionine in faux sweat than healthy females. Males reporting chronic fatigue had higher levels of numerous amino acids in faux sweat compared to healthy males. Higher amino acid loss in faux sweat associated with chronic fatigue could contribute to a hypometabolic state. Depending on activity levels, climatic conditions and gender, amino acid losses in sweat and skin leachate could influence daily protein turnover where periods of continuously high turnover could lead to a negative net nitrogen balance.

Objectives The main objective of this study was to investigate the tolerability and safety of the monoaminergic stabilizer (-)-OSU6162 in patients with multiple sclerosis (MS). In addition, a potential therapeutic effect of (-)-OSU6162 with focus on MS-related fatigue was estimated by means of various self-assessment rating scales as well as a clinical investigator-rated scale. Materials and methods In this open-label, single-arm study, 30 MS patients received treatment with the monoaminergic stabilizer (-)-OSU6162 during 12 weeks. The dose of (-)-OSU6162 was 15 mg twice daily during the first 4-week period, up to 30 mg twice daily during the second 4-week period and up to 45 mg twice daily during the third 4-week period, with follow-up visits after 16 and 20 weeks. MS-related fatigue was rated by the clinical investigator or by self-assessments, using mainly established rating scales. Twenty-five patients completed the study. Results (-)-OSU6162 was well tolerated by all patients, and no serious adverse events were observed. Therapeutically, improvements were observed with respect to fatigue and mood, as judged by ratings on the Mental Fatigue Scale (MFS), Short Form-36 (SF-36) scale and Beck Depression Inventory (BDI). Furthermore, the large majority of patients were rated as globally improved in the medical observers' rating scale Clinical Global Impression of Change (CGI-C). Conclusions In view of its good tolerability, (-)-OSU6162 may offer a new treatment option for alleviating mental fatigue, as well as depression, in MS. Larger, randomized double-blind controlled trials are warranted to confirm the present preliminary observations.

Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS. Funding Agencies|SolveME/CFS Initiative; Swedish ME Association; Open Medicine Foundation [1011454]; Uppsala Academic Hospital [FOU2017-0039]; Invest in ME Foundation, London

ObjectiveThe monoaminergic stabiliser (−)-OSU6162 has in previous studies shown promising effects on mental fatigue after stroke and traumatic brain injury. This study investigated the safety and effectiveness of (−)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome.MethodsA total of 62 patients were randomly assigned to placebo or (−)-OSU6162. Primary outcomes were assessment on the mental fatigue scale (MFS) and the clinical global impression of change (CGI-C) scale. Secondary outcomes were results on the FibroFatigue scale (FF), the Beck Depression Inventory (BDI), the pain visual analogue scale and neuropsychological tests. Assessments were performed at baseline, after 1 and 2 weeks of treatment and at follow-up after 6 weeks.ResultsMFS and CGI-C showed significant improvements for both treatment groups after treatment but not at follow-up; a similar pattern was seen for FF and BDI. However, significant differences between groups could not be demonstrated. On the other hand, correlation analyses showed a significant correlation between (−)-OSU6162 concentration and change in MFS, FF, and BDI score within the concentration interval 0.1–0.7 µM. Exploratory subgroup analyses showed a larger treatment effect with (−)-OSU6162 in improving MFS and FF symptoms in patients on antidepressant therapy compared to those without antidepressant treatment.Conclusion(−)-OSU6162 was found to be safe and well tolerated. When analysing the entire material (−)-OSU6162 was not found to differ significantly from placebo in alleviating fatigue in ME patients but was superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression.

One hundred and sixty patients with fibromyalgia and chronic fatigue syndrome, who were on a continuous treatment with a Staphylococcus vaccine, were followed during one year with repeated consultation visits. The patients had participated in controlled studies and been on continuous treatment with the vaccine for 22±10 months before inclusion into this follow-up study. They were treated with 1 mL of the vaccine subcutaneously every third to fourth week. Adverse events were few. The adherence to the treatment was very good. Over a period of one year, 8% withdrew, and in only 5%, the withdrawal was due to insufficient clinical effect. Only in two cases where the patients were allergic to the preservative of the vaccine, the side effects caused the withdrawal of the treatment. Ratings with scales (CPRS-15 and FibroFatigue) showed improvement from start of treatment and also further improvement during the follow-up year. In view of the natural history for these disorders the result is of interest.

Cerebrospinal fluid levels of methionine (MET), homocysteine (HCY) and cystathionine were studied in patients with psychotic disorders (n=36) and in healthy controls (n=25). Patients had significantly higher MET than controls (p

ResumenEn Suecia, una reforma psiquiátrica dirigida a mejorar las condiciones de vida de los pacientes psiquiátricos discapacitados entró en vigor en 1995. El propósito del presente estudio era evaluar el impacto de la reforma investigando la calidad de vida y el nivel de vida 2 años después en un grupo seleccionado aleatoriamente de personas con discapacidad psiquiátrica de larga duración. Se realizaron autoevaluaciones y entrevistas en un grupo de estudio y uno de control. El grupo de estudio constaba de 19 mujeres y 18 hombres (edad media: 46,1 años) diagnosticados con neurosis, esquizofrenia o trastorno afectivo. El grupo de control constaba de 19 mujeres y 17 hombres (edad media: 48,7 años). La autoevaluación de la calidad de vida fue significativamente peor en el grupo de estudio (P < 0,0001, prueba de la t para datos independientes) y también lo fue la vivienda (P < 0,001, prueba de proporciones similares en muestras independientes). No encontramos correlación positiva significativa entre la calidad subjetiva de vida y el nivel de vida en ninguno de los dos grupos, pero hubo una correlación negativa significativa en el grupo de control (P < 0,05, r = 0,40, coeficiente de correlación de Pearson). Los resultados indican que, en 1997, las personas con discapacidad psiquiátrica de larga duración tenían todavía una calidad de vida peor que la población general. Esto se puede deber a otros factores que el nivel externo de vida.

The 'membrane hypothesis' of schizophrenia postulates a disturbance in the metabolism and structure of membrane phospholipids resulting in a disturbance in the function of neuronal membrane proteins. Most studies exploring this hypothesis have examined components of peripheral blood. Since it may be questioned if these peripheral measurements reflect changes in the brain, we studied the fatty acid composition of glycerophospholipids in brain tissue. As a marker for synaptic density, we also measured the synaptic vesicle protein synaptophysin. Brain tissue (gyrus cinguli) from 11 schizophrenic patients (mean age 80 +/- 10 years) and 13 controls (mean age 75 +/- 14 years) was examined. The glycerophospholipid fatty acids were determined by gas chromatography. Synaptophysin protein level was determined using quantitative immunoblotting followed by Western blotting. There were no significant differences between the groups in the total or in any individual level of fatty acids, either in the n - 6 or n - 3 series. The level of synaptophysin was significantly p = (0.002) decreased in the schizophrenic group(0.73 + 0.18) as compared with the control group (1.02 + 0.21). The normal pattern and concentration of glycerophospholipids fatty acids found in the present study do not support the membrane hypothesis of schizophrenia. The possibility of a type II error should, however. be considered. On the other hand, the reduced synaptophysin' levels in the gyrus cinguli demonstrate that biological differences can be revealed in this relatively small sample. This also lends further support to the notion that a synaptic disturbance or loss is of importance in the pathogenesis of schizophrenia.

Depression has an overall prevalence of 5-8%. The prevalence of late life depression is estimated among people 65 years of age to be 15%. There is a great under-diagnosis and under-treatment of late life depression with the most serious consequence being premature death. Depression is also an important and independent risk factor for mortality following myocardial infarction, while patients with stroke associated with depression also have a higher death rate. The suicide rate is increased in elderly especially elderly men with depression. The aetiology of depression is more heterogeneous than depression in younger adults. Obviously age-related changes in the brain increase the risk for depression. Patients with neurodegenerative disorders also run a higher risk for being depressed. In Alzheimer's disease the frequency is around 50%. Deficiency of essential nutrients like folic acid and vitamin B12 is an obvious risk factor for both disorders with cognitive impairment and depression. Treatment of depression in the elderly follows the same lines as treatment of depression in younger patients. Many different drugs may be prescribed; however, the risk of adverse events is greater in the elderly. The drugs of choice are the selective serotonin re-uptake inhibitors (SSRIs), which have a response rate of around 65%. Of interest is that emotional disturbances like irritability, aggressiveness and anxiety also respond to treatment with SSRIs. A comprehensive treatment of late life depression, which includes social and psychological support, has a response rate of 80-90%.

Two hundred and four women with chronic fatigue and muscle pain, with no signs of autoimmune disorder, received immune stimulation injections with a Staphylococcus vaccine at monthly inter- vals over 6 months. Good response was defined as a decrease by at least 50% of the total score on an observer's rating scale. Nickel allergy was evaluated as probable if the patient had a positive history of skin hyper- sensitivity from cutaneous exposure to metal objects. The patient's smoking habits were recorded. Fifty-two percent of the patients had a

Occurrence of delirium is known to be related to, among other things, organic brain disorder, somatic disease and old age. It has been hypothesized that delirium is also associated with stress. Disturbances of the hypothalamic-pituitary-adrenal (HPA) system have been found in delirious patients in various studies. The aim of the present study was to determine the activity in the HPA axis in demented patients to ascertain whether the stress regulating system was more disturbed in patients with delirium than in those without delirium. Demented inpatients with no acute medical illness were included in the study. Basal cortisol levels in serum were measured and dexamethasone suppression test (DST) was performed. The most important finding of the study was a strong relationship between delirium and DST pathology irrespective of age and severity of dementia. It is suggested that certain demented individuals have an impaired HPA system and a low delirium threshold and respond to stress with delirium.

Background: It has been hypothesized that a lesion in the neuronal circuits of thalamus might contribute to the symptoms in schizophrenia. It has also been suggested that impaired synaptic transmission is an important component of the pathophysiology of schizophrenia. In the present study we assess the synaptic integrity of thalamus by means of examining the protein levels of: (1) synaptophysin, a membrane bound protein of small synaptic vesicles, and (2) chromogranins, a family of soluble secretory proteins stored and released from the secretory large dense-core vesicles. Methods: The brains of 9 patients with schizophrenia and 9 age-matched control subjects were studied. The levels of synaptophysin and chromogranins were measured by radioimmunoassays. Results: The amount of synaptophysin in the left thalamus was significantly decreased ( p = .036) in the schizophrenic group (2655 ± 605 nmol synaptophysin/mg total protein) compared to the control group (3248 ± 827 nmol synaptophysin/mg total protein). There were no differences between the groups in the levels of chromogranins, nor in the levels of synaptophysin of the right thalamus. Conclusions: These findings indicate defect synaptic function in the left thalamus of patients with schizophrenia. This may be the cause of a reduction of synaptic terminals or a defect limited to certain structures of the synapse, namely the small presynaptic vesicles.

The granins (secretogranins/chromogranins) are a family of soluble proteins stored and released from the secretory large dense-core vesicles of the synapse. Schizophrenia is a common and devastating brain disorder. Although the aetiology of schizophrenia is unknown, data are accumulating that synaptic disturbance or damage may be of importance. The objective of this study was to compare the levels of chromogranin A, B and C in the cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls. CSF chromogranin levels were measured by RIA in 33 subsequent admissions of patients with psychotic disorder and in 31 healthy controls. The levels of CSF chromogranin A (11.8±3.0 vs 14.8±4.8 nmol/l, P =0.004), chromogranin B (3.4±0.49 vs 3.7±0.58 nmol/l, P =0.02), but not chromogranin C (70.2±15.7 vs 65.3±20.4 pmol/l, P =0.29) were lower in the schizophrenic patients than in the healthy controls. These data indicate that two widespread constituents of large dense-core vesicles, i.e. chromogranin A and chromogranin B, are altered in chronic schizophrenic patients.

The gene for apolipoprotein E (APOE) is polymorphic, and its variant APOE4 is a major risk factor for the development of Alzheimer-type dementia (AD). Another risk factor for AD appears to be negative cobalamin balance, which is very common in elderly people. Cobalamin and folate are interdependent and essential components of the one-carbon metabolism. Another important component is methylenetetrahydrofolate reductase (MTHFR), the gene for which is also polymorphic. Thermolabile MTHFR (tMTHFR), a gene variant that reduces the activity of its enzyme, is common in the general population. In the present study, 75% of 140 AD patients had at least one APOE4 allele. The numbers of APOE4 and tMTHFR alleles correlated significantly with the serum folate levels, however, in opposite directions. The significance of this was augmented by an inverse correlation between APOE4 and tMTHFR. Thus, not only MTHFR but also APOE appears to be related to the one-carbon metabolism, suggesting that APOE4 and insufficient one-carbon metabolism may be synergistic risk factors for AD.

The prevalence of depression in elderly people varies strongly with the diagnostic criteria and methodology used, but it is often reported 12-15%. During a period of 3 months 1189 patients at two primary care centres were asked to participate in a study there a Swedish version of the Geriatric Depression Scale, GDS-20, were used. One-thousand and two patients were rated, and further analysis showed that 12.9% suffered from affective disorders. Depression in elderly is underdiagnosed in primary care centres. A screening instrument such as the GDS-20 is of value in identifying patients with depression. The 10 doctors who participated in the study found the GDS-20 easy to handle and it is recommended to be used at every primary care centre.

Positive results of pilot studies of the effect of staphylococcus toxoid vaccine in patients with fibromyalgia and chronic fatigue syndrome were the incitement to the present, placebo-controlled study. It included 28 patients who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome. The effect of vaccination with a staphylococcus toxoid was compared with the effect of injections of sterile water. Psychometric assessment was made using 15 items from the comprehensive psychopathological rating scale (CPRS), Zung's self-rating depression scale and clinical global impressions (CGI). The visual analogue scale (VAS) was used to measure pain levels, and a hand-held electronic pressure algometer was used to measure pressure pain thresholds. Significant improvement was seen in seven of the 15 CPRS items in the vaccine group when pretreatment values were compared to post-treatment values. In CPRSfatiguability, there were significant intergroup differences, and in CPRSpainintergroup differences bordered on significance. There was no significant improvement in CPRS items in the placebo group. Clinical global impressions showed significant improvement in the vaccine-treated group, and VAS did so in both groups. In a follow-up study of 23 patients, the vaccine treatment was continued for 2-6 years. Fifty percent were rehabilitated successfully and resumed half-time or full-time work. The results of this study support the authorshypothesis that treatment with staphylococcus toxoid may be a fruitful strategy in patients with fibromyalgia and chronic fatigue syndrome. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.

Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM) immune response was studied in 69 ME patients and 76 blood donors (BD) (the Training set) with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients), a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff (p

A method for clinical examination of patients with dementia, stepwise comparative status analysis (STEP), is presented. It combines psychiatric and neurologic status examination methods to identify certain common dementia symptoms by which the patient's regional brain symptom profile can be determined. Fifty status variables (items) are estimated with respect to occurrence and severity. The analysis is performed in three steps. The scores on the primary variables reflect observations of single dementia symptoms. These scores form the basis for the assessment of the ‘compound’ variables, which in turn form the basis for evaluation of the ‘complex’ variables, one of which describes the patient's regional (predominant) brain syndrome (subcortical, frontosubcortical, frontal, frontoparietal, parietal, or global). In 96 mildly and moderately demented inpatients, the global (42%) and frontosubcortical (31%) were the most common. Ninety-one percent of the patients with vascular dementia had a predominant frontal and/or subcortical symptomatology

In the present open study, the long-term safety, tolerability, and efficacy of citalopram in the treatment of elderly people with emotional disturbances were studied. One hundred twenty-three elderly patients with symptoms of depression-anxiety were included. Most of the patients (76%) were demented. Fifty-two patients completed a 12-month treatment. Irritability, depressed mood, anxiety, restlessness, and fear-panic were significantly reduced. The severity of illness from baseline to Month 9 was rated as significantly improved. The side effects were infrequent and mostly mild.

The quantitative utilization of various types of psychiatric care by a group of 56 schizophrenic patients was assessed for 1989-1993. This was a period of transformation of psychiatric services in Sweden, with institutionalization in large hospitals giving way to alternative types of care in the community. The group studied consisted of all schizophrenic patients from the southern part of the county council district who in 1989 or later were inpatients on short-term wards of a major psychiatric hospital which was closed down at the turn of 1991/1992. The patients' utilization of psychiatric care in the part of the county council district where they were domiciled was assessed retrospectively by means of various registers and records. With regard to inpatient psychiatric care, the number of utilizers and care occasions diminished markedly in the patient group over the study period. It is evident that the utilization of hospital psychiatric care diminished concurrently with the development of alternative ty...

Gangliosides and major membrane components were determined in caudate nucleus, putamen, and hippocampus of 12 cases with Alzheimer disease (AD) type I, also termed presenile or pure AD, and in age-matched controls. The concentration of gangliosides, a marker for axodendritic arborization, was reduced to 71% in caudate nucleus, 82% in putamen, and 66% in hippocampus of that in the controls. Significant diminution of total dry solids, protein, and phospholipids was also found in caudate nucleus and was most pronounced in hippocampus. The early signs of extrapyramidal features have been emphasized in AD type I. We now provide evidence that the neostriatum is affected in AD type I (the putamen, however, to a lesser extent than the caudate nucleus). The biochemical changes in these nuclei can be significantly related to scores of impairment of motor performance.

Numerous neuropeptides have been isolated from the human brain and postulated as neurotransmitter candidates. Their biochemical characteristics and anatomical distribution have been elucidated in some detail, but their possible physiological and pathophysiological roles, as well as their utility as diagnostic markers in brain disorders, have been more difficult to establish. The concentrations of several neuropeptides have been measured in postmortem human brain studies and in cerebrospinal fluid (CSF) of patients with Alzheimer's disease. Here we critically review these findings with focus on: (1) the relation between brain tissue and CSF neuropeptide alterations; (2) the specificity of neuropeptide alterations in Alzheimer's disease in relation to other degenerative brain diseases; (3) possible functional implications.

Many syndromes have a large number of differential diagnoses, a situation which calls for multiplex diagnostic systems. Myalgic encephalomyelitis (ME), also named chronic fatigue syndrome (CFS), is a common disease of unknown etiology. A mouse retrovirus, xenotropic murine leukemia-related virus (XMRV), was found in ME/CFS patients and blood donors, but this was not corroborated. However, the paucity of serological investigations on XMRV in humans prompted us to develop a serological assay which cover many aspects of XMRV antigenicity. It is a novel suspension array method, using a multiplex IgG assay with nine recombinant proteins from the env and gag genes of XMRV and 38 peptides based on known epitopes of vertebrate gammaretroviruses. IgG antibodies were sought in 520 blood donors and 85 ME/CFS patients and in positive- and negative-control sera from animals. We found no differences in seroreactivity between blood donors and ME/CFS patients for any of the antigens. This did not support an association between ME/CFS and XMRV infection. The multiplex serological system had several advantages: (i) biotinylated protein G allowed us to run both human and animal sera, which is essential because of a lack of XMRV-positive humans; (ii) a novel quality control was a pan-peptide positive-control rabbit serum; and (iii) synthetic XMRV Gag peptides with degenerate positions covering most of the variation of murine leukemia-like viruses did not give higher background than nondegenerate analogs. The principle may be used for creation of variant tolerant peptide serologies. Thus, our system allows rational large-scale serological assays with built-in quality control.

Concentrations of the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 114 healthy individuals, 18–88 years of age, without histories, symptoms or signs of central nervous system dysfunction. The mean values (± SD) were 253 ± 109 nmol/1 for HVA, 125 ± 54 nmol/1 for 5-HIAA, 47 ± 10 nmol/1 for HMPG, and 2.10 ± 0.52 for the HVA/5-HIAA ratio. Analyses of confounding factors revealed that all metabolites correlated negatively with body height, the values being lower in taller than in shorter individuals. This is probably attributable to a larger surface area for monoamine metabolite transport from the subarachnoid space in taller than in shorter individuals. These correlations make statistical adjustment for body height important in analyses of monoamine metabolite levels. Without considering body height, all monoamine metabolites showed a positive correlation with age, and higher levels of HVA and 5-HIAA were found in women than men. After statistical adjustment for the influence of body height, no differences in CSF monoamine metabolites levels were found between the sexes, and only 5-HIAA showed a positive correlation with age. There were no significant seasonal variations for any of the monoamine metabolites.

The prevalence of depression is higher among elderly than among younger people. If atypical depression, masked depression and dysthymic disorders are included, the prevalence is around 15% in a basic population above 65 years of age. In affective disorders in the elderly, not only environmental factors but also biological changes in the old brain in the form of disturbed monoaminergic function are assumed to be of pathogenetic importance. Somatic disorders, nutrition and treatment with drugs are other factors that must be recognized in the pathogenesis of depression in the elderly. Treatment strategies are electroshock therapy, the use of lithium, traditional antidepressants, monoamine oxidase inhibitors and selective serotonin re-uptake inhibitors. Electroshock therapy is recommended for patients who are refractory to drug treatment and patients with severe depression with delusion. The use of tricyclics is hazardous because of side effects and toxicity. Therefore, the new selective reversible monoamine ...

Analyses of the cerebrospinal fluid (CSF) to determine the blood-CSF barrier function and to detect intrathecal IgG production are used in the diagnosis of neurological and psychiatric diseases. There

Analyses of the cerebrospinal fluid (CSF) to determine the blood-CSF barrier function and to detect intrathecal IgG production are used in the diagnosis of neurological and psychiatric diseases. Therefore, accurate reference values for these parameters are of utmost importance. However, current reference values are based on 'reference groups' consisting of patients with psychiatric and/or neurological symptoms but without positive clinical findings and on groups of young students. The present study presents reference values for CSF proteins in a large sample (n = 105) of healthy individuals, with a large age-span (18-88 years of age). The parameter for the determination of the blood CSF barrier function, the CSF/serum (CSF/S) albumin ratio, was found to show an increasing variability in individuals over 45 years of age, suggesting a less stable blood-CSF barrier function than in younger individuals. The upper reference limit for the CSF/S albumin ratio was 6.8 for individuals under 45 years of age and 10.2 for individuals over 45 years of age. The IgG index, a dimensionless quotient for the determination of intrathecal IgG production, showed only a minor correlation with age and had an upper reference limit of 0.63.

The prevalence of exfoliation syndrome was studied in 39 patients suffering from dementia and cognitive impairment; a positive finding of exfoliation was detected in 11/39 of these patients. A comparison with an age-matched population survey showed that the prevalence of ocular exfoliation and the relative risk were significantly elevated. These results suggested that lesions related to the exfoliative process might be located also in the brain of patients suffering from dementia and cognitive impairment.

Patients (n = 191) living in four comparable somaic nursing homes (NH) (nursing homes for physical illness) were studied in order to evaluate dementia syndromes. Dementia and symptoms of depressed mood occurred frequently (72% and 63%, respectively). Dementia was often undiagnosed at admittance. Neither the length of time spent in institutions, nor marital status, age, or sex seemed to be of more than minor importance to the prevalence of dementia syndromes. Concerning functional impairment, convergence of findings across the societies studied indicates that psychiatric symptoms and psychopathology are intrinsic parts of long-term care of the elderly.

A total of 149 patients in 7 centers in Denmark, Norway and Sweden entered a 6-week double-blind trial intended to assess the antidepressant effect and safety of citalopram vs placebo in depressed elderly patients (65 years of age or older) who might also suffer from somatic disorders and/or senile dementia. Results of ratings on the Hamilton Rating Scale for Depression, the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impression Scale provided consistent evidence that the citalopram-treated patients improved more than the placebo-treated patients. Results of ratings on the Gottfries-Bråne-Steen dementia rating scale indicated that both cognitive and emotional functioning improved significantly more in the citalopram-treated subgroup of patients with dementia than in the placebo-treated subgroup.

In two inter-Nordic multicenter controlled studies the effect of Citalopram on elderly patients with depression and emotional disturbances has been studied. One investigation included 98 patients in whom Alzheimer type dementia (AD/SDAT) and vascular dementia (VD) had been diagnosed, many of whom also had emotional disturbances. After four weeks treatment with Citalopram (10-30 mg/daily) there was significant improvement in confusion, irritability, anxiety, depressed mood and restlessness. No effect was seen on the intellectual capacity or motor performance measured. In the other study, which was a six weeks trial comparing Citalopram and placebo, elderly patients with a treatment-requiring depression were treated. Demented as well as non-demented patients were included. The Hamilton Depression Scale, the Montgomery-Asberg Depression Rating Scale and The Clinical Global Impressions all recorded an effect of Citalopram superior to that of placebo. In both studies depressive symptoms as well as symptoms of agitation, anxiety, restlessness and irritability improved. Citalopram is therefore considered not only an antidepressive drug but also an emotional stabilizer. The drug was well tolerated by elderly often somatically ill patients. Side effects were few.

Ca-independent and Ca-dependent proteolytic activity were significantly higher in erythrocytes from male patients with Alzheimer''s disease compared to control subjects. The level of calpastatin, an endogenous inhibitor of the proteolytic enzyme calpain, was lower in male patients with Alzheimer''s disease. The small changes observed in the female group were not statistically significant. Control male subjects had significantly higher levels of calpastatin compared to female controls. The observed changes in the calpain/calpastatin system of erythrocytes may be caused by a general dysregulation of Ca homeostasis in cells of Alzheimer patients and may lead to calpain-induced pathological changes.

A political decision to decentralize psychiatric care in a county of Sweden was made in October 1984, leading to the closure of the only large mental hospital in the area (290,000 inhabitants). The hospital is of the traditional type, with 490 beds and 1,294 staff members. It has units for long-term care, short-term care and rehabilitation and a unit for research and education. The long-term care is to cease completely and be replaced by community-based alternative types of care. In this study, the long-term population (n = 199) was characterized and their levels of functioning were measured. The results showed that 91% of the patients were 65 years old or more and that more than half of them were organically demented. Only 20% were chronic schizophrenics. All patients were cognitively impaired and 80% were also impaired in ADL functioning. A correlation between length of stay in hospital and ADL functioning was found in the organically demented group, but not in the group of chronic psychiatrically ill patients. Thirty-nine per cent of the population were severely impaired in ADL functioning and needed nursing care around the clock; 34% were moderately impaired and needed help and support that could be given in alternative types of care; 27% were not impaired at all to mildly impaired and could be relocated to some type of service apartment. Thus, all patients needed sheltered living arrangements and care provided by staff with adequate training.

Thirty-one patients with the clinical diagnosis of vascualar dementia were examined with regard to symptoms reflecting disturbances in various brain regions. Frontal, parietal, subcortical and non-regional symptom complexes were used to characterize each patient. Frontal (77%) and subcortical (68%) symptoms were the most common clinical patterns. Using an overall evaluation, subcortical symptomatology was the most prominent clinical picture (45%) Extrapyramidal symptoms, an important aspect of the subcortical symptom complex, were associated with histories of hypertension (p

Thirty-one patients with early onset Alzheimer's disease (EAD) and 44 with late onset Alzheimer's disease (LAD) were examined with regard to symptoms reflecting disturbances in various brain regions, ie frontal, parietal and subcortical symptoms. Clinical vascular factors were recorded. The albumin ratio (CSF albumin/serum albumin) was used as a measure of the blood-brain barrier (BBB) function. Parietal symptoms were more common in EAD than in LAD, both among mildly demented patients (60% in EAD, 10% in LAD; p

Postmortem human brain data from normally aged individuals indicate an involution in the neurotransmitter metabolism, with onset in the sixties followed by a continuous progression. The reserve capacity of the brain is great and behavioural disturbances are therefore not seen until 20-25 years after the onset. Parkinson-like symptoms are common in men more than 80 years old, and the prevalence of symptoms of depression increases with age. Whether Parkinson-like symptoms can be pharmacologically treated with, for example, deprenyl, an MAO-B inhibitor, has not yet been investigated. Depression, and possibly also other symptoms of emotional disturbances, may well be treated with antidepressants. However, the toxic effects of tricyclics are often too troublesome for the elderly, selective 5-hydroxy-tryptamine (5-HT) reuptake blockers are instead the drugs of choice. Citalopram has shown beneficial effects in the treatment of elderly people with depressed mood and emotional disturbances. The increase in activi...

Serum and cerebrospinal fluid (CSF) from 118 patients with primary degenerative dementia (PDD; Alzheimer''s disease) and 50 healthy controls were examined in order to investigate intrathecal synthesis of immunoglobulin G (IgG), defined as an elevated IgG index (≧ 0.7) and/or the presence of oligoclonal IgG bands in CSF but not in serum. In the PDD group, 7 patients (6%) showed an intrathecal IgG synthesis. Eight patients (7%) showed oligoclonal IgG bands in serum and CSF, interpreted as a diffusion of IgG across the blood-brain barrier. In the early-onset PDD group, the mean IgG index was higher than in age-matched controls. The PDD patients with intrathecal IgG synthesis were less demented than those with normal CSF, but the intrathecal synthesis was not related to age, sex, or blood-brain barrier function. The findings suggest that immunological dysfunction could be related to PDD.

Cerebrospinal fluid (CSF) of 70 patients with Alzheimer''s disease (AD) and 36 age-matched healthy controls was examined for signs of immunological abnormality. In healthy adults, the CSF cytological picture was dominated by small lymphocytes and monocytes, together accounting for about 98% of cells. There were no changes related to sex or age in the cell composition. In the AD group, there was an increased percentage of monocytes compared with controls, but with great overlap between groups. Five AD patients displayed intrathecal synthesis of IgG, without a concomitant increase in the number of leukocytes, or a change in the cytological picture. This study shows that there is no major change in the cell-mediated immune system in AD. The discrete disturbance in the CSF cytological picture in AD may be a secondary phenomenon related to the cerebral degeneration.