Neuropsychiatric Manifestations of Wilson Disease: Correlation with MRI and Glutamate Excitotoxicity.

This study aims to identify neuropsychiatric manifestations in neurological Wilson disease (NWD), and their correlation with MRI changes and glutamate excitotoxicity. Forty-three consecutive patients with NWD from a tertiary care teaching hospital were evaluated prospectively who fulfilled the inclusion criteria. The neuropsychiatric evaluation was done using Neuropsychiatric Inventory (NPI) battery that assesses 12 domains including delusion, hallucination, agitation/aggression, dysphoria/depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, appetite change, and abnormal nighttime behavior. Cranial MRI was done using a 3 T machine, and locations of signal changes were noted including the total number of MRI lesions. Serum glutamate level was measured by a fluorescence microplate reader. Abnormal NPI in various domains and total NPI scores were correlated with MRI lesions, serum and urinary copper, and glutamate level. The median age of the patients was 16 years. Forty-one (48.8%) patients had cognitive impairment and 37 (86%) had movement disorder. Neurobehavioral abnormality was detected in all-commonest being agitation (90.7%) followed by appetite change (81.4%), elation (74.4%), irritability (69.8%), anxiety (67.4%), depression (65.1%), apathy (44.2%), night time abnormal behavior (32.6%), aberrant motor behavior (20.9%), delusions (16.3%), and hallucination (18.6%). The thalamic lesion was associated with depression, globus pallidus with depression and anxiety, caudate with anxiety and agitation, brainstem with irritability, and frontal cortex with apathy. Serum glutamate level was higher in NWD. NPI sum score correlated with MRI load and glutamate level. Varying severity of neurobehavioral abnormalities are common in the patients with NWD and correlate with the location of MRI lesion and glutamate level.

Shorter Chain Triglycerides Are Negatively Associated with Symptom Improvement in Schizophrenia.

Schizophrenia is a serious mental disorder requiring lifelong treatment. While medications are available that are effective in treating some patients, individual treatment responses can vary, with some patients exhibiting resistance to one or multiple drugs. Currently, little is known about the causes of the difference in treatment response observed among individuals with schizophrenia, and satisfactory markers of poor response are not available for clinical practice. Here, we studied the changes in the levels of 322 blood plasma lipids between two time points assessed in 92 individuals diagnosed with schizophrenia during their inpatient treatment and their association with the extent of symptom improvement. We found 20 triglyceride species increased in individuals with the least improvement in Positive and Negative Syndrome Scale (PANSS) scores, but not in those with the largest reduction in PANSS scores. These triglyceride species were distinct from the rest of the triglyceride species present in blood plasma. They contained a relatively low number of carbons in their fatty acid residues and were relatively low in abundance compared to the principal triglyceride species of blood plasma.

Increased prevalence of impulse control disorder symptoms in endocrine diseases treated with dopamine agonists: a cross-sectional study.

INTRODUCTION: Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions. MATERIALS AND METHODS: A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP). RESULTS: Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82). DISCUSSION: Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.

Is there an association between serum 25(OH)D3 and mental well-being in patients with type 2 diabetes? Results from a cohort study in primary care.

PURPOSE: There are limited and inconsistent results on the correlation between vitamin D and mental health in patients with type 2 diabetes (T2D). Thus, our aim was to explore the association between vitamin D and mental well-being in a community-based sample of participants with T2D. METHODS: We analyzed serum 25-hydroxyvitamin D3 (25(OH)D3) in 698 patients with T2D at the baseline examination. The cohort was reinvestigated after 4 years. Data from SF-36 questionnaires measuring vitality and mental health at baseline and after 4 years were used for analyses. RESULTS: Serum 25(OH)D3 was inversely associated with poor mental health at baseline (odds ratio (OR) for 10 nmol/l increase in 25(OH)D3, 0.90 (95% confidence interval (CI) 0.83-0.96, p = 0.003)) but not at follow-up (p > 0.05). Serum 25(OH)D3 was not associated with vitality at baseline (p > 0.05). At follow-up, there was an inverse association between 25(OH)D3 and low vitality (OR for 10 nmol/l increase in 25(OH)D3, 0.89 (95% CI 0.82-0.97, p = 0.009)) but not after adjustment. CONCLUSION: We found an inverse association between 25(OH)D3 and mental health in patients with T2D at baseline. We found no association between 25(OH)D3 and vitality after adjustment. Future studies are needed to determine the association between vitamin D and mental well-being in patients with T2D.

D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer's disease or mild cognitive impairment.

BACKGROUND: D-amino acids have been recognized as bioactive substances in humans. d-Serine and D-alanine are co-agonists of N-methyl-d-aspartate receptors. Glutamate has been suggested to be involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to explore the roles of amino acids, particularly D-amino acids, in cognitive decline among patients with AD or mild cognitive impairment (MCI). METHODS: We enrolled 144 patients: 20 amnestic MCI, 85 mild AD, 25 moderate AD, and 14 severe AD. Serum levels of amino acids were measured by high performance liquid chromatography and confirmed by D-amino acid oxidase assay. The cognitive function was mainly evaluated by Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog). RESULTS: ADAS-cog total scores were positively correlated with d-serine (r = 0.186, p = 0.026) and D-/Total- serine ratio (r = 0.191, p = 0.022). ADAS-cog behavior scores were negatively correlated with D-glutamate (r = -0.177, p = 0.034) and L-glutamate (r = -0.250, p = 0.003), but positively correlated with D-alanine (r = 0.236, p = 0.005) and D-/Total- alanine ratio (r = 0.252, p = 0.002). Among the 11 tasks of ADAS-cog, D-glutamate and d-serine were correlated with different items respectively, noteworthily in the opposite direction. CONCLUSION: This is the first study suggesting that D-amino acids in blood may be correlated with ADAS-cog in different items and in the opposite direction. Lower D-glutamate and higher D-alanine levels may predict more behavioral symptoms. In summary, D-glutamate, d-serine and D-alanine play different and characteristic roles in AD. Further longitudinal studies are warranted to elucidate the function and interaction of D-amino acids in specific cognitive domains as well as various phases of dementia.

AKT1, PRDM4, and BAX are the natural markers of psychological endurance threshold.

INTRODUCTION: Abnormal behavior can cause harm or loss to oneself, the family, and society and may be related to psychological endurance levels. With early identification and early intervention, the occurrence of harm can be prevented and the loss can be reduced. Now there is no clear definition of psychological endurance levels and no accurate measurement tools yet. METHODS: This study first proposes the concept of psychological endurance threshold (PET) and defines that as: "the psychological state threshold of human objective physiological characteristics and outbreaks of abnormal behavior led by subjective cognitive level difference". The study hypothesizes that human behavior is related to it, and constructs multiple measurement method tools to measure it. RESULTS: Here we show PET exists objectively and can be measured exactly by methods such as psychological endurance threshold measurement table, experience evaluation, dopamine level detection, and genetic testing. In particular, PET is determined by AKT1, PRDM4, and BAX which are the natural markers of PET. CONCLUSIONS: The significance of this study is to discover people with abnormal expression of AKT1, PRDM4, and BAX who have lower PET and tend to commit abnormal behavior more easily. Understanding PET will enable people to make self-adjustment or to intervene by professionals as soon as possible and in a timely manner in the face of various negative stimuli in work and life, especially for people with lower PET, people should intervene as early as possible to reduce the harm to the individual, family and society.

Circulating Levels of Brain-Derived Neurotrophic Factor and History of Suicide Attempts in Women.

A growing body of research examining biological factors associated with suicidal behaviors highlights the role of brain-derived neurotropic factor (BDNF), involved in neurogenesis and synaptic plasticity. There is evidence suggesting that suicide attempters have lower BDNF levels than those with no history of suicide attempts. The key question addressed in the current investigation is whether differences in circulating BDNF levels persist beyond the current suicidal episode and would be observed in those with a past history of suicide attempts (SA). Plasma levels of BDNF were assessed in 73 women from the community. We found that women with a history of SA exhibited lower levels of BDNF than women with no SA history and this difference was maintained after statistically controlling for the influence of other potential psychiatric or demographic factors. These findings support and extend existing research by suggesting that circulating BDNF levels are decreased among individuals with a history of SA compared to individuals with no history of SA. This relation appeared to be specific to women's history of SA and was not explained by other potential psychiatric or demographic factors, which further highlights the role of BDNF as a promising biomarker for suicidal behavior.

Decrease in brain-derived neurotrophic factor at plasma level but not in serum concentrations in suicide behavior: A systematic review and meta-analysis.

INTRODUCTION: Suicide is known as a major health concern worldwide. There is evidence for the role of brain-derived neurotrophic factor (BDNF) in suicide behavior. Therefore, this factor has been proposed as a biomarker for suicide behavior. Clinical studies have measured BDNF concentrations at central and peripheral levels. As a consequence, the aim of this study was to assess BDNF levels in blood plasma and serum to see whether there is a difference in concentrations in patients with suicide behavior when compared to those in controls, using a meta-analysis approach. METHODS: We conducted a systematic review and meta-analysis. The search strategy was performed using three databases: PubMed, EBSCO and ScienceDirect. The meta-analysis included a total of nine case-control studies, six measured the BDNF level in serum and three in plasma in suicide behavior. RESULTS: A decrease in BDNF levels in plasma was observed (d = -0.73, 95% CI -1.42 to -0.03 pg/ml). In the case of serum concentrations, no BDNF differences were encountered between cases and controls (d = 0.09, 95% CI -0.31 to 0.13 ng/ml, p(Q) = .92). CONCLUSIONS: According to the results found in the present meta-analysis, the plasma BDNF level could be suggest as a potential biomarker in suicide behavior. However, since the number of studies included in the analysis is limited, a larger number is necessary to determine conclusively the role of BDNF as a biomarker in suicide behavior.

Glycogen synthase kinase-3ß in patients with bipolar I disorder: results from a prospective study.

OBJECTIVES: The enzyme glycogen synthase kinase-3ß (GSK3ß) is involved in the mechanisms of action of lithium and may play a role in relation to affective states in bipolar disorder. The objectives of the present study were to compare the activity of GSK-3ß (measured as levels of phosphorylated GSK-3ß [p-GSK-3ß]) between patients with bipolar disorder in the euthymic state and healthy control subjects, and to investigate whether GSK-3ß activity varies with affective states in patients with bipolar I disorder. METHODS: In a prospective 6-12-month follow-up study, we investigated state-specific, intraindividual alterations in the activity of GSK-3ß in 60 patients with bipolar I disorder with an acute severe manic index episode and in subsequent euthymic, depressive and manic states and compared this with repeated measurements in healthy control subjects. Data were analyzed using linear mixed-effects models. RESULTS: From baseline to the end of follow-up, blood samples were drawn from the 60 patients during 181 affective states, comprising 60 manic, 11 mixed, 23 depressive, and 87 states of euthymia. A total of 69 blood samples were drawn from 35 healthy control subjects, with two samples from the same subject taken three months apart. In mixed-model analysis, p-GSK-3ß was decreased in the euthymic state of subjects with bipolar disorder compared with healthy control subjects (b=0.63, 95% confidence interval [CI]: 0.42-0.96, P=.03). In addition, p-GSK-3ß varied with affective states, being increased in depressive (b=1.68, 95% CI: 1.08-2.62, P=.02) and mixed (b=2.07, 95% CI: 1.12-3.84, P=.02) states but not in mania compared with euthymia. CONCLUSIONS: The activity of GSK-3ß is altered in euthymic bipolar disorder compared with healthy control subjects and varies with affective states.

[Peculiarities of Platelet Activation Changes in Patients with Chronic Schizophrenia, Depending on the Severity of Positive and Negative Symptoms during the Remission Formation].

OBJECTIVE: The aim of our study was to compare the changes in the severity of positive, negative and psychopathological PANSS symptoms which occur at an outcome of an attack in schizophrenic patients along with remission formation and the degree of platelet activation in these patients. METHODS: Psychometric scale of the Positive and Negative Syndrome Scale (PA NSS) and the method of estimation of platelet activation based on the calculation of cells number after elution from the column with sepharose CL-2B were used. RESULTS: The changes in the severity of the disease were estimated using the PANSS scale of chronic schizophrenic patients in remission formation. An increase in platelet activation was determined on the basis of the above described quantitative parameter. Comparison of changes in platelet activation parameter with changes in the disease severity rating detected similar statistically indistinguishable (p > 0.05) changes in the severity of positive symptoms and quantitative variable of platelet activation between the 1st and the 3rd visits in the period of remission formation. Platelet number after elution from the column during the 3rd visit was approximately two times less than during the 1st visit (p < 0.002). PANSS positive subscale shows a decrease of the severity of the syndrome by 1.6 times (p < 0.0002). In addition the difference between the platelet activation parameter and severity of the negative syndrome was fixed during the 3rd visit (p < 0.034). CONCLUSION: Similar changes in the severity of positive syndrome and platelet activation parameter were presented from 1st to 3rd visit in the remission formation. A distinction between the platelet activation parameter and severity of the negative syndrome was fixed during the 3rd visit.

Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment.

OBJECTIVES: Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFAs would be lower and those of n-6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. METHODS: This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, and between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using chi-square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. RESULTS: UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow-up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self-reported n-3 PUFA intake or use of medication by class. CONCLUSIONS: A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n-3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n-3 and decrease n-6 dietary PUFA intake.

Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype?

BACKGROUND: Some children with autism spectrum disorders (ASD) are characterized by fluctuating behavioral symptoms following immune insults, persistent gastrointestinal (GI) symptoms, and a lack of response to the first-line intervention measures. These children have been categorized as the ASD-inflammatory subtype (ASD-IS) for this study. We reported a high prevalence of non-IgE mediated food allergy (NFA) in young ASD children before, but not all ASD/NFA children reveal such clinical features of ASD-IS. This study addressed whether behavioral changes of ASD-IS are associated with innate immune abnormalities manifested in isolated peripheral blood (PB) monocytes (Mo), major innate immune cells in the PB. METHODS: This study includes three groups of ASD subjects (ASD-IS subjects (N = 24), ASD controls with a history of NFA (ASD/NFA (N = 20), and ASD/non-NFA controls (N = 20)) and three groups of non-ASD controls (non-ASD/NFA subjects (N = 16), those diagnosed with pediatric acute onset-neuropsychiatric syndrome (PANS, N = 18), and normal controls without NFA or PANS (N = 16)). Functions of purified PB Mo were assessed by measuring the production of inflammatory and counter-regulatory cytokines with or without stimuli of innate immunity (lipopolysaccharide (LPS), zymosan, CL097, and candida heat extracts as a source of ß-lactam). In ASD-IS and PANS subjects, these assays were done in the state of behavioral exacerbation ('flare') and in the stable ('non-flare') condition. ASD-IS children in the 'flare' state revealed worsening irritability, lethargy and hyperactivity. RESULTS: 'Flare' ASD-IS PB Mo produced higher amounts of inflammatory cytokines (IL-1ß and IL-6) without stimuli than 'non-flare' ASD-IS cells. With zymosan, 'flare' ASD-IS cells produced more IL-1ß than most control cells, despite spontaneous production of large amounts of IL-1ß. Moreover, 'flare' ASD-IS Mo produced less IL-10, a counterregulatory cytokine, in response to stimuli than 'non-flare' cells or other control cells. These changes were not observed in PANS cells. CONCLUSIONS: We observed an imbalance in the production of inflammatory (IL-1ß and IL-6) and counterregulatory (IL-10) cytokines by 'flare' ASD-IS monocytes, which may indicate an association between intrinsic abnormalities of PB Mo and changes in behavioral symptoms in the ASD-IS subjects.

Peer problems are associated with elevated serum leptin levels in children.

BACKGROUND: Leptin is thought to act as an important mediator in stress reactions. To date, no study has examined the association between psychological stress and leptin levels in children. This study aimed to assess the association between emotional symptoms and peer problems and serum leptin levels in children aged 10 years of the two population-based GINI-plus and LISA-plus birth cohorts. METHOD: Cross-sectional data from 2827 children aged 10 years were assessed with regard to leptin concentrations in serum and behavioral problems using the parent-reported Strengths and Difficulties Questionnaire (SDQ). Linear regression modeling was applied to determine the likelihood of elevated leptin levels in children with emotional symptoms and peer problems, controlling for socio-economic status (SES), body mass index (BMI), fasting serum leptin levels, pubertal development and sex hormones. RESULTS: We found that increases in emotional symptoms (exp ß adj = 1.03, s.e. = 0.02, p < 0.04) and peer problems (exp ß adj = 1.05, s.e. = 0.01, p = 0.0001) were significantly associated with higher serum leptin levels controlled for BMI and sociodemographic factors. Similar results were found when the fasting serum leptin sample was examined (exp ß adj = 1.08, s.e. = 0.04, p = 0.0294). Gender-stratified analyses showed a significant relationship between serum leptin and peer problems in girls (exp ß adj = 1.05, s.e. = 0.02, p = 0.03), and a borderline significant association in boys (exp ß adj = 1.04, s.e. = 0.02, p = 0.05). CONCLUSIONS: Children with peer problems have higher stress and eat more, acquire a higher body fat mass and thus, through increased leptin resistance, exhibit higher leptin levels.

Relationships between serum leptin level and severity of positive symptoms in schizophrenia.

The adipocytokine leptin is a key mediator of energy homeostasis. Recent papers have suggested that leptin may also have roles in the brain however it is unclear whether leptin is connected to symptoms of mental disorders. In this study, we sought to clarify the relationships between serum leptin level and psychopathology in schizophrenia (SZ) patients. The severity of positive symptoms inversely correlated with the serum leptin levels among SZ patients. There was no correlation between leptin levels and negative symptoms or neurocognition. Our data suggest a role of leptin in SZ positive symptoms.

The antemortem neurobehavior in fatal paramethoxymethamphetamine usage.

Paramethoxymethamphetamine (PMMA) is an emerging and prevalent psychoactive drug with a structure analogous to amphetamine and related psychostimulants. However, the neurobehavioral effect is only studied in experimental animals and is barely mentioned in human. The authors report the antemortem neurobehavioral manifestations in 8 patients with PMMA use. There were 2 different antemortem presentations. The first group of patients showed delirium, hypertalkativity, and incoherence speech and then turned into convulsion and death. They did not exhibit the typical hyperdopaminergic movement disorder. The second group of patients gradually fell asleep and then suffered respiratory or cardiovascular collapse. The heart blood PMMA level was higher in the second group than in the first group of patients. Forensic autopsy showed variable findings, ranging from no remarkable change to significant pathological damage similar to serotonin syndrome in both groups of patients. PMMA seems to enhance serotoninergism than dopaminergism, and exerts a concentration-related dual effect on human.

Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia.

OBJECTIVES: The purposes of this study were first, to evaluate the effectiveness of citalopram in treating behavioral disturbances in frontotemporal dementia (FTD) subjects and second, to determine whether an association exists between serotonergic function, as determined by a neuroendocrine challenge, and treatment response. DESIGN: Single-dose citalopram (30 mg per os) challenge followed by a 6-week open-label study. SETTING: Outpatients referred to memory clinics. PARTICIPANTS: Fifteen patients suffering from FTD with severe behavioral and psychological symptoms of dementia. INTERVENTION: Following citalopram challenge, all patients were treated with citalopram titrated to a target dose of 40 mg once daily. MEASUREMENTS: Behavioral disturbances, using the Neuropsychiatric Inventory (NPI) (primary outcome) and Frontal Behavioural Inventory (secondary outcome), were assessed. Change in prolactin concentration following citalopram challenge was used as an index of central serotonergic response. RESULTS: Citalopram treatment was effective in treating behavioral symptoms, with significant decreases in NPI total score (F[2, 28] = 6.644, p = 0.004), disinhibition (F[2, 28] = 4.030, p = 0.029), irritability (F[2, 28] = 7.497, p = 0.003) and depression (F[2, 28] = 3.467, p = 0.045) scores over the 6 weeks. Significant improvement in Frontal Behavioural Inventory scores suggested that citalopram was also effective in the treatment ofbehaviors specific to FTD. A lower change score in concentration of prolactin was significantly positively correlated with greater improvement in the total NPI score from baseline to endpoint (r = 0.687, p = 0.005). A blunted response to a citalopram challenge, implying a dysfunctional serotonergic system, predicted a more positive treatment outcome. CONCLUSIONS: The results suggest that despite the endogenous serotonin deficiency of FTD, citalopram treatment may be effective in targeting the behavioral disturbances characteristic of FTD.

[Ischemic heart disease in elderly patients of behavioral type A (psychosocial and clinic functional changes, possibilities for correction)].

833 patients aged 32 to 74 years who had coronary heart disease (CHD) were examined. Psychosocial and clinicofunctional features typical for elderly people of behavioral type A and with diagnosed CHD and ways for treatment optimization and disease prophylaxis are being under consideration. We studied the clinical efficiency and influence of Anaprilin, Metoprolol, Phenazepam, non-medical methods on psychoendocrine parameters in CHD elderly patients with behavioral type A. In addition to positive changes in the anginal syndrome sleep, decreases in hot temper, irritability, anxiety, phobic manifestations, hypochondrial trends, and neurotic asthenization, increased working and social orientation were improved. During Anaprilin, Metoprolol, Phenazepam therapy, cardialgias reduced or disappered, the incidence of arrhythmia decreased. There was a reduction in the personality profile in the neurotic triad and psychoasthenia scales, the reactive anxiety diminished significantly, and levels of aldosterone, cortisol, triiodothyronine, and thyroxine in the blood decreased. Thus, supplementation of Anapriline, Metoprolol, Phenazepam to the combined therapy for patients with CHD of behavioral type A positively effected to the clinical course of the disease. Configuration of the personality profile was leveled in patients with CHD of coronary type, signs of behavioral type A decreased.

Influence of anticholinergic activity in serum on clinical symptoms of Alzheimer's disease.

Alzheimer's disease (AD) is well known as a disease characterized by degeneration of cholinergic neuronal activity in the brain. It follows that patients with AD would be sensitive to an 'anticholinergic burden', and also that medicine with anticholinergic properties would promote various clinical symptoms of AD. Despite the relevance of this important phenomenon to the clinical therapeutics of AD patients, few reports have been seen concerning the relationship between anticholinergic burden and clinical AD symptoms. Therefore, we wished to investigate the relationship between serum anticholinergic activity (SAA) and the severity of clinical symptoms of AD patients. Twenty-six out of 76 AD patients referred by practitioners to our hospital were positive for anticholinergic activity in their serum, and the remaining 50 patients were negative. Cognitive and psychiatric symptoms in AD patients were compared between the positive SAA (SAA+) group and the negative SAA (SAA-) group. The SAA+ group showed a significantly (p < 0.05) lower total score on the Mini-Mental State Examination, and significantly (p < 0.05) higher scores on the Functional Assessment Staging and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). In particular, certain subscales of the BEHAVE-AD, i.e. the items of paranoid and delusional ideation, hallucinations and diurnal rhythm disturbances, had higher scores in the SAA+ group. Moreover, it was shown that many more psychotropic medicines were prescribed to the SAA+ group. By means of logistic regression analysis, the items of paranoid and delusional ideation and diurnal rhythm disturbances in the BEHAVE-AD were positively correlated with SAA in patients. We hypothesized that SAA in AD patients would be associated with clinical symptoms, especially delusion and diurnal rhythm disturbances.

Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E.

Apolipoprotein E (apoE) is involved in the risk to develop sporadic Alzheimer's disease (AD). Since impaired central acetylcholine (ACh) function is a hallmark of AD, apoE may influence ACh function by modulating muscarinic ACh receptors (mAChRs). To test this hypothesis, mAChR binding was measured in mice lacking apoE and wild type C57BL/6J mice. Mice were also tested on the pre-pulse inhibition, delay eyeblink classical conditioning, and 5-choice serial reaction time tasks (5-SRTT), which are all modulated by ACh transmission. Mice were also given scopolamine to challenge central mAChR function. Compared to wild type mice, mice lacking apoE had reduced number of cortical and hippocampal mAChRs. Scopolamine had a small effect on delay eyeblink classical conditioning in wild type mice but a large effect in mice lacking apoE. Mice lacking apoE were also unable to acquire performance on the 5-SRTT. These results support a role for apoE in ACh function and suggest that modulation of cortical and hippocampal mAChRs might contribute to genotype differences in scopolamine sensitivity and task acquisition. Impaired apoE functioning may result in cholinergic deficits that contribute to the cognitive impairments seen in AD.

Fetal asphyctic preconditioning protects against perinatal asphyxia-induced behavioral consequences in adulthood.

Perinatal asphyxia is one of the major causes of neuronal injury and impaired development in infants. We recently have shown that a brief episode of experimental fetal asphyxia (FA) can provoke an endogenous neuroprotection against subsequent severe perinatal asphyxia (SPA). The long-lasting functional consequences of FA preconditioning are not clear yet. The aim of the study was to determine if FA preconditioning can provide a long-lasting behavioral protection against SPA. FA was induced, as a preconditioning stimulus, by clamping the uterine vasculature for 30 min on E17. At birth, SPA was induced by placing the uterine horns in a water bath for 19 min. At 6 months of age, functional outcome was assessed using different behavioral tests: the open field for locomotor activity, the elevated zero maze for anxiety-related behavior, the forced swim test for depression-related behavior and the object recognition task for cognition. Data showed that FA preconditioning improved postnatal mortality after SPA. At the age of 6 months, the total distance moved in the open field and elevated zero maze was significantly less in the SPA group compared to the control groups. In addition, cognitive performance in the object recognition task was impaired in the SPA offspring compared to the control groups. Most importantly, FA preconditioning was able to preserve both locomotor activity and cognition function. In conclusion, FA preconditioning induces a long-lasting, functional protection against SPA. Therefore, this model seems to offer good opportunities for the identification and characterization of the underlying mechanisms of preconditioning.