Neurology Psychiatry and Brain Research最新文献

Background

Adjunctive immune-modulation can be safe and effective for treatment-resistant bipolar depression (TRBDD), but molecular work is needed to further characterize the safety and efficacy involved in treatment response and the reversal of treatment resistance. Here we profiled the kynurenine pathway (KP) for biomarkers associated with TRBDD and treatment response to celecoxib (CBX)-augmentation.

Methods

47 TRBDD patients with moderately severe HAMD-17 scores were randomized to receive either escitalopram (ESC) (10 mg twice daily) + CBX (200 mg twice daily), or ESC (10 mg twice daily) + placebo (PBO) (twice daily). Plasma kynurenine pathway (KP) metabolite levels were measured at baseline, week 4, and week 8, and in a healthy control (HC) group of subjects (N = 35) once.

Results

Patients receiving ESC + CBX had 4.278 greater odds of responding (p = 0.021) with NNT=3, and 15.300 greater odds of remitting (p < 0.001) with NNT=2, compared with ESC + PBO patients. Study patients exhibited elevated baseline tryptophan (p < 0.001), low kynurenine/tryptophan (p < 0.001), elevated 3-hydryoxykynurenine/kynurenine (adj-p*<0.001), low kynurenic acid/3-hydroxykynurenine, and low picolinic acid/quinolinic acid (p < 0.001) compared to healthy controls. Treatment responders exhibited tryptophan depletion (p = 0.020) without a concomitant change in kynurenine/tryptophan ratio by week 8 (p = 0.163).

Conclusion

Clinical response to CBX augmentation is not associated with altered neurotoxic or neuroprotective indices within the time frame of this study. TRBDD revealed alterations in neuroprotective and neurotoxic indices, in the context of low kynurenine/tryptophan and high tryptophan. Treatment responders revealed a depletion in tryptophan by week 8, without concomitant kynurenine pathway (KP) activation.

Objectives

Treatment-resistance is high in bipolar disorder and is associated with a pro-inflammatory state and diversion of tryptophan toward the kynurenine pathway. This study as part of a large clinical trial, sought to determine, if modulation of the inflammatory response by inhibiting cyclooxygenase-2 (COX-2) with celecoxib combined with escitalopram, would convert treatment-resistant bipolar depression to response or remission and whether blood levels of quinolinic acid (QA) differ from healthy controls and change with treatment response.

Methods

This was a randomized, double-blind, two-arm, placebo-controlled study. Subjects who met study criteria were randomized to receive escitalopram + celecoxib, or escitalopram + placebo. Inflammation biomarkers and kynurenine pathway intermediates were determined at baseline and weeks 4 and 8.

Results

Patients receiving the celecoxib combination showed improved response and higher remission rate. All patients had significantly lower QA levels at baseline compared to healthy controls. QA values did not change significantly over time, but a downtrend was noted through treatment. Responders had marginally lower QA values than non-responders. Factors that might have led to low QA levels may include prior exposure to a variety of psychoactive agents.

Conclusions

Although QA did not significantly change, symptom reduction and remission occurred more frequently in the celecoxib group, demonstrating the beneficial effect of inflammation modulation.

Background

Long-term follow up studies of functioning in people with bipolar (type I) and major depressive disorders (BD and MDD) have not been reported from Africa.

Objectives

To describe the long-term functional outcome of BD and MDD, and factors that influence such outcome.

Methods

Door-to-door survey of 83,282 adults (ages 15–49 years) in a rural district of Ethiopia to identify potential cases whose diagnosis was later confirmed by standardized clinician interviews were followed by for an average of 11 years. The Short-Form- SF-36 scale was used to describe the functional outcome. Mixed linear models were used to evaluate potential factors associated with outcome. A total of 311 people with BD and 187 people with MDD that were identified at baseline and with complete data on functional outcome were included in the analyses.

Results

Mean social functioning levels at baseline were 55–65% for people with BD and 55% for MDD but improved with follow-up. About 33% incident and 37% prevalent cases of people with BD had reduced social functioning for three years or more. Baseline functioning was significantly associated with longitudinal functioning. When baseline functioning is adjusted in the model, longitudinal functioning was not associated with socio-demographic or illness characteristics.

Conclusions

The level of functions of people with BP and MDD were significantly lower than that of the general population both at baseline and during the follow-up period. Although there were improvements in function with follow-up, a significant proportion had functional deficits during the follow-up period.

To evaluate clinically easy to obtain parameters such as area and T2 MR signal intensity (SI) profiles from right and left caudate, putamen and thalamus nuclei and to describe age-related and inter-nuclei changes in both genders in healthy subjects, 71 healthy subjects (22–80 years old, 52 females) were evaluated with 1.5 T MRI conventional axial T2-Fast axial spin echo sequences obtaining SI and cross-sectional areas from caudate, putamen and thalamus nuclei using manually defined ROIs. Regression analysis were performed between age and MR parameters for inter-nuclei, gender and hemisphere side. Male basal ganglia show lower SI than those from females. Aging was differentially associated to a progressive lowering of basal nuclei SI in both genders. Male basal ganglia show SI changes following a positive quadratic function. Aging modifies differentially SI from all nuclei pair combination in both genders, showing mainly negative quadratic function. Age-related reduction of female caudate and a right lateralization for caudate nucleus SI in both genders were found. Healthy age-related nonlinear changes in SI from basal ganglia were defined for both genders. Basal ganglia show differential age-related changes. These results can be helpful to differentiate normal from abnormal aging changes.

Background

Previous research has identified altered processing of emotional information associated with the bipolar spectrum, but results have been inconsistent. The current study assessed whether hypomanic personality traits, a potential indicator of bipolar risk, are associated with biases in attention to emotional facial stimuli, even after controlling for mood state.

Methods

Participants (N = 135) completed measures assessing current mood symptoms, positive and negative affect, and hypomanic personality traits. They then completed an eye-tracking task measuring two indices of attention (i.e., mean initial orientation latency, mean total gaze duration) for happy, sad, angry, and neutral facial expressions.

Results

Even after controlling for mood state, hypomanic personality traits were associated with a bias for emotion faces as well as a trend towards faster orientation to happy facial expressions.

Limitations

Due to relatively low levels of mania in this sample, further work is needed to assess the extent to which these effects exist at clinical levels of depression or mania. Additionally, further work is needed to determine if such a bias represents a risk factor for the development of bipolar disorder.

Conclusions

Hypomanic personality traits appear to be associated with differences in early attention for emotional information.

Purpose of the article

Autism spectrum disorder (ASD) is an impairing neurodevelopmental disorder with an unknown etiology. The present study aims to investigate if the auditory brainstem response (ABR) to complex stimuli in children and adolescents diagnosed with ASD can be a possible objective biomarker in autism.

Materials and methods

The ABR of 39 youth with ASD (7–18 years) were compared to the ABR of 34 typically developed youth (TD). The ABR consists of seven positive peaks (waves I–VII) that occur during 10 Ms following a sound stimulus.

Results

The amplitude of wave III (region 2.5–4.0 Ms) was higher in the ASD group compared to the TD group. The TD males showed a significant lower degree of correlation, between left and right ear compared to the ASD groups and the TD females.

Conclusions

Altered auditory processing was evident in the pons region of the brainstem for the ASD group when compared to the TD group. Implications of the findings are discussed in relation to the neurobiology and assessment of autism spectrum disorder in youth.

Objective

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by recurrent obsessions and/or compulsions. Applying classification algorithms for prediction of treatment response helps to individualize treatment with more effectiveness. OCD data set is heterogeneous including continuous and discrete variables which presents challenges for most of the traditional classifiers to avoid data over-fitting. Here, we aimed to develop an ensemble classifier which is suitable for mixed data types for prediction of treatment response in OCD.

Methods

One hundred fifty-one subjects with OCD aged between 18–65 underwent fluvoxamine pharmacotherapy for 12 weeks and categorized into two groups (responder, non-responder) based on the reduction in their symptom severity following treatment. Decision tree and support vector machines (SVM-tree) were combined to deal with discrete and continuous variables and were used as base classifiers to build an ensemble of classifiers.

Results

Some of the attributes such as sexual obsessions and occupation, factor 1 (aggressive, contamination, sexual, religious, symmetry obsessions), initial obsession score, age at onset and illness duration are the high ranked predictors of treatment response. Comparing accuracy, precision, sensitivity, specificity and f-measure of the new algorithm with traditional classification algorithms such as decision tree, support vector machines (SVM), k-nearest neighbor and random forest showed a stronger performance of the proposed algorithm in the prediction of OCD treatment response.

Conclusion

The proposed strategy introduced an effective classification method to deal with medical datasets with mixed data types which can be of great significance in medical datasets and personalized medicine.

Objectives

Alice in Wonderland syndrome (AIWS) is a pathological condition characterized by distortions of visual representation, with symptoms deforming images, figures, bodies, objects, which are seen larger or smaller than normal. Causes are sought in infectious diseases, psychiatric illness, migraines. It may be associated with alterations in the body schema such as non-recognition of own body in space. It's a rare form of visual aura. Unlike it, migraine with aura is a very frequent disorder, in which the phenomenon of visual aura is considered a consequence of cortical spreading depression(CSD), a wave of depolarization that propagates from the occipital cortex, creating a vasoconstriction and visual disturbances.

Methods

Recent studies have found an anatomical correlation between visual and somatosensory disorders such as those found in AIWS, located in the temporo- parieto-occipital junction.Neuroimaging studies allowed to identify the CSD and the occipital cortex responsible for the mechanism of the visual aura and the involvement of the parietal cortex in the genesis of the somatosensory aura.

Results

The mechanism of the initiation of the stage of visual and somatosensory aura could be a combination of two events.

Conclusions

Literature data now offer agreed confirmations on the role of the CSD associated to somatosensory aura.

In this review article we present an integrative overview of parameters and mechanisms underlying psychiatric and neuropsychiatric disorders that involve the immune and autonomic nervous systems along with neurotransmission and specific endocrine mechanisms. At the center of these highly complex and interactive mechanisms is stress and stress perception by the afflicted individual. Stress reactivity is governed by genetic and epigenetic factors that have yet to be fully clarified. Stress is defined as a state of threatened homeostasis following exposure to extrinsic or intrinsic adverse forces. The major pathways activated by stressors are the HPA axis and the autonomic nervous system. Loss of dynamic variability in the autonomic nervous system, during which one branch dominates over the other for extended periods of time and across multiple environmental demands, is associated with illness and eventually chronic disease. This state of dysregulation can be achieved by excessive sympathetic activation, too little parasympathetic activation, or some combination of both. Autonomic dysregulation leads to immune system dysregulation which in turn interferes with the metabolism of tryptophan leading to the formation of toxic and diabetogenic metabolites. We introduce the concept of neuroprogression as a suitable conceptual framework that allows integration of the complex component mechanisms that contribute to recurrence and chronicity of mental disorders if left untreated or undertreated. The complex interactions among the autonomic, endocrine, immune and metabolic systems and associated cascades provide unique opportunities for development of novel therapeutic agents.

Objective: Young women with breast cancer (BC) face emotional challenges as they deal with the disease and the related fear of adversity. This study evaluated the psychosocial complications experienced by younger women (38–50 age range) over a three year period after BC diagnosis.

Method: From an observational perspective, we detected late-stage complications involving psychological distress (variables included anxiety, anger, psychological distress, and depression) and sociodemographic influences on treatment and post-treatment paths for a 36-month period after diagnosis.

Results: Our data highlighted that good emotional regulation improved resilience in dealing with diagnoses and medical treatments. Findings highlighted that women with positive mental flexibility toward surgical and pharmacological treatments improved their resilience because they mentally focused on the medical treatments and following recovery periods. However, fragility was detected over a three-year period following diagnoses. Patients were mostly impacted around 12 months after diagnoses and soon after post-treatment paths (i.e., at 24 months and around 36 months after diagnosis).

Conclusion: Psychological status fluctuates among BC survivors. Here, resilience may be a useful trait in young patients by enabling them to regain normal lives. In fact, an increased likelihood of survival is strongly linked to the restoration of a normal life through modified and improved living. Our findings highlighted that young BC patients were emotionally challenged; a psychological resilience index can thus predict depression and/or anxiety patterns in dealing with adversity.