Fat loss and muscle gain: The possible role of cortical glutamate in determining the efficacy of physical exercise.

BACKGROUND: Physical exercise is widely acknowledged for its health benefits, but its effectiveness in treating obesity remains contentious due to variability in response. Owing to the roles of glutamate in appetite regulation, food addiction, and impulsivity, this observational cohort-study evaluated medial prefrontal cortex (mPFC) glutamate as a predictor of variability in exercise response, specifically in terms of fat loss and muscle gain. METHODS: Healthy non-exercising adult men (n = 21) underwent an 8-week supervised exercise program. Baseline glutamate levels in the mPFC were measured through magnetic resonance spectroscopy. For exercise-dependent changes in body composition (fat and muscle mass), basal metabolic rate (BMR), and blood metabolic biomarkers related to lipid and glucose metabolism, measurements were obtained through bioelectrical impedance and blood sample analyses, respectively. RESULTS: The exercise program resulted in significant improvements in body composition, including reductions in percentage body fat mass, body fat mass, and waist-to-hip ratio and an increase in mean muscle mass. Furthermore, BMR and metabolic indicators linked to glucose and lipids exhibited significant changes. Notably, lower baseline glutamate levels were associated with greater loss in percentage body fat mass (r = 0.482, p = 0.027), body fat mass (r = 0.441, p = 0.045), and increase in muscle mass (r = -0.409, p = 0.066, marginal) following the exercise program. CONCLUSION: These preliminary findings contribute to our understanding of the neurobiology of obesity and emphasize the significance of glutamate in regulating body composition. The results also highlight cortical glutamate as a potential predictor of exercise-induced fat loss and muscle gain.

Occupational evaluation of community-based psychiatric rehabilitation outcomes in individuals with severe mental illnesses: A ten-year retrospective study.

BACKGROUND: There is a lack of research on the effect of community-based psychiatric rehabilitation programs (CBPRs) in individuals with severe mental illness. This research used data from a retrospective study to examine the effect of a CBPR in a community rehabilitation center. MATERIALS AND METHODS: Clinical outcomes measures from a retrospective study were collected. Outcome measures were the Allen Cognitive Level Screen assessment, Purdue Pegboard Test, Chu's Attention Test, and Activities of Daily Living Rating Scale-III (ADLRS-III) before and immediately after 12 months of intervention. RESULTS: The 141 participants with mental illness were an average age of 35.29 years (SD = 8.75). The retrospective review of medical records showed 46 people dropped out within 12 months, and 95 people continued to participate in the rehabilitation program for 1 year. After 1 year of community rehabilitation, there was a trend for the participants who completed the intervention to improve on the ADLRS-III, Purdue Pegboard Test, and Chu's Attention Test. Participants who performed better on the occupational assessment were more likely to transit to the employment status. CONCLUSION: This study found the benefits of CBPR in work-related intervention for people with mental illness. Occupational assessments are relevant for studying changes in functional outcomes in people with mental illness receiving community-based rehabilitation.

Harm Avoidance is Correlated with the Reward System in Adult Patients with Attention Deficit Hyperactivity Disorder: A Functional Magnetic Resonance Imaging Study.

Objective: Hypoactivity in the reward system among patients with attention deficit hyperactivity disorder (ADHD) is a well-known phenomenon. Whether the activity in the reward pathway is related to harm avoidance, such as in sensitivity to punishment, is unclear. Evidence regarding the potential difference between ADHD patients and controls in terms of this association is scarce. Methods: Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa gambling test. Fourteen adults with ADHD and 14 controls were enrolled in the study. Results: Harm avoidance was found to be positively correlated with the activities of the bilateral orbitofrontal cortex and right insula in individuals with ADHD. A group difference was also confirmed. Conclusion: Understanding the roles of harm avoidance and brain activation during risk tasks is important.

Altered glutamate level and its association with working memory among patients with treatment-resistant schizophrenia (TRS): a proton magnetic resonance spectroscopy study.

BACKGROUND: Treatment-resistant schizophrenia (TRS) and non-TRS may be associated with different dopaminergic and glutamatergic regulations. The concept of dysregulated glutamatergic concentrations in specific brain regions remains controversial. Herein, we aimed to assess (i) the distribution of the glutamatergic concentration in the brain, (ii) the association between working memory (WM) differences in TRS and non-TRS patients, and (iii) whether an alteration in the glutamate (Glu) level is associated with WM. METHODS: The participants included 38 TRS patients, 35 non-TRS patients, and 19 healthy controls (HCs), all of whom underwent 1.5-Tesla proton magnetic resonance spectroscopy of anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC). The ratios of glutamatergic neurometabolites to N-acetylaspartate + N-acetyl aspartylglutamate (NAAx) were calculated. Cognitive function was assessed using the Wechsler Adult Intelligence Scales, 4th Edition, which included the working memory index (WMI). RESULT: The TRS patients had a higher glutamate + glutamine (Glx)/NAAx ratio compared to the non-TRS patients and HCs in the ACC, but this was not significantly different in the MPFC. WM was negatively correlated with Glx/NAAx in the ACC among the non-TRS patients, but not in the TRS patients or HCs. CONCLUSIONS: Our findings were consistent with most studies indicating that the glutamatergic concentration in the ACC plays important roles in the classification of TRS and cognition. Our results may provide potential evidence for predictors and treatment response biomarkers in TRS patients. Further research is needed to probe the value using the relationship between Glu and WM as a potential prognostic predictor of schizophrenia.

Striatal Dopamine Transporter Availability is Associated with Sleep Disturbance among Patients with Bipolar I Disorder: A Single-photon Emission Computed Tomography Study Using [99mTc] TRODAT-1.

Objective: Bipolar disorder (BD) is characterized by the poor sleep quality. Whether the striatal dopamine transporter (DAT) availability is related to sleep quality among patients with BD is unclear. Methods: Fifty-three euthymic patients with BD (24 BD-I and 29 BD-II) and sixty-eight healthy controls were enrolled. The Chinese Version of the Pittsburgh Sleep Quality Index (PSQI) was used, and the availability of DAT was assessed by single-photon emission computed tomography (SPECT) using [99mTc] TRODAT-1. Results: The sleep disturbance component of the PSQI was significantly associated with the level of DAT availability among patients with BD. Conclusion: The striatal dopaminergic activity that contributes to resilience to adversity was associated with sleep pattern among patients with BD.

Dopaminergic and glutamatergic biomarkers disruption in addiction and regulation by exercise: a mini review.

INTRODUCTION: Drug addiction is associated with disruption of a multitude of biomarkers in various brain regions, particularly in the reward centre. The most pronounced are dopaminergic and glutamatergic biomarkers, which are affected at various levels. Neuropathological changes in biomarkers alter the homeostasis of the glutamatergic and dopaminergic nervous systems and promote addiction-associated characteristics such as repeated intake, maintenance, withdrawal, reinstatement, and relapse. Exercise has been shown to have a buffering effect on such biomarkers and reverse the effects of addictive substances. METHODS: A review of the literature searched in PubMed, examining drug addiction and physical exercise in relation to dopaminergic and glutamatergic systems at any of the three biomarker levels (i.e. neurotransmitter, receptor, or transporter). RESULTS: We review the collective impact of addictive substances on the dopaminergic and glutamatergic systems and the beneficial effect of exercise in terms of reversing the damage to these systems. We propose future directions, including implications of exercise as an add-on therapy, substance use disorder (SUD) prognosis and diagnosis and designing of optimised exercise and pharmaceutical regimens based on the aforementioned biomarkers. CONCLUSION: Exercise is beneficial for all types of drug addiction at all stages, by reversing molecular damages caused to dopaminergic and glutamatergic systems.

Striatal subregional functional connectivity and its association with sustained attention in adults with attention deficit hyperactivity disorder.

The functional connectivity (FC) of striatal subregions is correlated with cognitive functions in child attention deficit hyperactivity disorder (ADHD). However, increasing age changes the pattern of cognitive functions and clinical presentation. The changes in the pattern of cognitive functions may be associated with underlying age­dependent striatal subregional FC alterations. We attempted to explore aberrancies in FC in striatal subregions and their associations with a predominant cognitive symptom (inattention) in adult ADHD. The FCs of ten bilateral subregions (seeds) of the striatum along with the whole brain were investigated, and FC maps of adults with ADHD (N=15) and healthy controls (N=15) were compared. Finally, we evaluated the associations of striatal subregional FCs with cognitive functions. Case­control differences in striatal subregional FC were not significant; however, attention scores were marginally significantly positively correlated with FC between the right dorsal­caudal putamen and right­superior temporal gyrus in the ADHD group. Our results suggested that cognitive deficits (inattention) may be associated with FC aberrancy in a substriatal connection (between the right dorsal­caudal putamen and right­superior temporal gyrus) in adult ADHD.

Transcranial direct current stimulation (tDCS) may reduce the expired CO concentration among opioid users who smoke cigarettes: a randomized sham-controlled study.

Transcranial direct current stimulation (tDCS) could be a potential treatment for nicotine dependency. Little is known with regards to the efficacy of this treatment in cigarette-smoking patients with heroin dependency. In this sham-controlled study, we probed the effect of 5-day, 20-min, 2-mA-intensity tDCS treatment on the outcomes of cigarette-smoking. Our objectives are to examine the effects of tDCS on two outcomes: objective expired CO concentration and subjective self-reported number of cigarettes smoked per day. A total of 30 patients were randomized into active or sham control groups. The stimulation site was randomized to anodal stimulation of the left dorsal lateral prefrontal cortex or the orbital frontal cortex. The expired CO concentration was recorded. The patients also reported their cigarette consumption and level of craving prior to each 5-day treatment period and after 5 days of follow-up. tDCS was found to be effective in terms of reducing the expired CO concentration, and both groups demonstrated reduced numbers of cigarettes smoked. However, no significant group difference was found with regards to craving tendency. tDCS may affect objective outcomes related to cigarette-smoking among patients with heroin dependence.

Positive Symptoms in Antipsychotic-naïve Schizophrenia are Associated with Increased Body Mass Index after Treatment.

OBJECTIVE: Weight gain is an important risk factor for morbidity and mortality among patients with schizophrenia. We speculated that positive symptoms, related to dopaminergic hyperactivity and altered mesolimbic function, are associated with weight gain. METHODS: Twenty-two antipsychotic-naïve, first-episode patients with schizophrenia were enrolled. The Positive and Negative Syndrome Scale was completed at enrollment and follow-up. Body mass index (BMI) was also measured. RESULTS: The increase in BMI, after 6.04 ± 2.16 years of follow-up, was associated with positive symptoms, but not negative symptoms, before treatment with antipsychotics in antipsychotic-naïve patients with schizophrenia. CONCLUSION: This finding implied that dopaminergic hyperactivity could be an important factor to predict the treatment outcome. Body weight control is important for the health management of patients with schizophrenia with more severe positive symptoms.

A pilot study on the association between the blood oxygen level-dependent signal in the reward system and dopamine transporter availability in adults with attention deficit hyperactivity disorder.

BACKGROUND: It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear. METHODS: Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test. RESULT: DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls. CONCLUSIONS: The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.

Heart Rate Variability with Deep Breathing in Drug-Naïve Patients with Schizophrenia.

Abnormal autonomic nervous system (ANS) function may result in poor outcomes in patients with schizophrenia. Altered cardio-respiratory coupling, which indicates suppression of vagal activity, was identified as an important trait in patients with schizophrenia and their unaffected relatives. Heart rate variability (HRV) in standardized bedside reflex tests has been studied, mostly in medicated patients with schizophrenia whose ANS function could be influenced by medication. Our study aimed to explore the autonomic function differences between drug-naïve patients with schizophrenia and healthy individuals during challenge tests combining respiration and HRV analysis. Forty-two drug-naïve patients with schizophrenia were matched with 42 healthy controls in terms of age and gender. Their beat-to-beat blood pressure and heart rate were monitored in the supine position as a survey of ANS function, and the mean heart rate range (MHRR) was measured under deep-breathing challenge. A decreased MHRR, a sensitive sign indicating an impaired parasympathetic response, during the deep-breathing challenge among the drug-naïve patients with schizophrenia was found. Drug-naïve patients with schizophrenia may have a parasympathetic dysfunction in the early stages of schizophrenia before medication is introduced, which could be considered a neurobiological marker in the pathophysiology of schizophrenia.

The integrated model of glutamate and dopamine hypothesis for schizophrenia: Prediction and personalized medicine for prevent potential treatment-resistant patients.

Treatment-resistant schizophrenia (TRS) is one of the subgroups of schizophrenia of which little is known with regard to its optimal mechanism. Treatment response, either as full remission of symptoms or prediction by biomarker, is important in psychiatry. We have proposed a model that integrates dopaminergic and glutamatergic systems with the biological interactions of TRS patients. We hypothesize that the subgroups of schizophrenia may be determined by glutamatergic and dopaminergic concentrations prior to medical treatment. This hypothesis implies that higher glutamatergic concentration in the brain with normalized or decreased dopamine synthesis capacity may explain aspects of TRS as observed in clinical medical practice, neuroimaging measurements, and brain stimulations. According to this hypothesis, the ability to prescribe a proper medication combination, to predict the outcome in first-episode psychosis, and personalized medicine for chronic schizophrenia patients can be applied into practice. This represents an initial step in explaining psychosis due to the valence of two neurotransmitters. Future studies are needed to examine the validity of this mechanism.

Correlation between interleukin-6 levels and methadone maintenance therapy outcomes.

BACKGROUND: The outcome of methadone maintenance therapy (MMT) varies in each patient with opioid use disorder (OUD). Opioid abuse activates proinflammatory processes by increasing cytokine production and impairing neurotrophic factor expression, and possibly leads to a vicious cycle that hinders recovery. Therefore, we investigated whether markers of inflammation and neurotrophic expression correlate with the MMT outcomes in OUD patients. METHOD: We investigated OUD patients undergoing MMT and followed them up for 12 weeks. We measured plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-1ß, transforming growth factor (TGF)-ß1, brain-derived neurotrophic factor (BDNF), urinary morphine tests, and plasma morphine levels at baseline and on weeks 1, 4, 8, and 12 during MMT. Multiple linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the cytokine and BDNF levels and MMT outcomes. RESULTS: We initially enrolled 104 patients, but only 78 patients completed end-of-study assessments. Plasma levels of CRP, TGF-ß1, and BDNF fell during MMT. Plasma IL-6 levels were significantly associated with plasma morphine levels (P = 0.005) and urinary morphine-positive (+) results (P = 0.04), and significantly associated with poor compliance (P = 0.009) and early dropout from MMT (P = 0.001). However, other cytokine and BDNF levels were not consistently associated with MMT outcomes. CONCLUSION: Higher IL-6 levels were associated with poor MMT outcomes. Additional studies on regulating IL-6 expression to improve treatment outcomes in OUD patients might be warranted.

The association between plasma cholesterol and the effect of tryptophan depletion on heart rate variability.

Studies on the cholesterol-serotonin hypothesis and its link to mood disorders are scarce. In addition, little is known about the association between cholesterol and the effects of tryptophan depletion (TD). The aim of the present study was to investigate the association between plasma cholesterol and changes in heart rate variability (HRV), an important marker of depression and anxiety, after TD. The plasma cholesterol levels of 28 healthy participants were noted, and their HRVs were measured by spectrum analysis. TD was carried out on testing day, and participants provided blood samples just before and 5 hours for tryptophan level after TD. HRV was measured again after TD. An association was found between plasma cholesterol levels and the change in HRV. Decreased high frequency HRV was marginally associated with lower levels of high-density lipoprotein cholesterol, while increased low frequency HRV was significantly associated with lower levels of total and low-density lipoprotein cholesterol. Our findings indicate that low cholesterol levels may play parts of role in the mechanism of the deactivation of parasympathetic, and activation of sympathetic, functions induced by altered serotonergic function.

Hypothesis of the optimal therapeutic effect of transcranial direct current stimulation (tDCS) for psychiatric disorders: Integration of positive cognitive tasks during the neuroplastic process.

Transcranial direct current stimulation (tDCS) is a promising intervention for psychiatric disorders; however, little is known with regards to the optimal regime. As cognition, either spontaneously generated by patients or guided by treatment, is important in psychiatry, we have proposed a model that integrates cognition activity with the biological mechanisms of the therapeutic effect of tDCS in psychiatric disorders. We propose that the valence of the outcome of these mechanisms may be determined by the cognitive activity of the patient before or during tDCS treatment. This hypothesis implies that proper cognition activity may work in cooperation with tDCS to achieve the maximum treatment effect. Negative cognition may decrease or even reverse the positive effect of tDCS. According to this hypothesis, the performance of explicit tasks or instructions before, during, or after tDCS is important. Harm caused by misuse of home-made tDCS equipment is also addressed in this hypothesis.

Heart Rate Variability is Associated with Memory in Females.

Research into the association between heart rate variability (HRV) and cognitive function is scarce, particularly with regard to gender differences. HRV in 182 healthy volunteers was assessed by the root mean square of the successive difference (RMSSD) and spectrum analysis, while the Wechsler Memory Scale-Revised (WMS-R) was used to determine memory function. Robust and significant associations were found to exist between HRV (RMSSD and high-frequency HRV) and domains of the WMS-R in females. Caution should therefore be taken to control for gender when conducting studies on the relationships between HRV and cognitive variables.

The Association between the Level of Plasma Oxytocin and Craving among Former Heroin Users.

BACKGROUND: Animal studies have demonstrated that oxytocin can influence addiction behaviors and might interact with the dopaminergic system, which is a key component of addiction behaviors. However, related evidence from clinical studies is scarce. The aim of our study was to explore the relationship between plasma oxytocin level and heroin craving among patients receiving methadone maintenance treatment, and to ascertain whether this relationship is moderated by novelty-seeking. METHODS: The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan. Seventy-seven patients with heroin addiction were enrolled. Plasma oxytocin was measured using an ELISA kit. Craving was assessed using an established instrument, the Chinese Craving Scale. RESULTS: A significant negative association was found between the plasma oxytocin level and craving score, which remained robust after controlling the effects of social support and low-density lipoprotein cholesterol. An interaction between oxytocin and novelty-seeking indicated that this relationship was stronger among patients with a lower level of novelty-seeking. CONCLUSION: This finding may be taken into account in future studies and may provide a basis for the development of potential treatment for addiction. The effect of oxytocin for the treatment of opioid dependence might be modulated by some psychological factors.