Aberrant brain insulin signaling has been posited to lie at the crossroads of several metabolic and cognitive disorders. Intranasal insulin (INI) is a non-invasive approach that allows investigation ...and modulation of insulin signaling in the brain while limiting peripheral side effects.
The objective of this systematic review and meta-analysis is to evaluate the effects of INI on cognition in diverse patient populations and healthy individuals.
MEDLINE, EMBASE, PsycINFO, and Cochrane CENTRAL were systematically searched from 2000 to July 2021. Eligible studies were randomized controlled trials that studied the effects of INI on cognition. Two independent reviewers determined study eligibility and extracted relevant descriptive and outcome data.
Twenty-nine studies (pooled N = 1,726) in healthy individuals as well as those with Alzheimer's disease (AD)/mild cognitive impairment (MCI), mental health disorders, metabolic disorders, among others, were included in the quantitative meta-analysis. Patients with AD/MCI treated with INI were more likely to show an improvement in global cognition (SMD = 0.22, 95% CI: 0.05-0.38 p = <0.00001, N = 12 studies). Among studies with healthy individuals and other patient populations, no significant effects of INI were found for global cognition.
This review demonstrates that INI may be associated with pro-cognitive benefits for global cognition, specifically for individuals with AD/MCI. Further studies are required to better understand the neurobiological mechanisms and differences in etiology to dissect the intrinsic and extrinsic factors contributing to the treatment response of INI.
Prescription rates of second-generation antipsychotics (SGAs) are rapidly increasing for non-indicated (i.e., off-label) usage. SGAs used for approved indications are associated with significant ...metabolic adverse effects, including weight gain. The objective of this systematic review and meta-analysis is to evaluate the metabolic adverse effects of SGA use for off-label management of psychiatric illnesses in the adult population. We performed a systematic database search to identify randomized controlled trials (RCTs) that reported on weight and other metabolic outcomes with off-label use of SGAs among adults. Thirty-eight RCTs met inclusion criteria for this review; 35 of these studies, with a total of 4930 patients, were included in the quantitative meta-analysis. Patients treated with olanzapine, risperidone, and quetiapine were more likely to report weight gain as a side effect and experience clinically significant (≥7%) weight gain compared to those treated with a placebo. Among studies that reported weight as a continuous outcome, olanzapine was associated with significantly greater weight gain across all disorders (mean difference (MD) = 3.24 kg, 95% CI: 2.57-3.90 p = 0.001, N = 12 studies). Similar trends were noted with quetiapine and risperidone. A meta-regression analysis revealed a positive dose-response association between olanzapine dose and weight gain (regression coefficient: 0.36, p = 0.001). This review demonstrates that off-label use of SGAs, and particularly olanzapine, is associated with significant weight gain among adult patients. Our findings are concerning given the widespread off-label use of SGAs. Further studies are required to better understand the effects of off-label SGA use on other metabolic parameters. The study was registered with the PROSPERO international database of prospectively registered systematic reviews (PROSPERO #143186).
Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and ...diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a ‘chamber of secrets’, particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.
Music performance anxiety is a common experience among elite and professional musicians and impedes performers from achieving flow state, or a state of focused, sustained engagement that promotes ...optimal performance.
The aim of this study was to use heart rate variability (HRV) to determine the psychophysiological underpinnings of optimal music performance.
We assessed HRV to study how autonomic-cardiac modulation was associated with flow during piano performance. Twenty-two pianists (15-22 years) with at least a Grade 8 Royal Conservatory of Music certification prepared two standardized pieces and a self-selected piece. Performer heart rate data were measured with a Polar 800 watch in 5-min periods immediately before performances, during performances and post-performance. HRV was employed to assess autonomic modulation of cardiac intervals. HRV indices of sympathetic and parasympathetic modulation of the heart were analyzed in 2.5-min segments to monitor short-term autonomic adjustments using the Kubios HRV Software. Flow state was measured using the 36-item Flow State Scale (FSS). Relationships were analyzed using zero-order correlations and multiple linear regressions.
Our sample consisted of 22 RCM Grade 8 certified pianists. Participants achieved the highest level of flow during performance of the Bach piece. Decreased HRV was observed during performance, as indicated by a significant drop in total power. Flow state was positively associated with High Frequency (HF) power during the pre-performance phase, and inversely associated with Low Frequency (LF) power during performance.
Inverse association of flow with LF-HRV during performance affirms the importance of vagal-HR modulation for achievement of flow state. Increased HF-HRV and reduced LF-HRV immediately prior to performance suggests that flow state may be shaped as much by physiological preparation during pre-performance as it is by physiologic responses during performance. Further research is required to validate the correlation between autonomic modulation of the heart and flow state. Evidence of this correlation between autonomic modulation of the heart and achievement of flow state may pave the way for further research on enhancing musical performance and targeting MPA through HRV-based interventions.
Disturbed eating behaviours have been widely reported in psychotic disorders since the early 19th century. There is also evidence that antipsychotic (AP) treatment may induce binge eating or other ...related compulsive eating behaviours. It is therefore possible that abnormal eating patterns may contribute to the significant weight gain and other metabolic disturbances observed in patients with psychosis. In this scoping review, we aimed to explore the underlying psychopathological and neurobiological mechanisms of disrupted eating behaviours in psychosis spectrum disorders and the role of APs in this relationship. A systematic search identified 35 studies that met our eligibility criteria and were included in our qualitative synthesis. Synthesizing evidence from self-report questionnaires and food surveys, we found that patients with psychosis exhibit increased appetite and craving for fatty food, as well as increased caloric intake and snacking, which may be associated with increased disinhibition. Limited evidence from neuroimaging studies suggested that AP-naïve first episode patients exhibit similar neural processing of food to healthy controls, while chronic AP exposure may lead to decreased activity in satiety areas and increased activity in areas associated with reward anticipation. Overall, this review supports the notion that AP use can lead to disturbed eating patterns in patients, which may contribute to AP-induced weight gain. However, intrinsic illness-related effects on eating behaviors remain less well elucidated, and many confounding factors as well as variability in study designs limits interpretation of existing literature in this field and precludes firm conclusions from being made.
•While a number of pharmacological and behavioral treatments exist for alcohol use disorder (AUD), the therapeutic effect of these interventions are relatively modest.•Repetitive transcranial ...magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) may provide new approaches to better treat alcohol craving.•There is evidence for a positive effect of rTMS, but not tDCS, on craving in AUD.
While several pharmacological and behavioral treatments are available for alcohol use disorder (AUD), they may not be effective for all patients. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of rTMS and tDCS for craving in AUD.
EMBASE, Cochrane Library, PsycINFO, and PubMed databases were searched for original, peer-reviewed research articles in the English language published between January 2000 and January 2022. Randomized controlled trials (RCTs) reporting changes in alcohol craving among patients with AUD were selected. Random-effects meta-analysis was employed to pool data.
Changes in alcohol craving were extracted from 15 RCTs. Six studies assessed the efficacy of rTMS while nine studies examined tDCS. Results demonstrated that in comparison to sham stimulation, active rTMS to the DLPFC yields small but significant reductions in alcohol craving (standardized mean difference SMD = -0.27, p = .03). However, DLPFC stimulation via tDCS was not superior to sham stimulation in producing changes in alcohol craving (SMD = -0.08, p = .59).
Our meta-analysis suggests that rTMS may be superior to tDCS in reducing alcohol craving in patients with AUD. However, additional research is needed to identify optimal stimulation parameters for both non-invasive neuromodulatory techniques in AUD.
Background
The
E
val
U
ation of goal-di
R
ected activities to pr
O
mote well-be
I
ng and he
A
lth (EUROIA) scale is a novel patient-reported measure that was administered to individuals with chronic ...heart failure (CHF). It assesses goal-directed activities that are self-reported as being personally meaningful and commonly utilized to optimize health-related quality of life (HRQL). Our aim was to evaluate psychometric properties of the EUROIA, and to determine if it accounted for novel variance in its association with clinical outcomes.
Methods
This study was a secondary analysis of the CHF-CePPORT trial, which enrolled 231 CHF patients: median age = 59.5 years, 23% women. Baseline assessments included: EUROIA, Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS), Patient Health Questionnaire–9 for depression (PHQ-9), and the Generalized Anxiety Disorder–7 (GAD-7). 12-month outcomes included health status (composite index of incident hospitalization or emergency department, ED, visit) and mental health (PHQ-9 and GAD-7).
Results
Exploratory Principal Axis Factoring identified four EUROIA factors with satisfactory internal reliability: i.e., activities promoting eudaimonic well-being (McDondald’s ω = 0.79), social affiliation (⍺=0.69), self-affirmation (⍺=0.73), and fulfillment of social roles/responsibilities (Spearman-Brown coefficient = 0.66). Multivariable logistic regression indicated that not only was the EUROIA inversely associated with incidence of 12-month hospitalization/ED visits independent of the KCCQ-OS (Odds Ratio, OR = 0.95, 95% Confidence Interval, CI, 0.91, 0.98), but it was also associated with 12-month PHQ-9 (OR = 0.91, 95% CI, 0.86, 0.97), and GAD-7 (OR = 0.94, 95% CI, 0.90, 0.99) whereas the KCCQ-OS was not.
Conclusion
The EUROIA provides a preliminary taxonomy of goal-directed activities that promote HRQL among CHF patients independently from a current gold standard state-based measure.
Clinical trial registration
NCT01864369;
https://classic.clinicaltrials.gov/ct2/show/NCT01864369
.
Schizophrenia (SCZ) is a psychiatric disorder characterized by a wide range of positive, negative and cognitive symptoms, along with an increased risk of metabolic syndrome and cardiovascular disease ...that contribute to a 15-20-year reduced life expectancy. Autonomic dysfunction, in the form of increased sympathetic activity and decreased parasympathetic activity, is postulated to be implicated in SCZ and its treatment. The aim of this narrative review is to view SCZ through an autonomic lens and synthesize the evidence relating autonomic dysfunction to different domains of SCZ. Using various methods of assessing autonomic activity, autonomic dysfunction was found to be associated with multiple aspects of SCZ pathophysiology, including symptom severity, cognitive impairment, and the development of cardiometabolic comorbidities, such as metabolic syndrome and high BMI. The strongest association of low heart rate variability was noted among patients on antipsychotic treatment with high-affinity muscarinic antagonism (i.e., clozapine, olanzapine and quetiapine). The review will also suggest ways in which studying autonomic dysfunction can help reduce morbidity and mortality associated with SCZ and its treatment.
Purpose of Review
Weight gain is a disconcerting issue experienced by patients treated with antipsychotics (APs). This review summarizes current knowledge on the prevalence, etiology, and risk ...factors for antipsychotic-induced weight gain (AIWG), and evidence for interventions, including special considerations.
Recent Findings
Predisposing risk factors for AIWG include lack of prior AP exposure, sex, and age. AP dose and duration of exposure are additional treatment-related factors that may contribute to this issue. Among current approaches to target AIWG, metformin has the most evidence to support its use, and this is increasingly reflected in clinical guidelines. While lifestyle approaches are recommended, cost-effectiveness and scalability represent limitations.
Summary
More research is needed to identify newer treatment options and inform clinical recommendations for AIWG. Concerns around scope of practice in psychiatry to address AIWG and related comorbidities will require enhanced training opportunities and interdisciplinary collaborations, as well as updated position statements/practice guidelines emphasizing prevention.
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