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Although considerable evidence supports the efficacy of exercise as an antidepressant treatment, critical reviews informing routine practice and future research directions are scarce.
We critically reviewed exercise studies for clinically depressed adults, focussing on the PICOS criteria referred to participants, interventions, comparisons, outcomes, and study designs.
Most studies have not screened their samples for symptom heterogeneity. Also, they have employed heterogeneous exercise interventions and control groups that may lead to an underestimation of the benefits of exercise. In addition, pragmatic trials allowing scalable replication and implementation in routine practice are scarce. Future studies, can consider the research domain criteria as a diagnostic framework, and conduct moderator analyses to identify depressed subgroups with symptomatology and biopsychosocial characteristics associated with differential responses to exercise interventions. The search for biomarkers of the antidepressant responses to exercise should be prioritised. Further, non-physically active comparison groups should be used to minimise treatment cross-overs and thus the underestimation of the effects of exercise interventions. Finally, the use of outcome measures that maintain their validity at low and moderate levels of symptom severity and the development of trials with a pragmatic design are essential.
The current evidence base is fraught with methodological considerations that need to be taken into account in order to increase further our understanding on the impact of exercise as medicine in depression. Future research should include moderator analyses, incorporate biomarker assays, use appropriate control and comparison groups, assess outcomes with psychometrically sensitive measures, and prioritise pragmatic trials towards transition to routine practice.
l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial.
Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS).
HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration.
Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.
The product of the G72 gene is an activator of d-amino acid oxidase and has been suggested to play a role in the pathogenesis of schizophrenia. Increased G72 protein levels may be associated with disturbed glutamatergic transmission and increased reactive oxygen species. Only one pilot study by Lin et al. has investigated the potential role of serum G72 protein levels as a biomarker for schizophrenia. In this study, we aimed to compare serum G72 protein levels between patients with schizophrenia and healthy controls, and to retest the results of the previous pilot study.
Materials and methods
In total, 107 patients with a diagnosis of schizophrenia according to the inclusion and exclusion criteria and 60 age–sex-matched healthy controls were included in the study. The groups were compared regarding serum G72 protein levels.
The mean serum G72 protein values were 495.90±152.03 pg/ml in the schizophrenia group and 346.10±102.08 pg/ml in the healthy control group. The mean serum G72 protein level was significantly increased in the schizophrenia group compared with the healthy control group (t=−3.89, p<0.001). A receiver operating characteristics analysis was performed to compare the schizophrenia and healthy control groups. It was determined that the cut-off value was 141.51 pg/ml with a sensitivity of 0.991 and a specificity of 0.821.
We suggest that serum G72 protein levels may represent a candidate biomarker for schizophrenia and have confirmed the results of the previous preliminary study. Additional studies with larger sample sizes and the inclusion of first episode schizophrenia patients are required to clarify the reliability and validity of serum G72 protein levels as a biomarker for schizophrenia.
Schizophrenia (SZ) is suggested to be a complex polygenetic disorder with high heritability. Genome-wide association studies have found that the rs1635, rs11038167, and rs10489202 polymorphisms are associated with SZ in Han Chinese. However, results of validation studies are inconsistent. This study aimed to test the association between the NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms and SZ in a Chinese population.
This study contained 700 unrelated SZ patients (300 Zhuang and 400 Han) and 700 gender- and age-matched controls (300 Zhuang and 400 Han). The polymorphisms in TSPAN18 (rs11038167), NKAPL (rs1635), and MPC2 (rs10489202) were genotyped using the Sequenom MassARRAY method. Statistical analyses were performed with PLINK program and SPSS l6.0 for Windows. STATA11.1 was used for meta-analysis.
No statistically significant difference was found in different allele and genotype frequencies of rs1635, rs11038167, and rs10489202 between SZ cases and controls of Zhuang and Han ethnicities and the total samples (all p>0.05). Further meta-analysis suggested that single-nucleotide polymorphism rs10489202 was significantly associated with SZ in a Han Chinese population (pOR=0.002).
Our case–control study failed to validate the significant association of NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms with SZ susceptibility in the southern Zhuang or Han Chinese population. However, meta-analysis showed a significant association between MPC2 variant rs10489202 and SZ susceptibility in Han Chinese.
Among cognitive reserve markers, educational attainment is the most widely studied, with several studies establishing a strong association with risk of dementia. However, it has not yet been fully examined in delirium. This study aims to analyse the relationship between educational attainment and delirium.
The study included elderly hospitalised patients admitted (≥48 h) into an intermediate care unit (IMCU) of Intensive Care Medicine Service. Exclusion criteria were as follows: Glasgow Coma Scale (total≤11), blindness/deafness, inability to communicate or to speak Portuguese. The European Portuguese Version of the Confusion Assessment Method (CAM) was used for delirium assessment.
The final sample (n=157) had a mean age of 78.8 (SD=7.6) the majority being female (52.2%), married (51.5%) and with low educational level (49%). According to CAM, 21% of the patients had delirium. The delirium group presented the fewest years of education (median 1 vs. 4), with statistical significance (p=0.003). Delirium was more frequent among male patients [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.12–0.86; p=0.023], as well as those patients with lower education (OR 0.76; 95% CI 0.62–0.95; p=0.016), and with respiratory disease (OR 3.35; 95% CI 1.20–9.33; p=0.020), after controlling for age and medication.
Similar to previous studies, these findings point to a negative correlation between education and delirium. This study appears as an attempt to contribute to the knowledge about the role of cognitive reserve in risk of delirium, particularly because is the first one that has been carried out in an IMCU, with lower educated elderly patients. Further studies are needed to clarify this relationship considering other markers (e.g. cognitive activities), which can contribute to the definition of preventive strategies.
Yoga and physical exercise have been used as adjunctive intervention for cognitive dysfunction in schizophrenia (SZ), but controlled comparisons are lacking.
A single-blind randomised controlled trial was designed to evaluate whether yoga training or physical exercise training enhance cognitive functions in SZ, based on a prior pilot study.
Consenting, clinically stable, adult outpatients with SZ (n=286) completed baseline assessments and were randomised to treatment as usual (TAU), supervised yoga training with TAU (YT) or supervised physical exercise training with TAU (PE). Based on the pilot study, the primary outcome measure was speed index for the cognitive domain of ‘attention’ in the Penn computerised neurocognitive battery. Using mixed models and contrasts, cognitive functions at baseline, 21 days (end of training), 3 and 6 months post-training were evaluated with intention-to-treat paradigm.
Speed index of attention domain in the YT group showed greater improvement than PE at 6 months follow-up (p<0.036, effect size 0.51). In the PE group, ‘accuracy index of attention domain showed greater improvement than TAU alone at 6-month follow-up (p<0.025, effect size 0.61). For several other cognitive domains, significant improvements were observed with YT or PE compared with TAU alone (p<0.05, effect sizes 0.30–1.97).
Both YT and PE improved attention and additional cognitive domains well past the training period, supporting our prior reported beneficial effect of YT on speed index of attention domain. As adjuncts, YT or PE can benefit individuals with SZ.
The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms.
In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls. The personality dimensions were assessed using the Temperament and Character Inventory (TCI). We genotyped two selected polymorphisms of the tryptophan hydroxylase 1 (TPH1) gene (rs1800532 218A>C and rs1799913 779A>C) and polymorphism in the promoter region of serotonin transporter gene (5-HTTLPR, rs25531) related to serotoninergic neurotransmission. Multiple poisson regression, logistic regression and Kruskal–Wallis tests were applied.
We found numerous differences between the BP patients and the control group in terms of their TCI dimensions/subdimensions. Significant differences were found between patients with, and without, suicidal attempts in fatigability and asthenia (Ha4), as well as in harm avoidance (Ha). We also found that the interactions between TCI subdimensions (the interaction of disordiness (Ns4) and spiritual acceptance (St3), disordiness (Ns4) and integrated conscience (C5), extravagance (Ns3) and resourcefulness (Sd3)) were significantly contributing for suicidal behaviour risk. We found association between all studied genetic polymorphisms and several TCI dimensions and subdimensions.
Our results confirm that personality traits are partially determined by genes. Both personality traits and the interactions between temperament and character traits, may be helpful in predicting suicidal behaviour.