Previous studies have demonstrated inconsistent findings regarding the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) in treating motor symptoms of Parkinson’s disease (PD). Therefore, this meta-analysis was conducted to assess the efficacy of low-frequency rTMS.

A comprehensive literature search (including PubMed, CCTR, Embase, Web of Science, CNKI, CBM-disc, NTIS,EAGLE, Clinical Trials, Current Controlled Trials, International Clinical Trials Registry) was conducted dating until June 2014. The key search terms (‘Parkinson’, ‘PD’, ‘transcranial magnetic stimulation’, ‘TMS’, ‘RTMS’ and ‘noninvasive brain stimulation’) produced eight high-quality randomised controlled trials (RCT) of low-frequency rTMS versus sham stimulation.

These eight studies, composed of 319 patients, were meta-analysed through assessment of the decreased Unified Parkinson’s Disease Rating Scale (UPDRS part III) score. Pooling of the results from these RCTs yielded an effect size of −0.40 (95%CI=−0.73 to −0.06, p<0.05) in UPDRS part III, which indicated that low-frequency rTMS could have 5.05 (95%CI=−1.73 to −8.37) point decrease in UPDRS part III score than sham stimulation.

Low-frequency rTMS had a significant effect on motor signs in PD. As the number of RCTs and PD patients included here was limited, further large-scale multi-center RCTs were required to validate our conclusions.

Studies on the determinants of the quality of life (QOL) after stroke bring differing results depending on the applied concept of QOL. This may lead to confusion about the contribution of various factors to the post-stroke QOL.

The aim of the study was: (i) to investigate functional and psychological QOL in the individuals after the first ischemic stroke; (ii) to identify the most important correlates of QOL; and (iii) to examine the significance of depression among the other possible predictors of QOL.

A hospital-based sample of 72 stroke patients was followed up to 6 months after stroke onset. QOL was assessed using the Polish version of the Quality of Life Index and the Sickness Impact Profile. A multiple regression procedure was performed to examine relationships between QOL and the study variables.

In spite of good recovery, the psychological and functional QOL of the examined patients was impaired, although the negative impact of stroke was greater on the objective QOL than on the subjective QOL. Stroke-related impairment, depression, functional disability and marital status predicted 80% of the variance in the functional QOL. Emotional support, depression and functional disability explained 38% of the variance in psychological well-being.

Depression and physical disability were the most important predictors of QOL after stroke since their impact on QOL was more robust in comparison to the remaining variables. For improving QOL, a comprehensive care for patients aimed at reducing physical dependence and ameliorating depressive symptoms could be recommended.

Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials.

We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function. Databases searched were: Medline, EMBASE, and PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP Medical database were also searched. All identified studies, were further hand-searched.

We identified six studies providing data on 227 participants, 150 of whom received dopaminergic therapy. Trials were compromised by cross-over design, inadequate wash out period, small numbers and heterogeneous outcome measures. However one good quality RCT demonstrates the efficacy of amantadine in behavioural management. One further RCT shows methylphenidate-levodopa is efficacious for mood post-stroke. One study shows rotigotine to improve hemi-inattention caused by prefrontal damage.

Our systematic review demonstrates an evolving evidence base to suggest some benefits in agitation and aggression, mood and attentional deficits. However, there are key limitations of the studies undertaken to date involving small numbers of participants, heterogeneous outcome measures, and variable study designs. There is a need for on-going large prospective double-blind RCTs in these medications using standardised criteria and outcomes to fully understand their effectiveness in this patient group.

Increasing evidence suggests that immunological and inflammatory dysfunctions may play an important role in predisposition, onset, and progression of schizophrenia and related psychosis. The activation of cells of the mononuclear phagocyte system, especially microglia and monocytes, has been reported in schizophrenia. We carried out this systematic review and meta-analysis to investigate if there are significant differences in monocyte count comparing healthy controls with people suffering from schizophrenia and related disorders.

We searched main electronic databases; nine records met all our criteria and were included in the meta-analysis. Meta-analyses based on random effects models have been carried out generating pooled standardised mean differences (SMDs) of monocyte count in peripheral blood between schizophrenia and related psychosis and healthy controls. Heterogeneity was estimated. Relevant sensitivity and subgroup analyses were conducted.

Patients showed higher monocyte count as compared with healthy control (SMD = 0.393; p = 0.001). Heterogeneity across studies was from moderate to high (I2 = 65.952%); sensitivity analysis leaving out two studies responsible for most of the heterogeneity showed a slightly higher SMD. Subgroup analyses confirmed this result, showing no significant differences in the effect size across different study characteristics.

Monocyte count can be considered an indirect marker of microglia activation in the central nervous system. Thus, the observed higher monocyte count in patients could be considered as a possible peripheral marker of microgliaʼs activation in schizophrenia disorder.

The 24-item Dysfunctional Attitude Scale (DAS-24) is a short version of the Dysfunctional Attitude Scale, which is a self-report inventory for depressogenic schemata.

The object of this study was to examine the reliability and validity of the Japanese version of the DAS-24 (DAS-24-J).

Subjects consisted of non-clinical sample 1 (248 university students), non-clinical sample 2 (872 Japanese company employees) and a clinical sample (59 depressed out-patients).

Internal consistency was satisfactory in all three samples, Cronbach’s α coefficient being higher than 0.85. Test–retest reliability was satisfactory in non-clinical sample 1. The interclass correlation coefficient was 0.79 and there was no significant difference in the average score of DAS-24-J between the two points. The DAS-24-J showed satisfactory concurrent validity with the Japanese Irrational Belief Test-20 (r= 0.76); Automatic Thoughts Questionnaire – Revised total (r= 0.46), negative (r= 0.53) and positive (r=−0.41); and the Beck Depression Inventory-II (r= 0.44 for non-clinical sample, r= 0.63 for clinical sample). The clinical sample showed a significantly higher DAS-24-J score than non-clinical sample 2. According to a factor analysis combining all three samples, three factors were extracted: factor 1 (11 items) corresponded with ‘achievement’ in the original version, factor 2 (6 items) with ‘self-control’ and factor 3 (5 items) with ‘dependency’.

The DAS-24-J is a reliable and valid instrument to measure depressogenic schemata in Japanese.

Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) are in increasing use in the general population to treat health problems. The objective of the current article is to review the evidence for the rationale and benefit of LCn-3PUFA in the treatment of common psychiatric disorders in children and adolescents.

A search of Psychlit, PubMed and Cochrane Databases was conducted using the terms child, adolescent, bipolar, depression, psychosis, first-episode psychosis, schizophrenia, attention deficit hyperactivity disorder (ADHD), autism, psychiatric, omega-3, n-3, docosahexaenoic acid and eicosapentaenoic acid. Further studies were identified from the bibliographies of published reviews.

One small randomized controlled trial with LCn-3PUFA supplementation in depression in children found a small beneficial effect over placebo. Four placebo-controlled trials showed uncertain benefit of LCn-3PUFA for ADHD. Single placebo-controlled trials showed no benefit in autism or bipolar disorder. There is an absence of studies examining benefit for first-episode psychosis or schizophrenia in children and adolescents.

While children and adolescents are receiving LCn-3PUFA for a range of psychiatric indications, there is only evidence of likely benefit for unipolar depression.

Among the 28 metalloproteinases described so far, 23 can be found in the human organism, but only few are expressed in the human brain. The main objective of this study was to analyse the relationship between MMP-2, MMP-9 and TIMP-2 gene expression and cognitive performance.

The study comprised 234 subjects: patients suffering from recurrent depressive disorder (rDD, n=139) and healthy subjects (HS, n=95). The cognitive function assessment was carried out with the help of the following tests: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Gene expression on the mRNA and protein level was evaluated for MMP-2, MMP-9 and TIMP-2 in both groups using RNA extraction, reverse transcription and enzyme-linked immunosorbent assay.

Both mRNA and protein expression levels of all the genes were significantly lower in rDD subjects as compared with HS. Having analysed the entire experimental group (N=234), significant interrelations were found between the expression of the analysed genes and the results of the tests used to measure cognitive functions. Increased expression on both the mRNA and the protein level was associated in each case with better performance of all the tests conducted. After carrying out a separate analysis on the people from the rDD group and the HS group, similar dependencies were still observed.

The results of our study show decreased expression of MMP-2, MMP-9 and TIMP-2 genes on both mRNA and protein levels in depression. Elevated expression of MMP-2, MMP-9, TIMP-2 positively affects cognitive efficiency: working memory, executive functions, attention functions, direct and delayed auditory–verbal memory, the effectiveness of learning processes and verbal fluency. The study highlights the important role of peripheral matrix metalloproteinases genes in depression and cognitive functions.

Among potential endophenotypes proposed for bipolar affective disorder focusing on circadian abnormalities associated with the illness has particularly high face validity. Melatonin sensitivity to light is one circadian endophenotype proposed as useful in bipolar disorder. The aim of this study was to investigate melatonin sensitivity to light over a range of light intensities in order to compare and contrast responses in bipolar I patients with those of healthy adult volunteers.

The study included seven patients (4 females, 3 males) with bipolar I disorder and 34 control participants (22 females, 12 males) with no personal or family history of affective illness. Melatonin sensitivity to light was determined in all patients and participants across a range of light intensities (0, 200, 500 and 1000 lux).

The results indicated that patients showed melatonin super-sensitivity to light in comparison with controls, a response that was consistent across the entire light intensity range investigated.

The study provides further evidence for a super sensitive response in bipolar I patients and suggests that its potential usefulness as an endophenotypic marker of the illness is deserving of further research.

Findings from animal studies indicate that the early gut bacteriome is a potential mechanism linking maternal prenatal stress with health trajectories in offspring. However, clinical studies are scarce and the associations of maternal psychological profiles with the early infant faecal bacteriome are unknown. This study aimed to investigate the associations of prenatal stressors and distress with early infant faecal bacterial profiles in a South African birth cohort study.

Associations between prenatal symptoms of depression, distress, intimate partner violence (IPV) and posttraumatic stress disorder (PTSD) and faecal bacterial profiles were evaluated in meconium and subsequent stool specimens from 84 mothers and 101 infants at birth, and longitudinally from a subset of 69 and 36 infants at 4–12 and 20–28 weeks of age, respectively, in a South African birth cohort study.

Infants born to mothers that were exposed to high levels of IPV had significantly higher proportions of Citrobacter and three unclassified genera, all of which belonging to the family Enterobacteriaceae detected at birth. Proportions of these Enterobacteriaceae remained significantly increased over time (birth to 20–28 weeks of life) in infants born to mothers with high levels of IPV exposure compared to infants from mothers with no/low IPV exposure. Infants born to mothers exposed to IPV also had higher proportions of the genus Weissella at 4–12 weeks compared to infants from mothers with no/low IPV exposure. Faecal specimens from mothers exposed to IPV had higher proportions of the family Lactobacillaceae and lower proportions of Peptostreptococcaceae at birth. Maternal psychological distress was associated with decreased proportions of the family Veillonellaceae in infants at 20–28 weeks and a slower decline in Gammaproteobacteria over time. No changes in beta diversity were apparent for maternal or infant faecal bacterial profiles in relation to any of the prenatal measures for psychological adversities.

Maternal lifetime IPV and antenatal psychological distress are associated with altered bacterial profiles in infant and maternal faecal bacteria. These findings may provide insights in the involvement of the gut bacteria linking maternal psychological adversity and the maturing infant brain.

The exact pathophysiology of bipolar disorder (BD) is not yet fully understood, and there are many questions in this area which should be answered. This review aims to discuss the roles of glial cells in the pathophysiology of BD and their contribution to the mechanism of action of mood-stabilising drugs.

We critically reviewed the most recent advances regarding glial cell roles in the pathophysiology and treatment of BD and the neuroprotective and neurotrophic effects of these cells.

Postmortem studies revealed a decrease in the glial cell number or density in the specific layers of prefrontal and anterior cingulate cortex in the patients with BD, whereas there was no difference in other brain regions, such as entorhinal cortex, amygdala and hippocampus. Astrocytes and oligodendrocytes were the most important glial types that were responsible for the glial reduction, but microglia activation rather than loss may be implicated in BD. The decreased number or density of glial cells may contribute to the pathological changes observed in neurons in the patients with BD. Alteration of specific neurotrophic factors such as glial cell line-derived neurotrophic factor and S100B may be an important feature of BD. Glial cells mediate the therapeutic effects of mood-stabilising agents in the treatment of BD.

Recent studies provide important evidence on the impairment of glial cells in the pathophysiology and treatment of BD. However, future controlled studies are necessary to elucidate different aspects of glial cells contribution to BD, and the mechanism of action of mood-stabilising drugs.

The aim of the controlled therapy study was to evaluate the effect of a 6 session biofeedback intervention program on cognitive aspects of patients with somatoform disorders. The treatment consisted of psycho-physiological demonstrations how mental processes can influence biological functions. We expected this treatment to be of high credibility, to change maladaptive cognitions, to enhance acceptance of psychosocial causal attribution and to improve coping.

Patients were assessed using a structured interview to diagnose somatization syndrome (SSI-8) and comorbidity according to DSM-IV criteria. Fifty patients were recruited and randomly assigned to biofeedback treatment or control relaxation group. Participants completed a questionnaire battery assessing cognitive characteristics, causal attributions and controllability before and after intervention as well as evaluation protocols for each session.

The results suggest that biofeedback modified the patients' cognitive schemata: Patients with somatization syndrome of the biofeedback group showed a greater reduction of catastrophizing of somatic sensations and higher acceptance of psychosocial causal attributions than the control group. Both groups improved significantly in the conviction of self-efficacy.

Cognitive impairment and depression are among the most prevalent and most disabling non-motor symptoms in Parkinson’s disease (PD). The genetic factors that are associated with these symptoms remain uncertain. This systematic review aims to summarise the prevailing evidence from all genetic association studies investigating the genetic variants associated with cognitive impairment and depressive symptoms in people with PD.

A systematic review using five online databases: PubMed, PsycINFO, CINAHL, EMBASE and OpenGrey (PROSPERO protocol: CRD42017067431). We completed the quality assessment using the Q-Genie tool.

2353 articles were screened, and 43 articles were found to be eligible to be included. A meta-analysis of studies investigating LRRK2 rs34637584 confirmed that the minor allele carriers had significantly less cognitive impairment (p = 0.015). Further meta-analyses showed that GBA variants rs76763715 (p < 0.001) and rs421016 (p = 0.001) were significantly associated with more cognitive impairment in people with PD. Minor alleles of GBA variants rs76763715, rs421016, rs387906315 and rs80356773 were associated with more depressive symptoms in PD. Moreover, APOE ε4 allele has been associated with more cognitive impairment in PD. BDNF (rs6265) and CRY1 (rs2287161) variants have been associated with more depressive symptoms in people with PD.

PD carriers of GBA variants are at high risk for cognitive decline and depression. Screening for these variants may facilitate early identification and effective management of these non-motor symptoms. The molecular mechanisms underlying favourable cognitive functioning in LRRK2 rs34637584 variant carriers warrant further investigation.

Here, we examined the cingulum bundle, a long-range white matter tract mediating dorsal limbic connectivity, using diffusion tensor imaging (DTI) tractography, in children and adolescents with autism spectrum disorder (ASD) versus controls. We hypothesised that cingulum bundle microstructure would be altered in ASD, based on evidence implicating abnormal white matter connectivity in this disorder.

DTI data were acquired for 19 ASD participants (IQ ⩾ 70; 7–18 years; mean = 12.4 ± 3.1) and 16 age-matched controls (7–18 years; mean = 12.3 ± 3.6) on a 3 T magnetic resonance imaging system. Deterministic tractography was used to isolate the cingulum bundle. Left and right cingulum bundles were examined for differences in several DTI metrics in ASD children/adolescents versus controls, including: fractional anisotropy (FA), mean, axial, and radial diffusivity.

Significant age × group interaction effects were found for all DTI metrics (mean diffusivity: F1,28 = 9.5, p = 0.005, radial diffusivity: F1,28 = 7.8, p = 0.009, axial diffusivity: F1,28 = 5.2, p = 0.03, FA: F1,28 = 4.4, p = 0.04). Interaction effects were driven by increases in cingulum bundle diffusivity (mean, radial, and axial diffusivity), and decreased FA, in younger ASD participants within our sample versus controls.

Our results point to immature microstructural organisation of the cingulum bundle in ASD, particularly during the early years of life, with implications for limbic network synchronisation and complex socio-emotional performance.

Pain perception is reported to be altered in patients with depression and schizophrenia. However, few studies have investigated the pain perception in patients with bipolar disorders. We therefore aimed to compare pain sensitivity between patients with bipolar disorder, schizophrenia and controls.

Study groups consisted of 30 patients with bipolar disorder, and control groups consisted of 27 patients with schizophrenia and 59 healthy subjects. Pain perception was assessed with cold pressor test (CPT) by exposure to ice-water.

Patients with schizophrenia had significantly higher pain thresholds (PTh) than patients with bipolar disorder. There were no differences between the PTh of patients with schizophrenia and healthy control subjects. However, patients with bipolar disorder had significantly lower pain tolerance (PT) in the CPT than patients with schizophrenia and corresponding healthy control subjects.

The higher PTh in the schizophrenia group compared with the bipolar group found in this study supports further investigation of a potential difference in the pain perception between patients with schizophrenia and bipolar disorder. Theoretical implications of these findings and possible relevant behavioural and neurochemical mechanisms are discussed.

This study investigated immersive virtual reality (IVR), as a novel technique to test executive function of healthy younger and older adults. We predicted IVR tasks to have greater predictive power than traditional measures when assessing age-related cognitive functioning due to the real-world validity of the tasks.

Participants (n=40) completed the Stroop colour–word test and the trail-making test (TMT) as traditional and commonly used assessments of executive functioning. Participants then completed three IVR tasks; a seating arrangement task, an item location task (both set in a virtual chemistry lab), and a virtual parking simulator.

Younger adults completed significantly more parking simulator levels (p<0.001), placed significantly more objects (p<0.001), and located significantly more items than older adults (p<0.01), demonstrating higher levels of performance. Significant correlations were found between performance on traditional neuropsychological measures and IVR measures. For example, Stroop CW performance significantly correlated with the number of parking simulator levels completed (τ=0.43, p<0.01). This suggests that IVR measures assess the same underlying cognitive constructs as traditional tasks. In addition, IVR measures contributed a significant percentage of the explained variance in age.

IVR measures (i.e. number of parking simulator levels completed and number of objects placed in the seating arrangement task) were found to be stronger contributors than existing traditional neuropsychological tasks in predicting age-related cognitive decline. Future research should investigate the implementation of these real-world-based tasks in clinical groups given this promising initial work.

This study aimed to explore effects of adjunctive N-acetylcysteine (NAC) treatment on inflammatory and neurogenesis markers in unipolar depression.

We embarked on a 12-week clinical trial of NAC (2000 mg/day compared with placebo) as an adjunctive treatment for unipolar depression. A follow-up visit was conducted 4 weeks following the completion of treatment. We collected serum samples at baseline and the end of the treatment phase (week 12) to determine changes in interleukin-6 (IL6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following NAC treatment.

NAC treatment significantly improved depressive symptoms on the Montgomery–Asberg Depression Rating Scale (MADRS) over 16 weeks of the trial. Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response. However, we found no significant changes in IL6, CRP and BDNF levels following NAC treatment.

Overall, this suggests that our results failed to support the hypothesis that IL6, CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression. IL6 may be a useful marker for future exploration of treatment response.

To investigate whether patients with Alzheimer's disease (AD) were able to alter their awareness of memory deficits after exposure to a memory task.

Thirty normal older adults and 23 mild AD patients participated in the study. Anosognosia was assessed using discrepancies between self- and informant-evaluations of cognitive and functional performance. Participants estimated their performance on the Verbal Paired Associates task at different points in time (before, immediately after the task and after a 1-h delay).

AD patients were generally less able to judge their memory abilities than healthy older adults, and tended to overestimate their task performance beforehand. Their prediction accuracy increased immediately after the task, but after a 1-h delay, they again misjudged their abilities at pretesting accuracy levels. Self-carer discrepancy scores of awareness of deficits in memory and other areas correlated significantly with memory tests but not with other neuropsychological tasks in the assessment, and larger discrepancy scores were associated with poorer performance.

AD patients can monitor their task performance online, but are unable to maintain awareness of their deficits over time. Loss of awareness of memory deficits (or of any other deficits) in early stage AD may indicate damage to a system which updates a personal knowledge base with recent information. Failure to retain this information impedes abstraction from episodic to semantic memory.