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BackgroundCognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis.MethodsA PRISMA systematic search was conducted for randomized controlled trials. Hedges'gwas used to quantify effect sizes (ES) for changes in cognition after TMS/tDCSv.sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition.ResultsWe included 82 studies (n= 2784). For working memory, both TMS (ES = 0.17,p= 0.015) and tDCS (ES = 0.17,p= 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20,p= 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains.ConclusionsOur results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).

BackgroundImpaired metacognition is associated with difficulties in the daily functioning of people with psychosis. Metacognition can be divided into four domains: Self-Reflection, Understanding the Other's Mind, Decentration, and Mastery. This study investigated whether Metacognitive Reflection and Insight Therapy (MERIT) can be used to improve metacognition.MethodsThis study is a randomized controlled trial. Patients in the active condition (n = 35) received forty MERIT sessions, the control group (n = 35) received treatment as usual. Multilevel intention-to-treat and completers analyses were performed for metacognition and secondary outcomes (psychotic symptomatology, cognitive insight, Theory of Mind, empathy, depression, self-stigma, quality of life, social functioning, and work readiness).ResultsEighteen out of 35 participants finished treatment, half the drop-out stemmed from therapist attrition (N = 5) or before the first session (N = 4). Intention-to-treat analysis demonstrated that in both groups metacognition improved between pre- and post-measurements, with no significant differences between the groups. Patients who received MERIT continued to improve, while the control group returned to baseline, leading to significant differences at follow-up. Completers analysis (18/35) showed improvements on the Metacognition Assessment Scale (MAS-A) scales Self Reflectivity and metacognitive Mastery at follow-up. No effects were found on secondary outcomes.ConclusionsOn average, participants in the MERIT group were, based on MAS-A scores, at follow-up more likely to recognize their thoughts as changeable rather than as facts. MERIT might be useful for patients whose self-reflection is too limited to benefit from other therapies. Given how no changes were found in secondary measures, further research is needed. Limitations and suggestions for future research are discussed.

BackgroundCortical glutamatergic dysfunction is thought to be fundamental for psychosis development, and may lead to structural degeneration through excitotoxicity. Glutamate levels have been related to gray matter volume (GMV) alterations in people at ultra-high risk of psychosis, and we previously reported GMV changes in individuals with high schizotypy (HS), which refers to the expression of schizophrenia-like characteristics in healthy people. This study sought to examine whether GMV changes in HS subjects are related to glutamate levels.MethodsWe selected 22 healthy subjects with HS and 23 healthy subjects with low schizotypy (LS) based on their rating on a self-report questionnaire for psychotic-like experiences. Glutamate levels were measured in the bilateral anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, and GMV was assessed using voxel-based morphometry.ResultsSubjects with HS showed GMV decreases in the rolandic operculum/superior temporal gyrus (pFWE = 0.045). Significant increases in GMV were also detected in HS, in the precuneus (pFWE = 0.043), thereby replicating our previous finding in a separate cohort, as well as in the ACC (pFWE = 0.041). While the HS and LS groups did not differ in ACC glutamate levels, in HS subjects ACC glutamate was negatively correlated with ACC GMV (pFWE = 0.026). Such association was absent in LS.ConclusionsOur study shows that GMV findings in schizotypy are related to glutamate levels, supporting the hypothesis that glutamatergic function may lead to structural changes associated with the expression of psychotic-like experiences.

Background.Few studies have investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for negative symptoms of schizophrenia, reporting inconsistent results. We aimed to investigate whether 10 Hz stimulation of the bilateral dorsolateral prefrontal cortex during 3 weeks enhances treatment effects.Method.A multicenter double-blind randomized controlled trial was performed in 32 patients with schizophrenia or schizo-affective disorder, and moderate to severe negative symptoms [Positive and Negative Syndrome Scale (PANSS) negative subscale ⩾15]. Patients were randomized to a 3-week course of active or sham rTMS. Primary outcome was severity of negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS) and the PANSS negative symptom score. Secondary outcome measures included cognition, insight, quality of life and mood. Subjects were followed up at 4 weeks and at 3 months. For analysis of the data a mixed-effects linear model was used.Results.A significant improvement of the SANS in the active group compared with sham up to 3 months follow-up (p = 0.03) was found. The PANSS negative symptom scores did not show a significant change (p = 0.19). Of the cognitive tests, only one showed a significant improvement after rTMS as compared with sham. Finally, a significant change of insight was found with better scores in the treatment group.Conclusions.Bilateral 10 Hz prefrontal rTMS reduced negative symptoms, as measured with the SANS. More studies are needed to investigate optimal parameters for rTMS, the cognitive effects and the neural basis.

BackgroundThe peak in age of onset of psychotic disorders such as schizophrenia during puberty and early adulthood suggests a relationship between the expression of psychopathology and the changes in the brain and body that take place during this dynamic maturational period, including a dramatic increase in circulating oestrogens and androgens. This study examined levels of salivary testosterone and oestradiol in adolescents with prepsychotic, prodromal symptoms, as this may mediate risk for psychosis by having an impact on brain development.MethodIn 21 male adolescents with prodromal symptoms and 21 male non-clinical controls levels of testosterone and oestradiol were measured in saliva. Tanner pubertal stage and prodromal symptoms were also assessed.ResultsLevels of testosterone were significantly lower in adolescents with prodromal symptoms as compared with non-clinical controls. No group differences in oestradiol were found. In the total sample, level of testosterone was significantly correlated with age and Tanner pubertal stage.ConclusionsOur observations are in line with current hypotheses stressing the role of neuroendocrine factors during adolescence in the expression of psychotic symptoms. From a developmental perspective, susceptibility to psychotic disorders increases during adolescence. Our data suggest that testosterone might, in part, mediate this increased vulnerability. Further research is needed to assess the mediating, neural, mechanisms through which testosterone may have an impact on the development of psychotic symptoms. In the search for early risk markers for psychosis, studying neuroendocrine factors might increase our understanding of ‘at-risk’ developmental pathways.

BackgroundBy studying behavior, cognitive abilities and brain functioning in adolescents at high risk for psychosis, we can gain an insight into the vulnerability markers or protective factors in the development of psychotic symptoms. Although many high-risk studies have focused on impairments in neurocognitive functions, such as memory and attention, very few studies have investigated problems in processing social cues such as facial expressions as a possible vulnerability marker for psychosis.MethodThirty-six adolescents at ultra-high risk (UHR) for psychosis and 21 non-clinical controls completed a face recognition test, a facial affect labeling test and an inhibitory control test. Schizotypal traits and schizophrenia symptoms were assessed using a schizotypy questionnaire and the Positive and Negative Syndrome Scale (PANSS).ResultsThe UHR group showed impairments in labeling facial expressions of others, in addition to a spared ability to recognize facial identity. More specifically, the UHR group made more errors in labeling neutral expressions compared to the controls, and an analysis of error types indicated that neutral faces were misattributed as being angry. The degree of misattribution of neutral-as-angry faces correlated significantly with reduced inhibitory control.ConclusionsOur findings suggest that misattributing social cues might contribute to vulnerability for psychosis. This social cognitive deficit may be related to problems in inhibitory control, which potentially plays an important role in the selection of appropriate social meaning. These findings may have relevance for understanding the mechanisms underlying prodromal social dysfunction, which should be targeted in future remediation interventions.

BackgroundIt has recently been suggested that auditory hallucinations are the result of a criterion shift when deciding whether or not a meaningful signal has emerged. The approach proposes that a liberal criterion may result in increased false-positive identifications, without additional perceptual deficit. To test this hypothesis, we devised a speech discrimination task and used signal detection theory (SDT) to investigate the underlying cognitive mechanisms.MethodSchizophrenia patients with and without auditory hallucinations and a healthy control group completed a speech discrimination task. They had to decide whether a particular spoken word was identical to a previously presented speech stimulus, embedded in noise. SDT was used on the accuracy data to calculate a measure of perceptual sensitivity (Az) and a measure of response bias (β). Thresholds for the perception of simple tones were determined.ResultsCompared to healthy controls, perceptual thresholds were higher and perceptual sensitivity in the speech task was lower in both patient groups. However, hallucinating patients showed increased sensitivity to speech stimuli compared to non-hallucinating patients. In addition, we found some evidence of a positive response bias in hallucinating patients, indicating a tendency to readily accept that a certain stimulus had been presented.ConclusionsWithin the context of schizophrenia, patients with auditory hallucinations show enhanced sensitivity to speech stimuli, combined with a liberal criterion for deciding that a perceived event is an actual stimulus.