Lower fractional anisotropy without evidence for neuro-inflammation in patients with early-phase schizophrenia spectrum disorders

Various lines of research suggest immune dysregulation as a potential therapeutic target for negative and cognitive symptoms in schizophrenia spectrum disorders (SSD). Immune dysregulation would lead to higher extracellular free-water (EFW) in cerebral white matter (WM), which may partially underlie the frequently reported lower fractional anisotropy (FA) in SSD. We aim to investigate differences in EFW concentrations – a presumed proxy for neuro-inflammation – between early-phase SSD patients (n = 55) and healthy controls (HC; n = 37), and to explore immunological and cognitive correlates. To increase specificity for EFW, we study several complementary magnetic resonance imaging contrasts that are sensitive to EFW. FA, mean diffusivity (MD), magnetization transfer ratio (MTR), myelin water fraction (MWF) and quantitative T1 and T2 were calculated from diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT). For each measure, WM skeletons were constructed with tract-based spatial statistics. Multivariate SSD-HC comparisons with WM skeletons and their average values (i.e. global WM) were not statistically significant. In voxel-wise analyses, FA was significantly lower in SSD in the genu of the corpus callosum and in the left superior longitudinal fasciculus (p < 0.04). Global WM measures did not correlate with immunological markers (i.e. IL1-RA, IL-6, IL-8, IL-10 and CRP) or cognition in HC and SSD after corrections for multiple comparisons. We confirmed lower FA in early-phase SSD patients. However, non–FA measures did not provide additional evidence for immune dysregulation or for higher EFW as the primary mechanism underlying the reported lower FA values in SSD

Auditory hallucinations, top-down processing and language perception: a general population study

Background: Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated. Methods: We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems. Results: A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not. Conclusions: The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.publishedVersio

Physical exercise improves quality of life, depressive symptoms, and cognition across chronic brain disorders: a transdiagnostic systematic review and meta-analysis of randomized controlled trials

We performed a meta-analysis to synthesize evidence on the efficacy and safety of physical exercise as an add-on therapeutic intervention for quality of life (QoL), depressive symptoms and cognition across six chronic brain disorders: Alzheimer’s disease, Huntington’s disease, multiple sclerosis, Parkinson’s disease, schizophrenia and unipolar depression. 122 studies ( = k) (n = 7231) were included. Exercise was superior to treatment as usual in improving QoL (k = 64, n = 4334, ES = 0.40, p < 0.0001), depressive symptoms (k = 60, n = 2909, ES = 0.78, p < 0.0001), the cognitive domains attention and working memory (k = 21, n = 1313, ES = 0.24, p < 0.009), executive functioning (k = 14, n = 977, ES = 0.15, p = 0.013), memory (k = 12, n = 994, ES = 0.12, p = 0.038) and psychomotor speed (k = 16, n = 896, ES = 0.23, p = 0.003). Meta-regression showed a dose–response effect for exercise time (min/week) on depressive symptoms (β = 0.007, p = 0.012). 69% of the studies that reported on safety, found no complications. Exercise is an efficacious and safe add-on therapeutic intervention showing a medium-sized effect on QoL and a large effect on mood in patients with chronic brain disorders, with a positive dose–response correlation. Exercise also improved several cognitive domains with small but significant effects

Antipsychotic medication after a first episode of psychosis:taper or continue?

In this paper we discuss the risks and benefits of discontinuing antipsychotic medication within one year after remission of a first episode of psychosis. We start with a fictional case report of a 21-year-old man, who was diagnosed with schizophreniform disorder four months earlier. While symptoms responded well to a daily dose of 10 mg ariprazole, he experienced side effects (tiredness and mild hypersomnia). Three months after symptom remission, he expressed the wish to discontinue his medication. How should psychiatrists respond to his wish? To answer that, we briefly summarize relevant evidence and discuss arguments for the different therapeutic approaches, i.e., maintaining vs. tapering antipsychotic medication, based on specific patient characteristics. Recommendations from the current Dutch guidelines are complemented with personal experience and considerations in finding the optimal balance between side effects, relapse risk, stigma and acceptance of mental health problems, while incorporating the principles of shared decision-making.</p

Social Deafferentation and the Relation Between Loneliness and Hallucinations

BACKGROUND AND HYPOTHESIS: The social deafferentation hypothesis (SDA) has been proposed as an explanatory mechanism of hallucinations, based on the theory that social withdrawal triggers the initial phase of schizophrenia. The current study tests the SDA by assessing how loneliness is associated with different types of hallucinations. Under the SDA, increased loneliness is hypothesized to affect the occurrence of hallucinations that carry social meaning, but not of nonsocial hallucinations. STUDY DESIGN: As part of an online survey, 2038 adolescents and young adults from the general population (median age 21 years; 75% female) filled out the Questionnaire for Psychotic Experiences, and the shortened De Jong Gierveld Loneliness Scale. Binomial logistic regression was used to investigate the effects of loneliness severity on past month prevalence of hallucinations, and on the presence of social versus nonsocial hallucinations. STUDY RESULTS: Loneliness increased the prevalence of hallucinations across modalities in the past month. Moreover, stronger degree of loneliness increased the likelihood of hearing voices or laughter, and of hallucinating being touched. Conversely, loneliness decreased the likelihood of experiencing the nonsocial hallucination of a tingling feeling. As expected, loneliness did not increase the prevalence of experiencing nonsocial hallucinations. Surprisingly, neither was loneliness associated with experiencing felt presence. CONCLUSIONS: Our results are novel in showing that loneliness specifically increases the likelihood of hearing human sounds such as voices or laughter, or feeling a human touch. Hallucinations without social meaning were not more likely to be experienced with increasing loneliness. This forms a confirmation of the SDA

Atopy increases risk of psychotic experiences : A large population-based study

Introduction: Building upon the comorbidity between atopy and schizophrenia, we conducted a large cross-sectional, observational population-based study to examine if such associations also exist between atopic disorders (eczema, allergic rhinitis, and asthma) and nonclinical psychotic experiences. Methods: We examined psychotic experiences in a Dutch population sample through an online survey (≥14 years of age). Participants filled out the Questionnaire for Psychotic Experiences, together with questions screening for atopic disorders (eczema, allergic rhinitis, and asthma). Prevalence rates were calculated; binary logistic regression was used to determine odds ratios (ORs) (age, gender, and years of education as covariates). Results: We included 6,479 participants. Individuals diagnosed with one or more atopic disorders had an increased risk of psychotic experiences as compared with controls (OR = 1.26). Analysis of individual symptoms revealed an OR of 1.27 for hallucinations, whereas delusions only showed a trend. With each additional atopic disorder, the risk of psychotic experiences increased. This was also observed for hallucinations alone but not for delusions alone. Atopy was associated with hallucinations across all modalities (OR ranging from 1.19 to 1.40). These results did not appear to be driven specifically by any one of the atopic disorders. Conclusion: In the largest population sample of adolescents and adults to date, we found that atopic disorders (asthma, eczema, and allergic rhinitis) increase the risk of psychotic experiences, in a dose-response fashion. These results provide further support for the role of immunological components in the predisposition for psychosis and can serve as a base for further research

Immediate and long-term effects of bilateral electroconvulsive therapy on cognitive functioning in patients with a depressive disorder

Background: Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from major depression. However, its use is limited due to concerns about negative effects on cognition. Unilateral ECT is associated with transient cognitive side-effects, while case-controlled studies investigating the effect of bilateral ECT on cognition remain scarce. We investigate the effects of bilateral ECT on cognition in depression in a longitudinal case-controlled study. We hypothesize that adverse cognitive effects of bilateral ECT are transient rather than long-term. Methods: A total of 48 depressed patients and 19 controls were included in the study and assessed with a battery of cognitive tests, including tests of: working memory, verbal fluency, visuospatial abilities, verbal/visual memory and learning, processing speed, inhibition, attention and task-switching, and premorbid IQ. Patients underwent three cognitive assessments: at baseline (n = 43), after ten ECT sessions (post-treatment; n = 39) and six months after the tenth ECT session (follow-up; n = 25). Healthy controls underwent the same cognitive assessment at baseline and after five-weeks. Results: Within the patient group, transient adverse cognitive side-effects were observed for verbal memory and learning, and verbal fluency. None of the cognitive domains tested in this study showed persisting impairments. Limitations: A relatively high attrition rate is observed and autobiographical memory was not assessed. Conclusion: This study shows that bilateral ECT has negative cognitive effects on short-term. These effects could be explained by a decrease in cognitive performance, a lack of learning effects or a combination. However, the decrease in cognitive functioning appears to recover after six months

Lower fractional anisotropy without evidence for neuro-inflammation in patients with early-phase schizophrenia spectrum disorders

Various lines of research suggest immune dysregulation as a potential therapeutic target for negative and cognitive symptoms in schizophrenia spectrum disorders (SSD). Immune dysregulation would lead to higher extracellular free-water (EFW) in cerebral white matter (WM), which may partially underlie the frequently reported lower fractional anisotropy (FA) in SSD. We aim to investigate differences in EFW concentrations – a presumed proxy for neuro-inflammation – between early-phase SSD patients (n = 55) and healthy controls (HC; n = 37), and to explore immunological and cognitive correlates. To increase specificity for EFW, we study several complementary magnetic resonance imaging contrasts that are sensitive to EFW. FA, mean diffusivity (MD), magnetization transfer ratio (MTR), myelin water fraction (MWF) and quantitative T1 and T2 were calculated from diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT). For each measure, WM skeletons were constructed with tract-based spatial statistics. Multivariate SSD-HC comparisons with WM skeletons and their average values (i.e. global WM) were not statistically significant. In voxel-wise analyses, FA was significantly lower in SSD in the genu of the corpus callosum and in the left superior longitudinal fasciculus (p < 0.04). Global WM measures did not correlate with immunological markers (i.e. IL1-RA, IL-6, IL-8, IL-10 and CRP) or cognition in HC and SSD after corrections for multiple comparisons. We confirmed lower FA in early-phase SSD patients. However, non–FA measures did not provide additional evidence for immune dysregulation or for higher EFW as the primary mechanism underlying the reported lower FA values in SSD

Lower fractional anisotropy without evidence for neuro-inflammation in patients with early-phase schizophrenia spectrum disorders

Various lines of research suggest immune dysregulation as a potential therapeutic target for negative and cognitive symptoms in schizophrenia spectrum disorders (SSD). Immune dysregulation would lead to higher extracellular free-water (EFW) in cerebral white matter (WM), which may partially underlie the frequently reported lower fractional anisotropy (FA) in SSD. We aim to investigate differences in EFW concentrations – a presumed proxy for neuro-inflammation – between early-phase SSD patients (n = 55) and healthy controls (HC; n = 37), and to explore immunological and cognitive correlates. To increase specificity for EFW, we study several complementary magnetic resonance imaging contrasts that are sensitive to EFW. FA, mean diffusivity (MD), magnetization transfer ratio (MTR), myelin water fraction (MWF) and quantitative T1 and T2 were calculated from diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT). For each measure, WM skeletons were constructed with tract-based spatial statistics. Multivariate SSD-HC comparisons with WM skeletons and their average values (i.e. global WM) were not statistically significant. In voxel-wise analyses, FA was significantly lower in SSD in the genu of the corpus callosum and in the left superior longitudinal fasciculus (p < 0.04). Global WM measures did not correlate with immunological markers (i.e. IL1-RA, IL-6, IL-8, IL-10 and CRP) or cognition in HC and SSD after corrections for multiple comparisons. We confirmed lower FA in early-phase SSD patients. However, non–FA measures did not provide additional evidence for immune dysregulation or for higher EFW as the primary mechanism underlying the reported lower FA values in SSD