Step away from depression-results from a multicenter randomized clinical trial with a pedometer intervention during and after inpatient treatment of depression.

Evidence for the effectiveness of physical activity (PA) in the treatment of depression prevails for outpatients with mild and moderate symptom levels. For inpatient treatment of severe depression, evidence-based effectiveness exists only for structured and supervised group PA interventions. The Step Away from Depression (SAD) study investigated the effectiveness of an individual pedometer intervention (PI) combined with an activity diary added to inpatient treatment as usual (TAU). In this multicenter randomized controlled trial, 192 patients were randomized to TAU or TAU plus PI. The two primary outcomes at discharge were depression-blindly rated with the Montgomery-Åsberg Depression Rating Scale (MADRS)-and average number of daily steps measured by accelerometers. Secondary outcomes were self-rated depression and PA, anxiety, remission and response rates. Multivariate analysis of variance (MANOVA) revealed no significant difference between both groups for depression and daily steps. Mean MADRS scores at baseline were 29.5 (SD = 8.3) for PI + TAU and 28.8 (SD = 8.1) for TAU and 16.4 (SD = 10.3) and 17.2 (SD = 9.9) at discharge, respectively. Daily steps rose from 6285 (SD = 2321) for PI + TAU and 6182 (SD = 2290) for TAU to 7248 (SD = 2939) and 7325 (SD = 3357). No differences emerged between groups in secondary outcomes. For severely depressed inpatients, a PI without supervision or further psychological interventions is not effective. Monitoring, social reinforcement and motivational strategies should be incorporated in PA interventions for this population to reach effectiveness.

Physical activity, physical self-perception and depression symptoms in patients with major depressive disorder: a mediation analysis.

Physical inactivity is discussed as one of the most detrimental influences for lifestyle-related medical complications such as obesity, heart disease, hypertension, diabetes and premature mortality in in- and outpatients with major depressive disorder (MDD). In contrast, intervention studies indicate that moderate-to-vigorous-intensity physical activity (MVPA) might reduce complications and depression symptoms itself. Self-reported data on depression [Beck-Depression-Inventory-II (BDI-II)], general habitual well-being (FAHW), self-esteem and physical self-perception (FAHW, MSWS) were administrated in a cross-sectional study with 76 in- and outpatients with MDD. MVPA was documented using ActiGraph wGT3X + ® accelerometers and fitness was measured using cardiopulmonary exercise testing (CPET). Subgroups were built according to activity level (low PA defined as MVPA < 30 min/day, moderate PA defined as MVPA 30-45 min/day, high PA defined as MVPA > 45 min/day). Statistical analysis was performed using a Mann-Whitney U and Kruskal-Wallis test, Spearman correlation and mediation analysis. BDI-II scores and MVPA values of in- and outpatients were comparable, but fitness differed between the two groups. Analysis of the outpatient group showed a negative correlation between BDI-II and MVPA. No association of inpatient MVPA and psychopathology was found. General habitual well-being and self-esteem mediated the relationship between outpatient MVPA and BDI-II. The level of depression determined by the BDI-II score was significantly higher in the outpatient low- and moderate PA subgroups compared to outpatients with high PA. Fitness showed no association to depression symptoms or well-being. To ameliorate depressive symptoms of MDD outpatients, intervention strategies should promote habitual MVPA and exercise exceeding the duration recommended for general health (≥ 30 min/day). Further studies need to investigate sufficient MVPA strategies to impact MDD symptoms in inpatient settings. Exercise effects seem to be driven by changes of well-being rather than increased physical fitness.

Effects of body-oriented yoga: a RCT study for patients with major depressive disorder.

The major depressive disorder is one of the most common mental illnesses worldwide. Current treatment standards recommend a combined therapy with medication and psychotherapy. As an additive component and to further improvements in treatment, physical activity such as yoga may be integrated into conventional treatment. This study investigates the impact of a 3-month body-oriented yoga in patients with major depressive disorder (MDD). In total, n = 83 patients were included. An intervention group received a vigorous Ashtanga-Yoga three times a week. The waiting-list control group obtained a treatment as usual (TAU). As a primary outcome depression scores (Beck Depression Inventory-II (BDI-II), Montgomery Asberg Depression Rating Scale (MADRS)) were tested at three time points. Secondary outcome was the positive and negative affect [Positive and Negative Affect Scale (PANAS)] and remission rates. To analyze the data, multilevel models and effect sizes were conducted. The results showed an improvement in BDI-II scores for both groups over time [γ = - 3.46, t(165) = - 7.99, p < 0.001] but not between groups [γ = 0.98, t(164) = 1.12, p = 0.263]. An interaction effect (time x group) occurred for MADRS [γ = 2.10, t(164) = 2.10, p < 0.038]. Positive affects improved over time for both groups [γ = 1.65, t(165) = 4.03, p < 0.001]. Negative affects decreased for all over time [γ = - 1.00, t(165) = - 2.51, p = 0.013]. There were no significant group differences in PANAS. Post hoc tests revealed a greater symptom reduction within the first 6 weeks for all measurements. The effect sizes for depression scores showed a positive trend. Remission rates indicated a significant improvement in the yoga group (BDI-II: 46.81%, MADRS: 17.02%) compared to the control group (BDI: 33.33%, MADRS: 8.33%). The findings suggest that there is a trendsetting additive effect of Ashtanga-Yoga after 3 months on psychopathology and mood with a greater improvement at the beginning of the intervention. Further research in this field can help to achieve more differentiated results.

Association of dietary fat composition with cognitive performance and brain morphology in cognitively healthy individuals.

BACKGROUND: Dietary lipids (omega-3 polyunsaturated fatty acids (n-3) PUFAs) and saturated fatty acids (SFA) seem to play an important role in brain health. (n-3) PUFAs have been shown to improve cerebral perfusion and to promote synaptogenesis. In this study, we investigated the relationship between dietary fat composition, cognitive performance and brain morphology in cognitively healthy individuals. METHODS: A total of 101 cognitively healthy participants (age: 42.3 ± 21.3 years, 62 females) were included in this study. Verbal memory was assessed using the California Verbal Learning Test (CVLT). Intake of (n-3) PUFA and SFA was calculated from food-frequency questionnaire-derived data (EPIC-FFQ). Magnetic resonance imaging (MRI) data were obtained (Siemens Trio 3T scanner) and grey matter volumes (GMV) were assessed by voxel-based morphometry (VBM/SPM8). We examined the association of SFA/(n-3) PUFA ratio and memory performance as well as GMV using regression models adjusted for age, sex, education, body mass index, apolipoprotein E (APOE) status and alcohol consumption. For VBM data, a multiple regression analysis was performed using the same covariates as mentioned before with intracranial volume as an additional covariate. RESULTS: A high SFA/(n-3) PUFA ratio was significantly (p < 0.05) correlated with poorer verbal memory performance and with lower GMV in areas of the left prefrontal cortex that support memory processes. CONCLUSIONS: These findings suggest that a diet rich in PUFAs is likely to exert favourable effects on brain morphology in brain areas important for memory and executive functions. This could constitute a possible mechanism for maintaining cognitive health in older age.

Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA.

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

The role of resources in the face of psychopathology.

OBJECTIVES: The current study compared resource realization and psychological distress in patients with different psychiatric diagnoses and healthy individuals and examined the moderating effect of intrapersonal resources (personal strengths) and interpersonal resources (relationships) on the association between incongruence (unsatisfactory realization of personal goals) and psychological distress. METHOD: In total, 218 participants (45.87% female, mean age = 39.83 years) completed standardized questionnaires at one measurement point. RESULTS: Healthy individuals (n = 56) reported the most resources, followed by patients with psychotic (n = 53), substance use (n = 53), and depressive disorders (n = 56). While patients with psychotic disorders benefited from intra- and interpersonal resources, patients with depression only benefitted from intrapersonal resources. Patients with substance use disorders did not benefit from resources at all. CONCLUSIONS: Depending on the diagnosis, patients evaluated their level of resources differently and benefitted in different ways. The results suggest that within psychotherapy, it might be useful to strengthen resources, especially for patients with depressive and substance use disorders.

Resting-state fMRI is associated with trauma experiences, mood and psychosis in Afro-descendants with bipolar disorder and schizophrenia.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SCZ) may exhibit functional abnormalities in several brain areas, including the medial temporal and prefrontal cortex and hippocampus; however, a less explored topic is how brain connectivity is linked to premorbid trauma experiences and clinical features in non-Caucasian samples of SCZ and BD. METHODS: Sixty-two individuals with SCZ (n = 20), BD (n = 21), and healthy controls (HC, n = 21) from indigenous and African ethnicity were submitted to clinical screening (Di-PAD), traumata experiences (ETISR-SF), cognitive and functional MRI assessment. The item psychosis/hallucinations in SCZ patients showed a negative correlation with the global efficiency (GE) in the right dorsal attention network. The items mania, irritable mood, and racing thoughts in the Di-PAD scale had a significant negative correlation with the GE in the parietal right default mode network. CONCLUSIONS: Differences in the activation of specific networks were associated with earlier disease onset, history of physical abuse, and more severe psychotic and mood symptoms in SCZ and BD subjects of indigenous and black ethnicity. Findings provide further evidence on SZ and BD's brain connectivity disturbances, and their clinical significance, in non-Caucasian samples.

Resting-state fMRI functional connectivity and clinical correlates in Afro-descendants with schizophrenia and bipolar disorder.

Schizophrenia (SCZ) and bipolar disorder (BD) exhibited altered activation in several brain areas, including the prefrontal and temporal cortex; however, a less explored topic is how brain connectivity and functional disturbances occur in non-Caucasian samples of SCZ and BD. Individuals with SCZ (n=20), BD (n=21), and healthy controls (HC, n=21) from indigenous and African ethnicity were submitted to clinical screening and functional assessments. Mood, compulsive and psychotic symptoms were also correlated to network dysfunction in each group. Two distinct networks' subcomponents demonstrated significant lower global efficiency (GE) in SCZ versus HC, corresponding to left posterior dorsal attention and medial left ventral attention (VA) networks. Lower GE was found in BD versus controls in four subcomponents, including the left medial and right VA. Higher compulsion scores correlated in BD with lower GE in the left VA, whereas increased report of alcohol abuse was associated with higher GE in left default mode network. Although preliminary, differences in the activation of specific networks, notably the left hemisphere, in SCZ versus controls, and lower activation in VA areas, in BD versus controls. Results highlight default mode and salient network as relevant for the emotional processing of SCZ and BD of indigenous and black ethnicity. Abstract: schizophrenia, bipolar disorder, functional neuroimaging, ethnicity, default network.

Reduced laterality as a trait marker of schizophrenia--evidence from structural and functional neuroimaging.

Laterality is a characteristic principle of the organization of the brain systems for language, and reduced hemispheric asymmetry has been considered a risk factor for schizophrenia. Here we sought support for the risk factor hypothesis by investigating whether reduced asymmetry of temporal lobe structure and function is also present in unaffected relatives. Sixteen schizophrenia patients, 16 age-matched first-degree relatives, and 15 healthy controls underwent high-resolution three-dimensional anatomical imaging and functional magnetic resonance imaging during auditory stimulation. Both the overall auditory cortex and planum temporale volumes and the lateralization to the left hemisphere were markedly reduced in patients. The decrease of lateralization correlated with increased severity of symptoms. In addition, both the overall functional activation in response to auditory stimulation and its asymmetry were reduced in the patients. Relatives had intermediate values between patients and controls on both structural and functional measures. This study provides added support for the idea that reduced hemispheric asymmetry is a biological risk factor for schizophrenia.

Transdiagnostic comparison of visual working memory capacity in bipolar disorder and schizophrenia.

BACKGROUND: Impaired working memory is a core cognitive deficit in both bipolar disorder and schizophrenia. Its study might yield crucial insights into the underpinnings of both disorders on the cognitive and neurophysiological level. Visual working memory capacity is a particularly promising construct for such translational studies. However, it has not yet been investigated across the full spectrum of both disorders. The aim of our study was to compare the degree of reductions of visual working memory capacity in patients with bipolar disorder (PBD) and patients with schizophrenia (PSZ) using a paradigm well established in cognitive neuroscience. METHODS: 62 PBD, 64 PSZ, and 70 healthy controls (HC) completed a canonical visual change detection task. Participants had to encode the color of four circles and indicate after a short delay whether the color of one of the circles had changed or not. We estimated working memory capacity using Pashler's K. RESULTS: Working memory capacity was significantly reduced in both PBD and PSZ compared to HC. We observed a small effect size (r = .202) for the difference between HC and PBD and a medium effect size (r = .370) for the difference between HC and PSZ. Working memory capacity in PSZ was also significantly reduced compared to PBD with a small effect size (r = .201). Thus, PBD showed an intermediate level of impairment. CONCLUSIONS: These findings provide evidence for a gradient of reduced working memory capacity in bipolar disorder and schizophrenia, with PSZ showing the strongest degree of impairment. This underscores the importance of disturbed information processing for both bipolar disorder and schizophrenia. Our results are compatible with the cognitive manifestation of a neurodevelopmental gradient affecting bipolar disorder to a lesser degree than schizophrenia. They also highlight the relevance of visual working memory capacity for the development of both behavior- and brain-based transdiagnostic biomarkers.

Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults.

Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD. Methods: A final sample of 185 young, high-risk German adults (aged 18-35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes. Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls. Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.

Mental imagery vividness as a trait marker across the schizophrenia spectrum.

We investigated the vividness of mental imagery and its possible relationship with the predisposition towards hallucinations in 52 schizophrenia (SZ) patients, 44 of their first-degree relatives (R) and two healthy control groups (high-schizotypy [CHS; n=24]; low-schizotypy [CLS; n=24]). We investigated phenomenological and cognitive trait markers of schizophrenia, including cognitive correlates of hallucinations and vividness of mental imagery, and the influence of individual psychopathology. Overall, scores on the mental imagery questionnaire (QMI [Sheehan, P.W., 1967. Reliability of a short test of imagery. Perceptual and Motor Skills 25, 744.]) suggested higher mental imagery vividness in first-degree relatives, high-schizotypy controls and patients, than in low-schizotypy controls. However, vividness of mental imagery was independent of predisposition towards hallucinations and cognitive test performance scores. These results suggest that vividness of mental imagery may be a trait marker across the schizophrenia spectrum. In addition we propose that imagery proneness is relatively independent of the individual psychopathology.

Aberrant brain network topology in fronto-limbic circuitry differentiates euthymic bipolar disorder from recurrent major depressive disorder.

INTRODUCTION: Previous studies have established graph theoretical analysis of functional network connectivity (FNC) as a potential tool to detect neurobiological underpinnings of psychiatric disorders. Despite the promising outcomes in studies that examined FNC aberrancies in bipolar disorder (BD) and major depressive disorder (MDD), there is still a lack of research comparing both mood disorders, especially in a nondepressed state. In this study, we used graph theoretical network analysis to compare brain network properties of euthymic BD, euthymic MDD and healthy controls (HC) to evaluate whether these groups showed distinct features in FNC. METHODS: We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 BD patients, 15 patients with recurrent MDD as well as 30 age- and gender-matched HC. Graph theoretical analyses were then applied to investigate functional brain networks on a global and regional network level. RESULTS: Global network analysis revealed a significantly higher mean global clustering coefficient in BD compared to HC. We further detected frontal, temporal and subcortical nodes in emotion regulation areas such as the limbic system and associated regions exhibiting significant differences in network integration and segregation in BD compared to MDD patients and HC. Participants with MDD and HC only differed in frontal and insular network centrality. CONCLUSION: In conclusion, our findings indicate that a significantly altered brain network topology in the limbic system might be a trait marker specific to BD. Brain network analysis in these regions may therefore be used to differentiate euthymic BD not only from HC but also from patients with MDD.

Associative Memory Impairments Are Associated With Functional Alterations Within the Memory Network in Schizophrenia Patients and Their Unaffected First-Degree Relatives: An fMRI Study.

Memory impairments are a major characteristic of schizophrenia (SZ). In the current study, we used an associative memory task to test the hypothesis that SZ patients and first-degree relatives have altered functional patterns in comparison to healthy controls. We analyzed the fMRI activation pattern during the presentation of a face-name task in 27 SZ patients, 23 first-degree relatives, and 27 healthy controls. In addition, we performed correlation analyses between individual psychopathology, accuracy and reaction time of the task and the beta scores of the functional brain activations. We observed a lower response accuracy and increased reaction time during the retrieval of face-name pairs in SZ patients compared with controls. Deficient performance was accompanied by abnormal functional activation patterns predominantly in DMN regions during encoding and retrieval. No significant correlation between individual psychopathology and neuronal activation during encoding or retrieval of face-name pairs was observed. Findings of first-degree relatives indicated slightly different functional pattern within brain networks in contrast to controls without significant differences in the behavioral task. Both the accuracy of memory performance as well as the functional activation pattern during retrieval revealed alterations in SZ patients, and, to a lesser degree, in relatives. The results are of potential relevance for integration within a comprehensive model of memory function in SZ. The development of a neurophysiological model of cognition in psychosis may help to clarify and improve therapeutic options to improve memory and functioning in the illness.

White Matter Microstructural Changes and Episodic Memory Disturbances in Late-Onset Bipolar Disorder.

Background: Bipolar disorder (BD) has been associated with distributed network disruption, but little is known on how different clinical subtypes, particularly those with an earlier and later onset of disease, are related to connectivity changes in white matter (WM) tracts. Methods: Diffusion tensor imaging (DTI) and volumetric measures were carried out in early-onset bipolar patients [(EOD) (n = 16)], late-onset bipolar disorder [(LOD)(n = 14)] and healthy controls (n = 32). We also computed ROI analysis of gray matter (GM) and white matter (WM) volumes using the regions with significant group differences in the DTI parameters. Cognitive and behavior measurements were analyzed between groups. Results: Lower fraction of anisotropy (FA) in the right hemisphere comprising anterior thalamic radiation, fornix, posterior cingulate, internal capsule, splenium of corpus callosum was observed in the LOD in comparison with EOD; additionally, lower FA was also found in the LOD in comparison with healthy controls, mostly in the right hemisphere and comprising fibers of the splenium of the corpus callosum, cingulum, superior frontal gyrus and posterior thalamic radiation; LOD also showed worse episodic memory performance than EOD; no statistical significant differences between mood symptoms, WM and GM volumes were found between BD groups. Conclusion: Even after correcting for age differences, LOD was associated with more extensive WM microstructural changes and worse episodic memory performance than EOD; these findings suggest that changes in the WM fiber integrity may be associated with a later presentation of BD, possibly due to mechanisms other than neuroprogression. However, these findings deserve replication in larger, prospective, studies.

Visual hallucinations in schizophrenia investigated with functional magnetic resonance imaging.

We investigated a 27-year old patient with paranoid schizophrenia. Brain activity related to visual hallucinations was found in higher visual areas corresponding to the content of the hallucinations (faces, bodies, scenes) and the hippocampus. We assume that the hippocampal activity is related to the retrieval of visual images from memory and that sensory cortex activity is related to the vividness of the perceptual experience.

Graphical illustration and functional neuroimaging of visual hallucinations during prolonged blindfolding: a comparison to visual imagery.

Visual hallucinations can occur in healthy subjects during prolonged visual deprivation. We investigated the visual percepts and the associated brain activity in a 37-year-old healthy female subject who developed visual hallucinations during three weeks of blindfolding, and then compared this activity with the cortical activity associated with mental imagery of the same patterns. We acquired fMRI data with a Siemens 3T Magnetom Allegra towards the end of the deprivation period to assess hallucination-related activity, and again after recovery from blindfolding to measure imagery-related activity. Detailed subjective descriptions and graphical illustrations were provided by the subject after blindfolding was completed. The subject reported the occurrence of simple and elementary hallucinations, consisting of flashes and coloured and moving patterns during the period of blindfolding. Neural activity related to hallucinations was found in extrastriate occipital, posterior parietal, and several prefrontal regions. In contrast, mental imagery of the same percepts led to activation in prefrontal, but not in posterior, parietal, and occipital regions. These results suggest that deprivation-induced hallucinations result from increased excitability of extrastriate visual areas, while mentally induced imagery involves active read-out under the volitional control of prefrontal structures. This agrees with the subject's report that visual hallucinations were more vivid than mental imagery.

The corpus callosum in schizophrenia-volume and connectivity changes affect specific regions.

The corpus callosum (CC) is of great interest for pathophysiological models of schizophrenia. Volume and structural integrity of the CC have been examined by volumetric and diffusion tensor imaging (DTI) studies, but results were not consistent across methods or studies. A possible explanation may be varying methodologies and accuracy of measurements based on a single slice or small regions of interest. In addition, none of the studies examined volume and diffusion values in the same group of patients, and thus the relationship between these anatomical measures is not clear. We used an automatic algorithm to segment seven midline slices of the CC from DTI images. We compared volume and the DTI measures fractional anisotropy (FA) and mean diffusivity (MD) in the CC and its subdivisions in the schizophrenia patients and matched controls. Patients had decreased volume, decreased FA and increased MD of the whole CC. The important novel finding is, however, that not all regions were equally affected by anatomical changes. The results emphasize the importance of using different methods in evaluation of white matter (WM) in schizophrenia to avoid false negative findings. In addition, the measures were highly correlated with each other, implying a common pathological process influencing FA, MD and volume of the CC. Although we cannot rule out other mechanisms affecting volume, FA and MD, converging evidence from cytoarchitectonic and genetic studies suggests that WM changes observed in schizophrenia may involve disintegration of healthy, functional axons and strengthening of aberrant connections resulting in increased severity of clinical symptoms.