Relationship between activity in human primary motor cortex during action observation and the mirror neuron system

The attenuation of the beta cortical oscillations during action observation has been interpreted as evidence of a mirror neuron system (MNS) in humans. Here we investigated the modulation of beta cortical oscillations with the viewpoint of an observed action. We asked subjects to observe videos of an actor making a variety of arm movements. We show that when subjects were observing arm movements there was a significant modulation of beta oscillations overlying left and right sensorimotor cortices. This pattern of attenuation was driven by the side of the screen on which the observed movement occurred and not by the hand that was observed moving. These results are discussed in terms of the firing patterns of mirror neurons in F5 which have been reported to have similar properties

A novel strategy for clustering major depression individuals using whole-genome sequencing variant data

Major depressive disorder (MDD) is highly prevalent, resulting in an exceedingly high disease burden. The identification of generic risk factors could lead to advance prevention and therapeutics. Current approaches examine genotyping data to identify specific variations between cases and controls. Compared to genotyping, whole-genome sequencing (WGS) allows for the detection of private mutations. In this proof-of-concept study, we establish a conceptually novel computational approach that clusters subjects based on the entirety of their WGS. Those clusters predicted MDD diagnosis. This strategy yielded encouraging results, showing that depressed Mexican-American participants were grouped closer; in contrast ethnically-matched controls grouped away from MDD patients. This implies that within the same ancestry, the WGS data of an individual can be used to check whether this individual is within or closer to MDD subjects or to controls. We propose a novel strategy to apply WGS data to clinical medicine by facilitating diagnosis through genetic clustering. Further studies utilising our method should examine larger WGS datasets on other ethnical groups.Chenglong Yu, Bernhard T. Baune, Julio Licinio and Ma-Li Won

Trajectories of anxiety and health related quality of life during pregnancy

Published: July 24, 2017Anxiety and health related Quality of Life (HRQoL) have emerged as important mental health measures in obstetric care. Few studies have systematically examined the longitudinal trajectories of anxiety and HRQoL in pregnancy. Using a linear growth modeling strategy, we analyzed the course of State-Trait Anxiety Inventory (STAI)- and Short Form (36) Health Survey (SF-36) scores between the 12th and the 36th week of gestation, in a sample of 355 women. We additionally analyzed the impact of depressive symptoms and a chronic medical condition (asthma), on STAI and SF-36 trajectory curves. STAI scores remained stable throughout pregnancy. A previous history of anxiety increased the overall STAI scores. Asthma and depressive symptoms scores had no impact on the STAI trajectory. Physical SF-36 scores decreased over the course of pregnancy, whereas mental SF-36 trended towards improvement. Asthma reduced physical SF-36 overall. While high depressive symptoms decreased the overall mental SF-36, they were also significantly associated with mental SF-36 improvements over time. Anxiety symptoms are stable during pregnancy and are not modulated by depressive symptoms or asthma. Physical HRQoL declines in pregnancy. In contrast, mental HRQoL appears to improve, particularly in women with high initial levels of depressive symptoms.K. Oliver Schubert, Tracy Air, Scott R. Clark, Luke E. Grzeskowiak, Edward Miller, Gustaaf A. Dekker, Bernhard T. Baune, Vicki L. Clifto

Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results: In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.Bernhard T Baune, Carsten Konrad, Dominik Grotegerd, Thomas Suslow, Eva Birosova, Patricia Ohrmann, Jochen Bauer, Volker Arolt, Walter Heindel, Katharina Domschke, Sonja Schöning, Astrid V Rauch, Christina Uhlmann, Harald Kugel and Udo Dannlowsk

Locomotor hyperactivity in 14-3-3Zeta KO mice is associated with dopamine transporter dysfunction

Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1–D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders.H Ramshaw, X Xu, EJ Jaehne, P McCarthy, Z Greenberg, E Saleh, B McClure, J Woodcock, S Kabbara, S Wiszniak, Ting-Yi Wang, C Parish, M van den Buuse, BT Baune, A Lopez and Q Schwar

Role of social cognition for young adults with recurrent depression

Aim: To investigate the results of social cognition tests on young adults with either recurrent or nonrecurrent depression. This study tested three hypotheses: (1) young adults with recurrent depressive episodes (>2 episodes) would perform significantly poorer on social cognition tasks than nonrecurrent depression (1 or 2 episodes only); (2) deficits in negatively balanced prosody would be associated with deficits in other cognitive tasks due to the requirement of extra cognitive resources; and (3) anxiety severity not depression severity would be a predictor of recurrent depression. Design: Cross-sectional design with purposive sampling. Purposive sampling was used to target young adults who had experienced a depressive episode. Method: Eighty-four young adults (M=21.69 years, SD=4.14; 61 females, 23 males) with recurrent depression (>2 major depressive episodes) and 36 young adults (M=20.03 years, SD=3.23; 29 females, 7 males) with non-recurrent depression (1 or 2 major depressive episodes only) completed a cognitive battery and semi structured interviews including a clinical interview. Results: The recurrent depression group performed significantly poorer than the non-recurrent group in prosody matching (p=.015), but not in facial affect (p=.365). By grouping individual prosodymatching items into happy, surprise, afraid, sad, angry, neutral, and sarcasm items it was found that the recurrent group performed significantly poorer than the non-recurrent group in sarcasm items (p=.004) only. As prosody matching did not correlate with depression severity (p=.292) or anxiety severity (p=.345), prosody may be a trait deficit. Using linear regression with bootstrapping negatively balanced prosody (sad, angry, surprised) was significantly predicted by the Nback (1) task (p=.005). A logistic regression model with bootstrapping was run to determine if sarcasm items would still be independently associated with recurrent depression when co-varied with age, depression severity, and anxiety severity. Age (p=.009) and sarcasm items (p=.035) were both independently associated while depression severity (p=.824) and anxiety severity (p=.100) were not. Therefore both anxiety and depression severity were not predictors of the recurrent depression group. Omitting "Age" from the logistic regression the significance of sarcasm items increased to p=.004. Conclusion: Prosody matching (sarcasm items) a possible trait deficit may play a role in differentiating recurrent and non-recurrent depression

High school subject selection in depression related cognitive tests

Aim: To investigate the effect of high school subject selection on cognitive tests relevant to young adults with depression. It was hypothesised that young adults (17-35) who studied advanced 76 mathematics rather than ordinary mathematics would perform significantly better on cognitive tests associated with problem solving such as Card Sort (perseverative errors) and Tower of London. Design: Cross-sectional design with purposive sampling. Purposive sampling was used to target young adults who had experienced depressive symptoms. Method: Thirty seven young adults (M=20.05 years, SD=2.97; 28 female, 9 male) studied advanced mathematics and 78 young adults (M=20.19 years, SD=3.61; 57 female, 21 male) studied ordinary mathematics. Participants were classified as either the "advanced mathematics" group: scored at least one high achievement (B grade) with no fails in advanced mathematics A, advanced mathematics B, physics, or chemistry; or the "ordinary mathematics" group who studied ordinary mathematics in their senior year at high school. Participants completed a battery of cognitive tests and semi structured interviews to determine depression severity and disorder classification. Results: Advanced mathematics group had significantly less: perseverative errors (p=.009), participants with depression (p=.004), depression severity (p=.002), anxiety severity (p=.015), number of depressive episodes (p=.035), and intelligence measure (p=.027) than the ordinary mathematics group. Other cognitive tests where the advanced group performed significantly better than the ordinary mathematics group included word recall trial 1 (p=.001), trial 2 (p=.036), and trial 3 (p=.023). A logistic regression with bootstrapping was run and demonstrated that perseverative errors (p=.016) as well as word recall trial 1 (p=.001) were still significant predictors of mathematics group when covaried with an intelligence measure, depression and anxiety variables. Conclusion: Young adults who studied advanced mathematics had significantly fewer perseverative errors than young adults who studied ordinary mathematics even when controlling for differences in depression. School subject selection should be included in depression studies to better evaluate whether it is a mediating factor for perseverative errors which are considered a possible trait cognitive deficit for depression

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

High school subject selection in depression related cognitive tests

Aim: To investigate the effect of high school subject selection on cognitive tests relevant to young adults with depression. It was hypothesised that young adults (17-35) who studied advanced 76 mathematics rather than ordinary mathematics would perform significantly better on cognitive tests associated with problem solving such as Card Sort (perseverative errors) and Tower of London. Design: Cross-sectional design with purposive sampling. Purposive sampling was used to target young adults who had experienced depressive symptoms. Method: Thirty seven young adults (M=20.05 years, SD=2.97; 28 female, 9 male) studied advanced mathematics and 78 young adults (M=20.19 years, SD=3.61; 57 female, 21 male) studied ordinary mathematics. Participants were classified as either the "advanced mathematics" group: scored at least one high achievement (B grade) with no fails in advanced mathematics A, advanced mathematics B, physics, or chemistry; or the "ordinary mathematics" group who studied ordinary mathematics in their senior year at high school. Participants completed a battery of cognitive tests and semi structured interviews to determine depression severity and disorder classification. Results: Advanced mathematics group had significantly less: perseverative errors (p=.009), participants with depression (p=.004), depression severity (p=.002), anxiety severity (p=.015), number of depressive episodes (p=.035), and intelligence measure (p=.027) than the ordinary mathematics group. Other cognitive tests where the advanced group performed significantly better than the ordinary mathematics group included word recall trial 1 (p=.001), trial 2 (p=.036), and trial 3 (p=.023). A logistic regression with bootstrapping was run and demonstrated that perseverative errors (p=.016) as well as word recall trial 1 (p=.001) were still significant predictors of mathematics group when covaried with an intelligence measure, depression and anxiety variables. Conclusion: Young adults who studied advanced mathematics had significantly fewer perseverative errors than young adults who studied ordinary mathematics even when controlling for differences in depression. School subject selection should be included in depression studies to better evaluate whether it is a mediating factor for perseverative errors which are considered a possible trait cognitive deficit for depression

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.M A Di Biase, A Zalesky, G O'keefe, L Laskaris, B T Baune, C S Weickert, J Olver, P D McGorry, G P Amminger, B Nelson, A M Scott, I Hickie, R Banati, F Turkheimer, M Yaqub, I P Everall, C Pantelis and V Crople