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

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

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

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

Microglia: an interface between the loss of neuroplasticity and depression

Depression has been widely accepted as a major psychiatric disease affecting nearly 350 million people worldwide. Research focus is now shifting from studying the extrinsic and social factors of depression to the underlying molecular causes. Microglial activity is shown to be associated with pathological conditions, such as psychological stress, pathological aging, and chronic infections. These are primary immune effector cells in the CNS and regulate the extensive dialogue between the nervous and the immune systems in response to different immunological, physiological, and psychological stressors. Studies have suggested that during stress and pathologies, microglia play a significant role in the disruption of neuroplasticity and have detrimental effects on neuroprotection causing neuroinflammation and exacerbation of depression. After a systematic search of literature databases, relevant articles on the microglial regulation of bidirectional neuroimmune pathways affecting neuroplasticity and leading to depression were reviewed. Although, several hypotheses have been proposed for the microglial role in the onset of depression, it is clear that all molecular pathways to depression are linked through microglia-associated neuroinflammation and hippocampal degeneration. Molecular factors such as an excess of glucocorticoids and changes in gene expression of neurotrophic factors, as well as neuro active substances secreted by gut microbiota have also been shown to affect microglial morphology and phenotype resulting in depression. This review aims to critically analyze the various molecular pathways associated with the microglial role in depression.Gaurav Singhal and Bernhard T. Baun

Knockout of CXCR5 increases the population of immature neural cells and decreases proliferation in the hippocampal dentate gyrus

BACKGROUND The process of neurogenesis in which new neurons are generated by proliferation and differentiation of neural stem/progenitor cells (NSCs/NPCs) has been a topic of intensive recent investigation. Investigations of the factors which regulate this process have recently begun to include immune factors including immune cells and cytokines, however the class of immune proteins designated as chemokines have been relatively neglected. Increasing evidence for novel brain-specific mechanisms of chemokines beyond their classical chemotactic functions has suggested that they may play a role in the regulation of NSC/NPC biology. METHODS We have investigated the role of the chemokine receptor CXCR5 (ligand is CXCL13) in the activity of these cells through neurobiological and behavioural analysis of CXCR5-deficient mice (CXCR5-/-). These investigations included: immunohistochemistry for the markers Ki67, nestin, doublecortin, and IBA-1, neurosphere assays, and the baseline behavioural tests: open field test and sucrose preference test. RESULTS We observed a significant increase in doublecortin and nestin staining in the hippocampal dentate gyrus (P = 0.02 and P = 0.0008, respectively) of CXCR5-/- animals as compared to wild-type controls. This was accompanied by a decrease in Ki67 staining subgranular zone (P = 0.009). Behavioural correlates included a significant increase in baseline locomotor activity in an open field test (P <0.00018) and a decrease in stress reactivity in that test (P = 0.015). Deficiency in CXCR5 was not associated with alterations in hippocampal microglial density, microglial activation or systemic cytokine levels, nor with loss of NSC/NPC populations in the neurosphere assay. CONCLUSIONS These findings are the first to describe a brain-specific function of CXCR5 under physiological conditions. CXCR5 reduces maintenance of immature neural cell populations and enhances proliferation of subgranular zone cells in the hippocampal dentate gyrus, however the mechanism of these effects remains unclear. Further research into the regulation of NSC/NPC activity should consider investigation of CXCR5 and other chemokines which may be relevant to the pathophysiology of psychiatric disorders including depression, anxiety and cognitive impairment/dementia.Michael J Stuart, Frances Corrigan and Bernhard T Baun

A review of the role of social cognition in major depressive disorder

BACKGROUND: Social cognition - the ability to identify, perceive, and interpret socially relevant information - is an important skill that plays a significant role in successful interpersonal functioning. Social cognitive performance is recognized to be impaired in several psychiatric conditions, but the relationship with major depressive disorder is less well understood. The aim of this review is to characterize the current understanding of: (i) the different domains of social cognition and a possible relationship with major depressive disorder, (ii) the clinical presentation of social cognition in acute and remitted depressive states, and (iii) the effect of severity of depression on social cognitive performance. METHODS: Electronic databases were searched to identify clinical studies investigating social cognition in a major depressive disorder population, yielding 31 studies for this review. RESULTS: Patients with major depressive disorder appear to interpret social cognitive stimuli differently to healthy controls: depressed individuals may interpret emotion through a mood-congruent bias and have difficulty with cognitive theory of mind tasks requiring interpretation of complex mental states. Social cognitive performance appears to be inversely associated with severity of depression, whilst the bias toward negative emotions persists even in remission. Some deficits may normalize following effective pharmacotherapy. CONCLUSIONS: The difficulties with social interaction observed in major depressive disorder may, at least in part, be due to an altered ability to correctly interpret emotional stimuli and mental states. These features seem to persist even in remission, although some may respond to intervention. Further research is required in this area to better understand the functional impact of these findings and the way in which targeted therapy could aid depressed individuals with social interactions.Michael James Weightman,Tracy Michele Air and Bernhard Theodor Baun

Effects of physical exercise on central nervous system functions: a review of brain region specific adaptations

Published: 18 April 2015Pathologies of central nervous system (CNS) functions are involved in prevalent conditions such as Alzheimer's disease, depression, and Parkinson's disease. Notable pathologies include dysfunctions of circadian rhythm, central metabolism, cardiovascular function, central stress responses, and movement mediated by the basal ganglia. Although evidence suggests exercise may benefit these conditions, the neurobiological mechanisms of exercise in specific brain regions involved in these important CNS functions have yet to be clarified. Here we review murine evidence about the effects of exercise on discrete brain regions involved in important CNS functions. Exercise effects on circadian rhythm, central metabolism, cardiovascular function, stress responses in the brain stem and hypothalamic pituitary axis, and movement are examined. The databases Pubmed, Web of Science, and Embase were searched for articles investigating regional brain adaptations to exercise. Brain regions examined included the brain stem, hypothalamus, and basal ganglia. We found evidence of multiple regional adaptations to both forced and voluntary exercise. Exercise can induce molecular adaptations in neuronal function in many instances. Taken together, these findings suggest that the regional physiological adaptations that occur with exercise could constitute a promising field for elucidating molecular and cellular mechanisms of recovery in psychiatric and neurological health conditions.Julie A Morgan, Frances Corrigan and Bernhard T Baun

Treating depression and depression-like behavior with physical activity: An immune perspective

The increasing burden of major depressive disorder makes the search for an extended understanding of etiology, and for the development of additional treatments highly significant. Biological factors may be useful biomarkers for treatment with physical activity (PA), and neurobiological effects of PA may herald new therapeutic development in the future. This paper provides a thorough and up-to-date review of studies examining the neuroimmunomodulatory effects of PA on the brain in depression and depression-like behaviors. From a neuroimmune perspective, evidence suggests PA does enhance the beneficial and reduce the detrimental effects of the neuroimmune system. PA appears to increase the following factors: interleukin (IL)-10, IL-6 (acutely), macrophage migration inhibitory factor, central nervous system-specific autoreactive CD4+ T cells, M2 microglia, quiescent astrocytes, CX3CL1, and insulin-like growth factor-1. On the other hand, PA appears to reduce detrimental neuroimmune factors such as: Th1/Th2 balance, pro-inflammatory cytokines, C-reactive protein, M1 microglia, and reactive astrocytes. The effect of other mechanisms is unknown, such as: CD4+CD25+ T regulatory cells (T regs), CD200, chemokines, miRNA, M2-type blood-derived macrophages, and tumor necrosis factor (TNF)-α [via receptor 2 (R2)]. The beneficial effects of PA are likely to occur centrally and peripherally (e.g., in visceral fat reduction). The investigation of the neuroimmune effects of PA on depression and depression-like behavior is a rapidly developing and important field.Harris A. Eyre, Evan Papps and Bernhard T. Baun