Catherine Toben - Academia.edu (original) (raw)

Papers by Catherine Toben

Advances in clinical chemistry, 2024

Psychoneuroendocrinology, 2023

Pharmacology, Biochemistry and Behavior, Aug 1, 2015

The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficac... more The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficacy in schizophrenia, bipolar, major depressive and general anxiety disorders, but to also have a possible anti-inflammatory effect, which could be important in the treatment of the inflammatory aspects of psychiatric diseases. Male C57BL/6 mice were given either quetiapine (i.p. 10 mg/kg), its main active metabolite norquetiapine (i.p. 10 mg/kg), or saline as a vehicle control, once a day for 14 days. On the 14th day, this dose was followed by a single dose of either LPS (i.p. 1 mg/kg) or saline. 24 h post LPS short-term recognition memory and anhedonia behaviour were measured using the Y-maze and saccharin preference test respectively. Immediately following behavioural testing, mice were culled before serum, prefrontal cortex and hippocampal analysis of cytokine levels was conducted. It was found that LPS challenge led to increased serum and brain cytokine levels as well as anhedonia, with no significant effect on recognition memory. Quetiapine and norquetiapine both increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the pro-inflammatory cytokine IFN-γ in serum 4 h post LPS. Within the brain, a similar pattern was seen in gene expression in the hippocampus at 4 h for Il-10 and Ifn-γ, however norquetiapine led to an increase in Il-1β expression in the PFC at 4 h, while both drugs attenuated the increased Il-10 in different regions of the brain at 24 h. These effects in the serum and brain, however, had no effect on the observed LPS induced changes in behaviour. Both quetiapine and its metabolite norquetiapine appear to have a partial anti-inflammatory effect on IL-10 and IFN-γ following acute LPS challenge in serum and brain, however these effects did not translate into behavioural changes.

I would especially like to thank: ... My supervisors Profs. Drs Anneliese Schimpl and Thomas Hüni... more I would especially like to thank: ... My supervisors Profs. Drs Anneliese Schimpl and Thomas Hünig for the stimulating project, the continuous scientific support as well as the ongoing willingness for discussions and alot of 'Menschlichkeit'. ... My initial supervisor Prof Dr rer. nat Lars Nitschke who not only guided me through my early cloning days but who was always open for discussions ... My supervisor Prof Jürgen Kreft from the biology department for his willingness to supervise this work ... All the present and past colleagues in the labs of Nitschke/Bommhardt and Schimpl (Sabine Wagner, Brigitte Nanan, Liza Feoktistova, Cao Yi, Alex Zant) for their helpfulness and wonderful working atmosphere. ... All the past and present colleagues of the Institute for Virology and Immunobiology who provided an inspiring and encouraging working environment. ... All the colleagues in the Neurology department including Prof. Ralph Gold for their expert tips and guidance for the histology work ... Members of my family who supported me during this time ... And last but not least my sincere gratitude to Kirsten Stark for the never ending support within and outside of the lab

neuroinflammation and changes in

Human Molecular Genetics, 2021

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory propertie... more Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and infla...

European Neuropsychopharmacology, 2017

101-164 cases with available data using PLINK and included covariates for age, sex, and principle... more 101-164 cases with available data using PLINK and included covariates for age, sex, and principle components accounting for population substructure. Results: Genome-wide significant associations (po5x10-8) resulted from all analyses with the exception of CSF derived levels of TIMP1. Multiple genomic regions exert regulatory effects for the majority of biomarkers tested, but there was little concordance between associated regions for CSF and serum-derived measures when both were available for a given biomarker. Discussion: Levels of inflammatory biomarkers in CSF and serum are both genetically mediated but probably differentially. The associated genetic markers, in conjunction with the biomarker levels previously associated with bipolar disorder, could be used to aid diagnoses and as possible targets for the development of novel therapeutics.

European Neuropsychopharmacology, 2017

Abstract Previous studies aiming to identify the transcriptome signature of depression show incon... more Abstract Previous studies aiming to identify the transcriptome signature of depression show inconsistent results with low replicability at the single gene level in both brain and peripheral tissues. The complexity of the depression phenotype may contribute to this inconsistency. An advance in this field could be made by utilising systems biology approach. In this study, we analysed whole blood transcriptomes of 521 elderly people from the general population (The Sydney Memory and Aging Study, MAS) to identify molecular networks involved in geriatric depression. Depression was assessed according to DSM-IV criteria yielding both categorical and continuous depression phenotypes. Pre-processing of 47,323 probes (Illumina HT-12 v4) resulted in the 11,018 top-varying genes for downstream analyses. Pre-processing included maximum likelihood estimation (MLE) background correction, variance-stabilising (VST) transformation, quantile normalisation and filtering by detection p-value (p Using WGCNA package (R) we constructed the co-expression network consisting of 29 modules, two of which were associated with depressive symptoms. Both modules showed a highly significant correlation between module membership (MM) and gene significance (GS) measures (r=0.55, p=1e-07, r=0.4, p=0.0011), indicating that genes in these modules are highly significantly associated with depression. Further analysis showed that 37 and 17 genes respectively from the two “depression modules” are significantly associated with depressive symptoms (p

Pharmacology, biochemistry, and behavior, 2015

The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficac... more The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficacy in schizophrenia, bipolar, major depressive and general anxiety disorders, but to also have a possible anti-inflammatory effect, which could be important in the treatment of the inflammatory aspects of psychiatric diseases. Male C57BL/6 mice were given either quetiapine (i.p. 10mg/kg), its main active metabolite norquetiapine (i.p. 10mg/kg), or saline as a vehicle control, once a day for 14days. On the 14th day, this dose was followed by a single dose of either LPS (i.p. 1mg/kg) or saline. 24h post LPS short-term recognition memory and anhedonia behaviour were measured using the Y-maze and saccharin preference test respectively. Immediately following behavioural testing, mice were culled before serum, prefrontal cortex and hippocampal analysis of cytokine levels was conducted. It was found that LPS challenge led to increased serum and brain cytokine levels as well as anhedonia, with no...

Universität Würzburg, 2005

I would especially like to thank: ... My supervisors Profs. Drs Anneliese Schimpl and Thomas Hüni... more I would especially like to thank: ... My supervisors Profs. Drs Anneliese Schimpl and Thomas Hünig for the stimulating project, the continuous scientific support as well as the ongoing willingness for discussions and alot of 'Menschlichkeit'. ... My initial supervisor Prof Dr rer. nat Lars Nitschke who not only guided me through my early cloning days but who was always open for discussions ... My supervisor Prof Jürgen Kreft from the biology department for his willingness to supervise this work ... All the present and past colleagues in the labs of Nitschke/Bommhardt and Schimpl (Sabine Wagner, Brigitte Nanan, Liza Feoktistova, Cao Yi, Alex Zant) for their helpfulness and wonderful working atmosphere. ... All the past and present colleagues of the Institute for Virology and Immunobiology who provided an inspiring and encouraging working environment. ... All the colleagues in the Neurology department including Prof. Ralph Gold for their expert tips and guidance for the histology work ... Members of my family who supported me during this time ... And last but not least my sincere gratitude to Kirsten Stark for the never ending support within and outside of the lab

Cambridge University Press eBooks, Sep 23, 2021

Psychiatry Research-neuroimaging, Jun 1, 2021

Cognitive and emotional remediation training for depression (CERT-D): a randomised controlled tri... more Cognitive and emotional remediation training for depression (CERT-D): a randomised controlled trial to improve cognitive, emotional and functional outcomes in depression The aim of the current study was to evaluate an experimental treatment designed to improve psychosocial function in patients with Major Depressive Disorder (MDD) by reinforcing cognitive, emotional, and social-cognitive abilities. Participants (N = 112) with current or lifetime MDD were recruited to participate in a randomised, blinded, controlled trial. Exclusion criteria included diagnosis of a substance abuse disorder, bipolar disorder organic, eating disorders, or illness which affect cognitive function. The treatment involved repeated cognitive training designed to improve cognitive, emotional, and social-cognitive abilities. In training sessions, the principles of cognitive training were applied across cognitive, emotional, and social domains, with participants completing repeated mental exercises. Exercises included critically analysing interpretations of social interactions (e.g., body language), exploring emotional reactions to stimuli, and completing game-like cognitive training tasks. Training sessions placed great emphasis on the application of trained cognitive, emotional, and social cognitive skills to psychosocial outcomes. Outcomes demonstrated significant improvement in psychosocial function, symptom severity, self-reported cognition, and social-cognition. Our findings demonstrate the efficacy of multi-domain cognitive training to improve psychosocial functioning in individuals with MDD. We suggest that the present treatment could be deployed at a lower cost and with minimal training in comparison to established psychological therapies.

Inflammation and Immunity in Depression

Abstract Considering the bidirectional link between the immune and central nervous systems (CNS) ... more Abstract Considering the bidirectional link between the immune and central nervous systems (CNS) involved in inflammation-associated major depressive disorder (MDD) revels T lymphocytes to play an integral role. Recent evidence shows T lymphocytes being involved not only in maladaptive neuroimmune responses but also in maintaining homeostasis and neural plasticity. Furthermore, the pleiotropic nature of the molecular and cellular communication gradients of the neuroendocrine and immune systems combined with dynamic T-lymphocyte phenotypes lends itself to a balancing act between adaptive and maladaptive roles. Imbalances between particular regulatory and pro-inflammatory activities determine CNS-specific responses and vice versa. Added to this complexity is the gene-environment interaction of which chronic psychogenic stress is one of the major inducers of MDD. T lymphocytes are important in the restoration of behavioral deficits and immune cell dysregulation associated with MDD; however, it remains to be understood which T-lymphocyte mechanism confers susceptibility or resilience including neurodegenerative and regenerative repair functions.

European Psychiatry, 2021

Introduction Immune system abnormalities exist across a range of psychiatric disorders. Autoimmun... more Introduction Immune system abnormalities exist across a range of psychiatric disorders. Autoimmunity, characterized by the production of antibodies against the body’s own antigens, is a feature of immune system dysfunction and could play a role in mental disorder pathophysiology. Better understanding of the associations of auto-immunoglobulin G (IgG) repertoires with clinical features of mental illness could yield novel models of psychosis pathophysiology and markers for biological patient stratification.ObjectivesTo undertake global screening for auto-IgG expression in a large cohort of people with psychotic disorders; to determine whether associations exist between autoantibody expression and clinical features.MethodsCross-sectional quantification of auto-IgGs in blood plasma of 461 people with established psychotic disorder diagnoses. For global screening, pooled samples of phenotypically representative patient groups were exposed to planar protein microarrays containing 42,000 h...

Behavioural Brain Research, 2021

BACKGROUND We recently reported that tumor necrosis factor (TNF) signaling via the TNFR1 and TNFR... more BACKGROUND We recently reported that tumor necrosis factor (TNF) signaling via the TNFR1 and TNFR2 receptors mediates the effects of long-term exercise on locomotion, cognition and anxiety, but not depressive-like behavior. We now investigated whether the TNF signaling via its receptors also mediates the effects of short-term exercise on cognition, anxiety and depressive-like behaviors. METHODS Thirteen-month-old C57BL/6 (WT), TNF-/-, TNFR1-/-, and TNFR2-/- mice were provided with 4 weeks of voluntary wheel running followed by behavioral testing using an established behavioral battery. Each genotype had a respective non-exercise control. RESULTS There was no interaction between genotype and exercise in any of the tests but the main effect of genotype, and not exercise, were found to be significant in the open field (OF), forced-swim test (FST) and Barnes maze (BM). In the OF, the control and exercise TNFR2-/- mice spent significantly less time in the inner zone than mice in the control and exercise WT and TNF-/- cohorts. In the FST, control and exercise WT mice showed significantly higher immobility time than their control and exercise TNF-/-, TNFR1-/- and TNFR2-/- cohorts. In the BM, the latency to escape over 4 days of training was significantly higher in all KO groups compared to WT, irrespective of exercise. Also, the latency to escape to the original location during the probe trial was higher for control and exercise WT compared to corresponding TNFR1-/- mice. In contrast, the latency to escape to the new location was lower for control and exercise WT compared to control and exercise TNFR1-/- and TNFR2-/- mice. The latency to escape to the new location in exercise groups was longer compared to control within all genotypes. CONCLUSION While TNF signaling via the TNF receptors mediates cognition, anxiety and depressive-like behaviors independently, it does not mediate the effects of short-term exercise on these behaviors in middle-aged mice.

Personalized Psychiatry, 2020

Abstract With an increasing worldwide phenomenon of psychiatric disorders and treatment regimens ... more Abstract With an increasing worldwide phenomenon of psychiatric disorders and treatment regimens with limited efficacy, personalized psychiatry is emerging as a best practice. Within this paradigm, genetic and other biological markers are integrated with clinical data to better define the heterogeneous nature of psychiatric disorders in terms of diagnosis, prognosis, and therapeutic response. Inherent challenges lie not only within the nature of the cohort, but also within the lack of standardization for collection, storage, and analyses of biospecimens and associated clinical data. Biobanks provide global research networks as a valuable resource in the discovery of key molecular signatures underlying mental health disorders. This chapter discusses the significant impact standardization of processes within biobanking and biomarker research will have in supporting advances in personalized psychiatry.

Neurobiology of Depression, 2019

Major depressive disorder (MDD) is a debilitating disorder of a complex nature with multiple risk... more Major depressive disorder (MDD) is a debilitating disorder of a complex nature with multiple risk factors contributing to its etiology. Candidate gene and genome-wide association studies (GWAS) partially explain the variance in pathology, indicating that environmental factors such as childhood maltreatment (CM) and stressful life events (SLEs) also play a key role in the etiology of MDD. Therefore, a thorough understanding of the current knowledge on gene-environmental (G × E) interaction effects in the prediction of MDD is valuable in terms of early and better intervention in those with increased genetic or environmental risks. In this chapter, we review current evidence of effects of G × E on MDD and epigenetics mechanisms mediating these effects. The review suggests that although high-risk polymorphisms such as the serotonin transporter variant and the brain-derived neurotrophic factor variants are critical in the pathology, the interactions are not replicated consistently. In co...

Translational Psychiatry, 2021

Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. ... more Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. Better understanding of the associations between auto-immunoglobulin G (IgG) repertoires and clinical features of mental illness could yield novel models of the pathophysiology of psychosis, and markers for biological patient stratification. We undertook cross-sectional detection and quantification of auto-IgGs in peripheral blood plasma of 461 people (39% females) with established psychotic disorder diagnoses. Broad screening of 24 individuals was carried out on group level in eight clinically defined groups using planar protein microarrays containing 42,100 human antigens representing 18,914 proteins. Autoantibodies indicated by broad screening and in the previous literature were measured using a 380-plex bead-based array for autoantibody profiling of all 461 individuals. Associations between autoantibody profiles and dichotomized clinical characteristics were assessed using a stepwise...

Advances in clinical chemistry, 2024

Psychoneuroendocrinology, 2023

Pharmacology, Biochemistry and Behavior, Aug 1, 2015

The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficac... more The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficacy in schizophrenia, bipolar, major depressive and general anxiety disorders, but to also have a possible anti-inflammatory effect, which could be important in the treatment of the inflammatory aspects of psychiatric diseases. Male C57BL/6 mice were given either quetiapine (i.p. 10 mg/kg), its main active metabolite norquetiapine (i.p. 10 mg/kg), or saline as a vehicle control, once a day for 14 days. On the 14th day, this dose was followed by a single dose of either LPS (i.p. 1 mg/kg) or saline. 24 h post LPS short-term recognition memory and anhedonia behaviour were measured using the Y-maze and saccharin preference test respectively. Immediately following behavioural testing, mice were culled before serum, prefrontal cortex and hippocampal analysis of cytokine levels was conducted. It was found that LPS challenge led to increased serum and brain cytokine levels as well as anhedonia, with no significant effect on recognition memory. Quetiapine and norquetiapine both increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the pro-inflammatory cytokine IFN-γ in serum 4 h post LPS. Within the brain, a similar pattern was seen in gene expression in the hippocampus at 4 h for Il-10 and Ifn-γ, however norquetiapine led to an increase in Il-1β expression in the PFC at 4 h, while both drugs attenuated the increased Il-10 in different regions of the brain at 24 h. These effects in the serum and brain, however, had no effect on the observed LPS induced changes in behaviour. Both quetiapine and its metabolite norquetiapine appear to have a partial anti-inflammatory effect on IL-10 and IFN-γ following acute LPS challenge in serum and brain, however these effects did not translate into behavioural changes.

I would especially like to thank: ... My supervisors Profs. Drs Anneliese Schimpl and Thomas Hüni... more I would especially like to thank: ... My supervisors Profs. Drs Anneliese Schimpl and Thomas Hünig for the stimulating project, the continuous scientific support as well as the ongoing willingness for discussions and alot of 'Menschlichkeit'. ... My initial supervisor Prof Dr rer. nat Lars Nitschke who not only guided me through my early cloning days but who was always open for discussions ... My supervisor Prof Jürgen Kreft from the biology department for his willingness to supervise this work ... All the present and past colleagues in the labs of Nitschke/Bommhardt and Schimpl (Sabine Wagner, Brigitte Nanan, Liza Feoktistova, Cao Yi, Alex Zant) for their helpfulness and wonderful working atmosphere. ... All the past and present colleagues of the Institute for Virology and Immunobiology who provided an inspiring and encouraging working environment. ... All the colleagues in the Neurology department including Prof. Ralph Gold for their expert tips and guidance for the histology work ... Members of my family who supported me during this time ... And last but not least my sincere gratitude to Kirsten Stark for the never ending support within and outside of the lab

neuroinflammation and changes in

Human Molecular Genetics, 2021

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory propertie... more Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and infla...

European Neuropsychopharmacology, 2017

101-164 cases with available data using PLINK and included covariates for age, sex, and principle... more 101-164 cases with available data using PLINK and included covariates for age, sex, and principle components accounting for population substructure. Results: Genome-wide significant associations (po5x10-8) resulted from all analyses with the exception of CSF derived levels of TIMP1. Multiple genomic regions exert regulatory effects for the majority of biomarkers tested, but there was little concordance between associated regions for CSF and serum-derived measures when both were available for a given biomarker. Discussion: Levels of inflammatory biomarkers in CSF and serum are both genetically mediated but probably differentially. The associated genetic markers, in conjunction with the biomarker levels previously associated with bipolar disorder, could be used to aid diagnoses and as possible targets for the development of novel therapeutics.

European Neuropsychopharmacology, 2017

Abstract Previous studies aiming to identify the transcriptome signature of depression show incon... more Abstract Previous studies aiming to identify the transcriptome signature of depression show inconsistent results with low replicability at the single gene level in both brain and peripheral tissues. The complexity of the depression phenotype may contribute to this inconsistency. An advance in this field could be made by utilising systems biology approach. In this study, we analysed whole blood transcriptomes of 521 elderly people from the general population (The Sydney Memory and Aging Study, MAS) to identify molecular networks involved in geriatric depression. Depression was assessed according to DSM-IV criteria yielding both categorical and continuous depression phenotypes. Pre-processing of 47,323 probes (Illumina HT-12 v4) resulted in the 11,018 top-varying genes for downstream analyses. Pre-processing included maximum likelihood estimation (MLE) background correction, variance-stabilising (VST) transformation, quantile normalisation and filtering by detection p-value (p Using WGCNA package (R) we constructed the co-expression network consisting of 29 modules, two of which were associated with depressive symptoms. Both modules showed a highly significant correlation between module membership (MM) and gene significance (GS) measures (r=0.55, p=1e-07, r=0.4, p=0.0011), indicating that genes in these modules are highly significantly associated with depression. Further analysis showed that 37 and 17 genes respectively from the two “depression modules” are significantly associated with depressive symptoms (p

Pharmacology, biochemistry, and behavior, 2015

The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficac... more The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficacy in schizophrenia, bipolar, major depressive and general anxiety disorders, but to also have a possible anti-inflammatory effect, which could be important in the treatment of the inflammatory aspects of psychiatric diseases. Male C57BL/6 mice were given either quetiapine (i.p. 10mg/kg), its main active metabolite norquetiapine (i.p. 10mg/kg), or saline as a vehicle control, once a day for 14days. On the 14th day, this dose was followed by a single dose of either LPS (i.p. 1mg/kg) or saline. 24h post LPS short-term recognition memory and anhedonia behaviour were measured using the Y-maze and saccharin preference test respectively. Immediately following behavioural testing, mice were culled before serum, prefrontal cortex and hippocampal analysis of cytokine levels was conducted. It was found that LPS challenge led to increased serum and brain cytokine levels as well as anhedonia, with no...

Universität Würzburg, 2005

I would especially like to thank: ... My supervisors Profs. Drs Anneliese Schimpl and Thomas Hüni... more I would especially like to thank: ... My supervisors Profs. Drs Anneliese Schimpl and Thomas Hünig for the stimulating project, the continuous scientific support as well as the ongoing willingness for discussions and alot of 'Menschlichkeit'. ... My initial supervisor Prof Dr rer. nat Lars Nitschke who not only guided me through my early cloning days but who was always open for discussions ... My supervisor Prof Jürgen Kreft from the biology department for his willingness to supervise this work ... All the present and past colleagues in the labs of Nitschke/Bommhardt and Schimpl (Sabine Wagner, Brigitte Nanan, Liza Feoktistova, Cao Yi, Alex Zant) for their helpfulness and wonderful working atmosphere. ... All the past and present colleagues of the Institute for Virology and Immunobiology who provided an inspiring and encouraging working environment. ... All the colleagues in the Neurology department including Prof. Ralph Gold for their expert tips and guidance for the histology work ... Members of my family who supported me during this time ... And last but not least my sincere gratitude to Kirsten Stark for the never ending support within and outside of the lab

Cambridge University Press eBooks, Sep 23, 2021

Psychiatry Research-neuroimaging, Jun 1, 2021

Cognitive and emotional remediation training for depression (CERT-D): a randomised controlled tri... more Cognitive and emotional remediation training for depression (CERT-D): a randomised controlled trial to improve cognitive, emotional and functional outcomes in depression The aim of the current study was to evaluate an experimental treatment designed to improve psychosocial function in patients with Major Depressive Disorder (MDD) by reinforcing cognitive, emotional, and social-cognitive abilities. Participants (N = 112) with current or lifetime MDD were recruited to participate in a randomised, blinded, controlled trial. Exclusion criteria included diagnosis of a substance abuse disorder, bipolar disorder organic, eating disorders, or illness which affect cognitive function. The treatment involved repeated cognitive training designed to improve cognitive, emotional, and social-cognitive abilities. In training sessions, the principles of cognitive training were applied across cognitive, emotional, and social domains, with participants completing repeated mental exercises. Exercises included critically analysing interpretations of social interactions (e.g., body language), exploring emotional reactions to stimuli, and completing game-like cognitive training tasks. Training sessions placed great emphasis on the application of trained cognitive, emotional, and social cognitive skills to psychosocial outcomes. Outcomes demonstrated significant improvement in psychosocial function, symptom severity, self-reported cognition, and social-cognition. Our findings demonstrate the efficacy of multi-domain cognitive training to improve psychosocial functioning in individuals with MDD. We suggest that the present treatment could be deployed at a lower cost and with minimal training in comparison to established psychological therapies.

Inflammation and Immunity in Depression

Abstract Considering the bidirectional link between the immune and central nervous systems (CNS) ... more Abstract Considering the bidirectional link between the immune and central nervous systems (CNS) involved in inflammation-associated major depressive disorder (MDD) revels T lymphocytes to play an integral role. Recent evidence shows T lymphocytes being involved not only in maladaptive neuroimmune responses but also in maintaining homeostasis and neural plasticity. Furthermore, the pleiotropic nature of the molecular and cellular communication gradients of the neuroendocrine and immune systems combined with dynamic T-lymphocyte phenotypes lends itself to a balancing act between adaptive and maladaptive roles. Imbalances between particular regulatory and pro-inflammatory activities determine CNS-specific responses and vice versa. Added to this complexity is the gene-environment interaction of which chronic psychogenic stress is one of the major inducers of MDD. T lymphocytes are important in the restoration of behavioral deficits and immune cell dysregulation associated with MDD; however, it remains to be understood which T-lymphocyte mechanism confers susceptibility or resilience including neurodegenerative and regenerative repair functions.

European Psychiatry, 2021

Introduction Immune system abnormalities exist across a range of psychiatric disorders. Autoimmun... more Introduction Immune system abnormalities exist across a range of psychiatric disorders. Autoimmunity, characterized by the production of antibodies against the body’s own antigens, is a feature of immune system dysfunction and could play a role in mental disorder pathophysiology. Better understanding of the associations of auto-immunoglobulin G (IgG) repertoires with clinical features of mental illness could yield novel models of psychosis pathophysiology and markers for biological patient stratification.ObjectivesTo undertake global screening for auto-IgG expression in a large cohort of people with psychotic disorders; to determine whether associations exist between autoantibody expression and clinical features.MethodsCross-sectional quantification of auto-IgGs in blood plasma of 461 people with established psychotic disorder diagnoses. For global screening, pooled samples of phenotypically representative patient groups were exposed to planar protein microarrays containing 42,000 h...

Behavioural Brain Research, 2021

BACKGROUND We recently reported that tumor necrosis factor (TNF) signaling via the TNFR1 and TNFR... more BACKGROUND We recently reported that tumor necrosis factor (TNF) signaling via the TNFR1 and TNFR2 receptors mediates the effects of long-term exercise on locomotion, cognition and anxiety, but not depressive-like behavior. We now investigated whether the TNF signaling via its receptors also mediates the effects of short-term exercise on cognition, anxiety and depressive-like behaviors. METHODS Thirteen-month-old C57BL/6 (WT), TNF-/-, TNFR1-/-, and TNFR2-/- mice were provided with 4 weeks of voluntary wheel running followed by behavioral testing using an established behavioral battery. Each genotype had a respective non-exercise control. RESULTS There was no interaction between genotype and exercise in any of the tests but the main effect of genotype, and not exercise, were found to be significant in the open field (OF), forced-swim test (FST) and Barnes maze (BM). In the OF, the control and exercise TNFR2-/- mice spent significantly less time in the inner zone than mice in the control and exercise WT and TNF-/- cohorts. In the FST, control and exercise WT mice showed significantly higher immobility time than their control and exercise TNF-/-, TNFR1-/- and TNFR2-/- cohorts. In the BM, the latency to escape over 4 days of training was significantly higher in all KO groups compared to WT, irrespective of exercise. Also, the latency to escape to the original location during the probe trial was higher for control and exercise WT compared to corresponding TNFR1-/- mice. In contrast, the latency to escape to the new location was lower for control and exercise WT compared to control and exercise TNFR1-/- and TNFR2-/- mice. The latency to escape to the new location in exercise groups was longer compared to control within all genotypes. CONCLUSION While TNF signaling via the TNF receptors mediates cognition, anxiety and depressive-like behaviors independently, it does not mediate the effects of short-term exercise on these behaviors in middle-aged mice.

Personalized Psychiatry, 2020

Abstract With an increasing worldwide phenomenon of psychiatric disorders and treatment regimens ... more Abstract With an increasing worldwide phenomenon of psychiatric disorders and treatment regimens with limited efficacy, personalized psychiatry is emerging as a best practice. Within this paradigm, genetic and other biological markers are integrated with clinical data to better define the heterogeneous nature of psychiatric disorders in terms of diagnosis, prognosis, and therapeutic response. Inherent challenges lie not only within the nature of the cohort, but also within the lack of standardization for collection, storage, and analyses of biospecimens and associated clinical data. Biobanks provide global research networks as a valuable resource in the discovery of key molecular signatures underlying mental health disorders. This chapter discusses the significant impact standardization of processes within biobanking and biomarker research will have in supporting advances in personalized psychiatry.

Neurobiology of Depression, 2019

Major depressive disorder (MDD) is a debilitating disorder of a complex nature with multiple risk... more Major depressive disorder (MDD) is a debilitating disorder of a complex nature with multiple risk factors contributing to its etiology. Candidate gene and genome-wide association studies (GWAS) partially explain the variance in pathology, indicating that environmental factors such as childhood maltreatment (CM) and stressful life events (SLEs) also play a key role in the etiology of MDD. Therefore, a thorough understanding of the current knowledge on gene-environmental (G × E) interaction effects in the prediction of MDD is valuable in terms of early and better intervention in those with increased genetic or environmental risks. In this chapter, we review current evidence of effects of G × E on MDD and epigenetics mechanisms mediating these effects. The review suggests that although high-risk polymorphisms such as the serotonin transporter variant and the brain-derived neurotrophic factor variants are critical in the pathology, the interactions are not replicated consistently. In co...

Translational Psychiatry, 2021

Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. ... more Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. Better understanding of the associations between auto-immunoglobulin G (IgG) repertoires and clinical features of mental illness could yield novel models of the pathophysiology of psychosis, and markers for biological patient stratification. We undertook cross-sectional detection and quantification of auto-IgGs in peripheral blood plasma of 461 people (39% females) with established psychotic disorder diagnoses. Broad screening of 24 individuals was carried out on group level in eight clinically defined groups using planar protein microarrays containing 42,100 human antigens representing 18,914 proteins. Autoantibodies indicated by broad screening and in the previous literature were measured using a 380-plex bead-based array for autoantibody profiling of all 461 individuals. Associations between autoantibody profiles and dichotomized clinical characteristics were assessed using a stepwise...