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.
Most patients with schizophrenia need life-long treatment. There is therefore a continued need for effective and tolerable treatment options. A 2-monthly LAI formulation of aripiprazole, Aripiprazole ...2-Month Ready-to-Use 960 mg (Ari 2MRTU 960) has recently been approved in the US. Here, the possible role in therapy for this new treatment option is discussed in a narrative review. PubMed was searched for literature on long-acting injectables with a focus on patient-reported outcomes and real-world evidence on extended injection intervals (2-3 months). Dopamine D2 partial agonists, one of which is aripiprazole, exhibit favorable tolerability and safety properties. Additionally, there are many advantages in using long-acting injectable formulations such as enhanced treatment persistence and stability of patients as well as reduced rates of relapses, hospitalizations, and death. Some of these advantages become more pronounced with longer injection intervals. Additional advantages of longer injection intervals are more room for non-medication-related communication between healthcare professionals and patients, patient and physician preferences, reduced caregiver burden, and easier transitioning from inpatient to outpatient treatment. Taken together, since aripiprazole may be a good treatment choice for many patients based on its favorable safety and tolerability profile, and given the advantages of LAI treatment over oral treatment and the advantages of reduced dosing frequency, Ari 2MRTU 960 may become an important treatment option for many clinically stable patients with schizophrenia.
Summary Accumulating evidence suggests that there is a rich cross-talk between the neuroimmune system and neuroplasticity mechanisms under both physiological conditions and pathophysiological ...conditions in depression. Anti-neuroplastic changes which occur in depression include a decrease in proliferation of neural stem cells (NSCs), decreased survival of neuroblasts and immature neurons, impaired neurocircuitry (cortical–striatal–limbic circuits), reduced levels of neurotrophins, reduced spine density and dendritic retraction. Since both humoral and cellular immune factors have been implicated in neuroplastic processes, in this review we present a model suggesting that neuroplastic processes in depression are mediated through various neuroimmune mechanisms. The review puts forward a model in that both humoral and cellular neuroimmune factors are involved with impairing neuroplasticity under pathophysiological conditions such as depression. Specifically, neuroimmune factors including interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, CD4+CD25+T regulatory cells (T reg), self-specific CD4+T cells, monocyte-derived macrophages, microglia and astrocytes are shown to be vital to processes of neuroplasticity such as long-term potentiation (LTP), NSC survival, synaptic branching, neurotrophin regulation and neurogenesis. In rodent models of depression, IL-1, IL-6 and TNF are associated with reduced hippocampal neurogenesis; mechanisms which are associated with this include the stress-activated protein kinase (SAPK)/Janus Kinase (JNK) pathway, hypoxia-inducible factors (HIF)-1α, JAK-Signal Transducer and Activator of Transcription (STAT) pathway, mitogen-activated protein kinase (MAPK)/cAMP responsive element binding protein (CREB) pathway, Ras-MAPK, PI-3 kinase, IKK/nuclear factor (NF)-κB and TGFβ activated kinase-1 (TAK-1). Neuroimmunological mechanisms have an active role in the neuroplastic changes associated with depression. Since therapies in depression, including antidepressants (AD), omega-3 polyunsaturated fatty acids (PUFAs) and physical activity exert neuroplasticity-enhancing effects potentially mediated by neuroimmune mechanisms, the immune system might serve as a promising target for interventions in depression.
Objectives
Bipolar disorder (BD) is associated with significant impairment in cognitive performance across multiple domains of function that often persist after clinical recovery. It remains unclear, ...however, as to whether this process is related to the clinical status of BD being depressed, manic/hypomanic, or euthymic. In this review, we examine the literature on the cross‐sectional and longitudinal relationships between cognitive function and general function depending on the clinical phase of BD.
Methods
A systematic review of original research that studied both cognitive function and general function in adults (18–60 years), restricted to BD, was conducted in a total of 18 studies meeting inclusion/exclusion criteria.
Results
Results show cross‐sectional and prospective relationships between cognitive function and general function in patients with BD in both symptomatic and euthymic patients with BD. While studies using general measures of function (e.g., Global Assessment of Function scale) show more inconsistent associations with cognitive function, those employing assessments of domain specific function, suggest a consistent relationship between social and occupational function and cognitive performance. Executive function is commonly affected by cognitive deficits in these patients, but in addition a variety of domains show associations with functional outcomes (e.g., social function, occupational function). Notably, the emerging evidence suggests that cognitive function may be a better predictor of future general function than affective symptom severity.
Conclusions
Despite some inconsistencies, in sum the literature on the relationship between cognitive function and general function in BD implicates both cross‐sectional and longitudinal associations, both in symptomatic and euthymic patients with BD. And in terms of capturing these changes functional scales in particular domain‐specific measures seem superior to general measures.
Cognitive impairments reported across psychiatric conditions (ie, major depressive disorder, bipolar disorder, schizophrenia, and posttraumatic stress disorder) strongly impair the quality of life of ...patients and the recovery of those conditions. There is therefore a great need for consideration for cognitive dysfunction in the management of psychiatric disorders. The redundant pattern of cognitive impairments across such conditions suggests possible shared mechanisms potentially leading to their development. Here, we review for the first time the possible role of inflammation in cognitive dysfunctions across psychiatric disorders. Raised inflammatory processes (microglia activation and elevated cytokine levels) across diagnoses could therefore disrupt neurobiological mechanisms regulating cognition, including Hebbian and homeostatic plasticity, neurogenesis, neurotrophic factor, the HPA axis, and the kynurenine pathway. This redundant association between elevated inflammation and cognitive alterations across psychiatric disorders hence suggests that a cross-disorder approach using pharmacological and nonpharmacological (ie, physical activity and nutrition) anti-inflammatory/immunomodulatory strategies should be considered in the management of cognition in psychiatry.
Machine learning methods hold promise for personalized care in psychiatry, demonstrating the potential to tailor treatment decisions and stratify patients into clinically meaningful taxonomies. ...Subsequently, publication counts applying machine learning methods have risen, with different data modalities, mathematically distinct models, and samples of varying size being used to train and test models with the promise of clinical translation. Consequently, and in part due to the preliminary nature of such works, many studies have reported largely varying degrees of accuracy, raising concerns over systematic overestimation and methodological inconsistencies. Furthermore, a lack of procedural evaluation guidelines for non-expert medical professionals and funding bodies leaves many in the field with no means to systematically evaluate the claims, maturity, and clinical readiness of a project. Given the potential of machine learning methods to transform patient care, albeit, contingent on the rigor of employed methods and their dissemination, we deem it necessary to provide a review of current methods, recommendations, and future directions for applied machine learning in psychiatry. In this review we will cover issues of best practice for model training and evaluation, sources of systematic error and overestimation, model explainability vs. trust, the clinical implementation of AI systems, and finally, future directions for our field.
Cognitive dysfunction is a prevalent and disabling symptom of Major Depressive Disorder (MDD), and is often retained in the remitted stage of illness. Emerging evidence suggests that cognitive ...impairment may be associated with dysfunction in a number of psychosocial domains (e.g., workplace productivity, social relationships). The current study explored the relationship between cognition and psychosocial functioning in remitted MDD and in healthy controls.
Data were obtained from 182 participants of the Cognitive Function and Mood Study (CoFaM-S), a cross-sectional study of cognition, mood, and social cognition in mood disorders. Participants' (Remitted MDD n = 72, Healthy n = 110) cognition was assessed with a battery of cognitive tests including the Repeatable Battery for the Assessment of Neuropsychological Function (RBANS) and other standard measures of cognition (e.g., The Tower of London task). Psychosocial functioning was clinically evaluated with the Functioning Assessment Short Test (FAST).
The results indicated that executive functioning was the strongest independent predictor of functioning in remitted MDD patients, whereas various cognitive domains predicted psychosocial functioning in healthy individuals.
Psychosocial functioning was measured with a clinical interview, and was therefore reliant on clinicians' judgement of impairment, as opposed to more objective measures of functioning.
These findings suggest that executive cognition plays an important role in functional recovery in remitted depression, and may be a crucial target in adjunctive treatment.
Abstract Cognitive dysfunction is of clinical significance and exerts longstanding implication on patients׳ function. Pharmacological and non-pharmacological treatments of cognitive dysfunction are ...emerging. This review evaluates pharmacological and non-pharmacological treatments of cognitive impairment primarily in the domains of memory, attention, processing speed and executive function in clinical depression. A total of 35 studies were retrieved from Pubmed, PsycInfo and Scopus after applying inclusion and exclusion criteria. Results show that various classes of antidepressants exert improving effects on cognitive function across several cognitive domains. Specifically, studies suggest that SSRIs, the SSRE tianeptine, the SNRI duloxetine, vortioxetine and other antidepressants such as bupropion and moclobemide may exert certain improving effects on cognitive function in depression, such as in learning and memory and executive function. Class-specific cognitive domains or specific dose–response relationships were not identified yet. The few non-pharmacological studies conducted employing cognitive orientated treatments and cognitive remediation therapy show promising results for the improvement of cognitive impairment in depression. However, several methodological constraints of studies limit generalizability of the results and caution the interpretation. Future direction should consider the development of a neuropsychological consensus cognitive battery to support the discovery, clinical assessment, comparison of studies and registration of new agents in clinical depression.
•Deficits in several cognitive domains predicts disability in quality of life, and social, occupational, and global functioning•Self-perceived daily functioning is primarily associated with executive ...functioning and global cognition•Longitudinal psychosocial functioning outcomes are related to executive functioning, attention, and memory•Older age and greater depression symptom severity appear to enhance the negative relationship between cognitive deficits on psychosocial functioning
Cognitive deficits are frequently observed in major depressive disorder (MDD), as well as impaired long-term psychosocial functioning. However, the relationship between cognitive deficits and psychosocial functioning in MDD is under-investigated. We aim to systematically review the literature on the relationship between specific cognitive impairments and psychosocial functioning in MDD. We systematically reviewed English-language literature in PubMed, PsychINFO, Scopus and Web of Science using search terms related to psychosocial functioning. Additional studies were identified by searching reference lists. Following our inclusion/exclusion criteria, 28 studies were reviewed. Inclusion criteria included age (> 18), MDD diagnosed by standard tools (e.g., DSM-IV), use of cognitive and psychosocial assessments. Cross-sectional studies indicated that cognitive deficits in domains of executive functioning, attention, memory, and global cognition are associated with psychosocial dysfunction in domains of as quality of life, and social, occupational, and global functioning. The cognition-functioning relationship was also observed in longitudinal studies, showing that only specific cognitive domains affected psychosocial outcomes over the long-term course of illness. Older age and greater MDD symptom severity appear to enhance cognition-psychosocial dysfunction relationship, however little is known regarding the role of a number of other clinical factors (e.g., psychosis, illness duration).
A meta-analysis of chemokines in major depression Eyre, Harris A.; Air, Tracy; Pradhan, Alyssa ...
Progress in neuro-psychopharmacology & biological psychiatry,
07/2016, Letnik:
68
Journal Article
Recenzirano
Odprti dostop
Chemokines are increasingly recognised as playing a role in depression. Here we meta-analyse the data on concentrations of all chemokines in patients diagnosed with a major depression versus healthy ...controls. We included studies which utilised Diagnostic and Statistical Manual (DSM)-IV diagnostic criteria for major depression, participants free from major medical conditions, studies with healthy controls, and unstimulated measurements of chemokines. We only included chemokines which had ≥3 studies performed. Two chemokines and 15 studies in total met criteria for this meta-analysis; 8 for Monocyte Chemotactic Protein (MCP)-1/CCL2 (n=747), and 7 for Interleukin (IL)-8/CXCL8 (n=560). There were significantly higher concentrations of CCL2/MCP-1 in depressed subjects compared with control subjects – overall mean difference of 36.43pg/mL (95% CI: 2.43 to 70.42). There was significant heterogeneity across these studies (I2=98.5%). The estimates of mean difference between the control and depression groups did not remain significant when the trim-and-fill procedure was used to correct for publication bias. There was no significant difference in concentrations of IL-8/CXCL8 in depressed subjects compared with control subjects. Significant heterogeneity was found across these studies (I2=96.7%). The estimates of mean difference between the control and depression groups remained non-significant when the trim-and-fill procedure was used to correct for publication bias. This meta-analysis reports significantly heterogeneity in this field among studies. There are higher concentrations of the chemokine MCP-1/CCL2 in depressed subjects compared with control subjects, and no differences for IL-8/CXCL8. More high quality research and consistent methodologies are needed in this important area of enquiry.
•Chemokines are increasingly recognised as having a role in depression.•Here we meta-analyse chemokines in major depression versus control.•Significantly higher concentrations of MCP-1 were found.•No significant differences in concentrations of IL-8 were found.•There was significant heterogeneity across studies.
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