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Objective: The mechanisms involved in the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, especially in the functioning of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in depressed patients, are not well elucidated. The objective of this study was to conduct a systematic review of articles that assess the HPA axis activity from GR and MR in depressed patients and healthy controls with or without early life stress.
Methods: We conducted a systematic review of articles in PubMed, SCOPUS and SciELO published between 2000 and 2011, using the following search terms: child abuse, depression, HPA axis, dexamethasone, prednisolone, fludrocortisone and spironolactone. Thirty-four papers were selected for this review.
Results: Most studies identified in this review used the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test. In these studies, hypercortisolaemia was associated with depression. We identified three studies with the Prednisolone suppression test, only one study with the use of fludrocortisone and one with spironolactone. This review found nine studies that evaluated the HPA axis in individuals with early life stress.
Conclusions: The majority of the studies assessed in this review show that early life stress leads to permanent changes in the HPA axis and may lead to development of depression in adults. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolaemia and reduced inhibitory feedback. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between GR and MR. Evidences have consistently showed that GR function is impaired in major depression, but few studies have assessed the activity of MR in depression and early life stress.
Objective: Deficits in adult and embryonic neurogenesis have been linked with neurological and psychiatric disorders, so it is important to understand the molecular mechanisms underlying this process. SOX11 is a transcription factor known to play a critical role in the regulation of the neuronal and glial differentiation stage of neurogenesis, so we hypothesised that the identification of its target genes would reveal underlying biological processes relevant to disease.
Methods: SOX11 protein was over-expressed in HEK293 cells and transcriptional changes assessed by microarray analysis. Selected candidate genes were further tested for SOX11 activation in quantitative reverse transcriptase PCR studies of HEK293 cells and Western analysis of SH-SY5Y cells.
Results: Regulated genes included a previously established SOX11 target, known markers of neurogenesis, as well as several genes implicated in neuropsychiatric disorders. Immunofluorescence localised several of the genes within the proliferative subgranular zone of the hippocampus. We observed multiple histone and zinc finger genes regulated by SOX11, many of which were located in two clusters on chromosomes 6 and 19. The chromosome 6 cluster lies within a region of the genome showing the strongest genetic association with schizophrenia.
Conclusion: SOX11 appears to regulate a complex programme of chromatin remodelling and downstream gene expression changes to achieve a mature neuronal phenotype. SOX11 target genes are shown to be involved in neurodevelopmental processes important in health and, potentially, disease.
Objective: We showed previously that glycogen synthase kinase-3β (GSK-3β) levels are significantly elevated in the hippocampi of patients with major depressive disorder (MDD). However, the exact cause of this elevation and its function are unknown. Recent animal studies have suggested a mechanism involving the N-methyl-d-aspartate (NMDA) NR2B–GSK-3β loop.
Methods: To investigate the existence of an NR2B–GSK-3β loop in the hippocampi of patients with MDD, we examined the expression of NR2B. We also attempted to identify markers that correlate with NR2B levels in the hippocampus, using the Stanley Neuropathology Consortium Integrative Database (SNCID). The SNCID is a web-based tool used to integrate Stanley Medical Research Institute (SMRI) data sets.
Results: We found that hippocampal levels of NR2B and DLGAP1 mRNA were higher in the MDD group (n = 8) than in unaffected controls (n = 12) (p < 0.05). NR2B expression levels were correlated with the expression levels of NR2A, NR1, DLGAP1, GSK-3β and nitric oxide synthase 1, as well as with the number of calretinin-immunoreactive neurons in the hippocampus in all subjects in the SNC (n = 42, p < 0.001).
Conclusion: The results of our study show the possible involvement of excessive activation of the NR2B–GSK-3β loop in the overexpression of GSK-3β in the hippocampi of patients with MDD.
Objective: Functional imaging studies of post-traumatic stress disorder (PTSD) have shown an increased activation of posterior cingulate gyrus (PCG) of the brain. The aim of this study was to explore white matter integrity of PCG in PTSD subjects.
Methods: White matter integrity, as determined from fractional anisotropy (FA) value using diffusion tensor imaging, was assessed for PCG in subjects with and without PTSD from a severe mine accident. All subjects were also measured by the PTSD Checklist Civilian Version (PCL-C), the State-Trait Anxiety Inventory (STAI), the logical memory subtest and the visual reproduction subtest of the Wechsler Memory Scale-Revised in China. Sixteen PTSD subjects (8 subjects in each group) in the longitudinal study and 13 PTSD subjects as well as 14 non-PTSD controls in the cross-sectional case–control study were respectively recruited.
Results: In the longitudinal study, subjects with PTSD showed increased FA values in left PCG during the follow-up scan. In the cross-sectional study, FA values in bilateral PCG in PTSD subjects were higher than controls. Within the PTSD group (n = 13), FA values in the left PCG correlated positively with logical memory and negatively with PCL-C intrusion and STAI-trait (STAI-t) subscores. FA values in right PCG correlated negatively with STAI-t and STAI-state subscores.
Conclusion: These findings suggest that alterations of white matter integrity in PCG link to mnemonic and affective processing in PTSD over the long-term follow-up period.
Objective: The ability to reflect rationally on one's own anomalous experiences and to recognise that their conclusions are incorrect is called as cognitive insight. It influences the delusion proneness of patients with schizophrenia. Structured instruments to assess cognitive insight have not been validated in any Indian languages so far. Hence, we aimed to evaluate the validity and factor structure of Tamil version of Beck Cognitive Insight Scale (BCIS-T).
Methods: One hundred and fifty consecutive patients with schizophrenia completed BCIS-T. We assessed their clinical insight with the reference standard, Schedule for Assessment of Insight-Expanded version (SAI-E). An independent psychiatrist evaluated their psychopathology using Brief Psychiatric Rating Scale (BPRS).
Results: BCIS-T was internally consistent with Cronbach's α 0.67 and Guttman's split-half coefficient as 0.63. BCIS-T composite index documented convergent validity with SAI-E total score (ρ = 0.38; p < 0.001) and discriminant validity with BPRS (ρ = −0.02; p = 0.85). Factor analysis showed a four-factor structure, namely self-certainty, self-reflectiveness, openness to external feedback and infallibility of self-reflection. BCIS-T composite index had significant linear relationship with clinical insight and treatment compliance on multivariate analyses (p < 0.01).
Conclusion: Our findings support the validity of BCIS-T to assess cognitive insight of the patients with schizophrenia. We suggest addressing the intricacies of cognitive insight beyond the traditional two-dimensional models in cross-cultural settings.
Background: It has been claimed that schizophrenia can be linked to the magnocellular system by way of N-methyl-d-aspartate (NMDA) receptors. The present report examines this claim.
Methods: A review is made of relevant research literature.
Results: The NMDA studies that have been referenced to connect visual deficits in schizophrenia to the magnocellular system are based on the cat, a species whose visual system is fundamentally different from that of primates. The cat visual system cannot easily be divided into magno- and a parvocellular portions.
Conclusions: Owing to the substantial differences between the visual systems of cats and primates, it is difficult to link sensory abnormalities in schizophrenia specifically to the magnocellular system based on data from the cat.
Background: A well-known technique to assess (psychological) arousal is to measure the skin conductance level (SCL). Although widely used in experimental psychological research, this technique has not been used often in (locked) psychiatric admission settings on patients who are at a high risk of engaging in aggressive behaviour. One of the obvious reasons for this is that measuring skin conductance, until recently, required a substantial amount of equipment.
Methods: As technology developed, it became possible to develop small wearable devices in the form of regular watches to measure the SCL as well as other psycho-physiological parameters. To illustrate the potential this may have for the prevention of aggressive behaviour, a case description is provided of a patient in crisis who became physically aggressive while wearing a skin conductance measurement device.
Results: Interestingly, the SCL of the patient had been rising sharply before the first signs of aggressive behaviour were visible.
Conclusion: Although it concerns an anecdotal case study, this finding suggests that measuring SCL on a continuous basis in patients who are at a high risk of becoming violent, without this procedure having to interfere with their daily life, may open new avenues for preventing aggression at an earlier stage. A large-scale empirical study in a substantial number of (potentially aggressive) patients is needed, however, to investigate the predictive validity of mobile skin conductance assessments on imminent inpatient aggression in a reliable way.