Rock art in the Northern Cape: the implications of variability in engravings and paintings relative to issues of social context and change in the precolonial past

Philosophiae Doctor - PhDThis thesis follows and builds upon a previous study at the rock engraving site of Driekopseiland (Morris 2002). The earlier findings are here contrasted with another site in the area, namely Wildebeest Kuil, as a means to highlight the variability which is a feature of the rock art of the Northern Cape as a whole. The main thrust of the thesis, which refers to a number of other rock art sites in the region, is to model the implications of this variability relative to social context and history in the precolonial past. Significant empirical obstacles, particularly the difficulties associated with dating rock art, render some aspects of the enterprise intractable for the time being. But opportunities are pursued to advance and evaluate ideas as to the social mechanisms and processes which might be implicated in the making and re-making of images on rock and in the generation of the diversity that is manifest in the rock art as it is found today. Whereas other approaches have tended to explain difference relative to social entities such as ‘cultures’ or ‘ethnic groups’, this thesis offers, as a point of departure, a critique of received concepts, reconsidering some of the fundamental metaphors and assessing the elaboration of analogies that have been used in the past. It proposes that better theoretical footholds might be those that explain variability relative to process and movement. It invokes Tim Ingold’s concept of a meshwork of dynamic relationships of people immersed in the world, of ‘entanglements’ that refer to multiple mechanisms that might explain how rock art has changed in place and time. The pertinence of these ideas is shown with reference to specific instances in the Northern Cape.As a parallel weave in this study, there is a concern over the social role of archaeology, with discussion on the burgeoning salience of rock art beyond the academy, in the heritage and tourism sectors and amongst descendants of the Khoean. The thesis gives consideration to the role of museums and research in terms of “heritage in practice,” and seeks to develop a discourse in which, following Alexander, “everything can be perceived as changing and changeable” – an underlying theme throughout the study. The thesis does not bring empirical closure to the topic but suggests a programme for future engagement, having opened up and shown the relevance of wider theoretical insights for addressing the variability in the rock art of the Northern Cap

Recognition and Treatment of Cognitive Dysfunction in Major Depressive Disorder

Major Depressive Disorder (MDD) is a prevalent, chronic, disabling, and multidimensional mental disorder. Cognitive dysfunction represents a core diagnostic and symptomatic criterion of MDD, and is a principal determinant of functional non-recovery. Cognitive impairment has been observed to persist despite remission of mood symptoms, suggesting dissociability of mood and cognitive symptoms in MDD. Recurrent impairments in several domains including, but not limited to, executive function, learning and memory, processing speed, and attention and concentration, are associated with poor psychosocial and occupational outcomes. Attempts to restore premorbid functioning in individuals with MDD requires regular screenings and assessment of objective and subjective measures of cognition by clinicians. Easily accessible and cost-effective tools such as the THINC-integrated tool (THINC-it) are suitable for use in a busy clinical environment and appear to be promising for routine usage in clinical settings. However, antidepressant treatments targeting specific cognitive domains in MDD have been insufficiently studied. While select antidepressants, e.g., vortioxetine, have been demonstrated to have direct and independent pro-cognitive effects in adults with MDD, research on additional agents remains nascent. A comprehensive clinical approach to cognitive impairments in MDD is required. The current narrative review aims to delineate the importance and relevance of cognitive dysfunction as a symptomatic target for prevention and treatment in the phenomenology of MDD

The Efficacy of Vortioxetine on Anhedonia in Patients With Major Depressive Disorder

Background: Anhedonia is a common, persistent, and disabling phenomenon in treated adults with Major Depressive Disorder (MDD). Hitherto, relatively few antidepressant agents have been evaluated with respect to their effect on anhedonia in MDD.Methods: This is a post-hoc analysis of a primary study that sought to evaluate the sensitivity to change of the THINC-integrated tool (THINC-it) in MDD (ClinicalTrials.gov Identifier: NCT03053362). Adults meeting DSM-5 criteria for MDD with at least moderate depressive symptom severity [i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥20] were eligible. Subjects were recruited between October 2017 and August 2018 in Toronto, Ontario at the Brain and Cognition Discovery Foundation. All subjects received open-label vortioxetine (10–20 mg/day, flexibly-dosed) for 8 weeks. Herein, the primary outcome of interest was the change from baseline to endpoint in the Snaith-Hamilton Pleasure Scale (SHAPS) total score, as well as the MADRS anhedonia factor. The mediational effects of improvements in anhedonia on general function and quality of life, as measured by the Sheehan Disability Scale (SDS) and the 5-Item World Health Organization Well-Being Index (WHO-5), were secondarily assessed.Results: A total of 100 subjects with MDD were enrolled in the primary study and began treatment with vortioxetine. Vortioxetine significantly improved anhedonia as evidenced by significant baseline to endpoint improvements in SHAPS and MADRS anhedonia factor scores (p < 0.0001). Improvements in the SHAPS and the MADRS anhedonia factor correlated with improvements in general function (i.e., SDS) and quality of life (i.e., WHO-5) (p < 0.0001). Notably, improvements in anhedonia were found to mediate the association between improvements in overall depressive symptom severity (i.e., MADRS total score) and social functioning (i.e., social life component of the SDS) (p = 0.026).Conclusion: The unmet need in depression is to improve patient functioning and other patient-reported outcomes (e.g., quality of life). Antidepressant interventions capable of attenuating anhedonia as well as cognitive dysfunction in MDD may help in this regard, as improvement in these domains have been associated with improvement in psychosocial function and quality of life

Effects of levomilnacipran extended-release on major depressive disorder patients with cognitive impairments

Performance-based cognitive data were collected using the Cognitive Drug Research System in a study of levomilnacipran extended-release (ER) 40-120 mg/day (NCT01034462) in adults with major depressive disorder. These data were analyzed post-hoc to explore the relationship between cognitive measures, depression symptoms (Montgomery-Asberg Depression Rating Scale, MADRS), and self-reported psychosocial functioning (Sheehan Disability Scale; SDS). Changes from baseline were analyzed in the intent-to-treat population and subgroups with impaired attention, as indicated by baseline Cognitive Drug Research System scores for Power of Attention and Continuity of Attention. Path analyses evaluated the direct and indirect effects of levomilnacipran ER on SDS total score change. Significantly greater improvements were observed for levomilnacipran ER versus placebo for Power of Attention, Continuity of Attention, MADRS, and SDS score changes; the mean differences were larger in the impaired subgroups than in the overall intent-to-treat population. Path analyses showed that the majority of SDS total score improvement (>=50%) was attributable to an indirect treatment effect through MADRS total score change; some direct effect of levomilnacipran ER on SDS total score improvement was also observed. In adults with major depressive disorder, levomilnacipran ER effectively improved measures of depression and cognition, which contributed toward reductions in self-reported functional impairment

Aripiprazole for the maintenance treatment of bipolar disorder: a review of available evidence

We aimed to review and synthesize results reporting on the maintenance efficacy of Aripiprazole in adults with bipolar I disorder. Aripiprazole is FDA approved for the acute and maintenance treatment of bipolar I disorder. Aripiprazole’s efficacy during the long-term treatment of bipolar disorder is supported by extension of acute phase studies and long-term (ie, 100-week) double-blind placebo controlled recurrence prevention registration trials. Aripiprazole is not established as efficacious in the acute or maintenance treatment of bipolar depression. Moreover, aripiprazole’s efficacy during the acute or maintenance phase of bipolar II disorder has not been sufficiently studied. Aripiprazole has a relatively lower hazard for metabolic disruption and change in body composition when compared to other atypical agents (eg, olanzapine, quetiapine). Moreover, aripiprazole has minimal propensity for sedation, somnolence and prolactin elevation. Aripiprazole is associated with extrapyramidal side effects, notably akathisia, which in most cases is not severe or treatment limiting. Future research vistas are to explore aripiprazole’s efficacy in bipolar subgroups; recurrence prevention of bipolar depression; and in combination with other mood stabilizing agents

Fasting Blood Glucose and Depressive Mood among Patients with Mental Illness in a Medicaid Managed Care Program

Objective. This study explores the relationship between depressive symptoms, as measured by the PHQ-9 depression screen and blood glucose levels among patients with diabetes enrolled in Gold Choice, a Medicaid managed care program for individuals with mental illness and/or substance abuse. Methods. The PHQ-9 was mailed to 454 Gold Choice members and a questionnaire was mailed to their physicians requesting current HbA1c% and fasting blood glucose (FBG) levels. The pearson product-moment correlation was used to describe the association between PHQ-9 scores and FBG levels. Results. The PHQ-9 response rate was 55% (N = 249). Laboratory results were received for 141 patients. The correlation between FBG and PHQ-9 scores was modest but statistically significant: r = 0.21 , P = 0.015. Conclusion. A statistically significant association was found between FBG and PHQ-9 depression scores. This finding supports current recommendations that physicians be alert to depressive symptoms among patients with diabetes or impaired glucose metabolism

Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder

Background: Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day. Methods: Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day). Results: After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day. Conclusion: Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability