This thesis comprises research investigating explicit EM biases in MDD during acute depression and euthymia (i.e., clinical remission). First, a systematic review was conducted to investigate whether acutely depressed and euthymic MDD participants display an explicit EM bias. An ‘explicit EM bias’ was operationally defined to denote enhanced memory for negative or positive stimuli compared to matched healthy controls (HCs). Studies that were included in this systematic review investigated explicit EM using free recall and recognition memory paradigms. The main finding from this investigation was that acutely depressed MDD participants do not display an explicit EM bias. An unintended consequence of this investigation was the identification that research on explicit EM in MDD during euthymia is surprisingly sparse. Next, building upon the findings from our systematic review, we conducted an empirical investigation of explicit EM within a sample of well-characterized euthymic MDD participants compared to age/sex/gender/IQ-matched HCs. In this study, participants performed incidental encoding (i.e., emotional reactivity) and recognition memory tasks (separated by one week). These tasks employed emotionally-valent picture stimuli obtained from the International Affective Picture System. Results from this study revealed that, compared to matched HCs, euthymic MDD participants do not display an emotional reactivity or explicit EM bias. Taken together, the findings from this thesis suggest that explicit EM represents a sub-domain of cognition that may be unaffected in individuals with MDD. Our findings have important implications for the unified model of depression and may represent a basis upon which future research can build in an attempt to understand the nuanced cognitive phenotypes associated with MDD. / Thesis / Master of Science (MSc) / Major depressive disorder (MDD) is one of the most common mental disorders worldwide. It is estimated that over 10% of Canadians will experience MDD at some point in their lifetime. The symptoms of MDD include, among other things: depressed mood, loss of interest in regular daily activities, and impairments in cognition (e.g., attention, emotion, memory, etc.). Clinicians and researchers have argued for years that MDD is associated with negative cognitive biases, including increased attention to, and more accurate memory for, negative information; however, attention, emotion and memory are general forms of cognition, and the existence of cognitive biases for specific sub-domains of cognition in MDD are largely unknown. Given that MDD has a negative effect on emotion and memory, one potentially important sub-domain of cognition is explicit emotional memory (EM; i.e., conscious memory for emotionally-stimulating information). The purpose of the current thesis was to investigate whether MDD, during both the active (i.e., acute) and euthymic (i.e., clinically-remitted) stages, is associated with explicit EM biases compared to healthy volunteers. This thesis discusses how patterns of explicit EM may be important for our understanding of the development of MDD.

<p> Major Depressive Disorder (MDD) is a common affective disorder associated with persistent states of negative mood and selective cognitive impairments. Fronto-temporal dysregulation in MDD patients is thought to contribute to the symptoms seen in these patients.</p> <p> Based on prior evidence of structural and functional alterations in the hippocampus (Hc) and prefrontal cortex (PFC) in MDD patients, we were interested in examining the changes in cerebral function that underlie the cognitive dysfunction seen in two different MDD populations. We studied psychotropically naïve depressed patients experiencing their first treated episode (FTE) of depression, MDD patients who had experienced multiple past treated episodes (MTE) of MDD and healthy controls.</p> <p> Two functional magnetic resonance imaging studies (fMRI) were conducted. The first study used an Hc dependent process dissociation task to examine Hc activation during recollection memory. The second fMRI study examined the activation in the PFC during reward and punishment conditions of a reversal-learning paradigm. Finally, we conducted magnetic resonance spectroscopy scans to measure levels of metabolites indicative of neuronal and glial cell integrity in the Hc of depressed patients and controls. </p> <p> We observed differing results across all three studies in our FTE and MTE depression groups. Our studies examining the Hc suggest that MTE patients have decreased activation in this region as well as corresponding memory errors during recollection memory. Additionally, these patients have smaller Hc volume and signs of increased neuronal membrane turnover. Conversely, our FTE patients displayed heightened Hc activation without memory deficits. Moreover, FTE patients had signs of increased glial cell density in the Hc without volumetric differences in this region. Our examination of reward processing revealed several health-to-illness gradients of activation in areas as the nucleus accumbens, anterior cingulate and ventral prefrontal cortices during the processing of rewards and punishers. </p> <p> These findings suggest that several regions in the brain may be sensitive to the impact of disease burden and repeated episodes of MDD. In the Hc, first treatment patients may engage in compensatory processes during the early stages of illness that are attenuated with repeated episodes of illness. Moreover, reward processing may be affected in the early course of the disorder, however with a protracted course of illness these regional alterations in activation become more pronounced.</p> / Thesis / Doctor of Philosophy (PhD)

Certain electrophysiological markers hold promise in distinguishing individuals with major depressive disorder (MDD) and in predicting antidepressant response, thereby assisting with assessment and optimizing treatment, respectively. This thesis examined resting brain activity via electroencephalographic (EEG) recordings, as well as EEG-derived event-related potentials (ERPs) to auditory stimuli and facial expression presentations in individuals with MDD and controls. Additionally, the utility of resting EEG as well as auditory ERPs (AEPs), and the associated loudness-dependence of AEPs (LDAEP) slope, were assessed in predicating outcome to chronic treatment with one of three antidepressant regimens [escitalopram (ESC); bupropion (BUP); ESC+BUP]. Relative to controls, depressed adults had lower pretreatment cortical activity in regions implicated in approach motives/positive processing. Increased anterior cingulate cortex (ACC)-localized theta was observed, possibly reflecting emotion/cognitive regulation disturbances in the disorder. AEPs and LDAEPs, putative indices of serotonin activity (implicated in MDD etiology), were largely unaltered in MDD. Assessment of ERPs to facial expression processing indicated slightly blunted late preconscious perceptual processing of expressions, and prolonged processing of intensely sad faces in MDD. Faces were rated as sadder overall in MDD, indicating a negative processing bias. Treatment responders (vs. non-responders) exhibited baseline cortical hypoactivity; after a week of treatment, cortical arousal emerged in responders. Increased baseline left fronto-cortical activity and early shifts towards this profile were noted in responders (vs. non-responders). Responders exhibited a steep, and non-responders shallow, baseline N1 LDAEP derived from primary auditory cortex activity. P2 LDAEP slopes (primary auditory cortex-derived) increased after a week of treatment in responders and decreased in non-responders. Consistent with overall findings, ESC responders displayed baseline cortical hypoactivity and steep LDAEP-sLORETA slopes (vs. non-responders). BUP responders also exhibited steep baseline slopes and high ACC theta. These results indicate that specific resting brain activity profiles appear to distinguish depressed from non-depressed individuals. Subtle ERP modulations to simple auditory and emotive processing also existed in MDD. Resting alpha power, ACC theta activity and LDAEP slopes predicted antidepressant response in general, but were limited in predicting outcome to a particular treatment, which may be associated with limited sample sizes.

Certain electrophysiological markers hold promise in distinguishing individuals with major depressive disorder (MDD) and in predicting antidepressant response, thereby assisting with assessment and optimizing treatment, respectively. This thesis examined resting brain activity via electroencephalographic (EEG) recordings, as well as EEG-derived event-related potentials (ERPs) to auditory stimuli and facial expression presentations in individuals with MDD and controls. Additionally, the utility of resting EEG as well as auditory ERPs (AEPs), and the associated loudness-dependence of AEPs (LDAEP) slope, were assessed in predicating outcome to chronic treatment with one of three antidepressant regimens [escitalopram (ESC); bupropion (BUP); ESC+BUP]. Relative to controls, depressed adults had lower pretreatment cortical activity in regions implicated in approach motives/positive processing. Increased anterior cingulate cortex (ACC)-localized theta was observed, possibly reflecting emotion/cognitive regulation disturbances in the disorder. AEPs and LDAEPs, putative indices of serotonin activity (implicated in MDD etiology), were largely unaltered in MDD. Assessment of ERPs to facial expression processing indicated slightly blunted late preconscious perceptual processing of expressions, and prolonged processing of intensely sad faces in MDD. Faces were rated as sadder overall in MDD, indicating a negative processing bias. Treatment responders (vs. non-responders) exhibited baseline cortical hypoactivity; after a week of treatment, cortical arousal emerged in responders. Increased baseline left fronto-cortical activity and early shifts towards this profile were noted in responders (vs. non-responders). Responders exhibited a steep, and non-responders shallow, baseline N1 LDAEP derived from primary auditory cortex activity. P2 LDAEP slopes (primary auditory cortex-derived) increased after a week of treatment in responders and decreased in non-responders. Consistent with overall findings, ESC responders displayed baseline cortical hypoactivity and steep LDAEP-sLORETA slopes (vs. non-responders). BUP responders also exhibited steep baseline slopes and high ACC theta. These results indicate that specific resting brain activity profiles appear to distinguish depressed from non-depressed individuals. Subtle ERP modulations to simple auditory and emotive processing also existed in MDD. Resting alpha power, ACC theta activity and LDAEP slopes predicted antidepressant response in general, but were limited in predicting outcome to a particular treatment, which may be associated with limited sample sizes.

Certain electrophysiological markers hold promise in distinguishing individuals with major depressive disorder (MDD) and in predicting antidepressant response, thereby assisting with assessment and optimizing treatment, respectively. This thesis examined resting brain activity via electroencephalographic (EEG) recordings, as well as EEG-derived event-related potentials (ERPs) to auditory stimuli and facial expression presentations in individuals with MDD and controls. Additionally, the utility of resting EEG as well as auditory ERPs (AEPs), and the associated loudness-dependence of AEPs (LDAEP) slope, were assessed in predicating outcome to chronic treatment with one of three antidepressant regimens [escitalopram (ESC); bupropion (BUP); ESC+BUP]. Relative to controls, depressed adults had lower pretreatment cortical activity in regions implicated in approach motives/positive processing. Increased anterior cingulate cortex (ACC)-localized theta was observed, possibly reflecting emotion/cognitive regulation disturbances in the disorder. AEPs and LDAEPs, putative indices of serotonin activity (implicated in MDD etiology), were largely unaltered in MDD. Assessment of ERPs to facial expression processing indicated slightly blunted late preconscious perceptual processing of expressions, and prolonged processing of intensely sad faces in MDD. Faces were rated as sadder overall in MDD, indicating a negative processing bias. Treatment responders (vs. non-responders) exhibited baseline cortical hypoactivity; after a week of treatment, cortical arousal emerged in responders. Increased baseline left fronto-cortical activity and early shifts towards this profile were noted in responders (vs. non-responders). Responders exhibited a steep, and non-responders shallow, baseline N1 LDAEP derived from primary auditory cortex activity. P2 LDAEP slopes (primary auditory cortex-derived) increased after a week of treatment in responders and decreased in non-responders. Consistent with overall findings, ESC responders displayed baseline cortical hypoactivity and steep LDAEP-sLORETA slopes (vs. non-responders). BUP responders also exhibited steep baseline slopes and high ACC theta. These results indicate that specific resting brain activity profiles appear to distinguish depressed from non-depressed individuals. Subtle ERP modulations to simple auditory and emotive processing also existed in MDD. Resting alpha power, ACC theta activity and LDAEP slopes predicted antidepressant response in general, but were limited in predicting outcome to a particular treatment, which may be associated with limited sample sizes.

Major depressive disorder (MDD) is a relevant condition to consider regarding Work Capacity Evaluation (WCE) because of its high prevalence, strong impact on short-term work disability, and low rate of treatment. The challenge that faces occupational therapists (OTs) is that there is no specific guideline and process to follow when conducting Work Capacity Evaluation with clients suffering from MDD. The researcher had also noted conflicting opinions with regard to the outcome of Work Capacity Evaluation (WCE) and recommendations in occupational therapy reports. The researcher is of the opinion that indeed occupational therapy assessments need to be clear about what to measure, and selection of appropriate standardised measures and non-standardised assessments is needed. Therefore, the research question was, what are the perceptions and practices of occupational therapists in determining work capacity of employees suffering from major depressive disorder? The aim of this study was to describe the perceptions and practices of occupational therapists in determining work capacity of employees suffering from major depressive disorder. The literature showed that Work Capacity Evaluation assists to determine the employee’s returnto- work. The Code of Good Practice: Dismissal contained in the Labour Relations Act of 1998, stipulates that incapacity on the ground of ill health or injury may be either temporary or permanent. The nature of this study was a mixed method design including both qualitative and quantitative approaches. The phenomenological strategy was used. The study had a sample size of 68 participants, practising as occupational therapists. Purposive sampling was used. The data were collected in four distinct phases, referred to as sequential exploratory strategy with elements of embedded design. Phase one, used descriptive open-ended questions; phase two was a close-ended questionnaire to confirm findings in phase one; phase three consisted of focus group interviews and phase four was member checking to confirm findings in phase three. During data analysis, five themes related to employees suffering from MDD emerged and they were identified as: (1) the content of comprehensive assessment for work capacity evaluation, (2) the process of work capacity evaluation, (3) the competency requirements of the occupational therapist, (4) occupational performance and (5) formulating return-to-work decision. Recommendations related to the five themes were formulated and suggestions for future research proffered. The study clarified and confirmed that occupational therapists have a major role to play in performing work capacity of employees suffering from major depressive disorder, and that they need to be competent in performing these evaluations. Copyright / Dissertation (MOccTher)--University of Pretoria, 2011. / Occupational Therapy / unrestricted

No description available.

Background and objectives: Whilst Active and Receptive Music Therapy techniques have been widely researched and are employed within a range of contexts and with diverse client populations, this study reports on their specific qualitative musical and verbal affordances in major depressive disorder and schizophrenia-spectrum psychotic disorders. The study also describes and compares the respective and joint contributions of the music therapy techniques in giving rise to the affordances as well as reporting on the similarities and differences within and between diagnostic groups. This is the first study of its kind within the South African context. Methods: A qualitative research approach using a case study design, sampled purposefully twenty patients of the above mentioned diagnostic groups for participation in this study comprising a course of eight twice weekly music therapy sessions. The primary data sources were transcribed video recordings of therapy sessions and an individual in-depth semi-structured interview after the course of therapy. Clinical session notes served as a corroborative data source. In-depth content and thematic analysis explored and compared qualitative affordances during music therapy comprising active and Receptive Music Therapy techniques. The qualitative affordances under investigation were i) musical qualities, and ii) verbal expressions. Emerging from these affordances were the respective and combined affordances of the music therapy techniques as well as the similarities and differences between the diagnostic groups. Findings: Thirteen themes emerged from the analysis of clients' verbatim verbal responses to both active music making and Receptive Music Therapy techniques. These themes are: i) not to feel; ii) to do or not to do; iii) grappling with the desired future; iv) hurt and fear of undesirable outcomes; v) sadness, brokenness and futility; vi) anger, trust and vulnerability; vii) desire for connection with and affection of others; viii) barricaded from being present, now; ix) tensing and un-tensing; x) personal relating to one’s musical expression; xi) reflections on the music and music making in therapy; xii) resilience and courage and xiii) invigoration and liberation. The Active Music Therapy techniques comprising clinical improvisation, structured musical exercises, drumming, vocal work, songwriting and movement, gave rise to ten themes expressing the musical affordances. The themes that emerged were i) reciprocal responding; ii) the explicit use of symbols through music; iii) regularity; iv) disturbance and difficulty; v) turning points; vi) energy bursting or lacking; vii) bodily synchrony; viii) intensified emotional expression; ix) exploring new territory and Active Music Therapy techniques comprising clinical improvisation, structured musical exercises, drumming, vocal work, songwriting and movement, gave rise to ten themes expressing the musical affordances. The themes that emerged were i) reciprocal responding; ii) the explicit use of symbols through music; iii) regularity; iv) disturbance and difficulty; v) turning points; vi) energy bursting or lacking; vii) bodily synchrony; viii) intensified emotional expression; ix) exploring new territory and x) resolution and arrival. The emerging themes express the extent of musical and verbal expression of all clients representing both diagnostic groups. Most saliently among clients with depression the affordances were the themes on accessing creativity, accessing and articulating internal feelings, experiencing resilient parts of self, reflecting on and integrating symbolic material, motivation to act and extending musical and verbal expression during social interaction. Among clients suffering from schizophrenia spectrum disorder, the most striking affordances were experiences of regularity and flow within disorganization, orientation to ‘here and now’ experiences through active music making and working with symbolic material expressed on a continuum of concrete to abstract. Clients from both diagnostic groups experienced a reduction in unwanted symptoms as expressed through increased energy levels, experiences of pleasure in music making and spontaneous musical and verbal self-expression. Conclusion: This study revealed qualitative affordances of specific music therapy techniques expressed through verbal content and musical qualities. These showed responses within a therapeutic relationship that express inter- and intra-personal connection, give voice to what is not always verbally accessible and facilitate multi-sensory, creative experiences, increased motivation, emotional expression, and the reclamation of energy, spontaneity and resilience. / Thesis (PhD)--University of Pretoria, 2017. / Psychiatry / PhD / Unrestricted

Genome-wide association studies (GWASs) have reported numerous associations between risk variants and major psychiatric disorders (MPDs) including schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD) and others. We reviewed all of the published GWASs, and extracted the genome-wide significant (p<10) and replicated associations between risk SNPs and MPDs. We found the associations of 6 variants located in 6 genes, including L type voltage-gated calcium channel (LTCCs) subunit alpha1 C gene (), that were genome-wide significant ( ) and replicated at single-point level across at least two GWASs. Among them, the associations between MPDs and rs1006737 within are most robust. Thus, as a next step, the expression of the replicated risk genes in human hippocampus was analyzed. We found had significant mRNA expression in human hippocampus in two independent cohorts. Finally, we tried to elucidate the roles of venlafaxine and ω-3 PUFAs in the mRNA expression regulation of the replicated risk genes in hippocampus. We used cDNA chip-based microarray profiling to explore the transcriptome-wide mRNA expression regulation by ω-3 PUFAs (0.72/kg/d) and venlafaxine (0.25/kg/d) treatment in chronic mild stress (CMS) rats. ω-3 PUFAs and venlafaxine treatment elicited significant up-regulation. We concluded that might confer the genetic vulnerability to the shared depressive symptoms across MPDs and CACNA1C might be the therapeutic target for depressive endophenotype as well.

Objective. Major depressive disorder (MDD) is a common condition following treatment in the Intensive Care Unit (ICU). Long-term data on MDD in chronically critically ill (CCI) patients are scarce. Hence, the primary aim of the present study was to investigate the frequency and predictors of MDD after intensive care of CCI patients. Materials and Methods. In a prospective cohort study, patients with long-term mechanical ventilation requirements () were assessed with respect to a diagnosis of MDD, using the Structured Clinical Interview for DSM-IV, three and six months after the transfer from acute ICU to post-acute ICU. Sociodemographic, psychological, and clinical risk factors with values ≤ 0.1 were identified in a univariate logistic regression analysis and entered in a multivariable logistic regression model. A mediator analysis was run using the bootstrapping method, testing the mediating effect of perceived helplessness during the ICU stay, between the recalled traumatic experience from the ICU and a post-ICU MDD. Results. 17.6% () of the patients showed a full- or subsyndromal MDD. Perceived helplessness, recalled experiences of a traumatic event from the ICU, symptoms of acute stress disorder, and the diagnosis of posttraumatic stress disorder (PTSD) after ICU could be identified as significant predictors of MDD. In a mediator analysis, perceived helplessness could be proved as a mediator. Conclusions. Every fifth CCI patient suffers from MDD up to six months after being discharged from ICU. Particularly, perceived helplessness during the ICU stay seems to mainly affect the long-term evolvement of MDD. CCI patients with symptoms of acute stress disorder/PTSD should also be screened for MDD.