Thesis (M.Ed. (Opvoedkundige Sielkunde))-Universiteit van Pretoria, 2005. / Includes bibliographical references. Available on the Internet via the World Wide Web.

Carisbamate (CRS) and lamotrigine (LTG) are anticonvulsants which act mainly on neuronal voltage-gated sodium channels, that have been shown to have antidepressant-like effects in animal models of depression. In vivo electrophysiological recordings were carried out following 2 and 14 days of CRS or LTG administration. Overall firing activity in the dorsal raphe, locus coeruleus and ventral tegmental area were decreased with CRS. Similarly, a decrease in the dorsal raphe was also observed with LTG. Despite these presynaptic decreases in firing activity, both anticonvulsants exhibited significant enhancement of serotonergic transmission in the hippocampus as demonstrated by increased tonic activation of postsynaptic 5-HT1A receptors. This may be attributed to the observed desensitization of the terminal 5-HT1B autoreceptors. This study suggests that the enhanced serotonergic effect may be associated with an antiglutamatergic effect, and may contribute to the antidepressant-like effect of CRS in the forced swim test and the antidepressant properties of LTG.

Social defeat is an ethologically relevant stressor that utilizes the natural establishment of social rank in male rodents and has been shown to be relevant to major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). In the present study, we wished to establish a social defeat stress model in combination with the chronic unpredictable stress model, which is considered a mild stressor to the rodent. In this way, we create a “double hit” model that may more accurately mimic severe stress that is common in both MDD and PTSD. In the present study, residents established dominance over the intruder for 10 consecutive days. In addition, social defeat stress was followed by another stressor given at random times during each day, i.e. chronic unpredictable stress. These unpredictable stressors included 30 min restraint, 1 h shaking/crowding, a cold water swim, a warm water swim or a tipped cage for 24 h. In one cohort of animals, brain tissue was taken 24 h after the last stressor for DNA. In a second cohort, animals were tested on a sucrose preference test in which two bottles containing 0.8% sucrose was placed on their cages for 3 consecutive days (days 8-10 of social defeat stress), and the total amount of sucrose was calculated relative to total volume consumed. Brain tissue analyses revealed significantly elevated DNA oxidation in white matter comparing stressed animals to non-stressed controls, consistent with what has been found in post-mortem white matter from MDD subjects. Further, animals given the social defeat + chronic unpredictable stress demonstrated a deficit in sucrose preference, a natural reward, revealing that these animals were anhedonic as compared to controls. Stressed animals also demonstrated fear of the intruder in a social interaction test performed one day after the social defeat/chronic unpredictable stress was complete. Therefore, it appears that social defeat plus chronic unpredictable stress produces a phenotype relevant to clinical data in humans.

If mania and depression are part of the same pathological processes, one would predict that episodes of one prospectively increase the odds of episodes of the other. The aim of the present study was to test this hypothesis. For comparison purposes, their relationship was contrasted to the relationship between mania and periods of psychosis. Exploratory analyses also tested the degree to which episodes of each occur with greater frequency over time (i.e., kindling). Participants for the present study came from the Suffolk County Mental Health Project (N = 628), a study of first-admission patients with psychosis. Of these participants, 144 met diagnostic criteria for bipolar I disorder and were analyzed for the current study. Results indicated that mania in a given month predicted depression the following month, even after controlling for other symptoms. The reverse, however, was not the case. Mania and psychosis, in contrast, were found to be robust predictors of one another from month to month. Effects were not due to treatment or demographic differences. These findings provide evidence that mania and depression are weakly related. In contrast, mania and psychosis are more closely linked. Findings are consistent with suggestions that psychiatric nosology regroup mania more closely with thought disorders rather than with internalizing or depressive ones. They also alert clinicians to the strong, longitudinal persistence and comorbidity among these syndromes.

Objectives: To validate the revised 12-item revised Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y), a self-report screening tool for depressive symptoms tailored to youth ages 12–17 with epilepsy. Methods: Youth at two sites completed the NDDI-E-Y during a routine epilepsy visit. Youth at one site also completed the Children's Depression Inventory-2 (CDI-2). Seizure and demographic data were abstracted from the electronic medical record. Exploratory factor analyses were conducted. Internal consistency, area under the curve (AUC), and construct validity were assessed. Results: NDDI-E-Y questionnaires were analyzed for 143 youth. The coefficient for internal consistency for the NDDI-E-Y was 0.92. Factor analyses suggested a one-factor solution with all 12 items loading on the factor. The NDDI-E-Y was positively correlated with the CDI-2 (N = 99). Sensitivity and specificity of the NDDI-E-Y were high. Significance: Reliability and construct validity were established for the revised 12-item NDDI-E-Y. The NDDI-E-Y is a brief, free measure of depressive symptoms that can be administered during a routine epilepsy visit.

The current study was designed to test the theory that daily exposure to humorous material would reduce depressive symptoms. Thirty-eight undergraduate students endorsing depressive symptoms were randomly assigned to either a humor or comparison group. Dependent variables were scores on the Beck Depression Inventory, the Social Activities Scale from the Interpersonal Events Schedule, and the Positive and Negative Daily Affect Schedule. The humor group intervention consisted of take-home videotaped recordings of humorous materials. The comparison group intervention consisted of take-home video taped recordings of educational materials with motivational themes. Results indicated that subjects in both groups exhibited significant reductions in depressive symptoms. However, subjects in the humor group showed significant increases in social activities and daily affectual gains, while the comparison group subjects showed no such changes. Plausible reasons for the current findings as well as implications are discussed.

A dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, in fulfilment of requirements for the degree of Medicine in Psychiatry. Johannesburg, March 1991. / In the first part of the dissertation a literature survey is done, looking at 1. An overview of dysthymic disorder. 2. An overview of serotonin and its involvement in psychiatric disorder [Abbreviated Abstract. Open document to view full version]

Neben Stimmungsschwankungen leiden viele bipolare Patienten unter kognitiven Beeinträchtigungen. Dies ist von hoher Relevanz, da neuropsychologische Defizite zur Aufrechterhaltung der bipolaren Störung beitragen können. Unsere Studie widmete sich zum einen der Untersuchung verzerrter Aufmerksamkeitsprozesse als auch der Erfassung dysfunktionaler Emotionsregulationsstrategien in der bipolaren Störung. Da es uns besonders interessierte, ob diese dysfunktionalen Prozesse im euthymen Intervall bestehen bleiben, rekrutierten wir akut depressive als auch euthyme bipolare Patienten. Weiterhin untersuchten wir, ob der Aspekt der prädominanten Polarität einen Einfluss auf die Informationsverarbeitung und Emotionsregulation haben könnte. Zur Erfassung selektiver Aufmerksamkeitsprozesse verwendeten wir eine Dot-Probe-Aufgabe. In der vorliegenden Arbeit konnte gezeigt werden, dass bei den akut depressiven bipolaren Patienten deutliche Defizite im Reaktionsvermögen vorlagen. Bei den euthymen Patienten mit manischer Polarität fand sich überraschenderweise ein Bias weg von positiven Stimuli, was möglicherweise als Schutzmechanismus vor potentiellen Triggern einer Manie interpretiert werden kann. Um zu testen, ob sich bipolare Patienten in den Emotionsregulationsstrategien von gesunden Kontrollpersonen unterscheiden, wurden zwei verschiedene Fragebögen eingesetzt. In der Auswertung zeigte sich, dass nicht nur akut depressive Patienten, sondern auch remittierte Patienten zu dysfunktionalen Emotionsregulationsstrategien neigten und dass die euthymen Probanden mit depressiver bzw. manischer Polarität in unterschiedlichen Emotionsregulationsstrategien von gesunden Probanden abwichen. Zusammenfassend lässt sich festhalten, dass Defizite in der selektiven Aufmerksamkeit und in der Emotionsregulation nicht nur in der akuten Krankheitsphase, sondern auch im „gesunden Intervall“ vorhanden sind. Darüber hinaus liefert die Studie erste Hinweise darauf, dass sich Patienten mit depressiver und manischer Polarität in der Informationsverarbeitung emotionaler Stimuli als auch in Emotionsregulationsstrategien unterscheiden. / An increasing amount of empirical evidence has documented that many patients with bipolar disorder show significant neurocognitive deficits and that these deficits have been associated with a longer illness duration. This experimental study examined the nature of attentional biases as well as the use of emotion regulation strategies in bipolar disorder. We included patients in the depressive phase of their illness and in remission because we were particularly interested in investigating the presence of dysfunctional processes during euthymic phases. Furthermore, we examined the aspect of predominant polarity regarding information processing and emotion regulation. In the current study we used a dot-probe task to examine attentional biases. We demonstrated that patients in the depressive state of the illness had slower reaction times than healthy controls. Surprisingly, the euthymic patients with manic predominant polarity showed a bias away from positive stimuli, suggesting that there might be a ‘protective bias’ for potential triggers of a relapse into mania. To examine differences in emotion regulation strategies we used two different questionnaires. Findings indicated that not only bipolar depressed patients but also euthymic patients displayed an increased use of maladaptive strategies and that euthymic patients with depressive and manic predominant polarity differed in different emotion regulation strategies from healthy controls. Overall, the study demonstrated that information-processing deficits and dysfunctional emotion regulation strategies are not restricted to bipolar patients in their acute state of the illness, but also persist during remission as vulnerability factors. Furthermore, the results provide some evidence to suggest that patients with depressive and manic predominant polarity differ significantly in information processing and emotion regulation strategies.

Obesity is a common medical illness that is known to confer risk for a large number of medical illnesses, such as Type II Diabetes, hypertension, cancer, and late-life dementia. More recently, the relation between obesity and decline in cognitive performance, independent of other comorbid medical conditions, has begun to be examined. Individuals with mood disorders (Bipolar Disorder [BD] or Major Depressive Disorder [MDD]) display an increased prevalence of both obesity and risk factors for cardiovascular disease. Moreover, BD and MDD are associated with impairment in cognitive functioning across multiple domains. The contribution of obesity to cognitive decline in this population has not been explored. This thesis begins with a systematic review of the literature examining the impact of obesity on cognition, providing a thorough background of this relation. The following chapter introduces a prospective cohort study designed to comprehensively explore the relation between obesity and cognition in individuals both with, or without, a mood disorder. The first of set of results from this study are presented in the remaining chapters. The neuropsychological study findings indicate that MDD and obesity may have an additive effect on cognition, resulting in significant cognitive decline in obese adults with MDD. Moreover, we show that different neural activation patterns are seen during a cognitive magnetic resonance imaging (MRI) task in obese versus obese MDD patients. Collectively, this provides strong evidence that populations already at risk for cognitive impairment, such as mood disorder populations, are susceptible to further cognitive changes due to increased weight. / Thesis / Doctor of Philosophy (PhD)

<p>Depression is a heterogeneous mental health condition, varying in presentation across individuals. A candidate etiology that may help account for this heterogeneity is the neurotrophin hypothesis of depression, which proposes that stress downregulates brain-derived neurotrophic factor (BDNF) expression, leading to aberrant neurogenesis and depression. This etiology may manifest in a distinct symptom profile that may be reflected in depressive symptoms or symptom clusters. The effect of psychological interventions on BDNF is not known. Additionally, it is not known if BDNF levels mediate intervention effects on depressive symptom clusters. Using data from the eIMPACT trial (NCT02458690, supported by R01 HL122245), I examined baseline associations of BDNF with depressive symptoms and depressive symptom clusters. Also, I examined if the modernized collaborative care intervention for depression (internet CBT, telephonic CBT, and select antidepressant medications) affected BDNF and if changes in BDNF mediated intervention effects on cognitive/affective and somatic depressive symptom clusters. 216 participants (primary care patients with depression and elevated cardiovascular disease risk ≥50 years from a safety net healthcare system) were randomized to 12 months of the eIMPACT intervention (<em>n</em>=107) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and affiliated psychiatrists; <em>n</em>=109). Plasma BDNF was measured with commercial ELISA kits. Depressive symptoms were assessed by the PHQ-9 (<em>M</em>=15.1, <em>SD</em>=5.0) from which cognitive/affective and somatic subscale scores were computed. No significant baseline associations were observed between BDNF and individual depressive symptoms or depressive symptom clusters. The intervention did not improve BDNF over 12 months. Similarly, 12-month changes in BDNF were not associated with 12-month changes in PHQ-9 cognitive/affective or somatic subscale scores. However, the intervention significantly improved PHQ-9 cognitive/affective and somatic subscale scores over 12 months. 12-month changes in BDNF did not mediate the effect of the intervention on 12-month changes in the PHQ-9 subscale scores. These findings suggest that modernized collaborative care for depression does not improve BDNF. Modernized collaborative care does yield improvements in both cognitive/affective and somatic depressive symptom clusters, albeit not via changes in BDNF.</p>