The prevailing utility, and indeed necessity, of clinical staging models applied in considerations of neuropsychiatric disease progressions is discussed from the perspectives of schizophrenia spectrum disorders and affective disorders, cannabis in schizopsychotic disorder, incidences of affect and psychosis, staging disorders in aging and the indices and prevalence of apathy. There would appear to be a strong current consensus that the pursuit of clinical staging of these and other brain disease states has contributed a systematic conceptual instrument to facilitate the better understanding, diagnosis, prognosis and treatment as derived from a multitude of genetic predispositions, symptoms and syndromes, early-onset and prodromal phases, recurrences and relapses, that have complicated the situation of the patient. Through a staging determination of the disorder, elements of diagnosis will describe the progression of symptoms/syndromes through pre-onset, prodromal, first-episode, recurrences and relapses, and treatment resistance thereby facilitating the eventual prognosis, intervention alternatives and treatment. This approach varies from observations of individuals at early stages of development (infancy, childhood, adolescece) to early middle age, in the case of diseases expressed through the aging processes. Essentially, the major contribution of the staging model may lie in the early identification, diagnosis, and treatments of disorders that afflict the brain and central nervous system.

Objective. The purpose of the study was to determine if there were significant relationships between dysfunction in sensory modulation, affective disorders, and adaptive behaviors in children and adolescents between the ages of 6 and 17. There were four main hypotheses: (a) there will be a positive relationship between sensory defensiveness and anxiety, (b) there will be a positive relationship between sensory hyposensitivity and depression, (c) there will be a negative relationship between the levels of anxiety and depression and overall adaptive behaviors, and (d) there will be a negative relationship between levels of hyper and hyposensitivity and overall adaptive behavioral functioning. Method. Parents of 46 children and adolescents between the ages of 6 and 17 diagnosed with Asperger Syndrome based on the DSM-IV-TM criteria completed the (a) Sensory Profile for children ages 6 to 10 or the Adolescent/Adult Sensory Profile for adolescents ages 11 to 17; (b) the Adaptive Behavior Assessment System: Parent Version; (c) Revised Children's Manifest Anxiety Scale Adapted Parent's Version; and (d) the Children's Depression Inventory Adapted Parent's Version. Descriptive statistics and the Pearson product-moment coefficient of correlation calculations were used for data analysis. Results. There were statistically significant positive correlations between anxiety and sensory defensiveness (r = .270, p = .035) in the total group and depression and sensory hyposensitivity in only the older group (r = .461, p =.024). There was an inverse significant relationship between depression and the total adaptive behaviors score (r = −.256, p = .043) and specific inverse relationships with the adaptive behaviors of functional academics, leisure and social skills. The relationship between anxiety and adaptive behaviors was not significant (r = −.121, p = .212) although there was a significant inverse relationship between sensory defensiveness and adaptive behaviors (r = −.254, p = .044). The relationship between hyposensitivity and adaptive behaviors approached significance (r = −.214, p = .077). Conclusion. The data supports relationships between anxiety and sensory defensiveness in all age ranges and the relationship between depression and hyposensitivity in older children. A temporal relationship between anxiety and depression may explain the developmental nature of the results. Depression and sensory defensiveness demonstrated significant inverse relationships with overall adaptive behavior functioning. Occupational therapy evaluations and interventions need to address these relationships when treating children with Asperger Syndrome.

Serotonin 2A receptor (5-HT2aR) agonists and κ-opioid receptor (KOR) agonists have been demonstrated to be effective treatments for several central nervous system (CNS) disorders including depression, anxiety, addiction, and pain. In a recent clinical study, psilocybin (a classical hallucinogen) was shown to significantly decrease the symptoms of Major Depressive Disorder (MDD) and Treatment Resistance Depression (TRD) in humans for up to six weeks after a single dose. Several KOR agonists have been shown to be effective treatments of chronic pain without the physical dependence risks of µ-opioid receptor agonists. Also, due to KOR’s involvement in a biological anti-reward system, agonists for this receptor possess anti-addiction properties as demonstrated by their ability to decrease the self-administration of drugs of abuse in multiple different animal species. Despite the great therapeutic potential for both these classes of molecules, their hallucinogenic and disassociate effects have been a major roadblock in the approval new pharmaceuticals.This dissertation describes the synthesis and behavioral evaluation of known and novel 5-HT2aR and KOR agonists. In the first half, the synthesis of several molecules related to the structure of ibogaine are described and the novel “oxa-iboga” class is introduced. One of the molecules in this class, oxa-noribogaine, has been evaluated in a variety of in vivo mouse tests including tail-flick, open field, and forced swim test. The results demonstrate that oxa-noribogaine is a potent KOR agonist and analgesic but has a lower side-effect profile compared to other KOR agonists such as noribogaine, epi-oxa-noribogaine, and U50,488H. In the second half, two emerging classes of antidepressants, NMDAR antagonists and 5-HT2aR agonists, are described. Molecules from both these classes cause rapid acting antidepressant effects that can be induced after a single dose. This is a sharp contrast to traditional antidepressants such as SSRIs which require 4-6 weeks of consistent use before therapeutic effects are achieved. In our lab, a set of substituted phenethylamines which act as 5-HT2aR agonists were evaluated in vivo in the head twitch assay, forced swim test, sucrose preference test, and fear extinction assays. Their hallucinogenic and antidepressant-like effects are reported. One molecule, 4-CT, was designed and synthesized based on the structure of Ariadne, a 5-HT2aR agonist with low or no psychedelics effects. 4-CT produced a decreased number of head twitches compared to DOI (a hallucinogenic research control) and showed possible antidepressant-like effects in the forced swim test.

D.Litt. et Phil. / Although rapid progress was made in the past decade in the development of short term treatment approaches, relatively little attention was given to the treatment of Dysthymic Depression as a separate disorder. It is therefore important that medical doctors and other health professionals recognize this disorder as a separate disorder from Major Depression and adjust their treatment of this disorder accordingly (Keller, 1994). Although Dysthymia is seen as 'n low grade disorder and not as severe as Major Depression, this disorder also has a hampering effect on the quality of the individual's life. It affects relationships with meaningful others, mental and physical well - being as well as productivity (Keller, 1994; Klerman & Weissman, 1992). With the hampering effect on the individual's life, Dysthymic Depression is also costly and is a substantial burden for the family and the community. According to Rupp (1995) appropriate treatment of individuals with affective disorders will be costeffective. , The prevalence of depression in primary care make this disorder an ideal target for treatment-(Robinson, 1995). In this regard, Robinson (1995) mentions that treatment for these disorders is less intensse and'more short term that specialized treatments. In the past few years there have been a.shift from long term treatment strategies to short term structured handbook orientated treatment programs for disorders like depression. Pantalon, Lubetkin & Fishman (1995) emphasize the need for objective and •knowledgeable guides for the treatment of mental disorders. According to these researchers selfhelp books and guides are effective together with cognitive behavioral therapy. The aim of this study was therefore the development of a short term cost effective handbook orientated treatment program for Dysthymic Depression as well as the effectiveness of the treatment program. Antoher aspect of this treatment program that makes it unique, is the exercise component that is incorporated into the program with the cognitive behavioral approach. A group of 23 Dysthymic patients have been evaluated to establish the degree of depression, personality pathology that is present and the course of the therapeutic intervention. This group , received treatment over a period of 8 weeks. A second group of 22 patients served as a control group. The control group received medication and other therapy. The results of this study indicate that not only 'did the intensity of the depression lift, but certain indexes of psychopathology were also reduced. The indexes of psychopathology that indicated an reduction, were the Avoidant, Self-defeating, Schizotypal, Borderline, Anxiety, Somatoform, Dysthymic as well as Major Depression disorders. The effectiveness of the therapy sessions were also monitored over the , period of 8 weeks and indicated a reduction in certain negative factors, namely: Aggression, Anxiety, Fatigue, Sadness and Skepticism. While these factors indicated a reduction in prevalence the following factors indicated an increase in preValence over the 8 therapy sessions: . Surgency, Elation, Concentration, Social Affect, Egotism and Vigor. Although the test sample were relatively small, it is accepted that it was representative of the universum of the Gauteng region where this sample was taken from. From the results obtained from this study it seems that - this handbook orientated treatment program was not only effective for Dysthymic Depression, but also for certain indexes of psychopathology over the 8-week therapy sessions. From the analysis of the components of the therapy sessions, is clear that the model of the Dysthymic individuals showed an improvement with the handbook orientated treatment program.

Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: The growing burden of mental illnesses in low- and middle-income countries, such as Uganda, necessitates effective interventions to promote mental and social well-being among their populations. Mood disorders contribute more substantially to the global burden of mental illnesses than do other forms of mental disorders. The substantial global burden of mental illnesses is projected to grow more rapidly in low- and middle-income countries than in high-income countries in the future. Because experiences of and responses to mood disorders are invariably patterned by social and cultural contexts, as argued in the growing field of cross-cultural psychiatry, health care systems, especially in low- and middle-income countries, need to design and deliver culturally relevant interventions that effectively deal with this problem. However, there is generally a paucity of suitable evidence to guide the planning and delivery of such interventions in countries like Uganda. As a response to the apparent knowledge and research gaps regarding experiences of mood disorders and care in Western Uganda, I conducted a qualitative study involving outpatients and their care providers, that is, outpatients’ families, psychiatric health workers, religious healers and traditional healers. Using purposive and snow ball sampling techniques, I selected participants, that is, outpatients as well as psychiatric health workers, outpatients’ families, religious healers and traditional healers involved in the care of the outpatients from the Mbarara Regional Referral Hospital (MRRH) and the “Greater Mbarara” region, respectively. The aim of this study is to explore explanatory models that outpatients and care providers in Western Uganda use in responding to mood disorders. I analysed the data collected in the fieldwork using ATLAS.ti 6.2, a computer-software programme designed to support qualitative data analysis. Results from the study indicate that outpatients and their care providers hold complex, diverse and contradictory explanatory models regarding mood disorders and care, which are shaped by their unique social and cultural contexts. Additionally, poor relationships and communication between patients and their care providers, especially between outpatients and psychiatric health workers, are strongly evident; structural barriers significantly hinder the provision and utilisation of care; care is generally inadequate, although it is conceptualised broadly to include biomedical, popular and folk treatments; and outpatients generally exhibit inconsequential (weak) agency in managing distress, which is primarily caused by mood disorders and care-seeking challenges. The results of the current study suggest several implications regarding mental health practice, training, policy and research. / AFRIKAANSE OPSOMMING: Weens die toenemende geestesiektelas in lae- en middelinkomstelande soos Uganda word intervensies vereis om die geestelike en maatskaplike welsyn van die bevolkings van daardie lande te bevorder. Gemoedsteurings maak ’n groter deel van die wêreldwye geestesiektelas uit as ander vorme van geestesongesteldheid. Die beduidende wêreldwye geestesiektelas sal in die toekoms na verwagting vinniger in lae- en middelinkomstelande as in hoë-inkomstelande toeneem. Aangesien ervarings van én reaksies op gemoedsteurings meestal deur maatskaplike en kulturele kontekste beïnvloed word, soos die groeiende dissipline van transkulturele psigiatrie beweer, moet gesondheidsorgstelsels, veral dié in lae- en middelinkomstelande, kultureel tersaaklike intervensies ontwerp en voorsien wat hierdie probleem doeltreffend hanteer. Tog is daar oor die algemeen ’n skaarste aan geskikte bewyse om die beplanning en voorsiening van sulke intervensies in lande soos Uganda te rig. In antwoord op die klaarblyklike kennis- en navorsingsleemtes met betrekking tot ervarings van gemoedsteurings en sorg in Wes-Uganda het ek ’n kwalitatiewe studie onder buitepasiënte en hul versorgers – met ander woorde hul familie, psigiatriese gesondheidswerkers, geloofsgenesers en tradisionele genesers – onderneem. Die steekproef het bestaan uit pasiënte en hul familielede, psigiatriese gesondheidswerkers sowel as geloofs- en tradisionele genesers wat gemoeid is met die versorging van buitepasiënte by die streeksverwysingshospitaal Mbarara (MRRH) én in die Mbarara-distrik onderskeidelik. Die doel met die studie was om te verken watter verklarende modelle pasiënte en versorgers in Wes-Uganda gebruik om op gemoedsteurings te reageer. Die data wat met die veldwerk ingesamel is, is ontleed met behulp van die rekenaarsagteware ATLAS.ti 6.2, wat ontwerp is om kwalitatiewe dataontleding te ondersteun. Die resultate van die studie toon dat buitepasiënte en hul versorgers oor komplekse, uiteenlopende en teenstellende verklarende modelle met betrekking tot gemoedsteurings en sorg beskik, wat deur hul unieke maatskaplike en kulturele kontekste gevorm word. My navorsing dui daarop dat swak verhoudings en kommunikasie tussen pasiënte en hul versorgers, veral tussen buitepasiënte en psigiatriese gesondheidswerkers, aan die orde van die dag is; dat strukturele versperrings die voorsiening en benutting van sorg beduidend verhinder; dat sorg oor die algemeen onvoldoende is, hoewel dit volgens die algemene begrip biomediese, populêre én volksbehandelings insluit, en dat buitepasiënte meestal ontoereikende (swak) vermoëns toon om nood wat uit gemoedsteurings en uitdagings in die soeke na sorg spruit, te hanteer. Die studie sit uiteindelik ook verskeie belangrike implikasies vir geestesgesondheidspraktyke, -opleiding, -beleid en -navorsing uiteen.

In recent years, empirical research has consistently supported an association between susceptibility to affective illness and creativity at the level of eminent achievement and at the non-eminent, or "everyday creativity" level. Although this research has provided greater evidence for the existence of this link, it has simultaneously unearthed more questions about how and why such an association exists. The purpose of this research was twofold: first, to provide further analysis of the nature of the relationship between hypomanic traits and creativity by employing a longitudinal study to determine the extent to which inter-individual differences over time in creativity are predicted by hypomanic traits. Second, the purpose of the cross-sectional analysis in the present study was to further determine how developmental components such as age and expertise may help unravel the ways in which hypomanic traits contribute to creativity and to further describe inter-individual differences among these variables. The first hypothesis, which proposed that the direction of the relationship between hypomanic traits and creativity could be predicted, was not supported by these results. The second research hypothesis was partially supported: hypomanic traits predict creativity in the combined adolescent and older adult samples. However, upon further examination of the regression analyses, the data indicate that the relationship between hypomanic traits and creativity is also influenced by age and developmental factors. Furthermore, the way in which the relationship is influenced by these other factors depends on the way in which the creativity construct is measured (e.g., process or personality. The findings suggest that the antecedents of creativity may differ between adolescents and older adults. In adolescents, the hypomanic traits measure is the only variable that predicts creative personality and creative process, while expertise is the only variable to predict creative personality and creative process among the older adults in this study. It appears expertise significantly and uniquely contributes to at least two areas of creativity in older adults, while hypomanic traits significantly and uniquely contributes to the same two areas of creativity in adolescents. Implications of these findings and limitations to this study are discussed.

Thesis (Ph. D.)--Illinois State University, 2006. / Title from title page screen, viewed on April 22, 2007. Dissertation Committee: Mark Swerdlik, Matthew Hesson-McInnis (co-chairs), Adena Meyers, Kathryn Hoff, Raymond Redick. Includes bibliographical references (leaves 102-113) and abstract. Also available in print.

The aim of this study is to evaluate the outcome of adoptions and to study the gene-environment influences on psychiatric illness as well as sick-leave patterns. The material consists of 2 966 adopted persons born between 1917 and 1949, their 5 932 adoptive parents and 5 438 identified biological parents.Adopted persons had a higher incidence of personality disorders and substance abuse than non-adopted controls. Adopted men also had an increased incidence of neuroses. Adopted women had an increased sick-leave because of somatic complaints, especially upper respiratory tract infections and abdominal complaints of short duration. Somatization i.e. more than 2 sick-leaves/year because of somatic complaint together with nervous complaints was more frequent among adopted women. Women with somatization could be separated into 2 types according to the pattern of sick-leave. Type 1 ("high frequency") had frequent sick-leaves for psychiatric, abdominal and back complaints. They also had a high frequency of alcohol abuse. Type 2 ("diversiform") had more diverse complaints and had fewer sick-leaves because of nervous complaints.High frequency somatizers had biological fathers with teenage onset of criminality and frequent registrations for alcohol abuse. Diversiform somatizers had the same genetic background as adopted men with petty criminality or male limited alcoholism.No specific genetic influences on treated depression or substance abuse were found in this study. However, a non-specific vulnerability of the biological mother influenced on the risk of depression and substance abuse among adopted women.There were some indications that placement in the adoptive home between 6 and 12 months of age was associated with reactive neurotic depression in adult life. Otherwise early negative experiences in term of unstable placements before adoption did not significantly influence on psychiatric illness in adulthood.Affective disorders in the adoptive father were associated with treatment for depressions or substance abuse in the adoptee. Low social status in the part of the adoptive father increased the risk of somatization of both types in the adoptee. / <p>S. 1-80: sammanfattning, s. 81-236: 6 uppsatser</p> / digitalisering@umu

Objective: The aim of the current study was to investigate the differences in baseline characteristics and three-year outcomes between two diagnostic categories with presentation of first-episode psychosis: bipolar affective disorder (mania with psychotic features) and schizophrenia. The comparison was based on pre-treatment characteristics, clinical presentation, symptomatic and functional outcomes, and engagement in risk behaviours. Methods:461 schizophrenic patients and 54 bipolar affective disorder (BAD) patients between the ages of 15 to 25 years from a local first-episode psychosis treatment program within the years2001 to 2003 were studied. Researchers collected detailed data on baseline and three-year follow up variables from systematic medical file review for statistical analyses. Results: At service entry, compared to schizophrenic patients, bipolar affective disorder(BAD)patients exhibited more prominent positive symptoms (p = 0.01), were younger at first presentation and had a higher unemployment rate (p < 0.01), were more likely to have acute onset of psychosis, shorter duration of untreated psychosis (DUP), a higher rate of hospital admission within first month after initial contact, and lower pre-treatment functioning (Social and Occupational Functioning Assessment Scale (SOFAS), p < 0.001). There was no significant difference in gender, education level, age of onset and pre-treatment risk taking behaviours. After applying univariate analysis of variance (ANCOVA)by controlling baseline variables that showed significant differences, the three year follow up reveals that schizophrenic patients displayed fewer numbers of hospitalization (p <0.01)with no difference in the total length (days) of hospitalization, more prominent positive symptoms(p < 0.01), poorer functioning at year 3 (p <0.05), and consistently significant lower employment rate at 12 month (p < 0.001), 24 month (p < 0.001) and 36 month (p < 0.01). Finally, more schizophrenic patients received social benefits (p < 0.05). Conclusion: The outstanding baseline poorer functioning level of bipolar affective disorder patients have progressively made a modest improvement in functional outcomes at the end of three-year follow up. BAD patients also displayed a marked improvement with fewer positive symptoms in the follow up. The results suggest a differentiation in symptomatology and the course of illness between bipolar affective disorder and schizophrenia with first-episode psychosis. In coherence with other scholastic literature, duration of untreated psychosis (DUP) associates with remission(Crumlish et al., 2009;Chang et al., 2012a), positive symptoms(Barnes et.al., 2008; Chang et.al., 2012b; Clarke et al., 2006; Crumlish et.al., 2009;), and functional outcomes(Barnes et al., 2008; Chang et al., 2012b; Clarke et.al., 2006; Crumlish et.al, 2009; Fusar-Poli et al., 2009). Moreover, further exploration about the diagnostic-specific therapeutic window for early intervention, symptoms management, and rehabilitation strategies in occupational training are in demand. / published_or_final_version / Psychological Medicine / Master / Master of Psychological Medicine

Diffusion tensor imaging (DTI) is a noninvasive MRI technique used to assess white matter (WM) integrity, fiber orientation, and structural connectivity (SC) using water diffusion properties. DTI techniques are rapidly evolving and are now having a dramatic effect on depression research. Major depressive disorder (MDD) is highly prevalent and a leading cause of worldwide disability. Despite decades of research, the neurobiology of MDD remains poorly understood. MDD is increasingly viewed as a disorder of neural circuitry in which a network of brain regions involved in mood regulation is dysfunctional. In an effort to better understand the neurobiology of MDD and develop more effective treatments, much research has focused on delineating the structure of this mood regulation network. Although many studies have focused on the structural connectivity of the mood regulation network, findings using DTI are highly variable, likely due to many technical and analytical limitations. Further, structural connectivity pattern analyses have not been adequately utilized in specific clinical contexts where they would likely have high relevance, e.g., the use of white matter deep brain stimulation (DBS) as an investigational treatment for depression. In this dissertation, we performed a comprehensive analysis of structural WM integrity in a large sample of depressed patients and demonstrated that disruption of WM does not play a major role in the neurobiology of MDD. Using graph theory analysis to assess organization of neural network, we elucidated the importance of the WM network in MDD. As an extension of this WM network analysis, we identified the necessary and sufficient WM tracts (circuit) that mediate the response of subcallosal cingulate cortex DBS treatment for depression; this work showed that such analyses may be useful in prospective target selection. Collectively, these findings contribute to better understanding of depression as a neural network disorder and possibly will improve efficacy of SCC DBS.