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The marked heterogeneity between individuals diagnosed as experiencing schizophrenia has troubled nosologists since the very coining of the term. Catalysed by Crows (1980) hypothesis of independent positive, and negative syndromes, which led to substantial breakthroughs in our comprehension of schizophrenia, the last two decades have seen a resurgence of interest in the characterisation of symptom dimensions to resolve the issue of heterogeneity. A three dimensional model, comprising 'psychotic', 'negative', 'disorganised' syndromes has received considerable research attention and has been proposed for inclusion in the Diagnostic and Statistical Manual of Mental Disorders. Similarly, a five-dimensional model, adding syndromes of 'affective disturbance'and 'excitement', has also attracted an increasing profile of literature. Mounting evidence suggests, however, that these models do not adequately reflect the diversity of symptoms seen among those with a diagnosis of schizophrenia, and that they may emerge as an artefact of lossy factor-analytic techniques applied to measurement models biased or inadequate in their coverage of symptoms. To overcome such limitations, in the present study one hundred in- and out- patients diagnosed with schizophrenia were assessed for completed a battery of neuropsychological tests tapping five aspects of attention, and smooth pursuit eye tracking was also recorded. Using cluster analyses to examine correlations between symptoms, eleven groups of symptoms were identified: 'hostility', 'conceptual disorganisation', 'bizarre behaviour', 'grandiosity', 'auditory hallucinations', 'loss of boundary delusions', 'paranoia', 'anxious intropunitiveness', 'cognitive dysfunction', 'negative signs' and 'social dysfunctions'. All groupings were internally consistent, largely independent of others, and supported by other symptom models proposed in the literature. Several of the symptom groupings were validated by demonstration of independent relationships with neuropsychological variables or aspects of eye movements, and the more complex symptom model was equivalent or superior in the prediction of neuropsychological performance than the three- and five- factor symptom models. Implicit in dimensional approaches to conceptualising schizophrenia is the notion that the identified groupings may reflect the functioning of distinct brain systems. This thesis has demonstrated that the 'syndromes' defined by the three- and five- dimensional models of schizophrenia are actually heterogeneous groupings of poorly correlated symptoms. This, in turn, obscures the relationships between symptoms and underlying pathology. Dimensional approaches to psychopathology hold great promise for unravelling the nature of psychosis. However, the existing facile descriptions may actively constrain the potential for research progress. The rigorously developed description of symptomatology presented here represents a compact and useful representation of the spectrum of symptoms experienced in schizophrenia, and has demonstrated an advantage over existing conceptions that demands implementation and vigorous research attention.

Thesis (Ph. D.)--Carleton University, 2003. / Includes bibliographical references (p. 187-221). Also available in electronic format on the Internet.

Thesis (doctoral)--University of Tartu, 2004. / Includes bibliographical references (p. 53-67)

Thesis (Ph. D.)--Carleton University, 1975. / Also available in electronic format on the Internet.

Thesis (M.S.)--University of North Carolina at Wilmington, 2006. / Includes bibliographical references.

Introduction Alcoholism represents a chronic recurring disorder that affects 15 million people nationwide, 4% of which fall within the adolescent age range (12-17). Clinical data indicate that adolescents who binge drink greatly increase their chances of suffering from several dangerous health outcomes (i.e., suicide, risky sexual behavior, car wreck, etc.) as well as the likelihood they will develop an alcohol-use disorder later in life. Moreover, research indicates that cues (i.e. flavors) paired with alcohol drinking produce significant cue-induced alcohol craving, contributing to relapse in adolescence and adult populations. Therefore, the current study sought to model the effect of adolescent exposure to flavor cues, paired with alcohol, on subsequent cue-induced alcohol-seeking in adulthood. Methods Alcohol naïve alcohol-preferring (P) rats were randomly assigned to a paired or unpaired group. During the adolescent period, all animals had 24-hour access to 3 bottles; (paired group: 0.1% blueberry flavor extract (BB) + 15% v/v alcohol, and two water; unpaired group: 0.1% BB, 15% v/v alcohol, and water). The animal’s body and bottle weights were recorded daily. In the first two weeks of adulthood, all rats experienced daily 60-minute self-administration sessions to measure fluid intake. Paired animals could consume 0.1% BB + 15% alcohol or water and unpaired animals could consume 0.1% BB or 15% alcohol. The following two weeks all rats were kept in their home cage with access to only water. Following this 2 week period of imposed abstinence, rats were returned to the chambers and consumption of 0.1% BB or water was measured to examine cue-induced alcohol-seeking. Results Data indicate adolescent exposure to BB + alcohol did not promote faster acquisition of self-administration. Additionally, during adolescence and adulthood, both groups consumed similar levels of alcohol. When tested for cue-induced alcohol-seeking, paired rats exhibited significant resistance to extinction of sipping on the BB sipper (no alcohol). Conclusions Overall, data suggest that cues paired with alcohol during adolescence and early adulthood may contribute to prolonged alcohol-seeking behavior thus increasing risk of relapse following subsequent cue exposure.

Thesis (DPhil)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: The use of psychiatric medication is an important part of modern medical and psychiatric practice. Clinical psychopharmacology raises a broad range of philosophical issues, including metaphysical, epistemological, and moral questions. This dissertation attempts to provide a conceptual framework for addressing several of these questions, and for formulating a conceptual basis for psychiatry in general and clinical psychopharmacology in particular. The dissertation begins by heuristically contrasting two broad approaches towards a range of questions in the philosophy of science, language, and medicine. A classical position takes an essentialist and objective view of categories while a critical position emphasizes that categories are often metaphoric and subjective. A synthetic or integrated position might be possible, in which radial categories are often based on metaphoric extensions of basic-level sensorimotor-affective experience, and are embodied in the brain-mind and in social practices. Rather than attempt to defend an integrated position in purely conceptual terms, the dissertation supports this view of categories using data from the cognitive-affective sciences. An important category for philosophy of medicine is disorder, and the dissertation argues that certain universal considerations explain agreement about prototypical disorders. Extensions of disorder metaphors are theory-driven and valueladen, and although disagreement about atypical conditions is likely, reasonable debate is possible. The dissertation then considers several conceptual questions, namely the nature of psychotropics, of emotion, and of the self. In each case, a classical position which attempts an essentialist definition is contrasted with a critical position which emphasizes that these constructs are socially constructed and crucially subjective. Cognitiveaffective data is then employed to support an integrative position which emphasizes the embodiment of complex brain-mind phenomena in the brain-mind and in social practices. Explanatory questions considered are how best to explain pharmacotherapy and psychotherapy, how to account for placebo responses, and the relevance of evolutionary explanations of disorder. It is argued that a functionalist account fails to explain psychopharmacological phenomena, including pharmacotherapy and placebo effects. Instead, an account which emphasizes how psychobiological mechanisms produce complex brain-mind phenomena is needed. Evolutionary explanations add to this account, but cannot by themselves differentiate disorder from non-disorder. Ethical questions include the question of whether psychiatric disorders should be treated, whether such disorders should be treated with psychotropics, and whether psychotropics should be used to enhance. The cognitive-affective sciences support the treatment of typical disorders. In more atypical cases, pharmacotherapy, psychotherapy, and non-medical interventions should be considered on an individual basis. As technologies expand, considerations about the value of accepting fate versus the value of attempting to improve life by a range of methods, will need to be weighed carefully. In summary, this dissertation puts forward a philosophy of psychopharmacology which argues that psychiatry practice can be viewed, naturalistically, as based on the natural and human sciences. At the same time, good psychiatric practice involves an engagement with the complex realities of the human condition, including a consideration of individuals’ suffering. Good psychopharmacological practice requires integrating the objective and the subjective, considering both explanation and understanding, and providing a balanced view of the good and bad of psychotropics that avoids both unrealistic optimism and undue pessimism. / AFRIKAANSE OPSOMMING: Die gebruik van psigiatriese medikasie maak belangrike deel uit van moderne mediese en psigiatriese praktyk. Psigofarmakologie bring wye reeks filosofiese kwessies ter sprake, met inbegrip van metafisiese, epistemologiese, en morele vrae. Hierdie proefskrif poog om konseptuele raamwerk te verskaf ten einde verskeie van hierdie vrae die hoof te bied, en na die formulering van konseptuele basis vir psigiatrie in die algemeen en kliniese psigofarmakologie in die besonder om te sien. Die proefskrif begin deur twee algemene benaderings ten opsigte van reeks vrae in die filosofie van wetenskap, taal en geneeskunde te kontrasteer. Klassieke posisie huldig essensialistiese en objektiewe siening van kategorieë, terwyl kritiese posisie klem daarop lê dat kategorieë dikwels metafories en subjektief is. Sintetiese of geïntegreerde posisie is dalk moontlik, met radiale kategorieë wat dikwels op metaforiese uitbreidings van konsepte op basiese vlak sensorimotor-affektiewe ervaring gebaseer word, en in die bewussyn-brein en in sosiale gebruike vergestalt word. Eerder as om te probeer om geïntegreerde posisie in suiwer konseptuele terme te verdedig, steun die proefskrif hierdie siening van kategorieë met behulp van data uit die kognitiewe-affektiewe wetenskappe. Belangrike kategorie vir die filosofie van geneeskunde is steuring, en die proefskrif voer aan dat sekere universele oorwegings ’n verklaring bied vir ooreenstemming ten opsigte van prototipiese steurings. Uitbreidings van die steuring metafoor is teoriegedrewe en waardebelaai, en alhoewel daar waarskynlik meningsverskil omtrent atipiese toestande kan voorkom, is redelike bespreking haalbaar. Die proefskrif neem dan verskeie konseptuele vrae in aanmerking, naamlik die aard van psigotropika, van emosie, en van die self. In elke geval word klassieke posisie wat essensialistiese definisie aandurf, gekontrasteer met kritiese posisie wat beklemtoon dat hierdie konstrukte sosiaal gekonstrueer en besonder subjektief is. Kognitiewe-affektiewe data word dan aangewend om integratiewe posisie te handhaaf wat die vergestalting van komplekse bewussyn-brein fenomene in die bewyssyn-brein en in sosiale praktyke beklemtoon. Verklarende vrae het aandag geskenk aan die beste wyse om farmakoterapie en psigoterapie te verklaar, aan die wyse waarop placebo-reaksies verklaar kan word, en aan die rol van proksimale en evolusionêre verklarings. Daar word aangevoer dat funksionalistiese verklaring nie daarin slaag om psigofarmakologiese verskynsels, met inbegrip van farmakoterapie en placebo-effekte, te verklaar nie. In plaas daarvan word verklaring wat beklemtoon hoe psigobiologiese meganisme komplekse fenomene kan laat ontstaan, benodig. Evolusionêre verklarings dra tot hierdie verklaring by, maar kan nie op sigself steuring van niesteuring onderskei nie. Etiese vrae sluit die vraag in of psigiatriese steurings behandel moet word, of sodanige steurings met psigotropika behandel moet word, en of psigotropika gebruik moet word om te verhoog. Die kognitief-affektiewe wetenskappe ondersteun die behandeling van tipiese steuringe. In meer atipiese gevalle moet farmakoterapie, psigoterapie, en nie-mediese intervensies op individuele basis oorweeg word. Algaande tegnologieë uitbrei, moet ons oorwegings van die waarde van lotsaanvaarding sowel as die waarde van ’n poging om ’n mens se lewe te verbeter, versigtig in ag neem. Ter opsomming, hierdie proefskrif stel filosofie van psigofarmakologie voor wat aanvoer dat psigiatriese praktyk naturalisties verstaan kan word, soos gebaseer op die natuur- en geesteswetenskappe. Terselfdetyd, behels goeie psigofarmakologiese praktyk ‘n verwantskap met die komplekse werklikhede van die menslike kondisie. Dit vereis ‘n omvattende oorweeging van en omgang met individuele pasiënte se lyding. Goeie psigofarmakologiese praktyk integreer die “objektiewe” en die “subjektiewe” aspekte van die menslike bestaan, streef na sowel verklaring en verstaan, verskaf ‘n gebalanseerde perspektief oor die goed en die sleg van psigiatriese medikasies, en middel tussen onrealistiese optimisme en buitensporige pessimisme.