Thesis (Ph.D)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Human Genetics. Title from title-page of electronic thesis. Bibliography: leaves 117-151.

NMDA receptor antagonists such as Ketamine and PCP are potent psychoactive drugs used recreationally. This class of drug induces a number of phenomena in humans similar to those associated with schizophrenia including reduced selective attention, altered working memory, thought disorders and hallucinations. These psychotomimetic drugs have thus been used as a longstanding model to study this disease in animals. Importantly, such animal models allow for recording of brain activity using invasive techniques that are inappropriate in humans. Previous electrophysiological studies have shown that MK-801, a potent non-competitive NMDA receptor antagonist, increases gamma-frequency oscillations and produces a state of disinhibition in the prefrontal cortex of rats wherein the activity of putative excitatory pyramidal neurons increases while the activity of putative inhibitory interneurons decreases. These features are relevant to schizophrenia because molecular evidence suggests dysfunction of inhibitory cortical interneurons, while electroencephalographic recordings show altered gamma-frequency oscillations in this disease. It has been hypothesized that the disinhibited cortical state produces “noisy” information processing, but this has not been directly observed in the interaction of neuronal firing in either humans or animal models. We therefore tested this hypothesis by examining the synchronization of neural activity in the NMDA receptor antagonist model of schizophrenia. We used high-density electrophysiological recordings in the medial prefrontal cortex of freely moving rats before and after systemic injection of MK-801. Analysis of these recordings revealed that drug administration: (i) increases gamma power in field potentials in a manner dissociated from increased locomotion; (ii) does not change the gamma power in multi-unit activity; (iii) decreases spike synchronization among putative pyramidal neurons in the gamma range (30ms), and despite of this it (iv) does not change the synchronization between gamma-range field potentials or between sum-of-spikes and field potentials. These effects in synchronization may be revealing of potent cognitive effects associated with NMDA receptor antagonism, and may reflect impaired communication processing hypothesized to occur in schizophrenia. / xi, 42 leaves : ill. ; 29 cm

<p>  </p> <p>Social withdrawal is a disabling feature of schizophrenia. To understand its development, researchers have focused on social anhedonia— diminished pleasure from social interactions. Discrepancies in anticipated versus consummatory pleasure for non-social stimuli are well-documented in schizophrenia. Thus, a similar emotional paradox may underlie social anhedonia. If so, our understanding of social anhedonia—including how to treat it in schizophrenia—could be enhanced. This project used a 5-day experience sampling method (ESM) to measure discrepancies between anticipated and consummatory pleasure for real-world social activities in people with schizophrenia and healthy controls (<em>n=</em>30/group). Results suggest people with schizophrenia exhibited similar levels of anticipated and consummatory social pleasure as controls, and both groups were accurate in their short-term predictions of pleasure. Yet, healthy control participants were somewhat more precise in their short-term pleasure predictions, and clinical interviews revealed those with schizophrenia showed moderate deficits in long-term social pleasure prediction. Negative symptoms and cognitive impairment in schizophrenia were related to anticipated, but not consummatory, social pleasure, suggesting anhedonia is driven by deficits in thinking about pleasure, rather than inability to experience pleasure. Clinical implications include focusing on building upon short-term ability to predict pleasure in therapy in order to increase social motivation in schizophrenia. Moreover, exploratory analyses revealed differences in qualitative aspects of social activities such as level of engagement may lead to social anhedonia in schizophrenia and are a promising treatment target for addressing social dysfunction.</p>

Indiana University-Purdue University Indianapolis (IUPUI) / This study investigates differences between Veterans and non-Veterans with severe mental illness (SMI) regarding perceptions of their illness, themselves, and treatment. I compare patient interviews (using the Indiana Psychiatric Illness Interview, IPII) of Veterans (N=20) and non-Veterans (N=26). Modified grounded theory and qualitative coding software Atlas-TI were used to develop codebooks for each group, and these were compared for differences. I examined differences in both code frequency and meaning. Statistically, more Veterans were male, employed, married, had higher income, and had higher education. Statistical differences in code frequency included: more Veterans discussing boredom, regret/guilt/loss, and wanting to be “normal.” More non-Veterans had codes of pessimism and religion/spirituality, wanting a different future, bringing up mental health, family, future: no change, life goals, and relapse. Key differences in narrative themes included: (1) Veterans’ “military mindset”/discussion of anger as part of mental illness, (2) non-Veterans’ focus on mental-illness, (3) differing attitudes regarding stigma, (4) active versus passive attitudes toward treatment, and (5) degree of optimism regarding the future. Differences are described and then potential relationships and interactions are proposed. Veterans appear to have several protective factors (i.e., finances, employment, marriage). Additionally, Veterans’ military-mindset seems to encourage greater stigma-resistance, and thereby also facilitate Veterans being more active and optimistic toward treatment and recovery. By contrast, non-Veteran focus on mental illness may be related to increased self-stigma, passive and pessimistic attitudes. I propose that Veteran identity can serve as an additional protective factor against stigma, pessimism, and passivity. Veteran-identity may also be a useful framework clinically, to help promote active approaches to treatment (e.g., “fighting symptoms”). Further, Veterans emphasized issues relating to anger as important and part of their mental health. It may be that Veterans are more comfortable discussing mental health in the language of “anger,” given stigma. Finally, findings suggest that helping individuals in both groups engage in meaningful, non-mental illness-related life activities may help shape self-perception, and thereby responses to stigma, attitudes toward treatment, and hope for the future.