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Meehl�s (1962, 1989, 1990b) schizotypy and Tsuang et al.�s (1999b, 2000a, 2000b) schizotaxia are fundamentally different notions of the schizophrenia precursor. Both represent a categorical precursor but differ in the nature of their relationships to schizophrenia. Specifically, schizotypy is dimensional, unchanging despite the presence or remission of schizophrenia. In contrast, schizotaxia is a transitional precursor; the presence of schizophrenia signals the end of schizotaxia. There are also differences in the way in which risk is determined. Schizotypy is reflected in a variety of information processing and experiential aberrations, is typically assessed using self-report measures, and is best identified using taxometric analyses. In contrast, schizotaxia is characterised by negative symptoms of schizophrenia and neurocognitive impairment, can be assessed using standardised clinical measures, and is diagnosed at the individual case level. The aim of Phase 1 of this study was to investigate the manifest structure of Meehl�s schizotypy in a sample of psychiatric patients. The aims of Phase 2 were to determine if schizotypy group membership was associated with poorer functioning and to determine the nature of the relationship between Meehl�s (1962, 1989, 1990b) schizotypy and Tsuang et al.�s (1999b, 2000a, 2000b) schizotaxia. Participants in Phase 1 were 109 psychiatric patients and all completed a self-report measure of schizotypy, the Thinking and Perceptual Style Questionnaire (TPSQ; Linscott & Knight, 2004). Multivariate taxometric analyses of TPSQ subscales yielded evidence of a manifest group structure within the sample. The prevalence of the latent group, presumed to reflect schizotypy, was estimated to be 32% (SD = 8%), as yielded by MAXCOV analyses. MAXCOV analyses also yielded a mean indicator validity of 1.02; variance of 7; base rate estimates of .08; and a goodness of fit index of .98. MAMBAC analyses yielded a mean base rate of 56% (SD = 18%). Twenty-nine participants from Phase 1 took part in Phase 2. Fourteen were from the schizotypy group (had a p value of .85 or higher of schizotypy group membership) and 15 from the nonschizotypy group (had a p value of .03 or lower of schizotypy group membership). Participants completed tests of attention, verbal memory, and executive functioning. Negative symptoms of schizophrenia were also rated and diagnosis was determined using a diagnostic interview. The schizotypy group was significantly impaired relative to the nonschizotypy group on neuropsychological test scores spanning domains of attention, verbal memory, and executive functioning. A current DSM-IV diagnosis was made for 71% of the schizotypy group and 43% of the nonschizotypy group. Individuals were classified as having met criteria for schizotaxia if they had a negative symptom impairment and a neuropsychological impairment in two domains. A total of 7 people of 29 met criteria for schizotaxia, 6 of these people were from the schizotypy group. There was statistical evidence that Meehl�s (1962, 1989, 1990b) schizotypy and Tsuang et al.�s (1999b, 2000a, 2000b) schizotaxia are not independent. The proposed precursors for schizophrenia may reflect the same construct, not separate entities. Limitations and implications of these results are considered.

Elevated serum homocysteine concentrations are neurotoxic and are strongly implicated as a risk factor for neuropsychiatric disease (Fabender, Mielke, Bertsch, & Hennerici, 1999; Kim & Pae, 1996; Kruman et al., 2000; Reutens & Sachdev, 2002). This study compares homocysteine levels in early stages psychosis patients and healthy controls. Data from 48 healthy controls were compared with 50 previously diagnosed psychosis patients, 15-25 years, and with a gender ratio males: females 7:3. Patients were outpatients or inpatients at ORYGEN Youth Health, with a diagnosis of first episode of psychosis defined as daily psychotic symptoms lasting longer than a week that could not be explained by other means such as “drug-induced” or “organic”. / All subjects were interviewed to collect information relating to family psychotic history. A possible history of psychotic disease in control subjects was tested using the SCID Psych Screening Module, drug use recorded using Alcohol Use Disorders Identification Test (AUDIT) (for alcohol use), The Modified Fagerström Tolerance Questionnaire (mFTQ) (for smoking), Opiate Treatment Index (OTI) (for opiate-type drugs). Dietary and medication histories were also taken. Blood tests were performed to determine serum homocysteine, serum folate, red blood cell folate and serum vitamin B12 levels. / An independent sample t test to compare homocysteine levels in patients and controls was performed. Serum homocysteine levels were significantly higher for patients (M = 12.9, S.D. = 3.6) than controls (M = 11.1, S.D. = 2.7) (t(96) = 2.7, p = 0.007, two-tailed). After General Linear Model (GLM) analysis it was found that group (patients or controls), and not serum folate, vitamin B12 and the T allele of MTHFR C677 polymorphism had significant effect on homocysteine levels. Thus a number of factors that may increase homocysteine levels were ruled out. / Although it was not possible to obtain a complete data set for some factors (alcohol, smoking and caffeine consumption) (a weakness of the study), strengths included consecutive recruitment, minimisation of selection bias, good matching for age and gender between patients and controls, and the consideration of (serum) folate and (serum) vitamin B12 as potential confounding variables. / A number of other studies have found significantly increased homocysteine levels in young patients compared with controls, particularly males. Most related studies favoured the homocysteine-psychosis link. / The probability of symptomatic recovery is very high (80-90%) after treatment for first episode psychosis (Robinson et al., 1999) and delayed treatment, but prolonged duration of treatment is associated with poorer response in treatment and worse outcome (Malla & Norman, 2002). This justifies studying homocysteine levels and cognitive function in that first period of psychosis. / This research offers evidence for the importance of serum homocysteine levels as showing involvement in the etiology of psychosis. Lowering homocysteine may have a beneficial effect on symptoms and cognitive dysfunction in psychotic illness. / Two randomised controlled trials have demonstrated benefit in psychotic illness of giving folate and consequently reducing homocysteine.(Godfrey & Toone, 1990; Levine et al., 2006b). Benefits of taking folate were found in both trials for both cognition and psychotic symptoms. By reducing homocysteine levels early in the illness, some of the excess cardiovascular mortality may be prevented. / Secondary prevention of CVD does not appear to influence outcome (Hermann, Herrmann, & Obeid, 2007), so the right time to intervene and reduce risk would appear to be early in the course of psychosis. Additionally, by lowering homocysteine cognitive functioning and psychotic symptoms may be improved (Levine et al., 2006b).

While research on religion and severe psychopathology is mixed, the majority of evidence suggests that greater religiosity and greater use of religious forms of coping relate to beneficial psychosocial outcomes for both patients with schizophrenia (Huguelet et al., 2006; Moss et al., 2006) and their family members (Pearce et al., 2006; Roff et al., 2004). However, this data is generally cross-sectional. To date, scant research has longitudinally examined how religious beliefs and practices relate to key indicators of psychosocial outcomes for patients with schizophrenia and their relatives. This study used a White and Hispanic sample of 41 patients with schizophrenia and 57 relatives of such patients to examine cross-sectional and longitudinal links between religion and mental health. Results showed that increases in the use of religious forms of coping over time significantly predicted decreases in emotional distress for family members. Results also supported the hypothesis that greater positive and lessor negative forms of religious coping would relate to beneficial outcomes for patients and family members. Lastly, this study found that, for patients, ethnicity appeared to moderate the link between religiosity and outcome. Findings from this study highlight the importance of religion to patients and caregivers coping with schizophrenia. Clinicians treating patients with schizophrenia and their loved ones are cautiously encouraged to explore religion with their clients, with particular attention to its differential influence among patients versus relatives and among Whites versus Hispanics.

DISC1 is an established susceptibility gene for schizophrenia. To gain insight on the neural mechanisms responsible for hippocampal deficits in schizophrenia, we sought to characterize place cell activity and theta rhythm in our Disc1-L100P mouse strain that we have previously shown to express deficits in spatial working memory. Our findings suggest that the rate code of place cells is intact. We found that Disc1-L100P mice have deficits in theta rhythm, increased neural noise, and lower levels of PV+ interneurons in the hippocampus. Our findings are supportive of impaired temporal coding in Disc1-L100P place cells. We found that Disc1-L100P place cell waveforms were broader than those of wild-type mice and putative interneuron waveforms were narrower. These findings suggest that ion-channel function and expression in the hippocampus is altered in Disc1-L100P mice. In schizophrenic subjects deficits in working memory are associated with aberrant oscillatory activity, increased noise, and lower PV+ interneuron expression.

DISC1 is an established susceptibility gene for schizophrenia. To gain insight on the neural mechanisms responsible for hippocampal deficits in schizophrenia, we sought to characterize place cell activity and theta rhythm in our Disc1-L100P mouse strain that we have previously shown to express deficits in spatial working memory. Our findings suggest that the rate code of place cells is intact. We found that Disc1-L100P mice have deficits in theta rhythm, increased neural noise, and lower levels of PV+ interneurons in the hippocampus. Our findings are supportive of impaired temporal coding in Disc1-L100P place cells. We found that Disc1-L100P place cell waveforms were broader than those of wild-type mice and putative interneuron waveforms were narrower. These findings suggest that ion-channel function and expression in the hippocampus is altered in Disc1-L100P mice. In schizophrenic subjects deficits in working memory are associated with aberrant oscillatory activity, increased noise, and lower PV+ interneuron expression.

Schizophrenia has long been considered a disorder of impaired brain connectivity, and such disconnectivity might be due to disruption of white matter tracts that connect brain regions. This thesis investigates the oligodendrocyte/myelin/white matter pathway in schizophrenia in vivo, and also considers aging effects, as similar substrates are affected during the healthy aging process. In study one, association of oligodendrocyte/myelin genes is examined with schizophrenia, and in study two association of a myelin gene is examined with basic MRI volumetric phenotypes. Then, in study three, diffusion tensor tractography, a technique that can visualize and measure white matter is applied, and is shown to be reliable in healthy controls and schizophrenia patients using a novel clustering segmentation method. In study four, this method is then used to examine interaction of schizophrenia and aging with respect to white matter, where fronto-temporal disconnectivity is demonstrated in younger chronic schizophrenia patients, but not in elderly community dwelling schizophrenia patients compared to age-matched controls. In study five, relationships among age, white matter tract integrity, and cognitive decline in healthy aging are demonstrated using diffusion tensor tractography and structural equation modeling. Genetics and neuroimaging are then combined using the intermediate phenotype approach in study six to demonstrate a key role for the BDNF gene across adult life in healthy aging. In these individuals, the BDNF val66met variant influenced neural structures and cognitive functions in a pathological aging risk pattern. Finally, in study seven, complex relationships are then demonstrated among oligodendrocyte gene variants, white matter tract integrity and cognitive performance in both healthy controls and schizophrenia patients. The combination of genetics and neuroimaging can parse out heterogeneity of disease phenotypes, and characterize the effects of gene variants on at-risk neural structures and cognitive functions in healthy and disease populations.

Schizophrenia has long been considered a disorder of impaired brain connectivity, and such disconnectivity might be due to disruption of white matter tracts that connect brain regions. This thesis investigates the oligodendrocyte/myelin/white matter pathway in schizophrenia in vivo, and also considers aging effects, as similar substrates are affected during the healthy aging process. In study one, association of oligodendrocyte/myelin genes is examined with schizophrenia, and in study two association of a myelin gene is examined with basic MRI volumetric phenotypes. Then, in study three, diffusion tensor tractography, a technique that can visualize and measure white matter is applied, and is shown to be reliable in healthy controls and schizophrenia patients using a novel clustering segmentation method. In study four, this method is then used to examine interaction of schizophrenia and aging with respect to white matter, where fronto-temporal disconnectivity is demonstrated in younger chronic schizophrenia patients, but not in elderly community dwelling schizophrenia patients compared to age-matched controls. In study five, relationships among age, white matter tract integrity, and cognitive decline in healthy aging are demonstrated using diffusion tensor tractography and structural equation modeling. Genetics and neuroimaging are then combined using the intermediate phenotype approach in study six to demonstrate a key role for the BDNF gene across adult life in healthy aging. In these individuals, the BDNF val66met variant influenced neural structures and cognitive functions in a pathological aging risk pattern. Finally, in study seven, complex relationships are then demonstrated among oligodendrocyte gene variants, white matter tract integrity and cognitive performance in both healthy controls and schizophrenia patients. The combination of genetics and neuroimaging can parse out heterogeneity of disease phenotypes, and characterize the effects of gene variants on at-risk neural structures and cognitive functions in healthy and disease populations.

No description available.

Schizophrenie ist eine schwere und zumeist chronisch verlaufende psychiatrische Erkrankung und stellt eine enorme finanzielle Belastung für das Gesundheitssystem dar. Daten zu den medikamentösen Kosten liefern Hinweise zur Verbesserung der Kosteneffektivität innerhalb der Patientenversorgung. In der vorliegenden Arbeit erfolgt eine Analyse der internationalen Unterschiede im Arzneimittelverbrauch und der Kosten der psychotropen Medikation im Rahmen der Behandlung von schizophren Erkrankten. Die Analyse basiert auf Daten aus einer naturalistischen, prospektiven Längsschnittstudie über einen Zeitraum von zweieinhalb Jahren (European Schizophrenia Cohort) in den Ländern Frankreich, Deutschland und Großbritannien. Ausgangspunkt der multivariaten Regressionsanalyse ist die Vermutung, dass die Höhe der Kosten in der medikamentösen Therapie von folgenden soziodemografischen Eigenschaften schizophren Erkrankter beeinflusst werden: dem Alter, klinischen Status, Geschlecht und der Zahl der vorangegangenen stationären Aufenthalte. Es ist festzustellen, dass es internationale Unterschiede im Medikamentenverbrauch gibt. Unterschiede in der Erstattungsfähigkeit, vorhandene Arzneimittelbudgets, verschiedene Behandlungsleitlinien und Verschreibungspraxen sind mögliche Erklärungen. Es wird gezeigt, dass ein an Schizophrenie erkrankter Patient in Deutschland signifikant höhere Arzneimittelkosten bei gleicher Therapie verursacht. Das ist möglicherweise durch die unterschiedlichen Gesundheitssysteme mit den unterschiedlichen Einflussnahmen des Staates auf die Pharmaindustrie zu erklären. Die Variablen Herkunftsland, Alter und Krankheitsschwere beeinflussen die Höhe der Kosten der medikamentösen Therapie.