Hippocampal, amygdala and nucleus accumbens volume in first-episode schizophrenia patients and individuals at high familial risk: A cross-sectional comparison.

It is unknown whether brain changes occur prior to onset of schizophrenia or after it develops. Prospective familial high risk studies provide a good method to investigate this. In the Edinburgh High Risk Study, structural MRI scans of 150 young individuals at familial high risk of schizophrenia, 34 patients with first-episode schizophrenia and 36 matched controls were obtained. Of the high risk participants with scans suitable for analysis, 17 developed schizophrenia after the scans were taken, whilst 57 experienced isolated or sub-clinical psychotic symptoms, and 70 remained well. We used Freesurfer to extract volumetric measurements of the hippocampus, amygdala and nucleus accumbens with the aim of assessing whether any alterations found were present in all those at high risk, or selectively in the high risk cohort based on future clinical outcome, or only in those experiencing their first-episode of psychosis. We found no significant differences in any examined regions between controls and those at high risk, or between those at high risk who later developed schizophrenia and those who remained well. However, patients with first-episode schizophrenia demonstrated significant volumetric reductions in the bilateral hippocampus, left amygdala, and right nucleus accumbens compared to high risk individuals and healthy controls, which were not significantly associated with the intake of anti-psychotic medication or duration of illness. We found that patients had significantly smaller left amygdalae and bilateral hippocampus compared to HR[ill]. Our findings suggest that volumetric reductions of the hippocampus, amygdala and nucleus accumbens occur early in the first-episode of psychosis. The apparent absence of high risk versus control differences we found using Freesurfer is at odds with our previous studies conducted on the same sample, and possible methodological reasons for these apparent discrepancies are discussed.

Cortical Surface Area Differentiates Familial High Risk Individuals Who Go on to Develop Schizophrenia.

BACKGROUND: Schizophrenia is associated with structural brain abnormalities that may be present before disease onset. It remains unclear whether these represent general vulnerability indicators or are associated with the clinical state itself. METHODS: To investigate this, structural brain scans were acquired at two time points (mean scan interval 1.87 years) in a cohort of individuals at high familial risk of schizophrenia (n = 142) and control subjects (n = 36). Cortical reconstructions were generated using FreeSurfer. The high-risk cohort was subdivided into individuals that remained well during the study, individuals that had transient psychotic symptoms, and individuals that subsequently became ill. Baseline measures and longitudinal change in global estimates of thickness and surface area and lobar values were compared, focusing on overall differences between high-risk individuals and control subjects and then on group differences within the high-risk cohort. RESULTS: Longitudinally, control subjects showed a significantly greater reduction in cortical surface area compared with the high-risk group. Within the high-risk group, differences in surface area at baseline predicted clinical course, with individuals that subsequently became ill having significantly larger surface area than individuals that remained well during the study. For thickness, longitudinal reductions were most prominent in the frontal, cingulate, and occipital lobes in all high-risk individuals compared with control subjects. CONCLUSIONS: Our results suggest that larger surface areas at baseline may be associated with mechanisms that go above and beyond a general familial disposition. A relative preservation over time of surface area, coupled with a thinning of the cortex compared with control subjects, may serve as vulnerability markers of schizophrenia.

Cortical thickness in first-episode schizophrenia patients and individuals at high familial risk: a cross-sectional comparison.

BACKGROUND: Schizophrenia is associated with cortical thickness reductions in the brain, but it is unclear whether these are present before illness onset, and to what extent they are driven by genetic factors. METHODS: In the Edinburgh High Risk Study, structural MRI scans of 150 young individuals at high familial risk for schizophrenia, 34 patients with first-episode schizophrenia and 36 matched controls were acquired, and clinical information was collected for the following 10 years for the high-risk and control group. During this time, 17 high-risk individuals developed schizophrenia, on average 2.5 years after the scan, and 57 experienced isolated or sub-clinical psychotic symptoms. We applied surface-based analysis of the cerebral cortex to this cohort, and extracted cortical thickness in automatically parcellated regions. RESULTS: Analysis of variance revealed widespread thinning of the cerebral cortex in first-episode patients, most pronounced in superior frontal, medial parietal, and lateral occipital regions (corrected p<10(-4)). In contrast, cortical thickness reductions were only found in high-risk individuals in the left middle temporal gyrus (corrected p<0.05). There were no significant differences between those at high risk who later developed schizophrenia and those who remained well. CONCLUSIONS: These findings confirm cortical thickness reductions in schizophrenia patients. Increased familial risk for schizophrenia is associated with thinning in the left middle temporal lobe, irrespective of subsequent disease onset. The absence of widespread cortical thinning before disease onset implies that the cortical thinning is unlikely to simply reflect genetic liability to schizophrenia but is predominantly driven by disease-associated factors.

Longitudinal volume reductions in people at high genetic risk of schizophrenia as they develop psychosis.

BACKGROUND: Structural differences between the brains of people with schizophrenia and control subjects are highly replicated but the timing and clinical correlates are unclear. In the Edinburgh High Risk Study, we have followed up 162 individuals at high genetic risk of schizophrenia and 36 healthy control subjects over 10 years. METHODS: Participants received detailed clinical and up to five structural magnetic resonance imaging (MRI) assessments at 2-year intervals. All 436 MRI scans acquired were parcellated and adjusted for between-scanner differences. The trajectory of any structural MRI changes was then investigated using mixed effects analysis of variance. RESULTS: Seventeen of the 146 high-risk subjects who were scanned developed schizophrenia over the 8 years of the study. People at high genetic risk of schizophrenia had significantly greater reductions over time than the control group for whole brain volume and left and right prefrontal and temporal lobes. Greater prefrontal reductions were shown in high-risk subjects who subsequently became unwell compared with those who did not. These changes were significantly associated with increasing severity of psychotic symptoms. CONCLUSIONS: Individuals at high genetic risk of schizophrenia exhibited reductions in cerebral volume that were not found in control subjects. Changes in brain structure were also associated with increasing psychotic symptom severity as people developed schizophrenia. The progressive reductions found in those who went on to develop schizophrenia suggest an additional brain insult near to the time of onset.

Pubovaginal sling using Duraderm graft: intermediate follow-up and patient satisfaction.

AIM: To assess outcome and patient satisfaction utilizing Duraderm allograft as sling material. METHODS: Twenty five patients undergoing the Duraderm sling procedure were evaluated by pelvic examination, post-void residual urine, and multi-channel urodynamics. Follow-up included repeat examination, stress test, and chart review. Patient satisfaction was assessed by phone interview with an independent examiner. Outcome was defined as dry (no leaking at all and patient perception of satisfaction), improved (minimal leak requiring < or =1 pad daily and patient perception of satisfaction), or failure. RESULTS: Average age was 62.0 years (30-83); average daily preoperative pad usage was 3.5 (2-8). Duraderm allograft measuring 2 x 12 cm was used. Mean postoperative catheter time was 7.7 days (3-37 days). At 6 months, 17/25 (68%) were dry, 6 (24%) improved, and 2 (8%) failed. Mean intermediate follow-up at 14.8 months (8-23 months) revealed 8/25 (32%) patients were dry, 9 (36%) were improved, and 8 (32%) failed Duraderm sling. Mean pad use after surgery was 1.4 (0-6). Of the 25, 19 (76%) were satisfied with the surgical outcome, 17 (68%) noted they would have surgery again, and 17 (68%) would recommend the procedure. CONCLUSIONS: Initial results of pubovaginal sling using Duraderm graft are satisfactory; however, longer term follow-up is disappointing. Graft degeneration previously described after utilization of cadaveric fascia lata may be possible following implantation of cadaveric dermis.