Interplay of hippocampal volume and hypothalamus-pituitary-adrenal axis function as markers of stress vulnerability in men at ultra-high risk for psychosis.

BACKGROUND: Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results. METHOD: Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol. RESULTS: Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size). CONCLUSIONS: Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.

Laser-rate-equation description of optomechanical oscillators.

We develop a set of laser rate equations that accurately describes mechanical amplification in optomechanical oscillators driven by photothermal or radiation pressure forces. In the process we introduce a set of parameters describing gain, stored energy, slope efficiency, and saturation power of the mechanical laser. We identify the three-phonon parametric interactions as a microscopic mechanism enabling self-oscillation. Our theory shows remarkable agreement with our experimental data, demonstrating that optomechanical self-oscillation is essentially a "phonon lasing" process in which an optical pump generates coherent acoustic phonons.

Enhanced electro-optic phase shifts in suspended waveguides.

We demonstrate enhanced electro-optic phase shifts in suspended InGaAs/InGaAsP quantum well waveguides compared to attached waveguides. The enhancement stems from an improved overlap between the optical mode and the multiple quantum well layers in thin waveguides when the semiconductor material beneath the waveguide is selectively etched. The measured voltage length product is 0.41 V-cm and the measured propagation loss is 2.3 +/- 0.7 dB/cm for the TE mode in the optical L-band.

Suspended AlGaAs waveguides for tunable difference frequency generation in mid-infrared.

A birefringent phase-matching scheme for difference-frequency generation in a slotted air-clad waveguide with a tunable gap is proposed and theoretically analyzed. A tunability of 300 cm(-1) and an efficiency of 400 W(-1) cm(-2) is predicted.

A microelectromechanically tunable asymmetric Fabry-Perot quantum well modulator at 1.55 microm.

Placing a quantum well modulator in an asymmetric Fabry- Perot cavity enables significantly higher contrast ratios than are possible in a conventional surface-normal quantum well modulator. However, fixed-cavity asymmetric Fabry-Perot quantum well modulators require extremely precise and uniform crystal growth and are sensitive to small fluctuations in temperature or angle of incidence. Here, we experimentally demonstrate an InP-based microelectromechanically tunable asymmetric Fabry-Perot quantum well modulator that operates in the optical C-band. By actuating a suspended InGaAlAs reflector, the cavity mode can be perfectly matched to the appropriate quantum well absorption wavelength. The devices exhibit contrast ratios over 30 (15 dB) at 8 volts quantum well bias and modulation speeds of 1 MHz.

Hippocampal volume is as variable in young as in older adults: implications for the notion of hippocampal atrophy in humans.

Previous studies in humans have shown the presence of an age-related reduction of hippocampal (HC) volume, as well as the presence of reduced HC volume in psychiatric populations suffering from schizophrenia, depression or post-traumatic stress disorder. Altogether, these data suggested that aging or psychiatric disease can have neurotoxic effects on the hippocampus, and lead to HC atrophy. However, these two sets of findings imply that HC volume in young healthy adults should present less variability than HC volume in older adults and psychiatric populations. In the present study, we assessed HC volume in 177 healthy men and women aged from 18 to 85 years of age. We show that the dispersion around the mean of HC volume is not different in young and older adults, so that 25% of young healthy adults present HC volume as small as the average participants aged 60 to 75 years. This shows that HC volume is as variable in young as in older adults and suggests that smaller HC volume attributed to the aging process in previous studies could in fact represent HC volume determined early in life. We also report that within similar age groups, the percentage of difference in HC volume between the individuals with the smallest HC volume (smallest quartile) and the group average is greater than the percentage of difference reported to exist between psychiatric populations and normal control in recent meta-analyses. Taken together, these results confront the notion of hippocampal atrophy in humans and raise the possibility that pre-determined inter-individual differences in HC volume in humans may determine the vulnerability for age-related cognitive impairments or psychopathology throughout the lifetime.

Age and gender predict volume decline in the anterior and posterior hippocampus in early adulthood.

Magnetic Resonance Imaging (MRI) provides a noninvasive method for investigating brain morphology. Within the medial temporal lobe, special attention has been paid to the hippocampus (HC) and amygdala (AG) because of their role in memory, depression, emotion, and learning. Volume changes in these areas have been observed in conjunction with certain disease states, e.g. Alzheimer's disease, post-traumatic stress disorder, and depression. Aging has also been shown to result in gray matter volume loss of the overall brain, including the HC. With regard to gender specificity, results suggest a larger shrinkage for men of brain gray matter, with controversial observations being made for the HC. With recently refined MRI acquisition and segmentation protocols, the HC and AG of 80 subjects in early adulthood (39 men and 41 women, age 18-42 years) were investigated. Whereas the volume of the AG appeared to be independent of age and gender, a significant negative correlation with age for both left and right HC was found in men (r = -0.47 and -0.44, respectively) but not in women (r = 0.01 and 0.02, respectively). The volume decline in men appeared to be linear, starting at the beginning of the third life decade and approximating 1.5% per annum. Using voxel-based regressional analysis, it was shown that changes with age occurred mostly in the head and tail of the HC. This finding underscores the need to include sociodemographic variables in functional and anatomical MRI designs.

Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories.

Within the medial temporal lobe, both the hippocampus and amygdala are frequently targeted by researchers and clinicians for volumetric analysis based on magnetic resonance imaging (MRI). However, different data acquisition techniques, analysis software and anatomical boundaries have in the past made it difficult to compare results of MRI studies from different laboratories. In order to reduce these differences, a segmentation protocol was established with 40 healthy normal control subjects recently scanned in our laboratory. Data acquisition was performed with a three-dimensional gradient echo technique, and scans were corrected for non-uniformity and registered into standard stereotaxic space prior to segmentation. Volumetric analysis was performed manually using three-dimensional software that allows simultaneous analysis of sagittal, coronal and horizontal images. Intra- and inter-rater coefficients yielded correlation coefficients comparable with other protocols. The hippocampal volume was larger in the right hemisphere (3324 versus 3208 mm(3)), while no interhemispheric differences for the amygdala (1154 versus 1160 mm(3)) could be observed. Most importantly, results from recent segmentation protocols for hippocampus and amygdala seem to approach each other with regard to mean volumes and interhemispheric differences. This indicates that the advances in scanning technique, volume preparation and segmentation protocols allow a more precise definition of medial temporal lobe structures with MRI, and that results for mean volumes for hippocampus and amygdala from different laboratories will eventually become comparable.