The androgen model of suicide completion.

Suicide is a devastating public health issue that imposes severe psychological, social, and economic burdens not only for the individuals but also for their relatives, friends, clinicians, and the general public. Among the different suicidal behaviors, suicide completion is the worst and the most relevant outcome. The knowledge of biological etiopathological mechanisms involved in suicide completion is limited. Hitherto, no objective markers, either alone or in combination, can reliably predict who will complete a suicide. However, such parameters are strongly needed to establish and optimize prediction and prevention. We introduce here a novel ideation-to-completion framework in suicide research and discuss the problems of studies aiming at identifying and validating clinically useful markers. The male gender is a specific risk factor for suicide, which suggests that androgen effects are implicated in the transition from suicidal ideation to suicide completion. We present multiple lines of direct and indirect evidence showing that both an increased prenatal androgen load (with subsequent permanent neuroadaptations) and increased adult androgen activity are involved in suicide completion. We also review data arguing that modifiable maternal behavioral traits during pregnancy contribute to the offspring's prenatal androgen load and increase the risk for suicide completion later in life. We conclude that in utero androgen exposure and adult androgen levels facilitate suicide completion in an synergistic manner. The androgen model of suicide completion provides the basis for the development of novel predictive and preventive strategies in the future.

[From freshmanship to the first "Staatsexamen"--increase of depression and decline in sense of coherence and mental quality of life in advanced medical students]. / Vom Studienstart bis zum ersten Staatsexamen--Zunahme von Depressivität bei gleichzeitigem Verlust des Kohärenzgefühls und der psychischen Lebensqualität in höheren Semestern Humanmedizin.

Psychiatric disorders (Burnout, depression, anxiety disorders) are common among medical students with a distinctly higher prevalence compared to the general public. Although medi-cal students show a normal health status at the beginning of their university study period, a deterioration of these aspects in higher semesters is evident and continues when they become residents. In our study ESTRELLAS we examined 530 medical students in the preclinical semesters (1st-4th) before their first "Staatsexamen" with validated psychological questionnaires for depression, anxiety, quality of life and sense of coherence. Students in their 1st semester show normal values like the general public. During the 4 semesters a slow and continuous rise of depressive symptoms and anxiety was detected. Quality of life and sense of coherence constantly deteriorated. An increase of physical symptoms was not detected. In the 4th semester the number of depressive students had already doubled. The development of worsening psychological problems and resulting psychiatric disorders seems to be a continuous process, starting with the beginning of the medical studies and growing continuously during the preclinical semesters. Effect-ive strategies for coping with distress should be integrated in the medical curriculum at universities from the very first semester on. Relaxation techniques could thus be an opportunity.

Morphological alterations within the peripheral fixation of the iris dilator muscle in eyes with pigmentary glaucoma.

PURPOSE: To analyze the peripheral fixation of the iris dilator muscle in normal eyes and in eyes with pigmentary glaucoma (PG). METHODS: Using 63 control eyes (age 18 months-99 years), the peripheral iris dilator was investigated by light microscopy, immunohistochemistry, and electron microscopy. Development was studied using 18 differently aged fetal eyes stained immunohistochemically against α-smooth muscle (SM) actin. The peripheral iris dilator muscle in PG was analyzed using semithin and ultrathin sections of six glutaraldehyde-fixed eyes from three donors aged 38, 62, and 74 years. RESULTS: In normal eyes, the peripheral end of the iris dilator muscle is arranged in a sphincter-like manner. Arcade-shaped tendinous connections associated with myofibroblasts (iridial strands) anchor the iris dilator within the elastic-fibromuscular ciliary meshwork that also serves as fixation area for the elastic tendons of the inner ciliary muscle portions. The iridial strands are innervated and can adapt their length during accommodation. The PG eyes show incomplete circular bundles and iridial strands that are mainly anchored to the iris stroma and the flexible uveal parts of the trabecular meshwork. CONCLUSIONS: The normal anchorage of the peripheral iris dilator and its presumably neuronally regulated length adaptation stabilize the peripheral iris during accommodation. Insufficient fixation in PG could promote posterior bowing of the iris with rubbing against the zonular fibers and pigment liberation from the iris pigmented epithelium.

Comparative anatomy of the human and canine efferent tear duct system--impact of mucin MUC5AC on lacrimal drainage.

PURPOSE: To investigate the histomorphology of the canine tear drainage system and to show the distribution of mucin MUC5AC within the tissue. METHODS: Conjunctiva and tear drainage systems of 19 long-nosed dogs were investigated histologically and ultrastructurally. The tissues were stained with eight different antibodies reactive against less glycosylated and highly-glycosylated MUC5AC. Results were compared with findings in human tissue received from 12 body donors. RESULTS: Except for a distinctly longer nasolacrimal duct and several accessory openings of the duct into the nasal cavity, the morphology of the canine tear drainage system is very similar to that of humans. MUC5AC in less- and highly-glycosylated forms was present in the conjunctival tissue of dogs as well of humans. Within the tear sac and the nasolacrimal duct only less-glycosylated MUC5AC could be found in dogs and in human. CONCLUSIONS: These findings demonstrate that the canine tear drainage system is very similar to its human equivalent. In particular the distribution of MUC5AC, supposed to play an important role within the pathogenesis of dry eye syndrome (DES), is the same as in humans. Therefore the canine model seems to be an appropriate model for further DES research.

Structure/function studies and the effects of memantine in monkeys with experimental glaucoma.

Purpose. The scanning laser polarimetry with variable corneal compensation (GDx VCC) methodology was established and verified in monkeys with experimental glaucoma (ExpG). Terminal GDx parameters were correlated with axon counts and electrophysiologic measures. The effects of memantine on these parameters were investigated. Methods. ExpG was induced in monkeys and intraocular pressure monitored weekly. Some monkeys received memantine in their diet before and after ExpG induction (1-10 months). GDx VCC scans, stereophotographs, and multifocal visual evoked potential (mfVEP) data were collected at baseline and every 6 to 8 weeks until euthanasia. Optic nerves were prepared for axon counting and other morphologic analysis. Results. There was no difference in IOP elevation exposure between memantine-treated and no-memantine-treated monkeys. The percentage of the optic nerve area composed of connective tissue septa was significantly greater in ExpG eyes than in Fellow eyes. There was a strong positive correlation between axon counts and terminal GDx parameter measures. Animals not receiving memantine exhibited significantly lower mfVEP amplitudes in ExpG eyes compared with the ipsilateral baseline or the final value in the Fellow eye. ExpG eyes from memantine-treated animals had higher overall mean amplitudes that were not significantly different relative to the ipsilateral baseline and final amplitudes in the Fellow eye. Conclusions. The authors' studies confirm that GDx VCC can be utilized in monkey ExpG studies to detect early retinal structural changes and that these changes are highly correlated with optic nerve axon counts. These structural changes may or may not lead to central functional changes as shown by the mfVEP in response to investigational therapies.