Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.

Rosalie Sattler-Feuerstein: An Austro-Hungarian Official Female Physician in Bosnia and Herzegovina, 1914-1919.

This short biography traces the life and medical activities of Rosalie Sattler, née Feuerstein (1883-19??), who was employed as an official female physician at the Austro-Hungarian (AH) provincial public health department in Sarajevo from 1914-1919. Born in 1883 into a Jewish middle-class family in Chernivtsi (then Czernowitz), Ukraine, in Bukovina, the easternmost province in Austria, Feuerstein moved to Vienna in 1904 to study medicine. After earning her MD from Vienna University in 1909, she started her career as an assistant physician at the Kaiser Franz Josef Hospital in Vienna. In spring 1912, Feuerstein moved to Sarajevo to work as an intern at the local provincial hospital (Landeskrankenhaus). In the same year, she married AH district physician Moritz Sattler (1873-1927) in Vienna. In 1914, Sattler-Feuerstein successfully applied to be an AH official female physician in Bosnia. She was an employee of the provincial public health department in Sarajevo and never functioned as an official female physician in the sense of the relevant AH service ordinance. After the collapse of the monarchy, Sattler-Feuerstein continued to be employed as an official female physician of the Kingdom of Serbs, Croats, and Slovenes. She resigned from service in 1919 and established herself as a private general practitioner in Sarajevo with her husband, who had also resigned as an official physician and started to practice privately at that point. Widowed in 1927, she left Sarajevo for an unknown destination, likely in 1938-1939, and vanished from historical records. CONCLUSION: Rosalie Sattler-Feuerstein (1883-19??) came to Bosnia as the eighth AH official female physician and worked as an employee of the AH provincial public health department in Sarajevo from 1914-1919, after which she practiced as a private physician in Sarajevo for more than 25 years.

Kornelija Rakic: A Woman Doctor for Women and Children in Serbia and Bosnia and Herzegovina.

This short biography focuses on the life and medical activities of Kornelija Rakic (1879-1952), a Serbian female pioneer of medicine from the then Hungarian province of Vojvodina, who acquired an MD from the University of Budapest in 1905. Rakic came from a humble background, and a Vojvodina Serbian women's organization enabled her to become a physician and pursue her social medicine mission. After a futile attempt to open a private practice as a "woman doctor for women" in Novi Sad in 1906, she successfully applied to the Austro-Hungarian provincial government in Sarajevo for the position of an official female physician in occupied Bosnia. Rakic began her career as an Austro-Hungarian (AH) official female physician in Bihac (1908-1912) and was transferred to Banja Luka in 1912 and to Mostar in 1917=1918. Kornelija Rakic stayed in Mostar after the monarchy collapsed in 1918 and continued to work as a public health officer in the service of the Kingdom of Serbs, Croats and Slovenes, founded in 1918. Subsequently, she served as the head of the "dispensary for mothers and children" at the Public Health Centre in Mostar, founded in 1929, where she practiced until her retirement in 1949. After World War II, Rakic served as Vice President of the Red Cross Society in Mostar. She received numerous awards and medals from the Austro-Hungarian Empire, the Kingdom of Yugoslavia and the Federal People's Republic of Yugoslavia. Kornelija Rakic died in Mostar in 1952 and was buried at the local Orthodox cemetery of Bjelusine. CONCLUSION: Kornelija Rakic (1879-1952) was the first Serbian female physician in Novi Sad, Vojvodina, and she was employed as an AH official female physician in Bihac (1908-1912), Banja Luka (1912-1917) and Mostar (1917-1918). After World War I, she participated in the establishment and expansion of public health institutions in Mostar and Herzegovina from 1918-1949 against the backdrop of the devastation of the two World Wars.

Rosa Einhorn (1872-1950): A Woman Pioneer in Medicine between Bosnia (1902-1913), New York, and Palestine.

This short biography details the life and medical activities of Rosa Einhorn, mariée Bloch (1872-1950), who practised as an Austro-Hungarian (AH) official female physician in Travnik in occupied Bosnia and Herzegovina (BH) from 1902 to 1904, and as a semi-official private physician from 1905 to 1912/13. Born in Hrodna district in the Russian Pale of Crescent, Einhorn had qualified and practised as a "feldsheritsa" in Russia and went to Switzerland to study medicine in 1896. Upon receiving her medical doctorate from the University of Lausanne in 1901, she became recommended as a particularly adequate candidate for the not-yet-created position of an AH official female physician in BH. After Einhorn functioned as a general practitioner for women and children in Travnik and the adjacent districts for two years, the AH public health authorities officially dismissed her due to her engagement and marriage to the AH judiciary Sigismund Bloch (1850-1927). However, she obtained a right to private practice in 1905 and was employed as a private physician in AH anti-syphilis campaigning. Struggling for her reinstatement as an official female physician in Travnik, she also strove for the accreditation of her Swiss diploma in Austria, though in vain. After two attempts to emigrate to the United States in 1904 and 1913, Rosa Einhorn finally left Europe to work as a physician in the United States and Mandatory Palestine/Eretz Israel in 1923. She died in New York on May 27, 1950. CONCLUSION: Rosa Einhorn was employed as a provisory official female physician in Travnik in 1903/1904, the AH authorities accepting her only as a local private female physician after her marriage in 1905. Struggling in vain for her reinstatement, she finally left Bosnia in 1913.

Jadwiga Olszewska: A Woman Pioneer in Medicine in Serbia and Bosnia and Herzegovina.

This article describes the life and medical activities of Jadwiga Olszewska (1855-1932) in Serbia from 1895-1899, AustroHungarian (AH)-occupied and annexed Bosnia and Herzegovina (BH) from 1899-1918, and the newly founded Kingdom of Yugoslavia, from 1919-1932. In summer 1899, Olszewska replaced Teodora Krajewska as an AH official female physician in Tuzla. Born in Congress Poland, Olszewska had enrolled in 1873 in the medical courses for women in St. Petersburg but had left Russia in 1880 to study medicine in France. She had lived as a student and single parent in Paris since 1883, and she was awarded her Doctorate in Medicine from the University of Paris in 1894. She could not practice medicine in Russian-occupied Poland because of her French diploma, and she could not practice in most Western countries due to her gender. Therefore, she decided to move to Serbia, where she worked as an assistant physician in the district hospitals of Loznica (1895-1897?) and Pozarevac (1897-1899). Driven by the need for a higher income to fund her son's education, she engaged her network of Polish compatriots and procured the position of an AH official female physician of Tuzla in 1899, where she performed her duties in an exemplary manner. After the breakdown of the Austro-Hungarian Empire (AHE) in 1918, Olszewska remained in Tuzla and retired as a Yugoslav official physician in 1923. When she died in Tuzla in 1932, local colleagues had to arrange for a proper funeral because Olszewska did not leave any savings due to her insufficient pension. Olszewska's grave never received a tombstone, and it is untraceable today. CONCLUSION: Jadwiga Olszewska (1855-1932) was a woman pioneer of medicine from Poland, who practiced her profession first as an assistant physician in Serbia (1895-1899) and then as an AH and Yugoslavian official female doctor in Tuzla, BH (1899-1923).

Gisela Januszewska (née Rosenfeld), an Austro-Hungarian 'Woman Doctor for Women' in Banjaluka, 1899-1912.

The focus of this article is on the biography and medical activity of Gisela Januszewska (née Rosenfeld) in Austro-Hungarian (AH) occupied Bosnia and Herzegovina (BH) between 1899 and 1912. Rosenfeld, later Januszewska and then Kuhn(ová) by marriage, was the fifth of a total of nine official female physicians who were employed by the AH administration to improve the health and hygienic conditions among Bosnian and Bosnian Muslim women. In 1893, Gisela Kuhn moved from Brno, Moravia to Switzerland to pursue her medical studies; she was awarded her Doctorate in Medicine (MD) from the University of Zurich in 1898. In the same year, she took up her first position as a local health insurance doctor for women and children in Remscheid but was prohibited from practising in the German Empire. In 1899, she successfully applied to the AH authorities for the newly established position of a female health officer in Banjaluka and began working there in July 1899. She lost her civil service status upon marrying her colleague, Dr Wladislaw Januszewski, in 1900 but carried out her previously officially assigned tasks as a private physician. In 1903, she was employed as a 'woman doctor for women' at the newly established municipal outpatient clinic in Banjaluka. Upon her husband's retirement in 1912, the couple left BH and settled in Graz, Styria. After, World War I Januszewska ran a general medical practice in Graz until 1935 and worked as a health insurance-gynaecologist until 1933. She received several AH and Austrian awards and medals for her merits as a physician and a volunteer for humanitarian organisations. Upon Austria's annexation to Nazi Germany 1938, however, she was classified a Jew and was deported to Theresienstadt concentration camp (Terezín, Bohemia), where she died in 1943. CONCLUSION: Gisela Januszewska, née Rosenfeld (1867-1943) viewed her medical practice as a social medicine mission which she put into practice as a 'woman doctor for woman' in Banjaluka, BH (1899-1912) and Graz, Austria (1919-1935).

Dr. Anna Bayerová: The First Official Female Doctor in Bosnia and Herzegovina.

This biographical note details Anna Bayerová's (1853-1924) activities as the first female Austro-Hungarian health officer in 1878 to1918 occupied Bosnia and Herzegovina (BH). Anna Bayerová is known as a heroine of Czech feminism and the 'first Czech female physician', though she only practised in the Czech lands from 1913 to 1916. In 1891, Bayerová was enrolled as the first Austro-Hungarian female health officer and assigned to treat Muslim women in the district of Tuzla, Bosnia. She pursued this mission for the first three months of 1892, had herself transferred to Sarajevo in the summer, and soon thereafter quitted the service. Her biographers point to a series of political and personal motivations to abandon her mission in Bosnia, which, from the viewpoint of Czech feminists, included fulfilling her professional duties in an exemplary way. She spent most of her professional life as a physician in Switzerland and did not request Austrian recognition of her medical degree until 1913. Bayerová died in Prague in 1924. Conclusion. Bayerová, partly for political reasons and partly due to her panic-fuelled fear of catching tuberculosis, quitted her role as the first Austro-Hungarian female health officer in BH soon after her arrival in 1892.

Boguslawa Keckova: An Official Female Doctor in Bosnia and Herzegovina, 1893-1911.

The purpose of this paper is to bring to light the biographical details, the professional work and the publishing activities of Boguslawa Keckova (Bohuslava Kecková in Czech and Keck in German), who functioned as an Austro-Hungarian health officer in Mostar from 1893 to 1911 during the period of the Austro-Hungarian occupation of Bosnia and Herzegovina (BH). Keckova, who came from Prague, was the second of nine female physicians to be employed by the Austro-Hungarian authorities between 1892 and 1918. Keckova contributed significantly to the improvement of public health and hygiene in BH, especially by organising the medical treatment of Muslim women. She published a series of popular medical articles, both in Czech and in Bosnian. Her medical articles in the Mostar newspaper, 'Osvit', were among the first in BH to promote public health education and aimed at improving the health of the population. In the Czech Republic, 'Bohuslava Kecková' is renowned for being the first Czech female physician to graduate, who, due to Austria's conservativism and anti-feminism, had been forced to study and practise abroad. After Keckova's efforts to have her Swiss MD degree (1880) recognised in Austria failed in 1882, she acquired an Austrian midwife's diploma and established a maternity home in Prague. In 1892, she accepted the invitation to serve as an Austro-Hungarian female health officer in Mostar, where she initialised and popularised the utilisation of public health among (Muslim) women. CONCLUSION: Boguslawa Keckova's work as a physician, medical writer and health educator, which she continued tirelessly until her death in 1911, was based on gender-specific socialmedical concepts, which were at the core of the contemporary Czech feminist movement.

Teodora Krajewska, Official Female Doctor of Tuzla and Sarajevo: Medical Practitioner, Woman of Science, Polish Patriot and Feminist.

A biographical note on Teodora Krajewska (1854-1935) reveals the details of her life and professional activities as an Austro-Hungarian and Yugoslav health officer (Amtsärztin) in Tuzla (1893-1899) and in Sarajevo (1899-1923). Teodora Krajewska, née Kosmowska was the third of nine official female doctors employed by the Austro-Hungarian administration in occupied Bosnia and Herzegovina (BH: 1878-1918) and charged with the special task of popularising public health and hygiene, particularly among Muslim women. A Polish intellectual and fervent patriot from Warsaw, Krajewska had left Congress Poland as a young widow in 1883 to study medicine in Geneva, Switzerland. In 1890, she became the first woman in Europe to be employed as an assistant professor at the medical faculty of the University of Geneva but was forced to resign in 1892. In the same year, she was both awarded her doctorate and appointed to the position of an Austro-Hungarian female health officer in Tuzla. After being nationalised in Austria, she reported for duty in Tuzla in March 1893. In 1899, she accepted her transfer to a newly created position in Sarajevo where she was active as an official physician until 1922/23. She contributed to contemporary medical science through her research on leprosy and osteomalacia in Bosnia. She returned to Warsaw in 1928 and devoted herself to the translation of Serbo-Croatian literature and writing her memoirs on her life and activities in BH.

Association of a Met88Val diazepam binding inhibitor (DBI) gene polymorphism and anxiety disorders with panic attacks.

Several lines of evidence suggest that anxiety disorders have a strong genetic component, but so far only few susceptibility genes have been identified. There is preclinical and clinical evidence for a dysregulation of the central gamma-aminobutyric acid (GABA)-ergic tone in the pathophysiology of anxiety disorders. Diazepam binding inhibitor (DBI) has been suggested to play a pivotal role in anxiety disorders through direct and indirect, i.e. via synthesis of neuroactive steroids, modulation of GABA(A) receptor function. These findings suggest that the DBI gene can be postulated as a candidate for a genetic association study in this disorder. Thus, single nucleotide polymorphisms (SNPs) of the DBI gene were investigated for putative disease associations in a German sample of anxiety disorder patients suffering from panic attacks and matched controls. We were able to detect a significant association between a non-synonymous coding variant of DBI with anxiety disorders with panic attacks. The rare allele of this polymorphism was more frequent in controls than in patients (OR=0.43; 95% CI: 0.19-0.95). In conclusion, these results suggest a central role of DBI genetic variants in the susceptibility for the development of anxiety disorders that are characterized by the occurrence of panic attacks.

Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression.

BACKGROUND: One of the most demanding tasks in psychiatry is to protect patients from suicidal attempts. Preventive strategies could be improved by increasing our knowledge on the pathophysiologic disturbances underlying this behavior. More than 70-80% of suicides occur in the context of depressive disorders, in which dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most prominent neurobiological findings. So far data on the involvement of the HPA axis in the pathophysiology of suicidal behavior in depressed patients are controversial. METHODS: In this retrospective study, we administered the combined dexamethasone-suppression/CRH stimulation (Dex/CRH) test to 310 patients with a depressive syndrome characterized at admission for acute and past suicidal behavior within the first 10 days after hospitalization. RESULTS: Suicidal behavior in depressed patients, including past and recent suicide attempts as well as suicidal ideation, was associated with a lower adrenocorticotropin and cortisol response in the combined Dex/CRH test, with lowest hormone levels observed in patients with a recent suicide attempt. DISCUSSION: The findings suggest that suicidal behavior may alter HPA axis regulation in depressed patients. Large-scale prospective studies assessing neuroendocrine changes may help to develop predictors for an early identification of patients at risk for committing suicide.