The research literature proposes that the concept of identity may be central to understanding responses to having severe and enduring mental health problems. Theorists hypothesise a relationship between identity and the individual's acceptance of having mental health problems mediated by societal pressures. Given the inconclusive findings from research carried out a decade ago, this study has attempted to explore whether the participants' identification as a community member or patient affected, or was affected by, their belief that they have mental health problems, need medication, need to see healthcare professionals and their awareness of disabilities. A quantitative methodology was employed to examine the main variables. Forty five individuals living in the community with a diagnosis of schizophrenia, bipolar affective disorder or schizoaffective disorder were interviewed. Both within-group and between-group analyses were employed. The relationship between the independent variables and their relationships with sociodemographic and diagnostic factors, self-esteem and health and social functioning were explored. Measures that had been either standardised or used in previous related research were employed. The three central measures were taken from previous research studies in this area. Socio-demographic information was obtained from clinical files. Neither beliefs about mental health problems nor awareness of disabilities were found to be associated with identity, as measured in this study. Health and social functioning and work-related variables appeared to contribute to an identification as a community member. It is suggested that defensive responses to disabilities existed to protect the individual's sense of self-worth. Furthermore, socially valued experiences prior to illness and level of ability may have contributed to the participants' identification as a community member. The clinical implications are discussed.

1H-Magnetic Resonance Spectroscopy (MRS) is a MRI paradigm that allows the levels of specific metabolites to be estimated in vivo [1]. This means that insights into the biochemical changes associated with a rare genetic change that raises the risk of mental disorders, and the impact of having a mental disorder, can potentially be made. In this study the levels of glutamate and N-acetyl-aspartate (NAA) were measured at 3T field strength in three separate voxels: right dorsolateral prefrontal cortex (DLPFC), left DLPFC and the anterior cingulate cortex (ACC). This thesis reports that members of a family that carry a unique t(1;11)(q42.2;q14) translocation that affects DISC1 have a substantially raised risk of developing a range of mental disorders, including bipolar affective disorder, schizophrenia and depression. A genetic change that leads to an increase in the susceptibility to a range of mental disorders is in line with other genetic studies that have been recently reported [2, 3]. The translocation was associated with a significant reduction in right DLPFC glutamate (mean difference= -2.11, CI= -0.24: -3.98, p=0.029) and left DLPFC NAA (mean difference= -1.97, CI= -0.34: -3.61, p=0.020). Changes in these metabolites offer some support to studies in cells and rodents trying to understand the impact of the t(1;11) translocation. More specifically the results offer support to studies that have linked alterations in DISC1's molecular biology to changes in glutamate receptors and mitochondrial function [4-6]. The results need to be interpreted with some caution due to the small sample size and the lack of a significant effect in the bilateral DLPFCs. People with a major mental disorder were also found to have significantly lower levels of glutamate in the left DLPFC (F=3.16, p=0.047). When compared to controls the reductions were significant in the people with a diagnosis of schizophrenia (mean difference= -0.86, CI= -0.19: -1.51, p=0.012), but not in people with bipolar affective disorder. Glutamate levels were significantly correlated with negative symptoms in people with schizophrenia (SANS r= -0.44, CI= -0.07: - 0.70, p= 0.024). The effect of experiencing depressive symptoms was also evaluated due to support for a link in previous studies [7, 8]. Whist the participants were not recruited due their experience of depressive symptoms, metabolite levels were found to be significantly associated with depressive symptoms in all participants with a mental disorder (all three voxels, both NAA and glutamate p < 0.05). The experience of depressive symptoms is not the same experiencing a depressive episode though, and further work may offer more insights into the association between metabolite changes and experience of depression. These findings provide insights into the relationship between diagnosis, current psychopathology and genetic risk in major mental disorders. The thesis provides some support that MRS imaging can be used to try understand neurobiological changes that are associated a genetic change, which is in turn linked to range of mental disorders. Interpreting the results of MRS imaging studies in humans remains challenging due to the complexity of the molecular biology that underpins the estimated metabolite levels, but where there has been a wide range of translational study into a specific protein (or genetic change) MRS may offer further information to help understand any effect in vivo.

Background: Traditional psychosocial treatments have been adapted for use with individuals with bipolar affective disorders due to the limited prophylactic nature of pharmacotherapy and the recognition of the role of psychosocial factors in the course of this disorder. Psychosocial interventions that include a prodromal monitoring and management component have been empirically shown to be an effective adjunct to medication for the treatment of bipolar disorder. Aims: There is a deficit of quantitative research that examines the impact of individualrelated (e.g. age, self-efficacy), disorder-related (e.g. time since diagnosis, experience of prodromal symptoms) and treatment-related (e.g. level of psychosocial input) factors on individuals’ ability to manage this disorder via the use of prodromal monitoring. The current research aimed to investigate factors that are associated with the identification and management of prodromal symptoms. Method: Participants completed five self-report measures in order to provide information on their experience of prodromal symptoms, current mood state, general self-efficacy, view of social support from significant others, and demographic and clinical-related variables. The data were collected from 101 participants, 58 of whom were female. The sample consisted of individuals with a diagnosis of bipolar disorder type I and II. Results: Univariate and bivariate analyses were used to explore the relationship between individual, disorder, and treatment-related variables associated with participants’ experience of bipolar disorder. Variables that were significantly associated with participants’ perception of their ability to identify and manage prodromes were further investigated using ordinal logistic regression analyses. The results indicated that general self-efficacy and prodromal-specific help from significant others were associated with an increase in participants’ perception of their ability to identify manic and depressive prodromal symptoms. General self-efficacy was also associated with participants’ view of their ability to manage cognitive and behavioural prodromes. Experience of prodromal symptoms (e.g. consistency of symptoms experienced, type of prodrome experienced) was associated the participants’ perception of their ability to identify and manage prodromes. In general, disorder-related variables (e.g. time since diagnosis, mood state, diagnosis type, and number of episodes experienced) were not significantly associated with the participants’ view of their ability to identify and manage prodromal symptoms. Individual-related variables such as gender and age, however, were associated with prodromal identification. Conclusion: The results indicated the need to consider constructs such as general selfefficacy and experience of prodromal symptoms (e.g. consistency of symptoms, types of prodromes experienced, and ability to recognise prodromes when they first present) when helping patients to learn how to identify and manage prodromal symptoms. In addition gender differences and the role of help from significant others were highlighted as variables that should be considered when using prodromal monitoring approaches with patients with bipolar disorder. Limitations of the research are reviewed in relation to the methodology used. Clinical implications and directions for future research are considered.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Rambousková Supervisor: Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Pharmacotherapy of mood disorder This diploma thesis deals with the characterization of mood disorders concentrating especially on depression disorders. It presents the classification of mood disorders according to classification MKN-10. The diploma thesis presents patophysiology of depression disorders, their causes, symptoms and progress. It analyses the choice of pharmacotherapy in depression disorders and bipolar affective disorder. It describes individual groups of antidepressants and drugs used for treatement of bipolar affective disorder. It analyses their mechanism of action, indications, contraindications and adverse effects. At the end of diploma thesis states the other use of antidepressants in non- psychiatric indications.

A literatura aponta que traumas emocionais precoces (TEP) podem ser um fator de risco para o desenvolvimento do transtorno afetivo bipolar (TAB). Estudos também indicam associações entre TAB, prejuízos no reconhecimento de expressões faciais de emoções (REFE) e no funcionamento psicossocial, envolvendo traços de personalidade e habilidades sociais, os quais podem estar presentes inclusive em indivíduos em risco para o transtorno, como os parentes de primeiro grau. O objetivo deste estudo foi avaliar as associações entre TEP, características psicossociais e REFE em sujeitos portadores (eutímicos) e em condição de risco para o TAB em comparação com um grupo de indivíduos saudáveis da comunidade. Foi avaliada uma amostra total de 109 sujeitos adultos de ambos os sexos, sendo 40 do grupo com TAB (GB), 30 do grupo em risco (GR) e 39 do grupo controle (GC). A avaliação do diagnóstico foi feita por meio da Entrevista Clínica Estruturada para o DSM-IV e do estado de humor atual pelo Questionário Sobre a Saúde do Paciente-9 e pela Escala de Avaliação de Mania (EAM). Para a avaliação dos desfechos foram utilizados instrumentos de auto relato (Inventário de Auto-avaliação de Traumas Precoces - Versão Reduzida, Inventário de Cinco Fatores NEO Revisad-versão reduzida, Inventário de Habilidades Sociais), e uma tarefa dinâmica de REFE. Os dados foram analisados por testes estatísticos paramétricos (teste do QuiQuadrado, teste para a comparação de duas proporções, ANOVA e ANCOVA) e pela análise de componentes principais (analise multivariada). Os resultados apontaram que o GB apresentou mais vivências de TEP, características psicossociais desadaptativas e maiores prejuízos no REFE em comparação ao GR e GC. Os sujeitos do grupo GR apresentaram um perfil com traços de prejuízo quando comparados ao GC, mas em menor nível que o GB, expressos sobretudo por presença de altos índices de neuroticismo na personalidade e de falhas no processo do REFE. Por outro lado, apresentaram fatores protetores como traços de abertura e bom nível de habilidades sociais. De maneira geral, os achados corroboram a literatura prévia reforçando a presença de possíveis marcadores genéticos para o TAB, subjacentes ao seu desenvolvimento, e apontam indicadores de resiliência que podem favorecer condutas de prevenção e intervenção precoce. / The literature shows that early emotional traumas (EETs) can be a risk factor for development of affective bipolar disorder (ABD). Studies have also reported associations between ABD and impairment in both recognition of emotional facial expressions (REFE) and psychosocial functioning, involving personality traits and social skills, and which may be present in at-risk individuals, such as first-degree relatives. The objective of this study was to assess the associations between EET, psychosocial characteristics and REFE in subjects who are euthymic (i.e. ABD carrier) and those who are at risk of ABD in comparison with healthy individuals in the community. In total, 109 male and female adults were divided into groups as follows: 40 subjects with ABD (GB), 30 subjects at risk (GR) and 39 healthy subjects as controls (GC). Diagnostic evaluation was carried out by means of a structured clinical interview for DSM-IV disorders and the current state of mood by using the patient health questionnaire-9 and mania assessment scale (MAS). For assessment of outcomes, self-report instruments (i.e. early trauma inventory self-report - short version, revised NEO five-factor inventory - short version, and social skills inventory) and a dynamic task of recognition of emotional facial expressions were used. The resulting data were analysed by using parametric statistical tests (i.e. chi-square test, two-proportion comparison test, ANOVA and ANCOVA) and analysis of the main components (i.e. multivariate analysis). The results showed that subjects of GB group had experienced more EETs, maladaptive psychosocial characteristics and more impaired REFE compared to those of GR and GC groups. The subjects of GR group had a worse psychological profile compared to that of GC group, but better than that of GB as subjects with ABD exhibited high levels of neurotic personality traits and poor REFE. On the other hand, they presented protective factors such as openness and good social skills. Overall, the findings corroborate the literature by reinforcing the presence of possible genetic markers for ABD secondary to its development and by suggesting indicators of resilience, which can favour preventive measures and early intervention.

Augmenting/reducing of the evoked potential has been shown to be related to sensation seeking (SS) and specific clinical disorders. Buchsbaum demonstrated that patients with bipolar affective disorders (BAD) tend to be augmenters, as is the case with sensation seekers, and patients with unipolar affective disorders (UPD) tend to be reducers. In addition, he reported that prophylactic medication reduced the tendency to augment in bipolar patients. However, evidence for these relations is restricted to a few studies. This study explores whether Buchsbaum’s initial findings can be found in a naturalistic clinical setting. Acoustic evoked potentials were recorded for six levels of intensity (59, 71, 79, 88, 92, 96 dB SPL) from 24 healthy adults, 21 unipolar depressed patients, and 21 patients with BAD. Participants also completed personality questionnaires, especially the Sensation Seeking Scales Form V. Results revealed a positive correlation between SS and augmenting/reducing in healthy controls, thereby replicating earlier findings. Bipolar depressed patients showed larger P1/N1 slopes than healthy controls, when medication was statistically controlled. Unipolar depressed patients showed smaller P2 slopes, but only when medication was not controlled. Implications of these results for further research on augmenting/reducing and affective disorders and their relationship to SS are discussed. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Augmenting/reducing of the evoked potential has been shown to be related to sensation seeking (SS) and specific clinical disorders. Buchsbaum demonstrated that patients with bipolar affective disorders (BAD) tend to be augmenters, as is the case with sensation seekers, and patients with unipolar affective disorders (UPD) tend to be reducers. In addition, he reported that prophylactic medication reduced the tendency to augment in bipolar patients. However, evidence for these relations is restricted to a few studies. This study explores whether Buchsbaum’s initial findings can be found in a naturalistic clinical setting. Acoustic evoked potentials were recorded for six levels of intensity (59, 71, 79, 88, 92, 96 dB SPL) from 24 healthy adults, 21 unipolar depressed patients, and 21 patients with BAD. Participants also completed personality questionnaires, especially the Sensation Seeking Scales Form V. Results revealed a positive correlation between SS and augmenting/reducing in healthy controls, thereby replicating earlier findings. Bipolar depressed patients showed larger P1/N1 slopes than healthy controls, when medication was statistically controlled. Unipolar depressed patients showed smaller P2 slopes, but only when medication was not controlled. Implications of these results for further research on augmenting/reducing and affective disorders and their relationship to SS are discussed. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.