Is a persistent global bias necessary for the establishment of planar cell polarity?

Planar cell polarity (PCP)–the coordinated polarisation of a whole field of cells within the plane of a tissue–relies on the interaction of three modules: a global module that couples individual cellular polarity to the tissue axis, a local module that aligns the axis of polarisation of neighbouring cells, and a readout module that directs the correct outgrowth of PCP-regulated structures such as hairs and bristles. While much is known about the molecular components that are required for PCP, the functional details of–and interactions between–the modules remain unclear. In this work, we perform a mathematical and computational analysis of two previously proposed computational models of the local module (Amonlirdviman et al., Science, 307, 2005; Le Garrec et al., Dev. Dyn., 235, 2006). Both models can reproduce wild-type and mutant phenotypes of PCP observed in the Drosophila wing under the assumption that a tissue-wide polarity cue from the global module persists throughout the development of PCP. We demonstrate that both models can also generate tissue-level PCP when provided with only a transient initial polarity cue. However, in these models such transient cues are not sufficient to ensure robustness of the resulting cellular polarisation

Contrasting Monosymptomatic Patients with Hallucinations and Delusions in First-Episode Psychosis Patients: A Five-Year Longitudinal Follow-Up Study

Objectives: This thesis explores different symptom profiles found in First Episode Psychosis (FEP) patients assessed at several points of time over a ten year period. Earlier studies have focused predominantly on groups of symptoms rather than individual symptoms when describing course of illness and outcome, and long-term studies of symptom development in epidemiological FEP samples assessed multiples times are lacking. By studying individual symptoms longitudinally from the onset of illness we aimed to gain more knowledge about symptom development and the relationship between symptoms and outcome variables that are known to be affected in psychotic disorders. The aim of the study was threefold: 1) to identify a group of patients with delusions only and a group with hallucinations only, and examine if the groups differed with regard to demographics, clinical variables and outcome measures, and in particular suicidality, 2) to assess the prevalence of apathy ten years after the first psychotic episode, and to explore the association between apathy and general functioning, and between apathy and quality of life, and 3) to identify different flat affect (FA) symptom profiles based on longitudinal symptom trajectories and assess the prevalence and correlates of these trajectories, to assess predictors of enduring FA, and to explore the longitudinal relationship between FA and social functioning. Methods: Three-hundred-and-one first episode, non organic psychosis patients were included in the TIPS Study (Early Treatment and Intervention in Psychosis) and followed over a ten year period. Patients were assessed at baseline, three months, and one, two, five and ten year follow-up with an extensive battery of instruments including measures of demographics, duration of untreated psychosis (DUP), premorbid function (PAS), diagnosis (SCID), symptom measures (PANSS, AES, CDSS), measures of functioning (GAF, SCLFS), suicidality and quality of life (L-QoLI). The relationship of the symptoms of interest, namely hallucinations and delusions (PANSS P1 and P3, respectively), apathy (AES-SApathy and PANSS N2+N4) and flat affect (PANSS N1), to the above measures were assessed with t-test, correlation and regression analyses. Results: Sub-groups of patients with hallucinations only and delusions only can be identified in a five year follow-up study, and the groups differed on multiple variables. Most importantly, the hallucination only group scored higher on measures of suicidality, and insight might be a possible mediator of suicidality in this group. Apathy was found to be a common symptom ten years after the first psychotic episode, affecting 30 % of the sample. Proxy-measures of apathy indicated that this symptom declined in the follow-up period. Clinical apathy was strongly related to poorer functioning and to poorer subjective quality of life in patients ten years after the first psychotic episode. Five different FA trajectory groups were identified. FA was more fluctuant than expected, and only 5 % of the sample experienced enduring FA. Furthermore, FA was related to poorer functional outcome measures, in particular to objective social functioning, both premorbidly and throughout the ten year follow-up period. Conclusions: By looking at individual symptoms rather than groups of symptoms it was possible to shed light on patients with symptom profiles that previously have received limited attention, and to learn more about the long-term development of the individual symptoms. Combined, the findings highlight the importance of looking at symptoms separately in order to both better understand the longitudinal association between symptoms, and to gain knowledge of how individual symptom profiles affect outcome measures including suicidality, quality of life, and social functioning