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Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response. Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders.

Repetitive transcranial magnetic stimulation (rTMS) is a neurostimulatory technique used to modulate orbital frontal corticostriatal (OFC) activity and clinical symptomatology for psychiatric disorders involving OFC dysfunction. We examined the effectiveness of rTMS in the treatment of major depressive disorder in an applied clinical setting (Awakening KC CNI) to assess efficacy and optimize rTMS parameters within clinical practice. A retrospective review of medical records was carried out on patients with major depressive disorder undergoing rTMS therapy at Awakenings KC Clinical Neuroscience Institute (CNI), a suburban tertiary psychiatric clinic. A detailed de-identified data set of clinical outcomes was compiled. Patient Health Questionnaire 9 (PHQ-9) total score, clinical remission rate and week achieved were evaluated over 6 weeks of treatment to assess clinical response referencing two different rTMS instruments (MagVenture; NeuroStar). Our survey included 247 participants from males (N=98) and females (N=149) with average baseline PHQ-9 scores of 21.7±4, classified as severe depression. Clinically rated remission rates of 72% were achieved in 3.1±1.0 weeks and associated with prior history of psychiatric hospitalization, suicide attempts and substance use disorder. Average baseline PHQ-9 scores decreased significantly over time with proportionately greater remission rates achieved for patients treated using the MagVenture over NeuroStar instrument. rTMS in applied clinical practice is efficacious over a wide range of settings and patients. Clinical response was related to severity of depression symptoms (e.g., prior hospitalization; suicide attempts) validating efficacy in critically ill groups. Clinical response may be impacted by rTMS instrument, magnetic field parameters or individual factors.

Some of the best entrepreneurs fail early and often. Less talented or less committed entrepreneurs do not even get a second chance. Failure and setbacks, however, can be instructive.What lessons can be learned from these experiences? How can the entrepreneur (and investors) navigate around the potholes on the New Venture Highway? Read on.

This study is a follow-up of inpatients diagnosed with severe depression/melancholia between 1956 and 1969. During this period, all inpatients at the Department of Psychiatry, University Hospital, Lund, were rated on a multidimensional diagnostic schedule on discharge. There were 471 patients born from 1920 onward. In the present follow-up, 2006 to 2010, 169 survivors could be traced. They were asked to participate in the study involving a telephone interview, in which a structured life chart was used. Of the patients contacted, 16 were ill or confused and 3 did not remember ever being depressed, leaving 150 who could participate. Seventy-five of these agreed to participate in the study. Long-term course of depression was evaluated by cluster analysis and compared to background variables, such as heredity for depression, perceived parental rearing behaviour, and treatment of index depressive episode. Using a cluster analysis the patients could be separated into six clusters describing the course: i) single or few episodes followed by long-lasting remission; ii) single or few episodes followed by long-lasting remission, although shorter; iii) single or few episodes followed by late recurrence; iv) single or few episodes, but more frequently ill, followed by late recurrence; v) several episodes followed by lasting remission; vi) chronic course of episodes. Remission or recurrence could therefore occur even after more than a decade. In summary, there was a short-term course with or without recurrence or a chronic course with or without late remission. Heredity for depression was significantly related to a chronic course with or without late remission.

Anxiety, depression and impaired health-related quality of life (HRQoL) are commonly reported in patients with multiple sclerosis (MS) and are of great interest for therapeutic approaches. Based on regional differences a quantitative assessment of these factors in comparison to the general population, and the consideration of demographic cofactors, would be useful when designing specific interventions. We adopted such an approach in a German cohort of MS patients. Anxiety, depression (HADS) and HRQoL (SF-36) were measured in 49 consecutive outpatients with MS and compared to age- and gender-adjusted control groups (n=1330 for HADS; n=5087 for SF-36) extracted from German National Health Surveys. Patients with MS showed significantly increased levels of anxiety and depression as well as decreased HRQoL with the exception of mental health; the effect sizes ranged from 0.39 (depression) to 1.06 (physical functioning). As could be expected, MS patients with relapsing-remitting clinical course had better physical functioning than patients with secondary progressive MS. There were strong relations between anxiety and depression (r=0.54; P<0.01), and between neurological impairment (EDSS) and physical functioning (r=-0.80; P<0.001) as well as depression (r=0.48; P<0.05). This investigation of MS patients confirms the prevalence and impact of anxiety, depression and most of the HRQoL dimensions in MS patients and provides evidence for the usefulness of a quantitative comparison to a region-specific general population as a starting point for therapeutic approaches.

Using the Panel Study of Entrepreneurial Dynamics II dataset, we examine the role that household income plays in the emergence of consumer-oriented start-ups by individual (solo), family-based (family), and non-family based start-ups (team). In particular, we address the research question: Does household income impact firm emergence, and if so, is emergence impacted differently based on start-up configuration? Our results indicate that household income does have a significant impact on average firm emergence, as well as on emergence growth rates for solo and family firms, playing an especially significant role for family firms. Furthermore, we found that household income is not a significant predictor of start-up activity completion for teams. Results from our study reinforce the extant literature on the benefits of starting a firm with teams, and suggests that these enterprise types may provide a more stable platform on which to launch a start-up. Implications of these findings and opportunities for future research are offered.

Rural consumers’ in- and out-shopping intention has been a research topic for many years. This study investigates the relationship between social identity and rural consumersʼ intent to shop within their local community, along with a number of moderating demographic variables. Using a sample of respondents from the Midwest, this study found a significant and positive relationship between rural consumers who socially identify with people in their local community and their intent to inshop. The influence of several demographic moderators is also explored, and implications for practice and future re-search are discussed.

This exploratory study examines the financial performance satisfaction of small business owners at two time periods: (1) nearing the end of the Great Recession and (2) three years into economic recovery. In addition to considering small business owners in general, special attention has been paid to women and minority owners. Using independent samples t-tests, results indicate that business owners are more satisfied with their financial performance in 2012 than they were in 2009. However, results were not consistent for all subgroups of the population; differences exist between men and women owners and between Caucasian and minority owners. Whereas men mirrored the results for all business owners, women did not report increased satisfaction in any of the five areas of financial performance examined. Caucasian owners reported increases in four of the five areas of financial health and minority owners saw an increase in only three. The study also provides practical implications and areas for future research.