RESUMOApesar dos recentes avanços no desenvolvimento de métodos complementares de diagnóstico e de novas terapêuticas dirigidas, o cancro colo-rectal continua a ser uma importante causa mundial de morbilidade e mortalidade. Neste sentido, têm sido desenvolvidos nos últimos anos inúmeros trabalhos de investigação com o intuito de encontrar possíveis marcadores de mau prognóstico ainda não caracterizados. A existência de uma arquitectura tumoral complexa formada por vários subclones com heterogeneidade genética entre si tem sido consistentemente apontada em linhas de investigação recentes como um elemento de particular importância. Esta característica parece ter implicações em factores tão relevantes como a representatividade da amostragem tumoral de biópsias para diagnóstico genético e a eficácia de terapias dirigidas, existindo um crescente grau de evidência da relação entre a heterogeneidade genética e o prognóstico dos doentes. O uso generalizado de técnicas de sequenciação de nova geração irá permitir uma melhor compreensão do verdadeiro grau de heterogeneidade genética dos tumores colo-rectais, das suas causas e do seu real impacto na evolução da doença. Nesta revisão pretendemos analisar as recentes descobertas relacionadas com a heterogeneidade genética do cancro colo-rectal, bem como as suas principais implicações clínicas. Palavras-chave: Heterogeneidade Genética; Investigação Médica Translacional; Neoplasias Colo-Rectais/genética; Terapia Molecular Dirigida. ABSTRACTDespite the recent advances in the development of complementary diagnostic exams and modern targeted therapies, colorectal cancer remains a major cause of morbidity and mortality worldwide. In this context, a lot of research has been conducted in the last years to find new markers of poor prognosis. The existence of a complex tumour architecture formed by multiple subclones genetically heterogeneous has been increasingly considered in recent studies as an element of particular importance. This feature seems to influence factors as relevant as the representativeness of tumour biopsies for genetic diagnosis and the efficacy of targeted therapies. There is growing evidence suggesting a relation between genetic heterogeneity and the patients' prognosis. The widespread use of next-generation sequencing techniques will allow a better understanding of the true degree of genetic heterogeneity in colorectal tumours, its causes and impact on the course of the disease. In this review we intend to analyse the recent findings related to the genetic heterogeneity of colorectal cancer, as well as its major clinical implications.

Background: Schizophrenia spectrum disorders (SSD) are the most impairing psychiatric disorders and are a major cause of social exclusion. Despite that, there are only two studies published assessing the socioeconomic characteristics of SSD patients living in Portugal. Aims: The purpose of this study is to assess the degree of social and family support for SSD patients living in the region of ‘Tâmega e Sousa’, in northern Portugal. Method: We conducted a cross-sectional observational study using patients under home-based care provided by the Department of Psychiatry and Mental Health of Centro Hospitalar do Tâmega e Sousa. We retrieved sociodemographic data from clinical records. The study was approved by the Hospital Ethics Committee. Results: Our sample consists on 67 patients with SSD, mostly men (74.6%). Although the majority was single (69.2%) and childless (85.7%), only a minority lived alone (21.2%). In relation to their professional status, only 5.0% were employed and 78.3% got a disability pension. Among the patients that lived accompanied, 68% lived with their parents or grandparents, and a quarter lived with family members affected by psychiatric disorders. Conclusions: These findings highlight the dependence of SSD patients on their family’s support. Lack of labour market integration, economic dependence and difficulty establishing stable relationships further aggravate their social exclusion. Although our results are consistent with a previous observational study held in Portugal, our patients display a worse functional status. Even considering the possible patient selection bias, there is evidence supporting the need for more investment in psychosocial rehabilitation that should take into account the sociodemographic idiosyncrasies of this Portuguese region.

Background: A manic state induced by antidepressant withdrawal is a rare clinical occurrence that has been increasingly reported in the last decades and currently represents a nosological entity with specified criteria. Objectives: This paper aims to report a case of mania induced by escitalopram withdrawal in a patient with unipolar depression. Furtherly, we intend to review the published case reports of manic states induced by antidepressant withdrawal, analysing its epidemiology and discussing the current theories concerning its pathophysiology. Methods: We conducted a search in PubMed database in July 2019, without restriction by year of publication, and selected case reports and literature reviews in English, which were fully read. Results: Only 29 reported cases fulfil the most accepted diagnostic criteria. This phenomenon is more frequent in patients with unipolar depression, may occur with any major class of antidepressant and it is still unclear whether it indicates a latent bipolar disorder. Our case report is the third case associated with the use of escitalopram published in the literature. Conclusion: Although a rare phenomenon, mania induced by antidepressant withdrawal poses relevant clinical challenges and its possible pathophysiological processes may shed some light on the mechanisms underlying affective disorders.

Manic and hypomanic states associated with antidepressant treatments are relatively common; however, when specifically considering mirtazapine, those side effects are infrequent. The authors report a clinical case regarding a manic episode with dysphoric features in a patient with no personal or family previous psychiatric history. It began two weeks after starting treatment with mirtazapine up to 30 mg/day. This episode was treated discontinuing mirtazapine and initiating olanzapine (10 mg), with symptomatic remission. Mirtazapine has a specific pharmacodynamics, blocking not only post-synaptic serotonergic receptors but also α2-presynaptic adrenergic receptors. Taking this into consideration, it was hypothesized that this case could be attributed to a noradrenergic syndrome, characterized by dysphoria, irritability, insomnia and psychomotor agitation.

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