The NEVERMIND e-health system in the treatment of depressive symptoms among patients with severe somatic conditions: A multicentre, pragmatic randomised controlled trial.

Background: This study assessed the effectiveness of the NEVERMIND e-health system, consisting of a smart shirt and a mobile application with lifestyle behavioural advice, mindfulness-based therapy, and cognitive behavioural therapy, in reducing depressive symptoms among patients diagnosed with severe somatic conditions. Our hypothesis was that the system would significantly decrease the level of depressive symptoms in the intervention group compared to the control group. Methods: This pragmatic, randomised controlled trial included 425 patients diagnosed with myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants were recruited from hospitals in Turin and Pisa (Italy), and Lisbon (Portugal), and were randomly assigned to either the NEVERMIND intervention or to the control group. Clinical interviews and structured questionnaires were administered at baseline, 12 weeks, and 24 weeks. The primary outcome was depressive symptoms at 12 weeks measured by the Beck Depression Inventory II (BDI-II). Intention-to-treat analyses included 425 participants, while the per-protocol analyses included 333 participants. This trial is registered in the German Clinical Trials Register, DRKS00013391. Findings: Patients were recruited between Dec 4, 2017, and Dec 31, 2019, with 213 assigned to the intervention and 212 to the control group. The sample had a mean age of 59·41 years (SD=10·70), with 44·24% women. Those who used the NEVERMIND system had statistically significant lower depressive symptoms at the 12-week follow-up (mean difference=-3·03, p<0·001; 95% CI -4·45 to -1·62) compared with controls, with a clinically relevant effect size (Cohen's d=0·39). Interpretation: The results of this study show that the NEVERMIND system is superior to standard care in reducing and preventing depressive symptoms among patients with the studied somatic conditions. Funding: The NEVERMIND project received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 689691.

Meaning-centered group psychotherapy in Portuguese cancer patients: A pilot exploratory trial.

OBJECTIVE: To describe the feasibility of a meaning-centered group psychotherapy (MCGP) adaptation in a sample of Portuguese cancer patients. METHOD: The study was carried out according to four steps: 1st - Transcultural adaptation and validation (focus groups); 2nd - Preliminary study with MCGP original version (to test its feasibility); 3rd - Adaptation of MCGP original version to a 4-session version (and internal pilot study); and 4th - Pilot exploratory trial (MCGP-4 session version), implemented between January 1, 2018 and December 31, 2019. Inclusion criteria were >18 years, psychological complaints, and difficulty to adapt to cancer. Allocation was according to participants' preference: MCGP vs. care as usual (CAU). Primary outcomes were: MCGP adapted version improved quality of life (QoL) and spiritual well-being; secondary outcomes were improvement of depression, anxiety, and distress. Assessments were done at baseline (T1) and 1 month after (T2), with self-report socio-demographic and clinical questionnaires, Distress Thermometer (DT), McGill Quality of Life Questionnaire (MQOL), Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being Scale (FACIT-Sp-12), Hospital Anxiety and Depression Scale, and its subscales (HADS - HADS-D, HADS-A). RESULTS: In the 1st step, and through focus groups, the manual was reformulated and tested. The preliminary study (2nd step) with MCGP original version showed a high number of dropouts which could jeopardize the study and, after reframing the sessions content, MCGP was adapted to a 4-session version, and its feasibility was tested by an internal pilot study (3rd step). The pilot exploratory trial (4th step) had 91 participants. Most socio-demographic and clinical characteristics between the groups (51: MCGP; 40: CAU) had no statistically significant differences. A comparison between the two groups at T2 showed that the MCGP group scored significantly higher in the general (U = 552.00, P < 0.001), and existential (U = 727.50, P = 0.018) domains and total score (U = 717.50, P = 0.015) of QoL, and CAU presented statistical higher levels in DT (U = 608.50, P = 0.001). Comparing the groups between T1 and T2, the MCGP group had a statistically significant improvement in the general (Z = -3.67, P < 0.001) and psychosocial (Z = -2.89, P = 0.004) domains and total score (Z = -2.71, P = 0.007) of QoL, and a statistically significant decrease in DT (Z = -2.40, P = 0.016). In terms of group effects, the MCGP group presented increased general (b = 1.42, P < 0.001, η2p = 0.179), and support (b = 0.80, P = 0.045, η2p = 0.048) domains and total score (b = 0.81, P = 0.013, η2p = 0.073) of QoL (small to elevated dimensions), and decreased levels of depression (b = -1.14, P = 0.044, η2p = 0.048), and distress (b = -1.38, P = 0.001, η2p = 0.127) (small to medium dimensions), compared with CAU. At T2, participants who attended ≥3 sessions (n = 38) had a statistically significant higher score in the general domain (U = 130.50, P = 0.009) of QoL, comparing with those who attended 1 or 2 sessions (n = 13). SIGNIFICANCE OF RESULTS: This study supports the benefits of an MCGP adapted version in improving QoL and psychologic well-being. More studies are necessary to address the limitations of this pilot exploratory trial, as its small sample size.

Correlation between emotional regulation and peripheral lymphocyte counts in colorectal cancer patients.

BACKGROUND: Colorectal cancer is one of the most common cancers worldwide. Psychological morbidity has an important impact on quality of life and major clinical outcomes. Several data have shown that the immune system may be a key player on the relation between psychological features and cancer outcomes. Natural Killer (NK) cells have been shown to be influenced by psychological factors. The aim of this investigation was to assess the impact of anxiety, depression, and anger state, trait, and expression on the immune response, particularly, their effect on NK cells and CD8+ T cells in surgical colorectal cancer patients. METHODS: We studied 54 surgical colorectal cancer patients and assessed patients pre-surgically, post-surgically, and 12 months after surgery (follow-up). We applied the Hospital Anxiety and Depression Scale and the State-Trait Anger Expression Inventory and measured peripheral T cells, CD8+ T cells, and NK cells. We did a cross-sectional analysis as well as a longitudinal assessment of the variables during the follow-up period. RESULTS: Pre-surgical assessment: Trait anger, angry reaction, and anger-out had a significant negative correlation with NK cells. The lymphocytes values were unaffected by the presence of clinical anxiety or depression. Post-surgical assessment: Patients without clinical anxiety had higher levels of T cells. Angry reaction was negatively correlated with NK cells. Lymphocytes values were unaffected by the presence of clinical depression. Follow-up assessment: Patients without clinical depression had higher T cell counts. Trait anger and angry reaction were negatively correlated with the levels of NK cells. The lymphocytes values were unaffected by the presence of clinical anxiety. Longitudinal assessment: Angry-temperament, anger expression, and anger-in reduced significantly from the first to the second assessment. Anxiety, state anger, and trait anger significantly diminished from the pre-surgical to the follow-up assessment. Depression levels did not alter during the follow-up period. The lymphocyte count, and particularly T cells and CD8+ T cells, was significantly higher in the follow-up when compared with the pre-surgical assessment. CONCLUSION: Our study suggests the existence of a relation between psychological response and immune response in colorectal cancer patients. We identified the importance of emotional regulation as a potential modulator for NK cell counts. Higher values of propensity to experience anger states and express them outwards seem to be associated with lower NK cell counts.

A protocol for a multicentre, parallel-group, pragmatic randomised controlled trial to evaluate the NEVERMIND system in preventing and treating depression in patients with severe somatic conditions.

BACKGROUND: Depressive symptoms are common in individuals suffering from severe somatic conditions. There is a lack of interventions and evidence-based interventions aiming to reduce depressive symptoms in patients with severe somatic conditions. The aim of the NEVERMIND project is to address these issues and provide evidence by testing the NEVERMIND system, designed to reduce and prevent depressive symptoms in comparison to treatment as usual. METHODS: The NEVERMIND study is a parallel-groups, pragmatic randomised controlled trial to assess the effectiveness of the NEVERMIND system in reducing depressive symptoms among individuals with severe somatic conditions. The NEVERMIND system comprises a smart shirt and a user interface, in the form of a mobile application. The system is a real-time decision support system, aiming to predict the severity and onset of depressive symptoms by modelling the well-being condition of patients based on physiological data, body movement, and the recurrence of social interactions. The study includes 330 patients who have a diagnosis of myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants are randomised in blocks of ten to either the NEVERMIND intervention or treatment as usual as the control group. Clinical interviews and structured questionnaires are administered at baseline, at 12 weeks, and 24 weeks to assess whether the NEVERMIND system is superior to treatment as usual. The endpoint of primary interest is Beck Depression Inventory II (BDI-II) at 12 weeks defined as (i) the severity of depressive symptoms as measured by the BDI-II. Secondary outcomes include prevention of the onset of depressive symptoms, changes in quality of life, perceived stigma, and self-efficacy. DISCUSSION: There is a lack of evidence-based interventions aiming to reduce and prevent depressive symptoms in patients with severe somatic conditions. If the NEVERMIND system is effective, it will provide healthcare systems with a novel and innovative method to attend to depressive symptoms in patients with severe somatic conditions. TRIAL REGISTRATION: DRKS00013391. Registered 23 November 2017.

Process of therapeutic changes in Meaning-Centered Group Psychotherapy adapted to the Portuguese language: A narrative analysis.

OBJECTIVE: The aim was to understand the processes of therapeutic changes in Meaning-Centered Group Psychotherapy (MCGP) in a Portuguese sample. METHOD: Adult cancer patients with distress motivated to participate in MCGP were identified; descriptive and narrative analyses were performed on the session content. RESULTS: The sample had 24 participants (mean age: 63.43 years); the majority were females (75%), with a median academic degree (54%). Breast cancer was most frequent (67%) at the localized stage (71%). The narrative analysis defined seven categories according to the MCGP themes. In "Moments with Meaning (MwM)," the most relevant dimensions were related to interpersonal relations, the moment of diagnosis, and personal achievements. This category established relations with almost all other categories, as did the category "historical sources of meaning (SoM)." The category "identity before and after cancer diagnosis" was only related to "attitudinal SoM" and "transitions." Historical SoM had two dimensions, "past" and "present and future" legacies, in which prominent topics related to family, childhood, achieved goals, and values to pass to others explored. Attitudinal SoM established relations only with the category "creative SoM," in which "courage" and "responsibility" were the main dimensions, which were also related to "MwM," "historical," and "attitudinal SoM." Experiential SoM, with the main dimension "love," was related to "MwM" and "historical SoM." Transitions only established relations with "historical SoM" and "identity before and after cancer." SIGNIFICANCE OF RESULTS: The findings that "MwM" and "historical SoM" were the categories which established a solid pattern of relations suggest that these are the main psychotherapy topics that can have more influence for the participants; one explanation is that these categories imply a concrete way of thinking, which is easier to understand. This process of therapeutic changes must be integrated in a cultural context, as it is well known to have an impact upon the "meaning" of life.

Association of Anger Expression-Out with NK Cell Counts in Colorectal Cancer Patients.

INTRODUCTION: There is growing evidence describing the relation between psychological factors and the progression of colorectal cancer. Several mechanisms have been proposed but the one showing more promising evidence relies on the modulation of the antitumoral immune response by psychological factors, particularly through natural killer cells. We aimed to study the relation between natural killer cell count and anxiety, depression and anger state, trait and expression in 54 pre-surgical colorectal cancer patients. MATERIAL AND METHODS: We measured peripheral blood natural killer cell count and applied the State-Trait Anger Expression Inventory and the Hospital Anxiety and Depression Scale to 54 pre-surgical colorectal cancer patients. We used the Mann-Whitney U test and the Kruskal-Wallis test when appropriate to compare independent groups. RESULTS: Patients with higher Anger Expression-Out had lower natural killer cell numbers than patients with lower Anger Expression-Out (p value = 0.008). No relation was found between natural killer cell levels and Anger State, Anger Trait, or Anger Expression-In. No difference in natural killer cell count was found between patients with and without clinical anxiety or depression. DISCUSSION: These results suggest that, in colorectal cancer patients, natural killer cell counts are influenced by Anger Expression-Out, but not by clinical anxiety or depression. CONCLUSION: The unregulated emotional expression might be a conditioning factor of innate immunity. Additional studies are needed to further investigate this relation and to ascertain the clinical impact of therapeutic interventions regarding emotional regulation on the anti-tumoral immune response.

Introdução: Existe crescente evidência da relação entre fatores psicológicos e progressão do cancro colorrectal. Vários mecanismos têm sido propostos porém o mais promissor baseia-se na modulação da resposta imune anti-tumoral pelos fatores psicológicos, particularmente através das células natural killer. Esta investigação teve como objetivo o estudo da relação entre as células natural killer e a ansiedade, a depressão e o estado, traço e expressão da raiva num grupo de 54 doentes pré-cirúrgicos com cancro colorrectal. Material e Métodos: Medimos a contagem periférica de células natural killer e aplicámos o Inventário de Estado-Traço de Raiva e a Escala Hospitalar de Ansiedade e Depressão a 54 doentes pré-cirúrgicos com cancro colorrectal. Usámos o teste U de Mann-Whitney e o teste Kruskal-Wallis para amostras independentes. Resultados: Os doentes que apresentaram níveis mais elevados de Anger Expression-Out revelaram contagens inferiores de células natural killer (p value = 0,008). Não encontrámos relação entre os níveis de células natural killer e o Anger State, Trait ou Expression-In. Não identificámos diferenças nas contagens de células natural killer entre doentes com e sem ansiedade clínica ou com e sem depressão clínica. Discussão: Estes resultados sugerem que em doentes com cancro colorrectal a contagem de células natural killer é influenciada pela Anger Expression-Out, mas não pela depressão ou ansiedade clínica. Conclusão: A desregulação da expressão emocional pode ser um factor condicionante da imunidade inata. São necessários estudos adicionais para investigar mais aprofundadamente esta relação e para estabelecer o impacto clínico na resposta imune anti-tumoral das intervenções terapêuticas dirigidas à regulação emocional.

Maturação Orbitofrontal, Marcadores Somáticos e Vulnerabilidade Precoce: para uma Hipótese Compreensiva de "Miopia Emocional" na Toxicodependência / Orbitofrontal Maturation, Somatic Markers and Early Vulnerability: A Comprehensive Hypothesis of "Emotional Myopia" in Drug Addiction

A hipótese de “miopia emocional” constitui uma reflexão teórica de compreensão da vulnerabilidade psicológica identificada em muitos toxicodependentes. Propõe-se uma cooperação, mas não incorporação, de níveis de conhecimento em torno dos determinantes do neurodesenvolvimento, de perspectivas psicanalíticas e de vinculação e de modelos psicobiológicos das toxicodependências. Salientam-se influências ambientais sobre as mudanças na morfologia cerebral, não apenas o trauma precoce ou a privação de cuidados, mas também as decorrentes de consumos abusivos como cernes de vulnerabilidade. Propõe-se que a hipótese Damasiana dos marcadores somáticos participe nessa formulação. A parca qualidade das interações precoces pode sustentar o desligamento afetivo progressivo, a hipomaturação do cérebro social, o incremento de um padrão alexitímico e a procura urgente de sensações, todos potenciais propiciadores da busca do prazer nas drogas.

The “emotional myopia” hypothesis is a theoretical reflection to increase the understanding of the psychological vulnerability showed by many drug addicts Instead of an incorporation, a cooperation is proposed of levels of knowledge on the determinants of the neurodevelopment, psychoanalytical and attachment perspectives and psychobiological models of drug addictions. Environmental inputs that change brain morphology are highlighted, not only early trauma or care deprivation but also others derived from the long-term use of drugs as the core of vulnerability. We propose that Damasio’s hypothesis of somatic markers forms part of this theoretical formulation. The low quality of early social interactions may support an increasing emotional disengagement, a poor maturation of the social brain, an increase of alexithymic patterns and novelty-seeking behaviours, all potential triggers for searching for pleasure in drugs.

From psychosomatic to psychological medicine: what's the future?

PURPOSE OF REVIEW: Recent research findings into putative psychobiological mechanisms of emotional disorders as the future development of psychosomatic medicine are discussed. RECENT FINDINGS: Recent studies reinforce the communication between the immune and central nervous systems and identify the large set of peptide and nonpeptide neurotransmitters and ligands they share. Cytokines are seen as humoral mediators that may explain the interaction between endocrine and immune systems. The hypothalamic-pituitary axis has been investigated as part of the regulatory circuits that interact with autonomic regulation to expose immunologic processes related to stress or depression, and also to several diseases. Immune dysregulation and psychological distress have been linked to each other in disease, chronic stress, bereavement and other major life events. Research findings in depressive disorders and cancer may generate new theoretical paradigms in psychosomatic medicine. SUMMARY: The clinical understanding and management of distress or emotional disorders associated with physical illness may change in future because of the results of interdisciplinary research, where environmental factors will be integrated with psychological and biological systems, mainly of endocrine or neuroimmunological nature. The ultimate goal of psychosomatic medicine may be the integration of different levels of individual functioning on a systemic basis.