Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor: Multidimensional Assessment of Neuropsychological Side Effects and Physical and Mental Health Outcomes in Adolescents and Adults.

BACKGROUND: Italy initiated elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (pwCF) in July 2021. It has led to dramatic improvements in lung function, BMI, sweat chloride, and respiratory symptoms. However, few data are available on side effects or effects on a broad range of outcomes. RESEARCH QUESTION: How does ETI affect mental health, cognitive processing, neuropsychological side effects, GI symptoms, and health-related quality of life over time? STUDY DESIGN AND METHODS: This was a prospective, "real-world" longitudinal study. Participants were recruited consecutively and evaluated at initiation (T0) and after 1 month, 3 months, and 6 months of starting treatment. Assessments included depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalized Anxiety Disorder), cognition (Symbol Digit Modalities Test), GI Symptom Tracker, and health-related quality of life (Cystic Fibrosis Questionnaire-Revised). Based on literature, an ad hoc questionnaire was developed to assess side effects: insomnia, headache, memory problems, "brain fog," and concentration problems. Following descriptive analyses, longitudinal data were analyzed by using mixed models for repeated measures, controlling for age and sex when appropriate. RESULTS: Ninety-two consecutive pwCF (female/male, 46/46; mean age, 25.4 years) participated. FEV1 increased initially and then remained stable. BMI also increased significantly from T0 to 6 months (P < .01). Depression improved from T0 to 1 month (P < .001); however, no changes in anxiety were found. Cognitive processing improved from T0 to subsequent assessments. Positive changes were reported on the GI Symptom Tracker for stools and adherence challenges, although no changes were found for abdominal pain and digestion. Side effects occurred in 10% to 29%, with no reduction over time; insomnia increased significantly across time. Female participants reported more side effects than male participants (ie, insomnia, headache, concentration problems, brain fog). INTERPRETATION: This prospective study evaluated the effects of ETI using multiple measures. Significant improvements were found in many domains; however, side effects were reported by a substantial proportion of pwCF, with no improvements over time. Female participants reported more side effects than male participants. pwCF should be followed up systematically to assess the frequency of side effects after starting this new modulator.

The role of family functioning, attachment style, and care setting on pre-loss grief symptoms and burden in caregivers of terminally cancer patients.

OBJECTIVES: The aim of the present cross-sectional study was to investigate the associations between caregivers' attachment styles, family functioning, the care setting and pre-loss grief symptoms, the burden, and the caregivers' belief of patients' awareness of the terminal cancer diagnosis. METHODS: A total of 101 caregivers of patients with terminal cancer in residential hospice care and home care were interviewed and completed self-report questionnaires. RESULTS: Insecure attachment style and home care setting were associated with worse psychological effects in caregivers of patients with terminal cancer. Moreover, family cohesion can promote low social burden and the patient's awareness of their terminal condition. SIGNIFICANCE OF RESULTS: This study highlighted the importance of evaluating the caregiver's attachment style, family functioning, and the setting of care during the terminal phase of the patient's life. These findings will be useful to planning interventions to prevent burden and the pre-loss grief symptoms in the caregivers.

Effectiveness of the expressive writing on the psychological distress and traumatic symptoms of the migrants: A prospective study multiarm randomized controlled trial.

OBJECTIVE: Migration is a phenomenon related to adverse impacts, including higher risk for psychological distress and trauma symptoms, highlighting the strong need for effective psychological treatments to help migrants. However, the use of expressive writing intervention (EW) has not been examined in this population. The aims of the study were to evaluate: (a) the effectiveness of a trauma-focused EW on psychological distress, trauma symptoms, alexithymia, and hope for the future in migrants, and (b) the role of alexithymia and hope for the future in the association with the EW and the psychological symptoms. METHOD: Twenty-eight migrants were enrolled in a multiarm double-blind randomized controlled trial (RCT) that included three groups: (a) trauma-focused EW, (b) neutral EW, and (c) control. Participants completed self-report measures at pretreatment, immediately after the intervention, and at 1 month follow-up. The study complied with the guidelines of Consolidate Standard of Reporting Trials (CONSORT) checklist and was retrospectively recorded on ClinicalTrials.gov. RESULTS: Trauma-focused EW was related to an immediate improvement in phobic anxiety and positive total symptoms and improvement in somatization, global severity index, and hope for the future at follow-up. Trauma symptoms and alexithymia did not show significant effects. Factorial regressions showed that the interaction group per time per hope for the future was a significant predictor on the phobic anxiety. DISCUSSION: EW may be an effective tool for reducing migrant's distress and may have long-term improvements in mental health. Moreover, the results suggest the potential influence of the hope for the future on anxiety in migrants. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Psychosocial treatment on psychological symptoms, adherence, and physiological function on transplanted patients: A systematic review and metanalysis.

OBJECTIVE: Transplantation represents an important source of hope for the candidates and produces an intense emotional effect. Psychosocial interventions can be helpful in all transplantation stages to better manage this extraordinarily stressful situation. Aim of the work is to verify the effects of the psychosocial interventions on recipients on psychological symptoms, medical adherence and transplanted solid organ functioning. METHODS: This work adhered to PRISMA, STROBE, Cochrane and New Castle Ottawa bias scales and it is registered in PROSPERO. Inserting "Transplant" and "Psychological intervention" as key words in PubMed, Psycinfo, Cochrane database resulted 977 studies from 2001 to 2021. A systematic review and metanalyses were processed on nineteen randomized controlled trials and observative prospective cohort studies. The difference between pre- and post- psychosocial intervention assessment on the psychological variables, medical adherence, and organ functioning outcome was processed. RESULTS: Main findings showed that the psychosocial interventions were effective on depression (0.62; CI: 0.32-0.92) and anxiety on kidney recipients (0.49; CI: 0.17-0.81), and on anxiety on heart recipients, mainly when administrated after the surgery (0.68; CI: 0.30-1.06). Moreover, the findings showed a lack of studies on the effectiveness of the psychosocial intervention on organ functioning. CONCLUSION: The work highlighted the effectiveness of the psychosocial interventions on psychological outcome, particularly after the surgery and the need to address the research on the evaluation of the effectiveness of the psychosocial interventions on the organ functioning. The findings suggest to integrate the transplantation procedures with psychosocial interventions considering the different needs of recipients in relation to the specific transplanted organ.

Effects of a motor imagery-based exercise protocol on chronic pain and emotional distress in patients with fibromyalgia syndrome: A pilot study.

BACKGROUND: Fibromyalgia (FM) is a chronic condition characterized by widespread muscular or musculoskeletal pain of at least 3 months' duration, occurring above and below the waist, on both sides of the body. OBJECTIVE: The aim of this study was to evaluate the effectiveness of a rehabilitation program based on motor imagery versus a conventional exercise program in FM in terms of pain, functional and psychological outcomes. METHODS: Twenty-nine female subjects were randomly assigned to a group receiving motor imagery-based rehabilitation (MIG) or to a control group (CG) performing conventional rehabilitation. Outcome assessments were performed before (T0) and after 10 sessions of treatment (T1) and at a 12-week follow-up (T2). Pain, function and psychological measurements were conducted by means of different questionnaires. RESULTS: Both treatments improved all outcomes at post-treatment (T1) and follow-up (T2). The MIG showed a significant improvement in anxiety disorder associated with FM with respect to the CG, as well as improvements in coping strategies. CONCLUSIONS: Rehabilitation treatment based on motor imagery showed a stronger effect on anxiety and coping behavior than traditional physiotherapy in patients with FM. Integrated psychological support would be desirable in this setting. Further research is needed to explore the aspects investigated in more depth.

Will I or my loved one die? Concordant awareness between terminal cancer patients and their caregivers is associated with lower patient anxiety and caregiver burden.

OBJECTIVE: The aims of this study were to investigate the association between patients' awareness of their terminal illness and the levels of anxiety and depression, whether the concordance between the patients' and caregivers' belief about the patient's terminal illness was associated with patient's anxiety and depression, and with the caregiver burden. METHOD: The study recruited 31 terminally ill patients with cancer along with their caregivers from a Palliative Care Unit. All data about patients and caregivers' awareness of the illness, patients' depression and anxiety, and caregiver burden were collected. RESULTS: Patients aware of their short-term prognosis of death showed lower levels of anxiety than the unaware ones, especially women. Aware patients with concordant caregivers showed lower levels of anxiety but not of depression. Caregivers concordant with the patients' awareness presented lower levels of strain and burden. Finally, terminal patients who had an adult child caregiver were less likely to be aware of their terminal condition. CONCLUSIONS: It appears that illness awareness and the caregiver's concordance with the patient's belief on the terminal condition are associated with lower anxiety, especially in women, and a reduced burden for caregivers.

Neural correlates of sex-related differences in attachment dimensions.

The purpose of this study was to investigate sex-related differences in the electrophysiological response to socioemotional stimuli (positive, negative, and ambiguous) depicting couple interactions. The associations between anxiety and avoidance attachment dimensions (measured with the Experiences in Close Relationships-Revised questionnaire) and the strength of cortico-limbic circuit intensity was explored, recorded using a 256-Hydrocel Geodesic Sensor-Net. Event-related potentials (ERPs) and standardized low-resolution electromagnetic tomography (sLORETA) data were analyzed for a total sample of 74 participants. Regression analyses showed that the women presented increased brain intensity compared with that in men, and the avoidance score was positively associated with brain intensity, particularly in response to negative socioemotional stimuli. The interaction sex per avoidance was a significant predictor of intensity in many brain areas, with women displaying significantly more pronounced positive associations between avoidance and brain intensity than men. In conclusion, the findings of the present study showed that women appeared to be more emotionally involved during the socioemotional task. Avoidance was positively associated with intensity of the cingulate and prefrontal regions, and these associations were more pronounced in women than in men. These findings suggested that avoidance seems to represent two different socioemotional strategies, in which women appear to activate an avoidant strategy to modulate increased emotional involvement in relationships, whereas men appear to adopt avoidance with a more intense emotional suppression.

Different Electrophysiological Responses to Pain-Related Visual Stimuli Between Fibromyalgia and Chronic low Back Pain Women: A Pilot Case-Control Study.

BACKGROUND: Fibromyalgia is a chronic pain syndrome which occurs in the absence of an organic damage, whom causes is still unclear. Aims of this pilot study were to investigate the neural correlates of fibromyalgia in response to pain-related visual stimuli and explore the psychological differences among fibromyalgia, chronic low back pain (CLBP) and healthy conditions. METHODS: After a clinical assessment, electrophysiological responses to pain-related visual stimuli were recorded using a 256-Hydrocel Geodesic-Sensor-Net. Event-related potentials (ERPs), standardised low-resolution electromagnetic tomography (sLORETA), and psychological (Symptom Checklist-90-Revised) data were analysed for a total sample of 23 women (5 healthy volunteers, 12 fibromyalgia patients, 6 CLBP patients). RESULTS: The main finding was that fibromyalgia women reported a different brain response to pain-related visual stimuli on the frontal montage compared to women with CLBP (p = .028). Moreover, fibromyalgia women showed an increased activity mainly on the hippocampus (p = .003) and the posterior cingulate cortex (p ≤ .001) in response to algic stimuli compared to not algic ones. Lastly, these women presented higher scores on the somatization (p = .002), obsession-compulsion (p = .045), depression (p = .043) and positive symptom distress (p = .023) dimensions compared to the healthy women. CONCLUSIONS: These preliminary results suggest that although the painful symptoms are similar, the central elaboration of pain could be different between women with fibromyalgia and those with CLBP. Moreover, these findings provide preliminary evidences about the great alert and the central sensitivity to pain-related information regarding fibromyalgia patients.

Beyond the dyad: the role of mother and father in newborns' global DNA methylation during the first month of life-a pilot study.

The study aimed to longitudinally explore the effects of parental prenatal attachment and psychopathological symptomatology on neonatal global DNA methylation (5-mC) variation between birth and the first month of life. Eighteen mothers and thirteen fathers were assessed before childbirth (t0) by Perceived Stress Scale (PSS), Prenatal-Attachment Inventory, and Paternal Antenatal Attachment Scale; 48 hr after childbirth (t1) by SCL-90-R; and one month after childbirth (t2) by PSS. At t1 and t2, buccal swabs from parents and newborns were collected. In newborns' 5-mC and single nucleotide polymorphisms (SNPs) of DAT, MAOA, BDNF, and 5-HTTLPR genes were detected, while in parents only SNPs were measured. At t1, newborns' 5-mC was negatively associated with maternal psychopathological symptoms, while at t2, newborns' 5-mC was positively associated with paternal psychopathological symptoms and negatively with paternal prenatal attachment. The variation of newborns' 5-mC from t1 to t2 was predicted by paternal psychopathological symptoms. No significant correlations among parental SNPs and 5-mC levels were found. Results highlight parent-specific influences on newborn's DNA methylation. At birth, maternal psychological symptoms seem to have an effect on newborns' 5-mC, while after one month of life, paternal psychological characteristics could have a specific role in modulating the newborns' epigenetic responses to the environment.

Neurophysiological correlates of emotional face perception consciousness.

Aim of the present study was to investigate the neurophysiologic correlates of the conscious and not conscious perception of faces (presented for 14, 40, 80 ms) with happy and sad emotional valence. Electroencephalographic data of 22 participants during a report-based visual task were recorded. Both happy and sad faces presented for 14 ms showed a longer N170 latency compared to the faces presented for 40 and 80 ms. A shorter latency of early components (before N170) was found in the right hemisphere and a longer latency in the left one in response to the happy faces presented for 14 ms compared to those presented for longer times. The faces presented for 14 ms, declared as consciously perceived, evoked a higher brain response compared to those declared as not perceived. Parietal and cingulate brain areas showed a lower intensity of the brain response to the consciously perceived faces in the early components. Happy faces showed a greater brain response when consciously detected, while the sad faces induced a greater brain response when not consciously detected. The findings suggest that the N170 may be the epiphenomenon of an earlier consciously detection. Moreover, these preliminary results seem to support a main role of parietal and cingulate brain areas into not conscious perception.

Violence in video game produces a lower activation of limbic and temporal areas in response to social inclusion images.

Exposure to violence in video games has been associated with a desensitization toward violent content, a decrease of empathy, and prosocial behavior. Moreover, violent video games seem to be related to a reduction of neural activation in the circuits linked to social emotional processing. The purpose of the present study was to compare the neural response to social inclusion images after violent and nonviolent video game playing. Electroencephalographic data of the 32 participants were recorded during a visual task with three presentations (T0, T1, T2) of 60 stimuli (30 social inclusion vs. 30 neutral images). After the T0 presentation, the participants played with a video game (orientation or violent). After the T1 presentation, the participants played with the other video game (orientation or violent). The two types of video games were randomly displayed. Event-related potential (ERP) components and low-resolution electromagnetic tomography (sLORETA) were analyzed. The main findings showed a longer latency of the P2 component on occipito-temporal montage and a lower activation of the limbic and temporal areas in response to the social inclusion images post violent video game compared with the post orientation video game. The findings suggest a reduction of emotional engagement in social processing after playing violent video game.

Neurophysiological Correlates of Collective Trauma Recall in 2009 L'Aquila Earthquake Survivors.

In the present study, we aimed to explore neural correlates of survivors of the 2009 L'Aquila, Italy earthquake in response to being shown pictures featuring their own city before and after an earthquake as well as those of an unfamiliar city. Moreover, we explored the associations among psychological variables and brain responses to the pictures of L'Aquila after the earthquake. Our final sample (N = 30 adults) comprised 15 survivors (M age = 31.40 years, SD = 9.42) and 15 controls (M age = 30.53 years, SD = 10.01). Participants' electroencephalographic (EEG) data were recorded during a visual task that included earthquake-related stimuli. Participants were assessed for posttraumatic and dissociation symptoms and event-related potential components, and low-resolution electromagnetic tomography (sLORETA) were analyzed. Compared to the control group, source localization in survivors indicated a lower intensity of the amygdala, hippocampal, parahippocampal, and temporopolar areas in response to visual stimuli concerning the earthquake, p < .001 to p < .0001. Results indicated a reduced limbic activation in response to visual stimuli that evoked the recall of earthquake in survivors. This finding suggests that survivors likely adopted a distancing strategy toward stimuli that may have elicited an emotional activation related to collective trauma.