Vincenzo Calvo

Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy

Objective Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. Methods A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. Results Patients were followed up to an average age of 15.9 ± 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). Conclusions We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts.

Efficacy of Hypnosis-Based Treatment in Amyotrophic Lateral Sclerosis: A Pilot Study

Background: Amyotrophic lateral sclerosis (ALS) and its devastating neurodegenerative consequences have an inevitably psychological impact on patients and their caregivers: however, although it would be strongly needed, there is a lack of research on the efficacy of psychological intervention. Our aim was to investigate the effect of hypnosis-based intervention on psychological and perceived physical wellbeing in patients and the indirect effect on caregivers. Methods: We recruited eight ALS volunteers patients as a pilot sample for an hypnosis intervention and self-hypnosis training protocol lasting 1 month. Anxiety and depression level was measured in patients and caregivers at pre and post treatment phase. Quality of life and perceived physical symptoms changes were also investigated in patients. Results: One month pre-post treatment improvement in depression, anxiety, and quality of life was clearly clinically observed and confirmed by psychometric analyses on questionnaire data. Moreover, decreases in physical symptoms such as pain, sleep disorders, emotional lability, and fasciculations were reported by our patients. Improvements in caregiver psychological wellbeing, likely as a consequence of patients psychological and perceived physical symptomatology improvement, were also observed. Conclusion: To the best of our knowledge, even if at a preliminary level, this is the first report on efficacy psychological intervention protocol on ALS patients. The findings provide initial support for using hypnosis and self-hypnosis training to manage some ALS physical consequences and mainly to cope its dramatic psychological implications for patients and, indirectly, for their caregivers.

“Reality” of near-death-experience memories: evidence from a psychodynamic and electrophysiological integrated study

The nature of near-death-experiences (NDEs) is largely unknown but recent evidence suggests the intriguing possibility that NDEs may refer to actually “perceived,” and stored, experiences (although not necessarily in relation to the external physical world). We adopted an integrated approach involving a hypnosis-based clinical protocol to improve recall and decrease memory inaccuracy together with electroencephalography (EEG) recording in order to investigate the characteristics of NDE memories and their neural markers compared to memories of both real and imagined events. We included 10 participants with NDEs, defined by the Greyson NDE scale, and 10 control subjects without NDE. Memories were assessed using the Memory Characteristics Questionnaire. Our hypnosis-based protocol increased the amount of details in the recall of all kind of memories considered (NDE, real, and imagined events). Findings showed that NDE memories were similar to real memories in terms of detail richness, self-referential, and emotional information. Moreover, NDE memories were significantly different from memories of imagined events. The pattern of EEG results indicated that real memory recall was positively associated with two memory-related frequency bands, i.e., high alpha and gamma. NDE memories were linked with theta band, a well-known marker of episodic memory. The recall of NDE memories was also related to delta band, which indexes processes such as the recollection of the past, as well as trance states, hallucinations, and other related portals to transpersonal experience. It is notable that the EEG pattern of correlations for NDE memory recall differed from the pattern for memories of imagined events. In conclusion, our findings suggest that, at a phenomenological level, NDE memories cannot be considered equivalent to imagined memories, and at a neural level, NDE memories are stored as episodic memories of events experienced in a peculiar state of consciousness.

Female gender doubles executive dysfunction risk in ALS: a case-control study in 165 patients

Background Cognitive impairment, mainly characterised by executive dysfunction, occurs in about half of cases in amyotrophic lateral sclerosis (ALS). There is evidence that gender influences some clinical features of the disease, but its influence on the cognitive spectrum is unknown. Our objective was to investigate the impact of gender on cognitive profiles of patients with ALS. Methods A retrospective study based on an exhaustive neuropsychological battery was performed in a group of 165 (70 females, 95 males) sporadic, non-demented patients with ALS compared with 134 healthy control participants. This assessment primarily focused on executive, memory and language functions. Results 47 (29%) patients revealed impairment in executive function and 30 (18%) patients revealed cognitive non-executive impairment. Independent from mood tone and clinical variables, a significantly greater executive impairment was determined in female patients than in male patients and control participants. The relative risk for ALS females having impairment in executive function compared with male patients was 2.6 (95% CI 1.6 to 4.4; p=0.0003). ALS females scored lower in Phonemic Fluency, Trial Making, and Wisconsin Card Sorting test. Conclusions Results highlight a significant vulnerability of ALS female patients to develop cognitive dysfunctions peculiar to the disease, independently of bulbar onset. The explicative hypotheses of the data are focused on two interpretative lines not mutually exclusive: the role of gonadal hormones and gender-related brain asymmetry pre-existing to the disease. These findings, never reported before in the literature, can have important implications for models of ALS pathogenesis and for future clinical trial designs.

Theory of mind, empathy and neuropsychological functioning in X-linked Spinal and Bulbar Muscular Atrophy: a controlled study of 20 patients

Recent studies have described brain involvement, mainly at frontal level, in patients with spinal and bulbar muscular atrophy (SBMA), a rare adult-onset motor neuron disease caused by a CAG repeat in the androgen receptor (AR) gene. The aim of our research was to investigate the poorly characterized neuropsychological and psychological profile of these patients, on the basis of previous literature. We administered a neuropsychological screening and tests relating to cognitive and affective empathy, attributed to the theory of mind (ToM) framework, to 20 males with SBMA, and to age- and education-matched controls. Although patients’ neuropsychological performance was unimpaired, a clear dissociation emerged between their cognitive and affective empathy. Patients had distinctive deficits in mentalizing, as assessed with the Faux Pas Test, whilst affective empathy (i.e., sharing experience), assessed with the Reading the Mind in the Eyes test, appeared to be preserved. The likely implications of subtle frontal lobe impairments on the one hand, and a protective influence of androgen insensitivity in these patients on the other, are discussed in the light of our results.

Reciprocal empathy and working alliance in terminal oncological illness: the crucial role of patients' attachment style.

Security of attachment is described as an inner resource that may also facilitate the adaptation of individuals during critical life adversity, even when facing end-stage illness and death. This study assessed the relation between attachment styles, patient–caregiver reciprocal empathy, and patient–physician working alliance, in the terminal phase of an oncological disease. We hypothesized that the attachment security of patients, as measured by the Relationship Questionnaire (RQ), is related to the reciprocal empathy with the caregiver, as measured by the Perception of Partner Empathy (PPE) questionnaire, and to the working alliance with the physician, as measured by the Working Alliance Inventory–Short Form (WAI-S). Thirty-seven end-stage cancer patients, their caregivers, and physicians participated in the study. The PPE and WAI-S were administered twice: immediately after the hospice recovery and a week later. Results showed a significant improvement in patient–caregiver empathy and in patient–physician alliance after a week at the hospice. Findings indicated that the patients’ attachment style influenced their perception of reciprocal empathy with the caregiver and the working alliance with the physician. Patients with a secure attachment had a greater capacity to show empathic closeness with their caregivers and enjoyed a better working alliance with their physicians. Caregivers’ attachment security, otherwise, did not show the same influence on empathy and alliance. Findings support the hypothesis that patients’ attachment security plays a crucial role in the relation with their own caregiver and with the physician, even at the terminal phase. Theoretical and clinical implications of these findings are explored in the discussion.

Abnormal Default System Functioning in Depression: Implications for Emotion Regulation

Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals’ capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects.

Perceptions of parental bonding, adult attachment, and marital adjustment in prospective adoptive parents. An empirical study in the pre-adoptive period

Adoptive parents face unique developmental and family challenges during the transition to adoptive parenthood. The study reported in this paper investigated the first transitional phase of parenthood, namely the early pre-adoptive period. We compared 60 prospective adoptive parents (30 couples) with a control group of 30 childless couples of prospective nonadoptive parents. Participants were evaluated by specific measures mainly from the attachment theory viewpoint, such as Parental Bonding Instrument, Experiences in Close Relationships, and Dyadic Adjustment Scale questionnaires. Results showed that prospective adoptive parents clearly reported more positive perceived parental characteristics of their own parents (i.e., more maternal and parental care), more adult attachment security (i.e., low anxiety and low avoidance), and higher levels of marital adjustment (i.e., higher levels of dyadic adjustment, dyadic consensus, dyadic cohesion, and affective expression) than prospective nonadoptive parents. Our findings were discussed in light of the literature in this field of the past 50 years.

Influence of adult attachment insecurities on parenting self-esteem: the mediating role of dyadic adjustment

Background: Parenting self-esteem includes two global components, parents’ self-efficacy and satisfaction with their parental role, and has a crucial role in parent–child interactions. The purpose of this study was to develop an integrative model linking adult attachment insecurities, dyadic adjustment, and parenting self-esteem. Methods: The study involved 118 pairs (236 subjects) of heterosexual parents of a firstborn child aged 0–6 years. They were administered the Experiences in Close Relationships-Revised (ECR-R) questionnaire, the Dyadic Adjustment Scale, and the Parenting Sense of Competence Scale. Results: Path analysis was used to design and test a theoretical integrative model, achieving a good fit with the data. Findings showed that dyadic adjustment mediates the negative influence on parenting self-efficacy of both attachment anxiety and attachment avoidance. Parenting satisfaction is positively influenced by parenting self-efficacy and negatively affected by child’s age. Attachment anxiety negatively influences parenting satisfaction. Conclusion: Our findings are in line with the theoretical expectations and have promising implications for future research and intervention programs designed to improve parenting self-esteem.

Impact on children of a parent with ALS: a case-control study

Background: Numerous studies have explored how patients and their caregivers cope with amyotrophic lateral sclerosis (ALS), but the literature completely lacks research on the psychological impact of the disease on patients’ children. The aim of our study was to investigate the emotional and psychological impact of a parent with ALS on school-age children and adolescents in terms of problem behavior, adjustment, and personality characteristics. Methods: The study involved 23 children (mean age = 10.62 years, six females) with a parent suffering from ALS, and both their parents. Children were matched for age, gender, and birth-order with a control group of children with healthy parents. They were administered the Youth Self Report (YSR) questionnaire and the Rorschach Comprehensive System, and their healthy parent completed the Child Behavior Checklist (CBCL). Results: Findings clearly showed that, compared with controls, children with a parent who had ALS had several clinically significant adverse emotional and behavioral consequences, with emotional and behavioral problems, internalizing problems, anxiety and depressive symptoms. Children of a parent with ALS scored higher than controls for the Total Problems, Internalizing Problems, Anxious/Depressed and Withdrawn/Depressed scales in the YSR. A relevant percentage of children fell within the clinical range (42.9%) and borderline range (28.6%) for Internalizing Problems. The Rorschach CS confirmed the substantial impact of ALS in a parent on their offspring in terms of internalizing behavior and depression, with adjustment difficulties, psychological pain, and thought problems. Conclusion: Our findings indicate that school-aged children and adolescents with a parent who has ALS are vulnerable and carry a substantially higher risk of internalizing behavior, depressive symptoms, and reactive problems than children with healthy parents. Families affected may need support to cope with such an overwhelming disease.