Reduced magnetic mismatch negativity: a shared deficit in psychosis and related risk.

BACKGROUND: Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR). METHODS: Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC). RESULTS: The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP. CONCLUSIONS: Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.

Factors associated with lifetime suicide attempts in bipolar disorder: results from an Italian nationwide study.

The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.

Processed meat consumption and the risk of incident late-onset depression: a 12-year follow-up of the Salus in Apulia Study.

BACKGROUND: the possible relationship between dietary habits and the incidence of late-onset depression (LOD), defined as first depression onset at later age, is unclear. OBJECTIVE: to investigate the relationship between consumption of different food groups and incident LOD. DESIGN: longitudinal population-based study with a 12-year follow-up. SETTING: Castellana Grotte, Bari, Italy. SUBJECTS: five hundred and forty-six older subjects from the Salus in Apulia Study. METHODS: baseline data were recorded in 2003-06, and diagnostic data were recorded in 2013-18 at follow-up. Dietary intake was assessed with a food frequency questionnaire. Depressive disorders were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders. Subjects who already suffered from depression or other psychiatric disorders at baseline were excluded from the analysis. The association between LOD and single dietary determinants was examined by Cox regression analysis and then applying the hazard ratio (HR). RESULTS: subjects with incident LOD (n = 34) had lower global cognition and total cholesterol levels and a higher body mass index (BMI) at baseline. Only processed meat significantly increased the risk of incident LOD of about 10% by 5 g/day intake (HR adjusted for age, sex, education, multimorbidity and BMI: 1.13, 95% confidence intervals: 1.04-1.22). A similar relationship was found for single foods in the processed meat food group such as sausages, salami and mortadella and baked ham, but not for raw ham. CONCLUSIONS: in midlife, a higher intake of processed meat was not only associated with an increased risk of cardiovascular- and metabolic-related chronic diseases in older age but also with an increased risk of developing LOD.

Delirium in heart failure.

Despite relative frequency of delirium in elderly hospitalized heart failure patients, skills and expertise in managing such complication are usually poor for physicians and nurses facing this clinical condition. International guidelines on heart failure do not provide detailed indication for such clinical condition, and evidence on this topic is limited. A multi-disciplinary approach (cardiologists, internists, geriatricians, psychologists, and psychiatrists) is often required; this review will therefore focus on diagnosis and clinical management of delirium in heart failure patients from a multidisciplinary point of view.

The effects of music on spatial reasoning.

Studies on the effects of music on spatial reasoning report conflicting results. Some studies show slight effects, and others show no effects but few seem to replicate the strong findings of the first study published in Rauscher et al. Nature, 365(6447), 611-612, (1993). Nonetheless, the debate about the performance enhancing "Mozart effect" remains to be of great interest. In this study, we manipulated different physical parameters of sound traces (amplitude and frequency) to investigate whether particular dimensions may explain the enhancement effects found in spatial tasks following music listening. To this end, we asked 179 undergraduates and 183 older adults to listen to 5-min sound traces (Mozart KV 448, amplitude modulation tone, frequency modulation tone, white noise) and then complete a spatial reasoning task. In particular, results showed that repetitive frequency changes, as occurring in Mozart's melodies or in a frequency modulation tone, enhance performance.

Comparison of the efficacy of gesture-verbal treatment and doll therapy for managing neuropsychiatric symptoms in older patients with dementia.

BACKGROUND: The prevalence of neuropsychiatric symptoms (NPS) diminishes the quality of life and increases the care burden in patients with dementia. Despite the clinical importance of dementia-associated NPS, no protocols for treating NPS are already well established. Attention has turned to the effectiveness of nonpharmacological treatments for NPS since their potential safe alternative to pharmacotherapy. OBJECTIVE: This study is aimed to compare the effects in older individuals with dementia living in a residential care, of two intervention programs, the gesture-verbal treatment (GVT), a treatment implemented by us on a previous method for word retrieval in individuals with aphasia, and the better-known doll therapy (DT). The GVT would act on both receptive and expressive language skills, the DT on attachment and emotional connections. METHODS: We evaluated NPS by the neuropsychiatric inventory in a total of 30 patients divided into 3 groups, the GVT, the DT, and control groups, using a pre-post design. The treatment groups completed 12-week nonpharmacological interventions in addition to standard rehabilitative therapies, while the control group participated only in standard rehabilitative therapies. RESULTS: The DT group showed significant improvements in agitation, irritability, apathy, depression, and delusions relative to controls. The GVT group showed significant improvements in apathy and depression with respect to controls. The DT intervention ameliorated symptoms of agitation compared to the GVT intervention whereas the GVT intervention improved apathy compared to the DT intervention. CONCLUSION: Improved understanding of the potential therapeutic benefits of different treatments for neuropsychiatric symptoms is crucial for establishing nonpharmacological interventions in dementia.

Facial Emotion Recognition in Bipolar Disorder and Healthy Aging.

Emotional face recognition is impaired in bipolar disorder, but it is not clear whether this is specific for the illness. Here, we investigated how aging and bipolar disorder influence dynamic emotional face recognition. Twenty older adults, 16 bipolar patients, and 20 control subjects performed a dynamic affective facial recognition task and a subsequent rating task. Participants pressed a key as soon as they were able to discriminate whether the neutral face was assuming a happy or angry facial expression and then rated the intensity of each facial expression. Results showed that older adults recognized happy expressions faster, whereas bipolar patients recognized angry expressions faster. Furthermore, both groups rated emotional faces more intensely than did the control subjects. This study is one of the first to compare how aging and clinical conditions influence emotional facial recognition and underlines the need to consider the role of specific and common factors in emotional face recognition.

Exploring the Relationship between Neuroticism and Perinatal Depressive Symptoms: Findings from a 2-Year, Multicenter Study in Italy.

Neuroticism is a personality trait associated with the risk of affective disorders and perinatal depression. We investigated the relationship between different levels of neuroticism, psychological characteristics, and depressive symptoms in a sample of pregnant women (N = 2631) who accessed the gynecology departments in the Puglia Region (Italy) from July 2020 to November 2022. Women were assessed for depressive symptoms and associated risk factors in their third trimester of pregnancy (T0) and after childbirth (T1), and followed-up at 6 months and 1 year after delivery if presenting signs of depression (T2-T3). The Edinburgh Postnatal Depression Scale (EPDS) was used to screen depressive symptoms, and neuroticism was assessed through the subscales of the NEO Five Factor Inventory. Standardized measures of resilience, coping strategies, partner attachment, and quality of life were also employed. Higher levels of neuroticism were significantly associated with: (a) higher scores on the EPDS; (b) higher anxiety in the experience of close relationships; (c) lower psychological wellbeing; (d) lower levels of resilience; (e) lower levels of active coping; and (f) higher levels of self-blame. Our findings may suggest that neuroticism is a specific associated factor of perinatal depression and should be routinely assessed in the clinical screening of pregnant women in order to promote an early referral to psychological or psychiatric support services.

Lessons learned from the failure of solanezumab as a prospective treatment strategy for Alzheimer's disease.

INTRODUCTION: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-ß (Aß), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aß clearance was supposed to primarily contribute to AD development and progression, disease-modifying therapies with anti-Aß monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab and donanemab) are ongoing in randomized clinical trials (RCTs) with contrasting results. AREAS COVERED: The present Drug Discovery Case History analyzes the failures of RCTs of solanezumab on AD. Furthermore, the authors review the pharmacokinetics, pharmacodynamics, and tolerability effect of solanezumab from preclinical studies with its analogous m266 in mice. Finally, they describe the RCTs with cognitive, cerebrospinal fluid and neuroimaging findings in mild-to-moderate AD (EXPEDITION studies) and in secondary prevention studies (A4 and DIAN-TU). EXPERT OPINION: Solanezumab was one of the first anti-Aß monoclonal antibodies to be tested in preclinical and clinical AD showing to reduce brain Aß level by acting on soluble monomeric form of Aß peptide without significant results on deposits. Unfortunately, this compound showed to accelerate cognitive decline in both asymptomatic and symptomatic trial participants, and this failure of solanezumab further questioned the Aß cascade hypothesis of AD.

Coping as a Mediator between Attachment and Depressive Symptomatology Either in Pregnancy or in the Early Postpartum Period: A Structural Equation Modelling Approach.

Peripartum depression (PPD) is a major complication of pregnancy, and numerous risk factors have been associated with its onset, including dysfunctional coping strategies and insecure attachment styles, both during pregnancy and postpartum. The aim of our study was to investigate the role of coping strategies in mediating the relationship between women's attachment style and depressive symptomatology in pregnancy and one week after giving birth in a large sample of women (N = 1664). Our hypothesis was that the relationship between anxious and avoidant attachment and depressive symptomatology would be mediated by use of maladaptive coping strategies. The assessment instruments were Edinburgh Postnatal Depression Scale (EPDS), Brief Coping Orientation for Problem Experiences (COPE), and Experiences in Close Relationship Scale (ECR). The results indicated that the effect of insecure attachment styles (anxious and avoidant attachment) on antepartum depressive symptomatology was partially mediated by dysfunctional coping styles. Anxious attachment also has an indirect significant effect on postpartum depressive symptomatology through emotional coping; however, avoidant attachment does not seem to be significantly related to postpartum depressive symptoms. Our findings revealed that not only is it important to consider attachment in understanding peripartum depressive symptomatology, but also that coping plays an important role in these relationships. These findings would help a preventive coping-based intervention strategy to enhance the capacity of women with insecure attachment styles to use more adaptive coping during and after pregnancy.

Personality Traits and Fatigue in Multiple Sclerosis: A Narrative Review.

(1) Background: Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease. Fatigue is a prevalent and debilitating symptom that significantly impacts the quality of life of these patients. A relationship between personality traits and fatigue in MS has been hypothesized but not clearly defined. (2) Methods: A literature search was carried out from databases up to April 2023 for studies correlating personality traits and fatigue in patients suffering from MS. (3) Results: A total of ten articles was included; most of the studies depict a neuroticism-fatigue correlation; however, they were not consistent in terms of the fatigue, personality, and covariate assessments. (4) Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the link between personality traits and fatigue in MS. Several models of personality and different fatigue assessments have been found. Despite this, a common pathway shows that the neuroticism trait or similar personality patterns has a role in fatigue diagnosis. This may be a useful target to improve the quality of life and enhance the modification of the disease treatment results. Further homogeneous and longitudinal studies are needed.

Clinical development of passive tau-based immunotherapeutics for treating primary and secondary tauopathies.

INTRODUCTION: Tauopathies are clinicopathological entities with increased and pathological deposition in glia and/or neurons of hyperphosphorylated aggregates of the microtubule-binding protein tau. In secondary tauopathies, i.e. Alzheimer's disease (AD), tau deposition can be observed, but tau coexists with another protein (amyloid-ß). In the last 20 years, little progress has been made in developing disease-modifying drugs for primary and secondary tauopathies and available symptomatic drugs have limited efficacy. AREAS COVERED: The present review summarized recent advances about the development and challenges in treatments for primary and secondary tauopathies, with a focus on passive tau-based immunotherapy. EXPERT OPINION: Several tau-targeted passive immunotherapeutics are in development for treating tauopathies. At present, 14 anti-tau antibodies have entered clinical trials, and 9 of them are still in clinical testing for progressive supranuclear palsy syndrome and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, APNmAb005, MK-2214, PNT00, and PRX005). However, none of these nine agents have reached Phase III. The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Further evidence on passive immunotherapeutics for treating primary and secondary tauopathies will come from ongoing Phase I/II trials.

Late-Onset Depression but not Early-Onset Depression may Increase the Risk of All-Cause Mortality in Older Age: 8-Year Follow-Up of the Salus in Apulia Study.

OBJECTIVES: Individuals with late-life depression (LLD) may have shorter survival, but there is a lack of findings in population-based settings about health-related outcomes of LLD and its subtypes: early-onset depression (EOD) and late-onset depression (LOD). We aimed to evaluate the risk of all-cause mortality of individuals with LLD and its subtypes in an older population-based cohort. Moreover, we investigated whether inflammatory, cognitive, genetic features and multimorbidity could modify the effect of this association. DESIGN: Longitudinal population-based study with 8-year follow-up. SETTING AND PARTICIPANTS: We analyzed data on a sample of 1479 participants, all aged >65 years, in the Salus in Apulia Study. METHODS: LLD was diagnosed through DSM-IV-TR criteria and LOD and EOD according to the age of onset. Multimorbidity status was defined as the copresence of 2 or more chronic diseases. RESULTS: The overall prevalence of LLD in this older sample from Southern Italy was 10.2%, subdivided into 3.4% EOD and 6.8% LOD. In multivariable Cox models adjusted for age, gender, education, global cognition, apolipoprotein E ε4 allele, physical frailty, interleukin-6, and multimorbidity, LLD showed a greater risk of all-cause mortality. LOD differed from EOD regarding gender, education, cognitive dysfunctions, and diabetes mellitus. There was a significantly increased risk of all-cause mortality for participants with LOD (hazard ratio:1.99; 95% CI 1.33-2.97) in the time of observation between enrollment date and death date (7.31 ± 2.17 months). CONCLUSIONS AND IMPLICATION: In older age, individuals with LOD but not with EOD had a significantly decreased survival, probably related to increased inflammation, multimorbidity, and cognitive impairments.

A multivariate approach to investigate the associations of electrophysiological indices with schizophrenia clinical and functional outcome.

BACKGROUND: Different electrophysiological (EEG) indices have been investigated as possible biomarkers of schizophrenia. However, these indices have a very limited use in clinical practice, as their associations with clinical and functional outcomes remain unclear. This study aimed to investigate the associations of multiple EEG markers with clinical variables and functional outcomes in subjects with schizophrenia (SCZs). METHODS: Resting-state EEGs (frequency bands and microstates) and auditory event-related potentials (MMN-P3a and N100-P3b) were recorded in 113 SCZs and 57 healthy controls (HCs) at baseline. Illness- and functioning-related variables were assessed both at baseline and at 4-year follow-up in 61 SCZs. We generated a machine-learning classifier for each EEG parameter (frequency bands, microstates, N100-P300 task, and MMN-P3a task) to identify potential markers discriminating SCZs from HCs, and a global classifier. Associations of the classifiers' decision scores with illness- and functioning-related variables at baseline and follow-up were then investigated. RESULTS: The global classifier discriminated SCZs from HCs with an accuracy of 75.4% and its decision scores significantly correlated with negative symptoms, depression, neurocognition, and real-life functioning at 4-year follow-up. CONCLUSIONS: These results suggest that a combination of multiple EEG alterations is associated with poor functional outcomes and its clinical and cognitive determinants in SCZs. These findings need replication, possibly looking at different illness stages in order to implement EEG as a possible tool for the prediction of poor functional outcome.

Depressive and Biopsychosocial Frailty Phenotypes: Impact on Late-life Cognitive Disorders.

In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer's disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links. The depressive frailty phenotype suggested by the construct of late-life depression (LLD) plus physical frailty is poorly operationalized. The biopsychosocial frailty phenotype, with its coexistent biological/physical and psychosocial dimensions, defines a biological aging status and includes motivational, emotional, and socioeconomic domains. Shared biological pathways/substrates among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders are hypothesized to be inflammatory and cardiometabolic processes, together with multimorbidity, loneliness, mitochondrial dysfunction, dopaminergic neurotransmission, specific personality traits, lack of subjective/objective social support, and neuroendocrine dysregulation. The cognitive frailty phenotype, combining frailty and cognitive impairment, may be a risk factor for LLD and vice versa, and a construct of depressive frailty linking physical frailty and LLD may be a good dementia predictor. Frailty assessment may enable clinicians to better target the pharmacological and psychological treatment of LLD. Given the epidemiological links of biopsychosocial frailty with dementia and MCI, multidomain interventions might contribute to delay the onset of late-life cognitive disorders and other adverse health-related outcomes, such as institutionalization, more frequent hospitalization, disability, and mortality.

The development of peptide- and oligonucleotide-based drugs to prevent the formation of abnormal tau in tauopathies.

INTRODUCTION: Tauopathies represent clinicopathological entities with increased and abnormal glial and/or neuronal inclusions of tau, a microtubule-binding protein. Antisense oligonucleotides (ASOs) are a promising therapeutic approach for treating tauopathies as they can target tau mRNA to reduce total human tau expression or tau exon 10 expression and 4 R tau. Additionally, targeting the tau specifically with peptides may be a unique pharmacological approach, between small molecules and proteins. AREAS COVERED: The present review investigates the chemical basis of designing ASOs and peptides currently known to treat tauopathies. Among ASOs targeting tau expression, BIIB080 was the first to enter clinical trial development for treating mild Alzheimer's disease (AD). Furthermore, the therapeutic potential of peptide 021 (P021, Ac-DGGLAG-NH2) in tauopathies is discussed based on preclinical studies. EXPERT OPINION: ASOs are a promising therapeutic approach for tauopathies, particularly because ASOs may suppress the expression of harmful genes and are directly delivered to the brain, showing little systemic side effects. However, whether a generalized brain tau decrease will produce positive clinical effects remains unclear. A Phase II trial of BIIB080 is ongoing in mild AD. Neurotrophic and neurogenic peptide mimetic compounds have also shown potential as treatment options for AD and other tauopathies.

Similarities and differences between multivariate patterns of cognitive and socio-cognitive deficits in schizophrenia, bipolar disorder and related risk.

Cognition and social cognition anomalies in patients with bipolar disorder (BD) and schizophrenia (SCZ) have been largely documented, but the degree of overlap between the two disorders remains unclear in this regard. We used machine learning to generate and combine two classifiers based on cognitive and socio-cognitive variables, thus delivering unimodal and multimodal signatures aimed at discriminating BD and SCZ from two independent groups of Healthy Controls (HC1 and HC2 respectively). Multimodal signatures discriminated well between patients and controls in both the HC1-BD and HC2-SCZ cohorts. Although specific disease-related deficits were characterized, the HC1 vs. BD signature successfully discriminated HC2 from SCZ, and vice-versa. Such combined signatures allowed to identify also individuals at First Episode of Psychosis (FEP), but not subjects at Clinical High Risk (CHR), which were classified neither as patients nor as HC. These findings suggest that both trans-diagnostic and disease-specific cognitive and socio-cognitive deficits characterize SCZ and BD. Anomalous patterns in these domains are also relevant to early stages of disease and offer novel insights for personalized rehabilitative programs.

The impact of body mass index on the pregnancy outcomes and risk of perinatal depression: Findings from a multicenter Italian study.

BACKGROUND: Body Mass Index (BMI) is an informative factor on body fatness which has been associated to higher levels of Perinatal Depression (PD) and complications during pregnancy. We aimed to explore the impact of pre-pregnancy and postnatal BMI on the risk of Perinatal Depression and pregnancy outcomes among women recruited at their third trimester of pregnancy. METHODS: We report on findings from a large multi-centre study conducted in the South of Italy and involving 1611 women accessing three urban gynaecological departments from July to November 2020. Pregnant women were assessed at their third trimester of pregnancy (T0) and after the childbirth (T1) ;The Edinburgh Postnatal Depression Scale (EPDS) has been employed for the screening of PD over time (T0 and T1) as well as other standardized measures for neuroticism, resilience, and quality of life at baseline. BMI (T0 and T1) and other socio-demographic and clinical characteristics have been collected. RESULTS: Over-weight and obesity (higher levels of BMI) were associated with higher risk of PD (higher scores of EPDS), higher neuroticism and poorer subjective psychological well-being among enrolled women. Also, obesity and over-weight were associated with lower education, higher number of physical comorbidities, medical treatments and complications during pregnancy. CONCLUSIONS: Over-weight and obesity may impact on mental health and pregnancy outcome of women enrolled. Psycho-educational interventions aimed to improve the management of physical and emotional issues may reduce the risk of PD and complications during pregnancy.

Associations Between Personality Traits, Perceived Stress and Depressive Symptoms in Gynecological Cancer Patients Characterized by the Short and Long Allele Variant of the 5-HTTLPR Genotype: Preliminary Results.

Objective: The study explored associations between personality traits, perceived stress and symptoms of depression in oncological patients characterized by the two variants of the serotonin transporter (5-HTTLPR) polymorphisms. Method: The sample was composed of 41 gynecological cancer patients who completed self-reported questionnaires including the NEO Five-Factor Inventory, the dimension of depression-dejection (D/D) of the Profile of Moods State and the Perceived Stress Scale (PSS). The polymerase chain reaction was also employed to identify genotypes in the serotonin (5HTT) polymorphism. Results: The one-way ANOVA test, across the 5-HTTLPR genotype groups, showed significant effects of the short variants on neuroticism (p=0.009) and of the long variant on agreeableness (p=0.022), as well as a tendency to a statistical significance of the l/l variant on consciousness (p=0.074). Bivariate correlations showed positive correlations of neuroticism with both psychopathological symptoms (D/D r=0.522; PSS r=0.586) in the combined group S, negative association of agreeableness with depression (D/D r=-0.613) and of consciousness with depression (D/D r=-0.750) and perceived stress (PSS r=-0.702) in the group of the long variant of 5-HT-TLPR genotype. Conclusions: Personalized medicine should consider the interaction between genotype and phenotype in reducing levels of clinical psychological distress, highlighting how psychotherapeutic processes should improve patients' quality of life.

Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease.

The therapeutic potential of ultramicronized palmitoylethanolamide (um-PEA) was investigated in young (6-month-old) and adult (12-month-old) 3 × Tg-AD mice, which received um-PEA for 3 months via a subcutaneous delivery system. Mitochondrial bioenergetics, ATP homeostasis, and magnetic resonance imaging/magnetic resonance spectroscopy were evaluated in the frontal cortex (FC) and hippocampus (HIPP) at the end of um-PEA treatment. Glutamate release was investigated by in vivo microdialysis in the ventral HIPP (vHIPP). We demonstrated that chronic um-PEA treatment ameliorates the decrease in the complex-I respiration rate and the FoF1-ATPase (complex V) activity, as well as ATP content depletion in the cortical mitochondria. Otherwise, the impairment in mitochondrial bioenergetics and the release of glutamate after depolarization was not ameliorated by um-PEA treatment in the HIPP of both young and adult 3 × Tg-AD mice. Moreover, progressive age- and pathology-related changes were observed in the cortical and hippocampal metabolism that closely mimic the alterations observed in the human AD brain; these metabolic alterations were not affected by chronic um-PEA treatment. These findings confirm that the HIPP is the most affected area by AD-like pathology and demonstrate that um-PEA counteracts mitochondrial dysfunctions and helps rescue brain energy metabolism in the FC, but not in the HIPP.