Federica Pinna’s research while affiliated with University of Cagliari and other places

Sexuality and gender identity are crucial aspects of human personal identity and experience. Both significantly affect the individual self-perception, any personal belief, thinking, social being, and connections with the family and community. Sexual variations (e.g., LGBTQIA+: lesbian, gay, bisexual, transgender, queer, intersex, asexual) are common expressions of sexuality beyond the binary model based on the heteronormative conception. Also, gender identity may be not aligned with the sex assigned at birth (biological) and this may lead to specific health needs among persons requiring an affirmative trail of their own gender identity. Non-binary expressions of gender and sexuality are often associated with variable social stigma and oppression with consequent psychosocial distress and mental health issues (including depression, anxiety, adjustment disorders, eating disorders, substance abuse as well as non-suicidal self-injury) for variants people experiencing minority stress. Minority stress may include any experienced childhood adverse event, non-acceptance in the family, school, peers-group, and workplaces. Clinicians and psychiatrists need to consider these specific health and mental health needs as well as psychotherapies should be focused on affirmative approaches. In addition, educational interventions aimed at contrasting social and cultural oppression should be encouraged in order to reduce the impact of minority stress on LGBTQIA+ people and their psychological burden.

The relationship between the experience of childhood adversity (CA) and the development of personality disorders (PDs) has been well documented. The dimensional PD alternative model (AMPD) has been introduced in nosography in 2013, and so far it is been used for CA research mostly on non‐clinical samples. We included in our study 137 psychiatric outpatients who were screened for history of maternal antipathy (MA), paternal antipathy (PA), maternal neglect (MN), paternal neglect (PN), maternal physical abuse (MPA), paternal physical abuse (PPA) and sexual abuse (SA) using the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and underwent personality assessment using the Personality Inventory for DSM‐5. Applying CECA.Q cut‐off scores, rates of participants reporting CA were as follows: 14.6% MA; 13.9% PA; 13.1% MN; 10.2% PN; 25.5% MPA; 24.8% PPA; and 22.6% SA. In multivariate regression models, accounting for age, gender and exposure to other types of CA, exposure to MA was associated with increased negative affect, detachment, disinhibition and psychoticism; exposure to PA with increased disinhibition; and exposure to SA with increased antagonism, disinhibition and psychoticism. All effect sizes were small, except for a moderate effect of SA on psychoticism. Results pointed to a small but specific and independent effect of MA on most maladaptive personality traits; a possible specific role of the paternal figure for externalizing traits; and a moderate effect of SA on psychoticism. The cumulative exposure to multiple CAs significantly predicted all maladaptive personality traits, with much larger effect sizes compared to those calculated for single CAs. CA explained the higher proportion of variance for antagonism and psychoticism. In conclusion, exposure to specific forms of childhood abuse was associated with specific maladaptive traits in psychiatric outpatients, even if the effect of cumulative multiple CAs was larger.

Schizophrenia (SCZ) and schizoaffective disorder (SAD) are severe and complex psychiatric disorders whose liability threshold is modulated by the interplay of biological, mainly genetic, and environmental factors. Consistent evidence has pointed to the role of serum brain‐derived neurotrophic factor (BDNF) as a plausible illness biomarker in SCZ spectrum disorders. There is no consensus, however, on the temporal trajectory of this decline. Here, we present a secondary analysis of the Longitudinal Assessment of BDNF in Sardinian Psychotic patients (LABSP) study, focusing on the impact of antipsychotic therapy, particularly long‐acting injectable (LAI), on the longitudinal trajectory of serum BDNF levels and analyzing the effect of BDNF genetic variants. LABSP patients were assessed every 6 months for a series of measures, including the assessment of BDNF serum levels over 24 months. Blood samples for each patient were taken at the same time of the day (between 8:00 and 10:00 a.m.). BDNF serum levels were determined using the BDNF ELISA Kit. Four tag single nucleotide polymorphisms (SNPs) within the BDNF gene (rs1519480, rs11030104, rs6265 [Val66Met], and rs7934165) were selected using standard parameters and analyzed with polymerase chain reaction (PCR). Mixed‐effects linear regression models (MLRMs) were used to analyze longitudinal data. Twenty‐four patients out of 105 LABSP (22.9%) patients received therapy with LAI. Analysis with MLRM showed a significant effect of LAI treatment associated with increasing serum BDNF levels ( Z = 2.2, p = 0.02). However, oral antipsychotics did not significantly impact the longitudinal trajectory of serum BDNF levels ( Z = 0.15, p = 0.9). There was no moderating effect of variants within the BDNF gene on the identified association. We identified a significant longitudinal increase in serum BDNF in SCZ and SAD patients treated with LAI antipsychotic therapy. The significant impact of this preparation of antipsychotic treatment on serum BDNF, despite the limited sample size, points to a moderate to large magnitude of effect that should be investigated in future prospective studies.

Identifying phenotypes at high risk of suicidal behaviour is a relevant objective of clinical and translational research and can facilitate the identification of possible candidate biomarkers. We probed the potential association and eventual stability of neuropsychological profiles and serum BDNF concentrations with lifetime suicide ideation and attempts (LSI and LSA, respectively) in individuals with schizophrenia (SCZ) and schizoaffective disorder (SCA) in a 2-year follow-up study. A secondary analysis was conducted on a convenience sample of previously recruited subjects from a single outpatient clinic. Retrospectively assessed LSI and LSA were recorded by analysing the available longitudinal clinical health records. LSI + LSA subjects consistently exhibited lower PANSS-defined negative symptoms and better performance in the BACS-letter fluency subtask. There was no significant association between BDNF levels and either LSI or LSA. We found a relatively stable pattern of lower negative symptoms over two years among patients with LSI and LSA. No significant difference in serum BDNF concentrations was detected. The translational viability of using neuropsychological profiles as a possible avenue for the identification of populations at risk for suicide behaviours rather than the categorical diagnosis represents a promising option but requires further confirmation.

Background Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium’s clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations. Content This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors’ preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections. Conclusions Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium’s ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.

Objective: The Psychological-Physical-Pain Visual Analogue Scale (PPP-VAS) was thought to probably help in identifying patients at risk of suicide. However, no data on its validity to measure psychological pain was available. Our main aim was to investigate the convergent validity of the PPP-VAS using two well-validated scales of psychological pain, the Orbach and Mikulincer Mental Pain scale (OMMP) and the Holden et al. Psychache Scale. Methods: This multicentre study recruited a total of 1,618 adult psychiatric inpatients and outpatients in Italy. Psychological pain was evaluated using the OMMP, Holden et al., and PPP-VAS scales. Psychiatric status, suicidal status, physical pain, depression, and hopelessness were also assessed. Results: A structural equation model (SEM) using the items of psychological pain from the PPP-VAS showed that items loaded significantly on the psychological pain factor and showed good fit. Similarly, a second SEM model using the three scales of psychological pain showed acceptable fit and converged into a psychological pain construct. Correlations between the PPP-VAS and depression, hopelessness, and physical pain showed moderate correlations (r = .43 to r = .67). Finally, psychological pain evaluated with the PPP-VAS was significantly related with recent suicidal ideation in all patients (OR [95% CI] = 1.07 [1.05, 1.09]) and recent suicide attempts in moderately to severely depressed patients, OR [95% CI] = 1.01 [1.02, 1.03]. Conclusion: The PPP-VAS showed good psychometric properties in evaluating psychological pain. The characteristics of the PPP-VAS makes this scale a great option for its use in clinical practice to detect patients at risk of suicide.

Remission, relapse prevention, and clinical recovery are crucial areas of interest in schizophrenia (SCZ) research. Although SCZ is a chronic disorder with poor overall outcomes, years of research demonstrated that recovery is possible. There are considerable data linking brain-derived neurotrophic factor (BDNF) to SCZ, however, evidence on the role of BDNF in remission in SCZ is scarce. This secondary analysis of the Longitudinal Assessment of BDNF in Sardinian patients (LABSP) data aimed to investigate the relationship between serum BDNF levels and symptomatic remission, simultaneous clinical and functional remission, and recovery in patients with SCZ. A total of 105 patients with SCZ or schizoaffective disorder were recruited for a longitudinal assessment of BDNF levels over 24 months. Longitudinal data were analyzed using mixed-effects linear regression models. The study found significant associations between use of long acting injectables (χ2 = 7.075, df = 1, p = 0.008), baseline serum BDNF levels (U = 701, z = −2.543, p = 0.011), and “childhood” (U = 475, z = −2.124, p = 0.034) and “general” (U = 55, z = −2.014, p = 0.044) subscales of the Premorbid Adjustment Scale (PAS) with patients maintaining remission and recovery. The diagnosis of SCZ was significantly associated with lower BDNF levels for patients with simultaneous clinical and functional remission (Z = 2.035, p = 0.0419) and recovery (Z = 2.009, p = 0.0445) compared to those without. There were no significant associations between remission in the entire sample and longitudinal serum BDNF levels or genetic variants within the BDNF gene. These findings provide further insight into the complex relationship between BDNF and SCZ.

Background Research suggests that microaggressions detrimentally impact the mental health of members of marginalized social groups. Aims The aim of this systematic review was to assess the exposure to microaggressions and related implications on mental health of Lesbian, Gay, Bisexual, Transgender, Intersex, and Queer (LGBTIQ) people. Method Medline, Scopus, PsycINFO, CINAHL, and EMBASE were searched until January 2023. Studies reporting data on the exposure to microaggressions toward LGBTIQ people were identified. Meta-analyses of rates of exposure to microaggression and of the association between microaggressions and mental health outcomes were based on odds ratio (OR) and standardized mean difference (SMD) with 95% confidence intervals (95% CI), estimated through inverse variance models with random effects. Results The review process led to the selection of 17 studies, involving a total of 9036 LGBTIQ people, of which 6827 identifying as cisgenders, and 492 as heterosexuals, were included in the quantitative synthesis. Overall, LGBTIQ people showed an increased risk of microaggression (SMD: 0.89; 95% CI [0.28, 1.50]), with Transgender people having the highest risk (OR: 10.0; 95% CI [3.08, 32.4]). Microaggression resulted associated with risk of depression (SMD: 0.21; 95% CI [0.05, 0.37]), anxiety (SMD: 0.29; 95% CI [0.17, 0.40]), suicide attempts (OR: 1.13; 95% CI [1.08, 1.18]), alcohol abuse (OR: 1.32; 95% CI [1.13, 1.54]), but not to suicidal ideation (OR: 1.56; 95% CI [0.64, 3.81]) and cannabis abuse (OR: 1.44; 95% CI [0.82, 2.55]). The quality of the evidence was limited by the small number of studies. Conclusions LGBTIQ people are at higher risk of microaggressions compared with their cisgender/heterosexual peers, which may lead to mental health consequences. This evidence may contribute to public awareness of LGBTIQ mental health needs and suggest supportive strategies as well as preventive interventions (e.g., supportive programs and destigmatizing efforts) as parts of tailored health-care planning aimed to reduce psychiatric morbidity in this population.