A new look at an old drug: Neuroprotective effects and therapeutic potentials of lithium salts

Increasing evidence highlights bipolar disorder as being associated with impaired neurogenesis, cellular plasticity, and resiliency, as well as with cell atrophy or loss in specific brain regions. This has led most recent research to focus on the possible neuroprotective effects of medications, and particularly interesting findings have emerged for lithium. A growing body of evidence from preclinical in vitro and in vivo studies has in fact documented its neuroprotective effects from different insults acting on cellular signaling pathways, both preventing apoptosis and increasing neurotrophins and cell-survival molecules. Furthermore, positive effects of lithium on neurogenesis, brain remodeling, angiogenesis, mesenchymal stem cells functioning, and inflammation have been revealed, with a key role played through the inhibition of the glycogen synthase kinase-3, a serine/threonine kinase implicated in the pathogenesis of many neuropsychiatric disorders. These recent evidences suggest the potential utility of lithium in the treatment of neurodegenerative diseases, neurodevelopmental disorders, and hypoxic-ischemic/traumatic brain injury, with positive results at even lower lithium doses than those traditionally considered to be antimanic. The aim of this review is to briefly summarize the potential benefits of lithium salts on neuroprotection and neuroregeneration, emphasizing preclinical and clinical evidence suggesting new therapeutic potentials of this drug beyond its mood stabilizing properties

Psychotic spectrum symptoms across the lifespan are related to lifetime suicidality among 147 patients with bipolar I or major depressive disorder

BACKGROUND: Conflicting evidence exists about the relationship between psychotic symptoms and suicidality in mood disorders. We aimed to investigate the lifetime suicidality and its relationship with dimensions of the psychotic spectrum over the lifespan among subjects with bipolar I (BD I) or major depressive disorder (MDD). METHODS: 147 Consecutive out- and inpatients with BD I or MDD presenting for treatment at 11 Italian Departments of Psychiatry were administered the Structured Clinical Interview for DSM-IV Axis I Disorders, the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY, lifetime version) and the Mood Spectrum Self-Report (MOODS-SR, lifetime version). RESULTS: Subjects with psychotic features did not differ from those without for MOODS-SR suicidality score. Controlling for age, gender and diagnosis (MDD/BD I), the SCI-PSY total score (p = .007) and Paranoid (p = .042), Schizoid (p = .007) and Interpersonal Sensitivity (p < .001) domain scores independently predicted lifetime MOODS-SR suicidality score in the overall sample. CONCLUSIONS: Psychotic features, as evaluated upon the presence of delusions or hallucinations, are not associated with suicidality among subjects with BD I or MDD. However, more subtle dimensions of the psychotic spectrum, such as Interpersonal Sensitivity, Paranoid and Schizoid symptoms, show a significant relationship with lifetime suicidality. Our findings highlight the potential usefulness of a spectrum approach in the assessment of psychotic symptoms and suicide risk among subjects with BD I or MDD

The Broad Autism (Endo)Phenotype: Neurostructural and Neurofunctional Correlates in Parents of Individuals with Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with an early-onset and a strong genetic component in their pathogenesis. According to genetic and epidemiological data, ASD relatives present personality traits similar to, but not as severe as the defining features of ASD, which have been indicated as the "Broader Autism Phenotype" (BAP). BAP features seem to be more prevalent in first-degree relatives of individuals with ASD than in the general population. Characterizing brain profiles of relatives of autistic probands may help to understand ASD endophenotype. The aim of this review was to provide an up-to-date overview of research findings on the neurostructural and neurofunctional substrates in parents of individuals with ASD (pASD). The primary hypothesis was that, like for the behavioral profile, the pASD express an intermediate neurobiological pattern between ASD individuals and healthy controls. The 13 reviewed studies evaluated structural magnetic resonance imaging (MRI) brain volumes, chemical signals using magnetic resonance spectroscopy (MRS), task-related functional activation by functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG) in pASD.The studies showed that pASD are generally different from healthy controls at a structural and functional level despite often not behaviorally impaired. More atypicalities in neural patterns of pASD seem to be associated with higher scores at BAP assessment. Some of the observed atypicalities are the same of the ASD probands. In addition, the pattern of neural correlates in pASD resembles that of adult individuals with ASD, or it is specific, possibly due to a compensatory mechanism. Future studies should ideally include a group of pASD and HC with their ASD and non-ASD probands respectively. They should subgrouping the pASD according to the BAP scores, considering gender as a possible confounding factor, and correlating these scores to underlying brain structure and function. These types of studies may help to understand the genetic mechanisms involved in the various clinical dimension of ASD

DSM-5 PTSD and posttraumatic stress spectrum in Italian emergency personnel: correlations with work and social adjustment

The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) has recently recognized a particular risk for posttraumatic stress disorder (PTSD) among first responders (criterion A4), acknowledging emergency units as stressful places of employment. Little data is yet available on DSM-5 among emergency health operators. The aim of this study was to assess DSM-5 symptomatological PTSD and posttraumatic stress spectrum, as well as their impact on work and social functioning, in the emergency staff of a major university hospital in Italy. One hundred and ten subjects (doctors, nurses, and health-care assistants) were recruited at the Emergency Unit of the Azienda Ospedaliero-Universitaria Pisana (Italy) and assessed by the Trauma and Loss Spectrum-Self Report (TALS-SR) and Work and Social Adjustment Scale (WSAS). A 15.7% DSM-5 symptomatological PTSD prevalence rate was found. Nongraduated persons reported significantly higher TALS-SR Domain IV (reaction to loss or traumatic events) scores and a significantly higher proportion of individuals presenting at least one maladaptive behavior (TALS-SR Domain VII), with respect to graduate ones. Women reported significantly higher WSAS scores. Significant correlations emerged between PTSD symptoms and WSAS total scores among health-care assistants, nongraduates and women. Our results showed emergency workers to be at risk for posttraumatic stress spectrum and related work and social impairment, particularly among women and nongraduated subjects. Keywords: posttraumatic stress disorder (PTSD), emergency, emergency care workers, work and social functioning/adjustment, maladaptive behaviors, gender, educatio

Impact of depression on circulating endothelial progenitor cells in patients with acute coronary syndromes

Aims: Depression has been identified as a risk factor for an adverse prognosis and reduced survival in patients with acute coronary syndrome (ACS). The number of endothelial progenitor cells (EPCs) is an independent predictor of clinical outcomes in patients with ACS. The aim was to evaluate the impact of depression on EPC levels in patients with ACS. Methods: Out of 74 ACS patients [23 non-ST-segment elevation myocardial infarction (NSTEMI), 48 STEMI], 36 had a diagnosis of major depressive episode (MDE) according to Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria at the time of the inclusion in the study. Control groups were as follows: 15 healthy individuals and 18 patients with current MDE without a history of cardiovascular diseases. EPCs were defined as CD34RCD133RKDRR and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed wherever appropriate. Results: ACS patients with MDE showed a significant decrease in circulating EPC number compared with ACS patients without MDE (P &lt;0.001). The ACS study population was then subdivided into STEMI and NSTEMI groups, and inside each group again patients with MDE showed a significant decrease in circulating CD34RCD133RKDRR EPCs compared with others (P &lt;0.001). Conclusion: We showed that ACS patients with MDE have a reduced number of circulating CD34RCD133RKDRR cells compared with ACS patients without MDE, suggesting that the presence of MDE reduces the response of bone marrow to acute ischemic events. Considering the reparative role of EPCs in ACS patients, we suppose that patients with MDE might be protected less than patients without MDE

Frequency and correlates of adult Separation Anxiety Disorder among individuals with Complicated Grief: an exploratory study

Introduction: Recent epidemiological data indicate that adult Separation Anxiety (SEPAD) has a lifetime prevalence of 6.6% in the general population. Moreover, adult SEPAD is highly co-morbid with other psychiatric disorders and associated with substantial impairment in role functioning. A growing body of data suggests that 10% to 20% of bereaved persons develop complicated grief (CG). Attachment theory might offer insight into both SEPAD and CG and childhood SEPAD was found to be linked to a higher risk of developing CG in adulthood. Even though adult SEPAD might be expected to be highly prevalent among CG patients and to impact functioning and treatment response, no studies have so far investigated adult SEPAD among people with CG. The proposed research attempts to explore the prevalence of adult SEPAD among CG patients, its possible association with specific dimensions of loss and its pattern of co-morbidity with PTSD, depression and PD. Moreover, we aim to investigate whether adult SEPAD might affect functioning of people with CG. Methods: 151 bereaved individuals were evaluated with the Inventory of Complicated Grief (ICG), the Structured Clinical Interview for the DSM-IV (SCID-I),the Hamilton Rating Scale for Depression (HAM-D), the Separation Anxiety Symptoms Questionnaire (ASA-27), the Grief Related Avoidance Questionnaire (GRAQ), the Peritraumatic Dissociative Experiences Questionnaire (PDEQ), the Impact of Events Scale (IES), the Work and Social Adjustment Scale (WSAS). Results: People with and without SEPAD did not differ significantly for gender distribution, age, education and marital status. A significant difference was found with respect to race (P=0.002). With respect to grief measures, no differences were found in terms of total number of losses, type of loss and relationship to the deceased. People with adult SEPAD showed higher scores on the ICG (P<0.001), the PDEQ(P=0.004), the GRAQ(P<0.001), the IES intrusion (P<0.001) and IES avoidance (P<0.001). People with adult SEPAD showed a greater grief related impairment as evaluated with the WSAS (P=0.006). People with adult SEPAD, compared to those without, had a significantly higher co-morbidity with PTSD lifetime (P=0.04) and PD (current: P=0.001; lifetime: P=0.001). Adult SEPAD was not significantly associated with MDD, either current or lifetime. Nevertheless, HAM-D total score was significantly higher among people with adult SEPAD than those without P<0.001). As to ASA-27 total score, people with PTSD (either current or lifetime) showed significantly higher scores than people without PTSD (current: P=0.02; lifetime: P=0.002), as did people with PD (current: P<0.001; lifetime: P<0.001) whereas people with MDD, either current or lifetime, did not. Conclusions: Adult SEPAD is highly frequent among patients with CG. As to other anxiety disorders, adult SEPAD is strongly associated with PTSD and PD. Even though there is a correlation between SEPAD symptoms and the severity of depressive symptoms, adult SEPAD is not significantly co-morbid with unipolar depression. Further studies will be necessary in order to confirm and generalize our results and to elucidate whether adult SEPAD might affect the course of CG and treatment response

The Impact of COVID-19 Pandemic First Wave on Healthcare Workers: A New Perspective from Qualifying PTSD Criterion A to Assessing Post-Traumatic Growth

Post-traumatic growth (PTG) and specific traumatic events have been poorly explored in the literature focusing on post-traumatic stress disorder (PTSD) among healthcare workers (HWs) tackling the COVID-19 pandemic. In a large sample of Italian HWs, we investigated the kinds of traumatic events and whether PTG affects the risk of PTSD, along with its prevalence and features, during the first COVID-19 wave. COVID-19-related stressful events, Impact of Event Scale-Revised (IES-R) and PTG Inventory-Short Form (PTGI-SF) scores were collected through an online survey. Out of 930 HWs included in the final sample, 257 (27.6%) received a provisional PTSD diagnosis based on IES-R scores. Events referring to the overall pandemic (40%) and to a threat to a family member (31%) were reported as the most stressful events. Female sex, previous mental disorders, job seniority, unusual exposure to sufferance and experiencing a threat to one&rsquo;s family significantly increased the provisional PTSD diagnosis&rsquo; risk, while being a physician, the availability of personal protective equipment and moderate/greater scores on the PTGI-SF spiritual change domain were found to be protective factors

Can high-frequency transcranial magnetic stimulation enhance cognition and negative symptoms in schizophrenia? A pilot study.

Schizophrenia (SCZ) is a chronic psychiatric disorder that severely impacts patients’ everyday functioning and quality of life. Unlike positive symptoms, cognitive impairment and negative symptoms can’t be treated pharmacologically and represent consistent predictors of illness prognosis and everyday patients’ functioning. Previous studies suggested that transcranial magnetic stimulation can effectively reduce SCZ’s negative symptoms. In contrast, findings on cognitive impairment remain heterogeneous, possibly due to the variability in stimulation protocols and patients’ characteristics. In the present study, we combined intermittent theta burst stimulation (iTBS) with cognitive training to improve negative symptoms and cognitive impairment in patients with a disorder in the schizophrenic spectrum. Twenty-one participants were randomized into four groups, varying on the stimulation condition (real vs. sham iTBS) and cognitive remediation (training vs. no training). Fifteen sessions of real or sham iTBS were delivered over the left dorsolateral prefrontal cortex once a day for three weeks, followed - or not - by 1-hour cognitive training. Clinical and cognitive assessments took place before and after the intervention, plus at three follow-ups 1, 3, and 6 months after the end of the treatment. Mixed-model analyses were run on patients’ cognitive performance and negative symptoms and stimulation condition, training, and time were added as fixed factors. A by-subject random intercept was included. The feasibility and limitations of the methodological approach and preliminary data are discussed