Search

Abstract Background Lithium stands as the gold standard in treating bipolar disorders (BD). Despite numerous clinical factors being associated with a favorable response to lithium, comprehensive studies examining the collective influence of clinical variables alongside psychopathological dimensions are lacking. Our study aims to enhance comprehension of lithium response in individuals with BD by integrating clinical variables with psychopathological traits and early adverse events. Methods We assessed 201 patients with BD for clinical characteristics, childhood trauma, temperament traits, impulsivity, and aggression. Lithium response was evaluated using the gold standard Alda scale, and predictors of lithium response were estimated through a multivariate model. Results On the total sample, 61 (30.3%) patients were lithium responders according to the Alda scale. Comparatively, lithium responders, in contrast to non-responders, demonstrated a higher prevalence of the mania-depression-interval (MDI) cycle, a more frequent diagnosis of BD type I, and reported an earlier age of onset. They also exhibited less lifetime substance abuse, emotional, physical, and sexual abuse, while scoring higher on hyperthymic and irritable temperament scales. In multivariate analyses, only the MDI cycle (OR,3.47; 95%CI,1.61–7.50) hyperthymic (OR,1.20; 95%CI,1.02–1.41) and irritable temperament (OR,1.28; 95%CI,1.08–1.52) persisted as significant predictors of a positive response to lithium treatment, while emotional (OR,0.87; 95%CI,0.76–0.98) and physical abuse (OR,0.83; 95%CI,0.70–0.98) were predictors of non-response. Conclusions In evaluating lithium response in BD, our study highlights the importance of considering clinical variables alongside temperament and childhood adversities. The assessment of hyperthymic and irritable temperament, emotional and physical abuse together with the type of cycle is of particular importance. Furthermore, our findings underscore the significance of systematically assessing the type of cycle in patients with BD through the use of life charts.

Background/Objectives: Although rare in the Western world, dog bites may be lethal or lead to physically severe outcomes. However, little attention is given to their psychological consequences. We aimed to review their psychological consequences in children 1–14 years of age, focusing on the prevalence and nature of psychological disorders, evaluating the impact on future mental health of children and their families, and assessing the effectiveness of preventive interventions and measures. Methods: On 23 May 2024, we investigated the PubMed, CINAHL, and PsycINFO/PsycARTICLES databases using (“dog bite” OR animal-induced OR animal-caused) AND (psychol* OR mental OR psychiatr* OR anxiety OR anxious OR depress* OR obsess* OR trauma* OR psychosis OR psychotic OR schizophren* OR schizoaffect*) filtered for ages 0–18 years. This resulted in 311 records, of which 50 were eligible. These included original research, case reports, patient surveys, and reviews/meta-analyses. Results: Findings indicate that younger children are particularly vulnerable, often suffering head/neck bites, leading to severe injuries and psychological distress, with post-traumatic stress disorder (PTSD) being a common outcome. Symptoms such as nightmares, flashbacks, anxiety, and social withdrawal were frequently reported. Positive parental support and timely psychological interventions were found to mitigate these effects. Conclusions: Interdisciplinary approaches integrating education, cognitive restructuring, and behaviour modification are needed to effectively prevent and address the psychological impacts of dog bites. Summarising, dog bites in children result in substantial psychological sequelae, necessitating robust prevention and intervention strategies to improve their quality of life and reduce the risk of chronic mental conditions.

Abstract Introduction Gender dysphoria (GD) is characterized by the incongruence between one’s experienced and expressed gender and assigned-sex-at-birth; it is associated with clinically significant distress. In recent years, the number of young patients diagnosed with GD has increased considerably. Recent studies reported that GD adolescents present behavioural and emotional problems and internalizing problems. Furthermore, this population shows a prevalence of psychiatric symptoms, like depression and anxiety. Several studies showed high rates of suicidal and non-suicidal self-injurious thoughts and behaviour in GD adolescents. To increase understanding of overall mental health status and potential risks of young people with GD, this systematic review focused on risk of suicide and self-harm gestures. Methods We followed the PRISMA 2020 statement, collecting empirical studies from four electronic databases, i.e., PubMed, Scopus, PsycINFO, and Web of Science. Results Twenty-one studies on GD and gender nonconforming identity, suicidality, and self-harm in adolescents and young adults met inclusion criteria. Results showed that GD adolescents have more suicidal ideation, life-threatening behaviour, self-injurious thoughts or self-harm than their cisgender peers. Assessment methods were heterogeneous. Conclusion A standardised assessment is needed. Understanding the mental health status of transgender young people could help develop and provide effective clinical pathways and interventions.

The literature emphasizes the importance of addressing the misuse of ADHD medications as a potential significant healthcare issue within the general population. Nevertheless, there are no systematic reviews that specifically examine whether the misuse of psychostimulant medication among clinical populations diagnosed with ADHD who are undergoing prescribed stimulant therapy is a rational concern or a false myth. This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. We searched PubMed databases for articles indexed up to 12th July 2023, without language restrictions. Our systematic search generated 996 unique articles. After a full-text revision, 13 studies met the eligibility criteria and were included in the systematic review. In the 50% of the study on the adult population, the reported prevalence of stimulant misuse was 0%. In other studies, the range of stimulant misuse rates varied from 2% to 29%, with no available data specifically focusing on the youth population. It has been noted that misuse of prescribed stimulant treatment is linked with particular subject characteristics, such as older age, prior or more frequent use of ADHD medication, use of short-acting medication, and a history of alcohol/substance misuse diagnosis. Despite certain limitations, our study highlights that while a significant proportion of individuals undergoing psychostimulant treatment for ADHD follow their prescribed medication regimens without resorting to misuse behaviors, there is variability in adherence, with occurrences of misuse behaviors. The misuse of prescribed ADHD treatment appears to be associated with distinct subject characteristics, underscoring the importance for tailored interventions addressing the specific requirements of these individuals to attain optimal treatment outcomes while mitigating misuse risks.

Long COVID-19 is characterized by ongoing symptoms or prolonged or long-term complications of SARS-CoV-2 contraction which persist beyond 4 weeks from the initial onset of symptoms. Gender and duration of hospitalization (DH) are key risk factors for developing long COVID-19 syndrome, but their impact and interplay need further study. This research involved 996 long COVID-19 patients, and we compared the levels of general psychopathology, depression, agitated depression, anxiety, and medication use between hospitalized and non-hospitalized males and females. In the hospitalized patients, multivariate regressions assessed the impact of gender, DH, and the interaction of these variables. The females had higher levels of long COVID-19 symptoms, psychotropic drug use, depression, anxiety, and general psychopathology than the males. The non-hospitalized females exhibited more severe agitated depression than the non-hospitalized males. In females, DH was more strongly correlated with the number of psychotropic medications used during long COVID-19. A negative correlation was found between DH and severity of agitated depression in the female patients only. These results highlight that the gender-specific relationship between DH and agitated depression severity should be explored further.

IntroductionPsychological distress may result in impairment and difficulty understanding oneself and others. Thus, addressing metacognitive issues in psychotherapy may improve psychopathology in adolescents and young adults (AYAs). We aimed to compare metacognitive interpersonal therapy (MIT)-informed psychotherapy with other treatment-as-usual (TAU) therapies.MethodsWe administered the Global Assessment of Functioning (GAF) scale, the Clinical Global Impressions–Severity (CGI-S) scale, and the Brief Psychiatric Rating Scale (BPRS) at baseline (BL) and at treatment termination (the endpoint was at 6 months and any last results obtained before that term were carried forward in analyzes). Patients received concomitant psychiatric and psychological treatment.ResultsSixty AYAs were involved in the study. There was a significant reduction in symptomatology after the intervention. Twelve patients (17%) dropped out; treatment adherence was 83%. In the MIT group, 2 patients dropped out (11%), and in the TAU group, 9 patients dropped out (19%). All scales showed a significant reduction in symptoms between baseline (BL) and the 6-month endpoint: GAF (χ2 = 6.61, p

Abstract Background Lithium is one of the most consistently effective treatment for mood disorders. However, patients may show a high level of heterogeneity in treatment response across the lifespan. In particular, the benefits of lithium use may vary in special clinical conditions. The aim of this study was to test this hypothesis by conducting an umbrella review on the efficacy and safety of lithium in childhood and adolescence, peripartum and old age. Methods We applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA) to identify systematic reviews/meta-analyses on the efficacy and/or safety of lithium in mood disorders in special clinical conditions: (i) childhood and adolescence; (ii) peripartum (pregnancy, postpartum and lactation); (iii) old age. The Risk of Bias Assessment Tool for Systematic Reviews (ROBIS) tool was used to assess the risk of bias. Overlap in primary studies across systematic reviews was calculated through the Corrected Covered Area (CCA). Results We included 20 independent studies, for a total of 8209 individuals treated with lithium. Regarding paediatric age, efficacy and safety results suggested that lithium may be superior to placebo in bipolar disorders (BD) and not associated with serious adverse events. Nevertheless, primary available data are very limited. Efficacy in paediatric major depressive disorder (MDD) is not clear. During peripartum, lithium use was superior to non-lithium in preventing mood episodes and it was associated with low risk of congenital anomalies and with normal child neurodevelopment. Regarding old age, limited evidence supported lithium as an effective treatment in BD and resistant MDD; low doses should be used in this population. Systematic reviews on paediatric age showed the lowest risk of bias (80% of the studies at low risk). The CCA range of included studies was 13–47%. Conclusions This umbrella review supports the use of lithium across the lifespan, including special clinical condition. Nevertheless, more studies with increased methodological homogeneity are needed.

BackgroundCOVID-19 may result in persistent symptoms in the post-acute phase, including cognitive and neurological ones. The aim of this study is to investigate the cognitive and neurological features of patients with a confirmed diagnosis of COVID-19 evaluated in the post-acute phase through a direct neuropsychological evaluation.MethodsIndividuals recovering from COVID-19 were assessed in an out-patient practice with a complete neurological evaluation and neuropsychological tests (Mini-Mental State Examination; Rey Auditory Verbal Test, Multiple Feature Target Cancellation Test, Trial Making Test, Digit Span Forward and Backward, and Frontal Assessment Battery). Pre- and post-COVID-19 global and mental health status was assessed along with the history of the acute phase of infection. Post-COVID-19 cognitive status was modeled by combining persistent self-reported COVID-related cognitive symptoms and pathologic neuropsychological tests.ResultsA total of 406 individuals (average age 54.5 ± 15.1 years, 45.1% women) were assessed on average at 97.8 ± 48.0 days since symptom onset. Persistent self-reported neurological symptoms were found in the areas of sleep (32%), attention (31%), and memory (22%). The MMSE mean score was 28.6. In total, 84 subjects (20.7%) achieved pathologic neuropsychological test results. A high prevalence of failed tests was found in digit span backward (18.7%), trail making (26.6%), and frontal assessment battery (10.9%). Cognitive status was associated with a number of factors including cardiovascular disease history, persistent fatigue, female sex, age, anxiety, and mental health stress.ConclusionCOVID-19 is capable of eliciting persistent measurable neurocognitive alterations particularly relevant in the areas of attention and working memory. These neurocognitive disorders have been associated with some potentially treatable factors and others that may stratify risk at an early stage.

Interleukin 6 (IL-6) receptor inhibitors tocilizumab and sarilumab have recently been approved for severe coronavirus disease 2019 (COVID-19). They also affect mood, even though their effect on the post-COVID-19 syndrome-related psychopathology still has to be investigated. The aim of this study was to investigate their effect on psychopathology in a sample of patients with post-COVID-19 syndrome. We included 246 patients (34% female, 66% male) aged 18–75 years who had been hospitalized for COVID. Patients were split into those who received anti-IL-6 receptor agents (Anti-IL-6-R, N = 88) and those who did not (Ctrl, N = 158). The former group was further split into those receiving tocilizumab (TOC, N = 67) and those receiving sarilumab (SAR, N = 21). Groups were compared based on clinical characteristics before and during COVID-19 as well as on physical and psychiatric symptoms after COVID-19. Ctrl had less psychiatric and physical symptoms during hospitalization and more post-COVID-19 diarrhea, headache, cough, and dyspnea upon exertion than those receiving IL-6-receptor inhibitors. Ctrl also showed greater difficulties in emotion regulation. These differences were driven by TOC vs. Ctrl, whereas differences between SAR and Ctrl or TOC did not reach significance. IL-6 receptor inhibitors are related to a lower post-COVID-19 illness burden and seem to be effective in emotion regulation. Further research is needed to confirm these findings.

(1) Background: Bipolar disorder (BD) is divided into type I (BD-I) and type II (BD-II). Polarity at onset (PO) is a proposal to specify the clinical course of BD, based on the type of the first episode at disorder onset—depressive (D-PO) or manic (M-PO). At the same time, affective temperaments represent preexisting variants of the spectrum of affective disorders. Our objectives were to investigate the hypothesis that temperament may exert an influence on PO, and that this factor can serve as an indicator of the forthcoming course of the disorder, carrying significant therapeutic implications. (2) Methods: We included 191 patients with BD and examined clinical variables and temperament; the latter was assessed using the short version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego—Auto-questionnaire (TEMPS-A-39-SV). We tested the associations between these variables and PO using standard univariate/bivariate methods followed by multivariate logistic regression models. (3) Results: 52.9% of the sample had D-PO and 47.1% had M-PO. D-PO and M-PO patients scored higher for dysthymic and hyperthymic temperaments, respectively (p < 0.001). Also, they differed in BD subtypes, age at first affective episode, illness duration, number of depressive episodes, seasonality, suicide risk, substance use, lithium, and benzodiazepine use (p < 0.05). Only BD-II and age at first depressive episode were predictors of D-PO, whereas BD-I, age at first manic/hypomanic episode, and hyperthymic temperament were predictors of M-PO (p < 0.01). (4) Conclusions: Our findings point to the importance of carefully assessing temperament and PO in patients with BD, to better predict the clinical course and tailor therapeutic interventions to individual patients’ needs.

The relationship between depression and post-COVID-19 disease syndrome (post-COVID-19 syndrome) is established. Nevertheless, few studies have investigated the association between post-COVID-19 syndrome and mixed depression, i.e., a specific sub-form of depression characterized by high level of excitatory symptoms. Aims of the present study are: (a) to compare the post-COVID-19 syndrome’s burden in depressed and non-depressed patients, and (b) to investigate the correlation between post-COVID-19 syndrome’s burden and the severity of mixed depression. One thousand and forty six (n = 1460) subjects with post-COVID-19 syndrome were assessed. Subjects were divided into those with (DEP) or without (CONT) depression. Sociodemographically, post-COVID-19 syndrome’s symptoms number and type were compared. In DEP, association between levels of excitatory symptoms and the presence of post-COVID-19 syndrome’s symptoms were additionally assessed. DEP showed greater percentages of family history of psychiatric disorders than CONT. DEP showed higher percentages of post-COVID-19 symptoms than CONT. A greater level of excitatory symptoms were associated to higher frequencies of post-COVID-19 syndrome’ symptoms. Higher levels of post-COVID-19 syndrome’s symptoms in DEP corroborate the evidence of a common pathway between these two syndromes. Presence of excitatory symptoms seem to additionally add a greater illness burden. Such findings might help clinicians choose the appropriate treatment for such states. More specifically, therapies aimed to treat excitatory symptoms, such as antipsychotics and mood stabilizers, might help reduce the illness burden in post-COVID-19 patients with mixed depression.

There is increasing interest in the involvement of antioxidative systems in protecting from depression. Among these, Nrf2 occupies a central place. We aimed to review the role of Nrf2 in depression. For this reason, we conducted a PubMed search using as search strategy (psychiatr*[ti] OR schizo*[ti] OR psychot*[ti] OR psychos*[ti] OR depress*[ti] OR MDD[ti] OR BD[ti] OR bipolar[ti] OR Anxiety[ti] OR antidepress*[ti] OR panic[ti] OR obsess*[ti] OR compulsio*[ti] OR “mood disord*”[ti] OR phobi*[ti] OR agoraphob*[ti] OR anorex*[ti] OR anorect*[ti] OR bulimi*[ti] OR “eating disorder*”[ti] OR neurodevelopm*[ti] OR retardation[ti] OR autism[ti] OR autistic[ti] OR ASM[ti] OR adhd[ti] OR “attention-deficit”[ti]) AND nrf2, which on the 9th of March produced 208 results of which 89 were eligible for our purposes. Eligible articles were studies reporting data of Nrf2 manipulations or content by any treatment in human patients or animals with any animal model of depression. Most studies were on mice only (N = 58), 20 on rats only, and three on both rats and mice. There were two studies on cell lines (in vitro) and one each on nematodes and fish. Only four studies were conducted in humans, one of which was post mortem. Most studies were conducted on male animals; however, human studies were carried out on both men and women. The results indicate that Nrf2 is lower in depression and that antidepressant methods (drugs or other methods) increase it. Antioxidant systems and plasticity-promoting molecules, such as those in the Nrf2–HO-1, BDNF–TrkB, and cyclic AMP–CREB pathways, could protect from depression, while glycogen synthase kinase-3β and nuclear factor κB oppose these actions, thus increasing depressive-like behaviours. Since Nrf2 is also endowed with tumorigenic and atherogenic potential, the balance between benefits and harms must be taken into account in designing novel drugs aiming at increasing the intracellular content of Nrf2.

Severe mental disorders (SMD) are highly prevalent psychiatric conditions exerting an enormous toll on society. Therefore, prevention of SMD has received enormous attention in the last two decades. Preventative approaches are based on the knowledge and detailed characterization of the developmental stages of SMD and on risk prediction. One relevant biological component, so far neglected in high risk research, is microbiota. The human microbiota consists in the ensemble of microbes, including viruses, bacteria, and eukaryotes, that inhabit several ecological niches of the organism. Due to its demonstrated role in modulating illness and health, as well in influencing behavior, much interest has focused on the characterization of the microbiota inhabiting the gut. Several studies in animal models have shown the early modifications in the gut microbiota might impact on neurodevelopment and the onset of deficits in social behavior corresponding to distinct neurosignaling alterations. However, despite this evidence, only one study investigated the effect of altered microbiome and risk of developing mental disorders in humans, showing that individuals at risk for SMD had significantly different global microbiome composition than healthy controls. We then offer a developmental perspective and provided mechanistic insights on how changes in the microbiota could influence the risk of SMD. We suggest that the analysis of microbiota should be included in the comprehensive assessment generally performed in populations at high risk for SMD as it can inform predictive models and ultimately preventative strategies.

Background: The coronavirus disease 2019 (COVID-19) pandemic represents a condition of increased vulnerability and frailty for elderly patients with Parkinson's disease (PD). Social isolation may worsen the burden of the disease and specifically exacerbate psychiatric symptoms, often comorbid with PD. This study aimed at identifying risk/protective factors associated with subjective worsening of psychiatric symptomatology during the COVID-19 outbreak in a sample of individuals with PD aged 65 years or older.Methods: Patients with PD routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for subjective worsening of psychiatric symptoms through a dedicated telephone survey, after Italy COVID-19 lockdown. Patients' medical records were reviewed to collect sociodemographic and clinical data, including lifetime psychiatric symptoms and pharmacological treatment.Results: Overall, 134 individuals were assessed and 101 (75.4%) reported lifetime psychiatric symptoms. Among those, 23 (22.8%) presented with subjective worsening of psychiatric symptomatology during the COVID-19 outbreak. In this group, the most frequent symptom was depression (82.6%), followed by insomnia (52.2%). Subjective worsening of neurological symptoms (Wald = 24.03, df = 1, p = 0.001) and lifetime irritability (Wald = 6.35, df = 1, p = 0.020), together with younger age (Wald = 5.06, df = 1, p = 0.038) and female sex (Wald = 9.07 df = 1, p = 0.007), resulted as specific risk factors for ingravescence of psychiatric presentation. Lifetime pre-existing delusions, having received antipsychotics, and not having received mood stabilizer were also associated with subjective worsening of psychiatric symptomatology due to the COVID-19 pandemic.Conclusions: Individuals with PD and lifetime history of psychiatric symptoms may be exposed to increased vulnerability to the stressful effect of COVID-19 outbreak. Interventions aimed at reducing irritability and mood instability might have an indirect effect on the health of patients with PD during the COVID-19 pandemic.

To study the long-term psychological effects of Covid-19 disease, we recruited 61 patients older than 60 years of age and administered the Kessler questionnaire K10 to assess psychological distress and classify them according to mental health risk groups. Patients' affective temperaments were assessed with the 39-item form of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A-39) and emotional dysregulation with the Difficulties in Emotion Regulation Scale (DERS). Patients were divided in two samples according to their scores on the K10, i.e., a high likelihood of psychological distress group (N = 18) and a low likelihood of psychological distress group (N = 43). The two groups differed on their gender composition, in that more women (N = 11) were in the former and more men in the latter (N = 29) (χ2 = 4.28; p = 0.039). The high likelihood of psychological distress group scored higher on the Cyclothymic (3.39 ± 3.45 vs. 0.93 ± 1.08, p < 0.001) and the Depressive (2.28 ± 2.82 vs. 0.65 ± 1.09, p = 0.01) affective temperaments of the TEMPS and on the lack of Impulse control (12.67 ± 4.04 vs. 9.63 ± 3.14, p = 0.003) and lack of Clarity (15.00 ± 5.56 vs. 9.85 ± 4.67, p = 0.004) scales of the DERS. Our results show that having had Covid-19 may be related with high likelihood for psychological distress in advanced-age people and this may in turn be associated with impaired emotional regulation and higher scores on depressive and cyclothymic temperaments.

BackgroundNeuropsychiatric symptoms (NPS) of dementia, such as anxiety, depression, agitation, and apathy, are complex, stressful, and costly aspects of care, and are associated to poor health outcomes and caregiver burden. A steep worsening of such symptoms has been reported during Coronavirus Disease 2019 (COVID-19) pandemic. However, their causes, their impact on everyday life, and treatment strategies have not been systematically assessed. Therefore, the aim of this review is to provide a detailed description of behavioral and psychopathological alterations in subjects with dementia during COVID-19 pandemic and the associated management challenges.MethodsA PubMed search was performed focusing on studies reporting alterations in behavior and mood and treatment strategies for elderly patients with dementia, in accordance with PRISMA guidelines. The following search strategy was utilized: (COVID* OR coronavirus OR “corona vir*” OR SARS-CoV-2) AND (dementia OR demented OR dement* OR alzheimer* OR “pick’s disease” OR “lewy body” OR “mild cognitive” OR mild cognitive impairment OR MCI).ResultsApathy, anxiety and agitation are the most frequently NPS during the COVID-19 pandemic and are mainly triggered by protracted isolation. Most treatment strategies rely on pharmacotherapy; technology is increasingly utilized with mixed results.ConclusionsNPS of dementia during COVID-19 appear to arise from social restrictions occurring as a consequence of the pandemic. Implementation of caregiver support and the presence of skilled nursing home staff are required to restore social interaction and adjust technological support to the patients’ needs.

Objective: Neurological sequelae of SARS-CoV-2 infection have already been reported, but there is insufficient data about the impact of the pandemic on the management of the patients with chronic neurological diseases. We aim to analyze the effect of COVID-19 pandemic and social restriction rules on these fragile patients.Methods: Patients with chronic neurologic diseases routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for symptoms suggestive of SARS-CoV-2 infection in the pandemic period, consequences of social restrictions, and neurological disease features, concomitant medical conditions, current medical and disease-specific treatments. Data source: a dedicated telephone survey designed to encompass questions on COVID-19 symptoms and on pandemic effects in chronic neurologic conditions.Results: Overall, 2,167 individuals were analyzed: 63 patients reported contact with COVID-19 positive cases, 41 performed the swab, and 2 symptomatic patients tested positive for COVID-19 (0.09%). One hundred fifty-eight individuals (7%) needed urgent neurological care, deferred due to the pandemic; 641 patients (30%) suspended hospital treatments, physiotherapy or other support interventions; 405 individuals (19%) reported a subjective worsening of neurological symptoms.Conclusions: In our population, the presence of neurological chronic diseases did not increase the prevalence of COVID-19 infection. Nevertheless, the burden of neurological disorders has been worsened by the lockdown.

BackgroundThere are different ways to define stabilization and currently, the main standpoint regards it as no-depression/no-mania. Furthermore, each person is physiologically different from childhood to adulthood, and in old age, thus the meaning of stabilization should take into account both growth and maturity. We aimed to review systematically studies focusing on mood stabilization in all phases of bipolar disorder (BD) and across all life phases, including pregnancy and the perinatal period, which is still a different phase in women's life cycles.MethodsWe carried out a PubMed search focusing on studies of bipolar disorder treated with drugs and aimed at stabilization with the following search strategy stabiliz*[ti] OR stabilis*[ti] OR stable[ti] OR stability[ti]) AND mood[ti] AND bipolar. In conducting our review, we followed the PRISMA statement. Agreement on inclusion was reached by consensus of all authors through a Delphi rounds procedure.ResultsThe above search strategy produced 509 records on January 25, 2020. Of them, 58 fitted our inclusion criteria and were discussed. The eligible studies spanned from September 1983 to July 6, 2019.ConclusionsNo clear-cut indications could be drawn due to a number of limitations involving sample inconsistency and different methods of assessing mood stabilization. The evidence collected so far does not allow recommended treatments for Adolescents, pregnant or perinatal women, and aged patients. However, adults, not within these groups, better focused upon. For their manic/mixed phases, second generation antipsychotic drugs may be useful in the short-to-medium run, alone or combined with mood stabilizers (MSs). However, MSs, and especially lithium, continue to be pivotal in chronic treatment. Bipolar depression should rely on MSs, but an antidepressant may be added on and can prove to be helpful. However, there are concerns with the tendency of antidepressants to induce the opposite polarity or mood instability, rendering the need for concurrent MS prescription mandatory.

AbstractBackground.The default mode network (DMN) dysfunction has emerged as a consistent biological correlate of multiple psychiatric disorders. Specifically, there is evidence of alterations in DMN cohesiveness in schizophrenia, mood and anxiety disorders. The aim of this study was to synthesize at a fine spatial resolution the intra-network functional connectivity of the DMN in adults diagnosed with schizophrenia, mood and anxiety disorders, capitalizing on powerful meta-analytic tools provided by activation likelihood estimation.Methods.Results from 70 whole-brain resting-state functional magnetic resonance imaging articles published during the last 15 years were included comprising observations from 2,789 patients and 3,002 healthy controls.Results.Specific regional changes in DMN cohesiveness located in the anteromedial and posteromedial cortex emerged as shared and trans-diagnostic brain phenotypes. Disease-specific dysconnectivity was also identified. Unmedicated patients showed more DMN functional alterations, highlighting the importance of interventions targeting the functional integration of the DMN.Conclusion.This study highlights functional alteration in the major hubs of the DMN, suggesting common abnormalities in self-referential mental activity across psychiatric disorders.

The effects of lithium treatment duration on deep grey matter structures in bipolar disorder are not well known. In this cross-sectional neuroimaging case-control study, we tested the hypothesis that shape characteristics of deep grey matter structures in bipolar disorder are associated with the duration of lithium treatment and with clinical phenomenology.In a setting of neuropsychiatry outpatient clinic, we included 74 patients with bipolar disorder (BD) and 74 matched healthy control subjects (HC). Both groups underwent a Magnetic Resonance Imaging acquisition and an exhaustive assessment of clinical and psychiatrics dimensions. Shape measures of seven deep grey matter structures (hippocampus, amygdala, caudate, nucleus accumbens, putamen, globus pallidus and thalamus) were obtained from T1 weighted images in both groups, using FSL FIRST segmentation tool. The segmented structures were then analysed vertex-by-vertex with FSL Randomise tool. First, we investigated the presence of significant associations between the duration of lithium treatment and shape measures in BD sample. Then, for structures that resulted significantly associated with the duration of lithium treatment, comparisons between BD and HC were performed either considering the BD group as a whole or dividing it in three groups based on the duration of treatment (lithium drug-naïve, short and long treated). Any deformation uncovered by group comparisons was subsequently associated with depressive and hypomanic/manic symptoms.The relationship between structures shape and the duration of lithium treatment in BD sample was significant for bilateral nucleus accumbens. Specifically, significant bilateral extroflection effects, related to longer duration of lithium treatment, were found bilaterally over the surface shape of core accumbens nuclei (r2R-Accu-Core = 0.12, p = 0.016, r2L-Accu-Core = 0.1, p = 0.031). Moreover, introflection effect related to longer duration of treatment resulted over the shell of right accumbens (r2R-Accu-Shell = 0.17, p = 0.002). Nucleus accumbens shape did not differ between BD and HC considering BD group as a whole. By contrast, categorizing BD in subgroups as a function of the duration of lithium treatment revealed significant inward deformation on the core of left accumbens nucleus and outward deformation on the shell of the right accumbens nucleus in lithium-naive patients, compared to both patients with long duration of lithium treatment (pL-Accu-Core = 0.016, pR-Accu-Shell = 0.005) and HC (pL-Accu-Core = 0.002; pR-Accu-Shell = 0.005). Moreover, compared to HC, inward deformation on the core of the left accumbens surface was found for patients with short duration of treatment (pLAccu-Core = 0.027). Finally, measures of surface deformation on the core of left accumbens observed in the group comparison showed significant positive correlations with depressive symptoms severity, as assessed by the Hamilton Depression Rating Scale (total score: r2L-AccuCore = 0.07, p = 0.02, somatic score: r2L-Accu-Core = 0.1, p = 0.005) and Beck Hopelessness Scale (r2LAccu-Core = 0.05, p = 0.03).Findings demonstrate that lithium untreated BD patients are characterised by localized shape abnormalities in the nucleus accumbens. Lithium treatment could act modulating these morphometric features as part of its mechanism of action in mood stabilizing. Keywords: Bipolar disorder, Nucleus accumbens, Shape analysis, Lithium, Reward system, Neuroimaging, Grey matter

Background: early onset is frequent in Bipolar Disorders (BDs), and it is characterised by the occurrence of mixed states (or mixed features). In this systematic review, we aimed to confirm and extend these observations by providing the prevalence rates of mixed states/features and data on associated clinical, pharmacological and psychopathological features. Methods: following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched from inception to 9 February 2021 for all studies investigating mixed states/mixed features in paediatric BD. Data were independently extracted by multiple observers. The prevalence rates of mixed states/features for each study were calculated. Results: eleven studies were included in our review, involving a total patient population of 1365 individuals. Overall, of the patients with paediatric age BD, 55.2% had mixed states/features (95% CI 40.1–70.3). Children with mixed states/features presented with high rates of comorbidities, in particular, with Attention Deficit Hyperactivity Disorder (ADHD). Evidences regarding the psychopathology and treatment response of mixed states/features are currently insufficient. Conclusions: our findings suggested that mixed states/features are extremely frequent in children and adolescents with BD and are characterised by high levels of comorbidity. Future investigations should focus on the relationship between mixed states/features and psychopathological dimensions as well as on the response to pharmacological treatment.