Showing papers in "Cns Spectrums in 2021"

Urbanization and emerging mental health issues.

Abstract: Rapid urbanization worldwide is associated to an increase of population in the urban settings and this is leading to new emerging mental health issues. This narrative mini-review is based on a literature search conducted through PubMed and EMBASE. A total of 113 articles published on the issue of urban mental health have been selected, cited, reviewed, and summarized. There are emerging evidences about the association between urbanization and mental health issues. Urbanization affects mental health through social, economic, and environmental factors. It has been shown that common mental syndromes report higher prevalence in the cities. Social disparities, social insecurity, pollution, and the lack of contact with nature are some of recognized factors affecting urban mental health. Further reserach studies and specific guidelines should be encouraged to help policy makers and urban designers to improve mental health and mental health care facilities in the cities; additional strategies to prevent and reduce mental illness in the urban settings should be also adopted globally.

Substance-related exogenous psychosis: a postmodern syndrome.

Abstract: There is growing recognition that substance use is associated with the emergence of psychosisElements of post-modernity dominate contemporary social contexts and operate as existential background factors that contribute to the emergence of substance-related psychotic phenomena, particularly use of potent and highly rewarding novel psychoactive substances (NPS) About 25% of first-episode psychoses are substance-induced (SIP) DSM-5 SIP diagnosis is based on the assumption that symptoms are transient and disappear after sustained abstinence This narrowed definition does not consider the issue of persistent SIP There is a clear need for a new diagnostic framework that provides reliable, unambiguous clinical criteria to differentiate between comorbid conditions (ie, schizophrenia patients with a substance use disorder) and substance-related psychoses In the present contribution, we aim to outline a novel and separate clinical entity: substancerelated exogenous psychosis (SREP) Within this diagnostic category, we refer to both transientand persistent psychoses associated with substance use SREP is conceived as a distinct psychoticdisorder with psychopathological specificities that clearly differentiate it from schizophrenia We address differences in terms of clinical presentation, epidemiology, etiological models and treatment response SREP is characterized by altered states of consciousness, persecutory delusions, visual and cenesthetic hallucinations, impulsivity and psychomotor agitation, affectiveand negative symptoms, a pervasive feeling of unreality and intact insight Delusions are typically secondary to abnormal perception resulting from a characteristic "sensorialization" of the world Longitudinal studies are warranted to substantiate our hypothesis of a novel diagnostic categoryand support the clinical validity of SREP This may have important implications in terms of early differential diagnosis and staging (ie, between comorbid conditions, persistent and transientsubstance-related psychotic states) as well as choice of treatment interventions

Environmental pollution and mental health: a narrative review of literature.

Abstract: Pollutant agents are exponentially increasing in modern society since industrialization processes and technology are being developed worldwide. Impact of pollution on public health is well known but little has been described on the association between environmental pollutants and mental health. A literature search on PubMed and EMBASE has been conducted and 134 articles published on the issue of pollution and mental health have been included, cited, reviewed, and summarized. Emerging evidences have been collected on association between major environmental pollutants (air pollutants, heavy metals, ionizing radiation [IR], organophosphate pesticides, light pollution, noise pollution, environmental catastrophes) and various mental health disorders including anxiety, mood, and psychotic syndromes. Underlying pathogenesis includes direct and indirect effects of these agents on brain, respectively, due to their biological effect on human Central Nervous System or related to some levels of stress generated by the exposure to the pollutant agents over the time. Most of emerging evidences are still nonconclusive. Further studies should clarify how industrial production, the exploitation of certain resources, the proximity to waste and energy residues, noise, and the change in lifestyles are connected with psychological distress and mental health problems for the affected populations.

Impact of economic crisis on mental health: a 10-year challenge.

Abstract: The worldwide economic crisis of the last decade, and still unresolved, led to a great recession involving all major economies. Since economic factors may influence mental wellbeing, not surprisingly a rise in poor mental health was observed in different countries, while representing a great challenge to psychiatric interventions. This paper aims at reviewing the available English literature focusing on the impact of the current economic crisis on mental health, with a special focus on depression and suicide. Available studies indicate that consequences of economic crisis, such as unemployment, increased workload or work reorganization, and reduced staff and wages, may constitute important stressing factors with a negative impact on mental health. Although data are not easily comparable in different countries, depression seems to be the most common psychiatric disorders especially in middle-aged men. Even suicide rates seem to be increased in men, mainly in countries with no public welfare or poor family relationships. All these findings require a careful attention from both governments that cut resources on public health instead of investing in it, and psychiatric associations that should implement appropriate strategies to face and to manage this sort of depression epidemic driven by economic crisis. Again, as available data suggest that the impact of the crisis might have been attenuated in countries with higher spending in social protection, they clearly urge policy makers to take into account possible health externalities associated to inadequate social protection systems.

Schizophrenia phenomenology revisited: positive and negative symptoms are strongly related reflective manifestations of an underlying single trait indicating overall severity of schizophrenia

Abstract: Schizophrenia comprises various symptom domains the two most important being positive and negative symptoms. Nevertheless, using (un)supervised machine learning techniques it was shown that a) negative symptoms are significantly interrelated with PHEM (psychosis, hostility, excitation, and mannerism) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR); and b) stable phase schizophrenia comprises two distinct classes, namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with deficit schizophrenia) and Simple NP (SNP). In this study, we recruited 120 MNP patients and 54 healthy subjects and measured the above-mentioned symptom domains. In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. Soft Independent Modeling of Class Analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled with PHEM symptoms, FTD and PMR than with negative symptoms. In conclusion, in MNP, a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting general psychopathology and, therefore, may be used as an overall severity of schizophrenia (OSOS) index. The bi-dimensional concept of positive and negative symptoms and type I and II schizophrenia is revised.

Efficacy and safety of dasotraline in adults with binge-eating disorder: a randomized, placebo-controlled, fixed-dose clinical trial.

Abstract: Objective. The aim of this fixed-dose study was to evaluate the efficacy and safety of dasotraline in the treatment of patients with binge-eating disorder (BED). Methods. Patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for BED were randomized to 12 weeks of double-blind treatment with fixed doses of dasotraline (4 and 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating (BE) days per week at week 12. Secondary efficacy endpoints included week 12 change on the BE CGI-Severity Scale (BE-CGI-S) and the Yale-Brown Obsessive-Compulsive Scale Modified for BE (YBOCS-BE). Results. At week 12, treatment with dasotraline was associated with significant improvement in number of BE days per week on the dose of 6 mg/d (N = 162) vs placebo (N = 162; -3.47 vs -2.92; P = .0045), but not 4 mg/d (N = 161; -3.21). Improvement vs placebo was observed for dasotraline 6 and 4 mg/d, respectively, on the BE-CGI-S (effect size [ES]: 0.37 and 0.27) and on the YBOCS-BE total score (ES: 0.43 and 0.29). The most common adverse events on dasotraline were insomnia, dry mouth, headache, decreased appetite, nausea, and anxiety. Changes in blood pressure and pulse were minimal. Conclusion. Treatment with dasotraline 6 mg/d (but not 4 mg/d) was associated with significantly greater reduction in BE days per week. Both doses of dasotraline were generally safe and well-tolerated and resulted in global improvement on the BE-CGI-S, as well as improvement in BE related obsessional thoughts and compulsive behaviors on the YBOCS-BE. These results confirm the findings of a previous flexible dose study.

Mental health consequences for survivors of the 2011 Fukushima nuclear disaster: a systematic review. Part 1: psychological consequences.

Abstract: To integrate scholastic literature regarding the prevalence and characteristics of the psychological consequences faced by survivors of the 2011 Fukushima earthquake/tsunami/nuclear disaster, we conducted a systematic review of survivor studies concerning the Fukushima disaster. In August 2019, four literature databases (PubMed, PsycINFO, Psychology and Behavioral Sciences Collection, and ICHUSHI) were used in the literature search. Peer-reviewed manuscripts reporting psychological consequences, either in English or Japanese, were selected. A total of 79 studies were selected for the review. Twenty-four studies (30.4%) were conducted as part of the Fukushima Health Management Survey-large-scale cohort study recruiting the residents of the entire Fukushima prefecture. Study outcomes were primarily nonspecific psychological distress, depressive symptoms, post-traumatic stress symptoms, and anxiety symptoms. The rates of high-risk individuals determined by the studies varied significantly owing to methodological differences. Nevertheless, these rates were mostly high (nonspecific psychological distress, 8.3%-65.1%; depressive symptoms, 12%-52.0%; and post-traumatic stress symptoms, 10.5%-62.6%). Many studies focused on vulnerable populations such as children, mothers of young children, evacuees, and nuclear power plant workers. However, few studies reported on the intervention methods used or their effect on the survivors. As a conclusion, high rates of individuals with psychological conditions, as well as a wide range of mental conditions, were reported among the Fukushima nuclear disaster survivors in the first 8 years after the disaster. These findings demonstrate the substantial impact of this compound disaster, especially in the context of a nuclear catastrophe.

Insomnia, sleep loss, and circadian sleep disturbances in mood disorders: a pathway toward neurodegeneration and neuroprogression? A theoretical review.

Abstract: The present paper aims at reviewing and commenting on the relationships between sleep and circadian phasing alterations and neurodegenerative/neuroprogressive processes in mood disorder. We carried out a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, in PubMed, PsycINFO, and Embase electronic databases for literature related to mood disorders, sleep disturbances, and neurodegenerative/neuroprogressive processes in relation to (1) neuroinflammation, (2) activation of the stress system, (3) oxidative stress, (4) accumulation of neurotoxic proteins, and (5) neuroprotection deficit. Seventy articles were collectively selected and analyzed. Experimental and clinical studies revealed that insomnia, conditions of sleep loss, and altered circadian sleep may favor neurodegeneration and neuroprogression in mood disorders. These sleep disturbances may induce a state of chronic inflammation by enhancing neuroinflammation, both directly and indirectly, via microglia and astrocytes activation. They may act as neurobiological stressors that by over-activating the stress system may negatively influence neural plasticity causing neuronal damage. In addition, sleep disturbances may favor the accumulation of neurotoxic proteins, favor oxidative stress, and a deficit in neuroprotection hence contributing to neurodegeneration and neuroprogression. Targeting sleep disturbances in the clinical practice may hold a neuroprotective value for mood disorders.

A pathway phenotype linking metabolic, immune, oxidative, and opioid pathways with comorbid depression, atherosclerosis, and unstable angina.

Abstract: Background There is strong comorbidity between atherosclerosis (ATS) and depression which is attributed to increased atherogenicity, insulin resistance (IR), and immune and oxidative stress. Aim of the study To examine the role of the above pathways and mu-opioid receptor (MOR), β-endorphin levels, zinc, copper, vitamin D3, calcium, and magnesium in depression due to ATS/unstable angina (UA). Methods Biomarkers were assayed in 58 controls and 120 ATS patients divided into those with moderate and severe depression according to the Beck Depression Inventory-II (BDI-II) scores >19 and >29, respectively. Results Neural network and logistic regression models showed that severe depression due to ATS/UA was best predicted by interleukin-6 (IL-6), UA, MOR, zinc, β-endorphin, calcium and magnesium, and that moderate depression was associated with IL-6, zinc, MOR, β-endorphin, UA, atherogenicity, IR, and calcium. Neural networks yielded a significant discrimination of severe and moderate depression with an area under the receiver operating curves of 0.831 and 0.931, respectively. Using Partial Least Squares path analysis, we found that 66.2% of the variance in a latent vector extracted from ATS/UA clinical features, and the BDI-II scores, atherogenicity, and IR could be explained by the regression on IL-6, IL-10, zinc, copper, calcium, MOR, and age. The BDI-II scores increased from controls to ATS to UA class III to UA class IV. Conclusions Immune activation, the endogenous opioid system, antioxidants, trace elements, and macrominerals modulate a common core shared by increased depressive symptoms, ATS, UA, atherogenicity, and IR.

Prazosin for treatment of post-traumatic stress disorder: a systematic review and meta-analysis.

Abstract: Background Prazosin has been an accepted treatment for patients with post-traumatic stress disorder (PTSD) who experience sleep disturbances, including nightmares. Results of a recent large randomized control trial did not find benefit of prazosin vs placebo in improving such outcomes. A meta-analysis that includes this most recent trial was conducted to examine the pooled effect of prazosin vs placebo on sleep disturbances and overall PTSD symptoms in patients with PTSD. Methods A systematic review of the published literature on trials comparing prazosin vs placebo for improvement of overall PTSD scores, nightmares, and sleep quality was conducted. Hedges’ g standardized mean differences (SMD) between prazosin and placebo were calculated for each outcome across studies. Results Six randomized placebo-controlled studies representing 429 patients were included in the analysis, including two studies with a crossover design. Results showed prazosin significantly improved overall PTSD scores (SMD = −0.31; 95% confidence intervals [CI]: −0.62, −0.01), nightmares (SMD = −0.75; 95% CI: −1.24, −0.27), and sleep quality (SMD = −0.57; 95% CI: −1.02, −0.13). In the largest trial, prazosin showed a reduction in clinical outcome measures similar to past studies, but a relatively large placebo effect size, particularly for nightmares, contributed to no treatment differences. Conclusions Despite the results of a recent, large randomized study, pooled effect estimates show that prazosin has a statistically significant benefit on PTSD symptoms and sleep disturbances. Limitations that should be considered include heterogeneity of study design and study populations as well as the small number of studies conducted and included in this meta-analysis.

Camouflaging: psychopathological meanings and clinical relevance in autism spectrum conditions.

Abstract: In the last decade, increasing literature focused on camouflaging as a strategy adopted to cope with social environment by patients with autism spectrum disorder (ASD). A better understanding of this phenomenon may shed more light on cognitive mechanisms and coping strategies of patients in the autism continuum, eventually leading to reconsider some previous "dogmas" in this field, such as the gender discrepancy in ASD diagnosis. Moreover, shared features can be observed in the camouflaging strategies adopted among the general population, among patients of the autism spectrum, and among patients with different kinds of psychiatric disorders, further challenging our perspectives. Camouflaging behaviors might be considered as a transdiagnostic element, closely associated with the continuous distribution of the autism spectrum among the general and the clinical population.

In (deficit) schizophrenia, a general cognitive decline (G-CoDe) partly mediates the effects of neuro-immune and neuro-oxidative toxicity on the symptomatome and quality of life.

Abstract: BACKGROUND Schizophrenia and deficit schizophrenia are accompanied by neurocognitive impairments. The aim of this study was to examine whether a general factor underpins impairments in key Cambridge Neuropsychological Test Automated Battery (CANTAB) probes, verbal fluency test (VFT), world list memory (WLM), True Recall, and mini mental state examination (MMSE). METHODS We recruited 80 patients with schizophrenia and 40 healthy controls. All patients were assessed using CANTAB tests, namely paired-association learning, rapid visual information processing, spatial working memory, one touch stockings of Cambridge, intra/extradimensional set-shifting (IED), and emotional recognition test. RESULTS We found that a general factor, which is essentially unidimensional, underlies those CANTAB, VFT, WLM, True Recall, and MMSE scores. This common factor shows excellent psychometric properties and fits a reflective model and, therefore, reflects a general cognitive decline (G-CoDe) comprising deficits in semantic and episodic memory, recall, executive functions, strategy use, rule acquisition, visual sustained attention, attentional set-shifting, and emotional recognition. Partial least squares analysis showed that 40.5% of the variance in G-CoDe is explained by C-C motif ligand 11, IgA to tryptophan catabolites, and increased oxidative toxicity, and that G-CoDe explains 44.8% of the variance in a general factor extracted from psychosis, hostility, excitation, mannerism, negative symptoms, formal thought disorders, and psychomotor retardation, and 40.9% in quality-of-life scores. The G-CoDe is significantly greater in deficit than in nondeficit schizophrenia. CONCLUSIONS A common core shared by a multitude of neurocognitive impairments (G-CoDe) mediates the effects of neurotoxic pathways on the phenome of (deficit) schizophrenia.

Frontotemporal degeneration in amyotrophic lateral sclerosis (ALS): a longitudinal MRI one-year study.

Abstract: Objective Advanced neuroimaging techniques may offer the potential to monitor disease progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative, multisystem disease that still lacks therapeutic outcome measures. We aim to investigate longitudinal functional and structural magnetic resonance imaging (MRI) changes in a cohort of patients with ALS monitored for one year after diagnosis. Methods Resting state functional MRI, diffusion tensor imaging (DTI), and voxel-based morphometry analyses were performed in 22 patients with ALS examined by six-monthly MRI scans over one year. Results During the follow-up period, patients with ALS showed reduced functional connectivity only in some extramotor areas, such as the middle temporal gyrus in the left frontoparietal network after six months and in the left middle frontal gyrus in the default mode network after one year without showing longitudinal changes of cognitive functions. Moreover, after six months, we reported in the ALS group a decreased fractional anisotropy (P = .003, Bonferroni corrected) in the right uncinate fasciculus. Conversely, we did not reveal significant longitudinal changes of functional connectivity in the sensorimotor network, as well as of gray matter (GM) atrophy or of DTI metrics in motor areas, although clinical measures of motor disability showed significant decline throughout the three time points. Conclusion Our findings highlighted that progressive impairment of extramotor frontotemporal networks may precede the appearance of executive and language dysfunctions and GM changes in ALS. Functional connectivity changes in cognitive resting state networks might represent candidate radiological markers of disease progression.

Post-traumatic stress symptoms in an Italian cohort of subjects complaining occupational stress.

Abstract: Objective Work-related stress presents a significant impact on work performance and physical health. It has been associated with the onset of a multitude of symptoms. The main aim of this investigation is to better understand the impact of post-traumatic stress symptomatology, using a specific self-assessment questionnaire, in subjects experiencing occupational stress with the rationale to address the variegated symptoms expressed by this particular population in a post-traumatic dimensional perspective. Methods Authors collected socio-demographic, occupational, and clinical data. They utilized Trauma and Loss Spectrum Self Report (TALS-SR), a questionnaire investigating post-traumatic stress symptoms. The population size was 345 subjects who presented at the Occupational Health Department of a university hospital over a 3 years period (2016–2018). Results Data analysis revealed 33.9% of subjects who met post-traumatic stress disorder (PTSD) criteria. Gender distribution of this set was (36.4% female, 31% male). A family history or personal history of mental disorders were related to higher scores in almost all TALS-SR domains and were related, respectively, to higher scores of criterion B “intrusion symptoms” (P = .014), criterion D “negative alterations in cognitions and mood” (P = .023), and criterion E “arousal” (P = .033) of PTSD. Differences in TALS-SR scores also emerged based on age and gender. Conclusions PTSD symptoms manifest at a significant level in those who experience work-related stress. Personal background of individuals, both in terms of family and personal history for mental disorders, seems to increase their vulnerability to develop post-traumatic stress symptoms. This study suggests the importance of evaluating occupational stress from a post-traumatic stress perspective also at an early stage.

Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study

Abstract: Background Combination olanzapine and samidorphan (OLZ/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported. Methods Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Assessments included adverse events (AEs), weight, vital signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ/SAM in the extension study. Results In total, 281 patients enrolled, 277 received ≥1 OLZ/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported in eight patients (2.9%); none were considered treatment related. There were no deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 52: −16.2 [−18.5, −14.0] and −0.9 [−1.0, −0.8], respectively). Conclusion OLZ/SAM was generally well tolerated in this extension study; most patients completed the 52-week treatment period with sustained improvement in schizophrenia symptoms. Mean increases in weight stabilized by week 6 with limited subsequent change through end of treatment.

Analysis of the superior temporal gyrus as a possible biomarker in schizophrenia using voxel-based morphometry of the brain magnetic resonance imaging: a comprehensive review.

Abstract: The lack of predictive biomarkers for therapeutic responses to schizophrenia leads clinical procedures to be decided without taking into account the subjects' neuroanatomical features, a consideration, which could help in identifying specific pharmacological treatments for the remission of symptoms. Magnetic resonance imaging (MRI) is a technique widely used for radiological diagnosis and produces 3-dimensional images in excellent anatomical detail, and with a great capacity to differentiate soft tissue. Various MRI techniques of the human brain have emerged as a result of research, enabling structural tests that may help to in consolidate previous findings and lead to the discovery of new patterns of abnormality in schizophrenia. A literature review was undertaken to assess the superior temporal gyrus (STG) as a possible biomarker in schizophrenia with the use of voxel-based morphometry of the brain using MRI. Many findings in studies of schizophrenia using MRI have been inconclusive and, in some cases, conflicting, although interesting results have been obtained when attempting to correlate neuroimaging changes with aspects of clinical features and prognosis of the disease. The individuals affected by this mental illness appear to have smaller STG volumes when compared to healthy controls and also to subjects with a diagnosis of first-episode affective psychosis or groups of individuals at high risk of psychosis. However, the wide variety of definitions surrounding the STG found in a number of studies is a contributing factor to the lack of correlation between brain abnormalities and clinical symptoms. For instance, disagreements have arisen due to studies using regions of interest to analyze the STG whereas other studies prioritize the analysis of only STG subregions or specific supratemporal plane regions. It is necessary to standardize the nomenclature of the areas to be studied in the future, as this will enable more consistent results, allowing higher clinical and morphological correlations.

Individualization of attention-deficit/hyperactivity disorder treatment: pharmacotherapy considerations by age and co-occurring conditions.

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood and can persist into adolescence and adulthood. Impairments associated with ADHD can impact quality of life, social interactions, and increase the risk of morbidity and mortality; however, for many patients, effective treatment can lessen these effects. Pharmacotherapy with stimulants or nonstimulants is recommended in conjunction with psychosocial therapy for most patients. Determining the optimal pharmacotherapy can be complex, and the clinician needs to consider many factors such as the patient's age, comorbidities, and lifestyle. Furthermore, the needs of the patient with ADHD will change over time, with specific challenges to consider at each stage of life. A variety of Food and Drug Administration (FDA)-approved stimulant and nonstimulant formulations are available with different modes of delivery and durations of effect. This armamentarium of ADHD medications can be used to individualize ADHD treatment for each patient's needs. This article combines current information from the literature and the first-hand experience of the authors to provide guidance on ADHD treatment options for patients of different ages and for some of the more common comorbidities.

Toward a transdiagnostic neurocircuitry-based biomarker model for pro-cognitive effects: challenges, opportunities, and next steps.

Abstract: Cognitive impairment has emerged as a key treatment priority in neuropsychiatric disorders. However, there is a lack of treatments with solid and lasting efficacy on cognition. A neurocircuitry-based biomarker model of pro-cognitive effects is critically needed to select among new candidate treatments. In a recent review of functional magnetic resonance imaging (fMRI) studies in mood disorders, we found that cognitive impairments are consistently accompanied by aberrant (hypo- and hyper-) activity in the dorsal prefrontal cortex (PFC) and the default mode network (DMN), and that activity change in these regions commonly occurs with cognitive improvements. Here, we (i) review the putative model from our recent review article, which explains the discrepant findings regarding the direction of aberrant dorsal PFC activity and treatment-related activity change in mood disorders. Inspired by the Research Domain Criteria project, we do this in order to (ii) examine whether a similar pattern of activity change occurs across distinct neuropsychiatric disorders and thereby provides a common biomarker for pro-cognitive effects. Lastly, we (iii) discuss whether dorsal PFC and DMN target engagement is a putative transdiagnostic neurocircuitry-based biomarker model for pro-cognitive effects, and (iv) outline the necessary next steps to address this question.

Long-acting injectable antipsychotics: what, when, and how

Abstract: Current guidelines for the treatment of patients with schizophrenia advocate that patients receive treatment with a long-acting injectable (LAI) antipsychotic medication if they prefer such treatment or if they have a history of poor or uncertain adherence. Available LAI formulations in the United States include first-generation antipsychotics (fluphenazine decanoate and haloperidol decanoate), risperidone/paliperidone containing products (risperidone microspheres, paliperidone palmitate, and risperidone subcutaneous), aripiprazole containing products (aripiprazole monohydrate and aripiprazole lauroxil), and olanzapine pamoate. LAI antipsychotics can address the guesswork about adherence status and patients may prefer them if they are offered this as a choice, including individuals early in their disease course. Additional approved indications in the United States for LAI antipsychotics include bipolar I disorder maintenance treatment for risperidone microspheres and aripiprazole monohydrate, and schizoaffective disorder for paliperidone palmitate once monthly. Differences and similarities among the different products are discussed, including guidance regarding optimal treatment selection. Tips are provided to enhance effective patient communication to maximize the likelihood of acceptance of this treatment modality.

Deficit schizophrenia and its features are associated with PON1 Q192R genotypes and lowered paraoxonase 1 (PON1) enzymatic activity: effects on bacterial translocation.

Abstract: Background Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS) No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology Methods In this case-control study, Thai women and men, aged 18 to 65 years, were divided in DS (n = 40) and NDS (n = 40) and were compared to controls (n = 40) PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined Moreover, subjects were genotyped for their PON1 Q192R polymorphism and immunoglobulin A (IgA) levels responses directed to Gram-negative bacteria were measured Results DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers Conclusions The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota

Suicidal ideation and suicidal attempts in patients with obsessive-compulsive tic-related disorder vs obsessive-compulsive disorder: results of a multicenter Italian study.

Abstract: Background Obsessive-compulsive disorder (OCD) and tic disorder (TD) represent highly disabling, chronic and often comorbid psychiatric conditions. While recent studies showed a high risk of suicide for patients with OCD, little is known about those patients with comorbid TD (OCTD). Aim of this study was to characterize suicidal behaviors among patients with OCD and OCTD. Methods Three hundred and thirteen outpatients with OCD (n = 157) and OCTD (n = 156) were recruited from nine different psychiatric Italian departments and assessed using an ad-hoc developed questionnaire investigating, among other domains, suicide attempt (SA) and ideation (SI). The sample was divided into four subgroups: OCD with SA (OCD-SA), OCD without SA (OCD-noSA), OCTD with SA (OCTD-SA), and OCTD without SA (OCTD-noSA). Results No differences between groups were found in terms of SI, while SA rates were significantly higher in patients with OCTD compared to patients with OCD. OCTD-SA group showed a significant male prevalence and higher unemployment rates compared to OCD-SA and OCD-noSA sample. Both OCTD-groups showed an earlier age of psychiatric comorbidity onset (other than TD) compared to the OCD-SA sample. Moreover, patients with OCTD-SA showed higher rates of other psychiatric comorbidities and positive psychiatric family history compared to the OCD-SA group and to the OCD-noSA groups. OCTD-SA and OCD-SA samples showed higher rates of antipsychotics therapies and treatment resistance compared to OCD-noSA groups. Conclusions Patients with OCTD vs with OCD showed a significantly higher rate of SA with no differences in SI. In particular, OCTD-SA group showed different unfavorable epidemiological and clinical features which need to be confirmed in future prospective studies.

Do somatic symptoms relate to PTSD and gender after earthquake exposure? A cross-sectional study on young adult survivors in Italy.

Abstract: Objective Increasing evidence confirms a strict relationship between mental disorders and physical health. Particularly, stressful life events and post-traumatic stress disorder (PTSD) have been closely correlated with various physical disorders and somatic symptoms, such as chronic pain, gastrointestinal disorders, and headaches. The aim of this study was to investigate the emergence of somatic symptoms in a sample of young adult survivors 21 months after exposure to the L’Aquila 2009 earthquake, with particular attention to PTSD and gender impact. Methods Four hundred and fifty high-school senior students (253 male and 197 female) exposed to the 2009 L’Aquila earthquake, 21 months earlier, were enrolled and evaluated by the Trauma and Loss Spectrum Self-Report (TALS-SR), for symptomatological PTSD, and the Mood Spectrum Self-Report-Lifetime Version (MOODS-SR) “rhythmicity and vegetative functions” domain, for somatic symptoms. Results Significantly higher rates of endorsement of the MOODS-SR somatic symptoms emerged in survivors with PTSD compared to those without. Females reported higher rates of endorsement of at least one MOODS-SR somatic symptom compared to males; however, a Decision Tree model and a two-way analysis of variance model confirmed a significant effect of PTSD only. A multivariate logistical regression showed a significant association between the presence of at least one MOOD-SR somatic symptom and re-experiencing and maladaptive coping TALS-SR domains. Conclusion This study corroborates a relevant impact of symptomatological PTSD, across both the genders, on somatic symptoms occurring in young adults after months from exposure to a massive earthquake.

Efficacy and safety of topiramate in binge eating disorder: a systematic review and meta-analysis.

Abstract: BACKGROUND To assess the efficacy and safety of topiramate in treating binge eating disorder (BED), using a systematic review and meta-analysis of the available randomized clinical trials (RCTs). METHODS The RCTs assessing topiramate vs placebo with or without adjunctive psychotherapy in BED were reviewed using a systematic search in the PubMed, Web of Science, PsycINFO, Cochrane Database of Systematic Review, and ClinicalTrials.gov search Websites, from inception to November 2019. Main outcomes were the changes in binge frequency, quality of life, and weight, respectively. Effect estimates were pooled using random-effect models and presented as risk ratios (RRs) or mean differences (MDs) and their 95% confidence interval (95% CI). Data extraction was performed by two independent reviewers. RESULTS Three studies were eligible for inclusion, involving 528 BED patients. Topiramate was found to be significantly more efficacious than placebo in reducing: (a) the number of binge episodes per week (MD = -1.31; 95% CI = -2.58 to -0.03; I2 = 94%); (b) the number of binge days per week (MD = -0.98; 95% CI = -1.80 to -0.16; I2 = 94%); and (c) weight (MD = -4.91 kg; 95% CI = -6.42 to -3.41; I2 = 10%). However, participants in the topiramate groups withdrew significantly more frequently for safety reasons, relative to placebo participants (RR = 1.90; 95% CI = 1.13-3.18, I2 = 0%). CONCLUSIONS Preliminary findings support a possible efficacy of topiramate for the treatment of BED, even if safety concerns could limit the practical use of this treatment in BED subjects.

Investigating the relationship between orthorexia nervosa and autistic traits in a university population.

Abstract: BACKGROUND Orthorexia nervosa (ON) is an emerging condition featuring restrictive eating behaviors on the basis of subjective beliefs about food healthiness. Many authors have stressed the similarities between ON and anorexia nervosa (AN) in both cognitive and behavioral patterns. Despite that, while the link between AN and female autism presentations is well known in the literature, no study has yet investigated the relationship between ON and autism spectrum. This work aims to investigate the relationship between ON and autistic traits in a university population. METHODS An e-mail invitation was sent to all the students and University workers of University of Pisa. Subjects were asked to fulfill the ORTO-15 and the Adult Autism Subthreshold spectrum (AdAS spectrum) questionnaires. RESULTS A total of 2426 subjects joined the survey: 623 subjects (26.3%) reported a score associated with significant orthorexic symptoms according to ORTO-15 (ON group), while 1789 subjects (73.7%) did not report ON symptomatology and were considered as healthy controls (HC). The ON group scored significantly higher on almost all AdAS spectrum domains. Moreover, being female and scoring higher on AdAS spectrum were statistically predictive factors for the presence of ON symptomatology. Among AdAS spectrum domains, higher scores on AdAS spectrum inflexibility and adherence to routine and restricted interests and rumination domains, as well as lower scores on verbal communication domain, were statistically predictive of orthorexic symptoms. CONCLUSIONS Our findings highlight an overlap between ON and autism spectrum psychopathology. Further studies are needed to clarify the relationship between restrictive eating disorders and female autism phenotypes.

Schizophrenia–schizoaffective–bipolar spectra: an epistemological perspective

Abstract: For decades clinicians and researchers have been thinking and writing about the spectrum of schizophrenia disorders. Indeed both Kraepelin and Bleuler believed in schizophrenia as a spectrum, both in a clinical (individual) and hereditary (family) continuum, from just some exquisite personality traits to unquestionable chronic and debilitating psychosis. Other authors would put the schizophrenia spectrum disorders on different levels of continuum: developmental, psychofunctional, existential, and genetic. Here, we would like to present an historical chronology for the schizophrenia-schizoaffective-bipolar spectra plus a tridimensional model for these spectra: the first axis for categories (affective versus nonaffective psychoses), the second axis for dimensions (personality versus full blown psychosis), and a third axis for biomarkers (remission versus relapse). We believe that without the schizophrenia-schizoaffective-bipolar spectra concept in our minds all our efforts will keep failing one the hardest quest: searching for biomarkers in schizophrenia and related disorders.

Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study.

Abstract: Background The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. Methods Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. Results The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. Conclusions The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Autism spectrum in patients with schizophrenia: correlations with real-life functioning, resilience, and coping styles.

Abstract: BACKGROUND Previous researches highlighted among patients with schizophrenia spectrum disorders (SSD) a significant presence of autistic traits, which seem to influence clinical and functional outcomes. The aim of this study was to further deepen the investigation, evaluating how patients with SSD with or without autistic traits may differ with respect to levels of functioning, self-esteem, resilience, and coping profiles. METHODS As part of the add-on autism spectrum study of the Italian Network for Research on Psychoses, 164 outpatients with schizophrenia (SCZ) were recruited at eight Italian University psychiatric clinics. Subjects were grouped depending on the presence of significant autistic traits according to the Adult Autism Subthreshold Spectrum (AdAS Spectrum) instrument ("AT group" vs "No AT group"). Other instruments employed were: Autism Spectrum Quotient (AQ), Specific Levels of Functioning (SLOF), Self-Esteem Rating scale (SERS), Resilience Scale for Adults (RSA), and brief-COPE. RESULTS The "AT group" reported significantly higher scores than the "No AT group" on SLOF activities of community living but significantly lower scores on work skills subscale. The same group scored significantly lower also on SERS total score and RSA perception of the self subscale. Higher scores were reported on COPE self-blame, use of emotional support and humor domains in the AT group. Several correlations were found between specific dimensions of the instruments. CONCLUSION Our findings suggest the presence of specific patterns of functioning, resilience, and coping abilities among SSD patients with autistic traits.

Mental health consequences for survivors of the 2011 Fukushima nuclear disaster: a systematic review. Part 2: emotional and behavioral consequences.

Abstract: To compile the findings of studies assessing emotional and behavioral changes in the survivors of the 2011 Fukushima nuclear disaster, we performed a systematic review in August 2019 using four literature databases (PubMed, PsycINFO, Psychology and Behavioral Sciences Collection, and ICHUSHI). Peer-reviewed manuscripts, either in English or Japanese, were included in the searches. Sixty-one studies were retrieved for the review. Of these, 41 studies (67.2%) assessed emotional consequences, 28 studies (45.9%) evaluated behavioral consequences, and 8 studies (13.1%) evaluated both emotional and behavioral outcomes. The main research topic in emotional change was radiation exposure-associated risk perception, as reported in 15 studies. This risk perception included immediate health effects (eg, acute radiation syndrome) as well as future health effects (eg, future cancer and genetic effects). Lowered subjective well-being was reported in eight studies. Six studies reported perceived discrimination/stigmatization in the disaster survivors. The most critical behavioral change was an increase in suicides compared with residents in the whole of Japan or affected by the earthquake and tsunami, but not by the nuclear disaster. Increased rate of alcohol and tobacco use was reported, although the effect on one's health was inconsistent. As a conclusion, the Fukushima nuclear disaster survivors suffered issues in risk perception, well-being, stigmatization, and alcohol/tobacco use in the first 8 years after the disaster. The present study is important in order to better understand the emotional and behavioral responses to future nuclear/radiological disasters as well as other "invisible" disasters, such as chemical and biological public health crises.

Role of obesity in systemic low-grade inflammation and cognitive function in patients with bipolar I disorder or major depressive disorder.

Abstract: BACKGROUND Studies have suggested the detrimental effects of obesity and systemic inflammation on the cognitive function of patients with bipolar or major depressive disorder. However, the complex associations between affective disorder, obesity, systemic inflammation, and cognitive dysfunction remain unclear. METHODS Overall, 110 patients with affective disorder (59 with bipolar I disorder and 51 with major depressive disorder) who scored ≥61 on the Global Assessment of Functioning and 51 age- and sex-matched controls were enrolled. Body mass index ≥25 kg/m2 was defined as obesity or overweight. Levels of proinflammatory cytokines-including interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)-were measured, and cognitive function was assessed using various methods, including the Wisconsin Card Sorting Test (WCST) and go/no-go task. RESULTS Patients with bipolar I disorder or major depressive disorder were more likely to be obese or overweight, had higher CRP and TNF-α levels, and had greater executive dysfunction in the WCST than the controls. TNF-α level (P < .05) but not affective disorder diagnosis or obesity/overweight was significantly associated with cognitive function deficits, although obesity/overweight and diagnosis were significantly associated with increased TNF-α level. CONCLUSIONS Our findings may indicate that proinflammatory cytokines, but not obesity or overweight, have crucial effects on cognitive function in patients with bipolar I disorder or major depressive disorder, although proinflammatory cytokines and obesity or overweight were found to be strongly associated. The complex relationships between affective disorder diagnosis, proinflammatory cytokine levels, obesity or overweight, and cognitive function require further investigation.