Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses.

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

Methylphenidate is more effective to improve inhibitory control and working memory compared to tDCS in children and adolescents with attention deficit/hyperactivity disorder: a proof-of-concept study.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD. Methods: After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH. Results: Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual-spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS. Discussion: In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms.

Age-related clinical characteristics of children and adolescents with ADHD.

Introduction: Attention deficit hyperactivity disorder (ADHD) has been associated with difficulties in regulating aversion states, high functional impairment, and a high risk of psychopathology across the lifespan. ADHD is clinically heterogeneous, with a wide spectrum of severity and associated symptoms. Clinical characteristics need to be carefully defined in different periods of life as ADHD course, symptoms, and comorbidities may fluctuate and change over time. Adolescence usually represents the transition from primary to secondary education, with a qualitative and quantitative change in environmental and functional demands, thus driving symptoms' change. Methods: In order to characterize age-related clinical features of children (<11 years) and adolescents (≥11 years) with ADHD, we conducted a naturalistic study on 750 children and adolescents assessed for ADHD at our Neuropsychiatry Unit over the course of 3 years (2018-2020). Results: We found that ADHD symptoms were significantly higher in children than adolescents. More importantly, we found worse global functioning, lower adaptive skills, higher levels of anxiety and depressive symptoms, somatic complaints, emotional dysregulation, social problems, and aggression in adolescents, despite a lower severity of ADHD-specific symptoms. Conclusion: These results should be confirmed in longitudinal observational studies of adequate sample size in order to reliably describe a potential course characterized by worsening of functioning, reduction in ADHD-specific symptoms and increase in general psychopathology during the transition from childhood to adolescence.

Long-term treatment of adult ADHD in a naturalistic setting: Clinical predictors of attrition, medication choice, improvement, and response.

OBJECTIVES: The aim of this study was to identify clinical predictors of treatment attrition, medication choice, improvement and response to pharmacotherapy in adult attention-deficit/hyperactivity disorder (ADHD). METHODS: 150 ADHD patients were enrolled and naturalistically followed-up for at least 4 months. Conners' Adult ADHD Rating Scales-Observer: Screening Version (CAARS-O:SV) were used to measure ADHD severity. RESULTS: 58 subjects (38.7%) were lost at follow-up, while 75 (50%) completed follow-up assessment, on average after 26.05 ± 11.99 weeks; 35 were treated with atomoxetine (ATX) and 40 with methylphenidate (MPH). Treatments were moderately effective (d = 0.72) and 37 patients (49.3%) were responders (≥30% CAARS-O:SV decrease). Patients lost at follow-up had lower inattentive symptoms, less generalised anxiety and family history of bipolar disorder, more amphetamine use disorder than follow-up completers. Compared to ATX-treated subjects, MPH-treated patients had greater severity of hyperactivity/impulsivity and were more frequently diagnosed with alcohol use disorder. While MPH and ATX showed similar efficacy, more pronounced improvements were observed in patients with combined ADHD, anxiety and substance use disorders. ADHD severity and comorbid substance use positively predicted response. CONCLUSIONS: Consensus-based hierarchical treatment of ADHD comorbidity is not consistently supported. Comorbid anxiety, mood and substance use disorders should not discourage the treatment of adult ADHD.

Comparing the Effect of Methylphenidate and Anodal tDCS on Inhibitory Control and Working-Memory in Children and Adolescents with Attention Deficit/Hyperactivity Disorder: A Study Protocol for a Randomized, within-Subject Trial.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inappropriate levels of attention, hyperactivity, and impulsivity that interfere with individual functioning. The international guidelines recommend targeting ADHD-related neurochemical brain abnormalities by intervening via drug treatment, such as methylphenidate (MPH), as first choice. Drug treatments are usually associated with a huge amount of cost for families and the healthcare system, suspension for low compliance, poor long-term efficacy, and side effects. Transcranial direct current stimulation (tDCS) has been suggested as a possible noninvasive means to safely manipulate brain activity and, in turn, improve behavior and cognition in developmental ages. Several studies have shown that tDCS has the potential to improve ADHD-related cognitive deficits, but the effect of tDCS compared with MPH has never been evaluated. The aim of the present within-subject, sham-controlled, randomized proof-of-concept study is to demonstrate the positive effect of one-session anodal tDCS analogous to the MPH drug on inhibitory control and working memory in children and adolescents with ADHD. We strongly believe that this study protocol will serve to accelerate research into low-cost, drug-free, feasible interventions for ADHD.

Clinical characteristics of children and adolescents with ADHD with or without methylphenidate prescription at their first diagnostic assessment.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most prevalent neurodevelopmental disorder diagnosed in the scholar age. It is associated with significant impairment in global functioning, and in moderate/severe presentations the outcome is critically dependent on pharmacological optimization of the multi-modal treatment. Methylphenidate (MPH) is the first-choice pharmacological treatment in children and adolescents with ADHD, with substantial evidence of significant efficacy and effectiveness on global functioning and symptoms' severity. There is some evidence supporting a few clinical and socio-demographic variables as predictors of pharmacological treatment prescription in children with ADHD independently of ADHD symptoms severity. However, it is warranted to investigate clinical and general psychopathological characteristics potentially associated with negative outcomes and the need for pharmacological treatment to inform appropriate prescription strategies. In this context, we compared 268 children and adolescents who were prescribed MPH (ADHD/MPH) for the first time after their first diagnostic assessment at our center, and 444 children and adolescents with ADHD (ADHD/noMPH) who were recommended non-pharmacological evidence-based interventions alone. ADHD/MPH group had higher severity of non-ADHD psychopathological symptoms compared to the ADHD/noMPH group, as documented by higher scores on the Child Behavior Checklist (CBCL) subscales, higher severity of ADHD symptoms, lower average IQ and lower adaptive levels independently of IQ. More specifically, beside externalizing symptoms, also internalizing symptoms were significantly higher in the ADHD/MPH group. The presence of significant non-ADHD psychopathology should be considered as a clinical factor associated with the need for MPH prescription in children and adolescents with ADHD.

Moderators and Other Predictors of Methylphenidate Response in Children and Adolescents with ADHD.

Methylphenidate (MPH) is the treatment of first choice for developmental ADHD. To date, no reliable method to predict how patients will respond to MPH exists and conflicting results are reported on clinical characteristics of responders. The present study aims to give a more precise characterization of the patients who will respond best to MPH to help clinicians in defining the treatment plan. Age, neuropsychological functioning (i.e., attention and working memory), and behavioral/emotional symptoms of 48 drug-naïve children and adolescents with ADHD (42 boys and 6 girls, age-range 6-16 years, mean age 10.5 ± 2.5 years, mean IQ 101.3 ± 11.2) were studied to assess how these different characteristics affected a single-dose MPH response. Four hierarchical linear regression models were used to explore whether age, neuropsychological measures at baseline, and behavioral/emotional symptoms could predict attention and working memory measures after a single-dose MPH administration. We found that improvement in attention and working memory was predicted by age, neuropsychological measures at baseline, and severity of ADHD symptoms. No behavioral and emotional symptoms predicted single-dose MPH response with the exception of conduct symptoms.

Gender-Related Clinical Characteristics in Children and Adolescents with ADHD.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder in school-age children, and it is usually associated with a significant impairment in global functioning. Traditionally, boys with ADHD are more likely to be referred for clinical assessments due to a higher prevalence of externalizing symptoms. However, as regards gender-related differential clinical characteristics between boys and girls with ADHD, further investigation is warranted in light of conflicting results found in currently available literature. In fact, a more precise clinical characterization could help increase appropriate diagnoses and treatment planning. In this context, we carried out a retrospective observational study on 715 children and adolescents diagnosed with ADHD from 2018 to 2020 at our center, in order to describe their gender-related clinical characteristics. Boys displayed higher average IQs, but they were comparable to girls in functional impairments and adaptive skills. Girls displayed higher scores on the Attention Problems subscale of the CBCL 6-18 and on several CPRS-R:L subscales, suggesting higher general ADHD symptom severity. Boys showed higher scores on CBCL 6-18 subscales, such as withdrawn/depressed, internalizing, and obsessive-compulsive problems. In conclusion, girls showed more severe ADHD features and lower IQ in clinically referred settings, while boys showed more internalizing problems and obsessive-compulsive symptoms.

Survey on centres and procedures for the diagnosis and treatment of adult ADHD in public services in Italy.

Attention deficit/hyperactivity disorder (ADHD) often persists into adulthood. Although its persistence and relative high prevalence, ADHD in adults is often underdiagnosed and undertreated in Italy, leading to poor clinical and functional outcomes, and higher costs of illness. The aims of the study were to identify the Italian mental health services for ADHD in adults, describe the diagnostic and treatment procedures they follow, and compare this offer with the recommendations of the German and English guidelines. The centres, that adopt a clinical and assessment protocol for adult ADHD diagnosis (carried out by specifically trained personnel) and prescribe pharmacological treatment for adult ADHD, were selected from the list of accredited services provided by the Appendix B.2 of the ISTISAN 16/37 Reports of the ISS. An ad-hoc survey including open-ended and close-ended questions was sent to each selected centre in February 2020. The overall picture resulting from the data analysis was compared with the recommendations of the German and English guidelines. The present survey shows that only a few centres are specialised in the diagnosis and treatment of ADHD in adults in Italy. Furthermore, there are no national guidelines for adult ADHD in Italy. The collected data also suggest that there is no a unified practice shared by the Centres both for the patient's transition from child and adolescent to adult mental health services and for the diagnostic-therapeutic process. It is therefore crucial to create specific protocols and develop national guidelines to better identify and diagnose ADHD in adults and provide targeted and more efficient multimodal treatments.

Methylphenidate challenge test in adults with attention deficit/hyperactivity disorder (ADHD): Clinical effects and their predictors.

OBJECTIVE: Adult and children attention deficit/hyperactivity disorder (ADHD) share similar symptoms and responses to drugs such as methylphenidate (MPH). Yet, in Europe, these drugs remain unlicensed for adults. We aimed to assess the effects of an acute MPH challenge on the four dimensions concentration, impulsivity, tension, and general well-being in ADHD adults, and identify predictors of improvement. METHODS: Therapeutic Drug Monitoring was performed to measure MPH plasma levels. A Visual Analogue Scale was administered to patients before and after the acute MPH challenge to measure self-reported changes in the four dimensions. RESULTS: After the acute MPH challenge, our 71 patients showed significant improvement in concentration and tension. The MPH challenge dose correlated with lower patients' age, greater side effects, increased concentration (p = .008) and decreased tension (p = .001). At multiple linear regression MPH plasma levels and absence of postdose side effects predicted concentration improvement, MPH plasma levels predicted tension improvement. MPH plasma levels were significantly higher in patients who reported an improvement in concentration, tension, and impulsivity compared to nonimprovers (p's from .001 to .004). CONCLUSIONS: These findings point to the efficacy of MPH challenge in improving concentration and tension in adult ADHD, thus emphasizing the need for a broader treatment access for these patients.

Current and emerging pharmacotherapy for the treatment of adult attention deficit hyperactivity disorder (ADHD).

Introduction: ADHD is characterized by a developmentally inappropriate level of inattentiveness, impulsivity and/or hyperactivity. In adults, the disorder is frequently accompanied by Emotional Dysregulation (ED), associated to a variety of related psychiatric comorbidities, complicating its recognition and treatment management. Areas covered: This paper reviews randomized active comparator-controlled or placebo-controlled trials evaluating the use of pharmacotherapy in adults with ADHD and ED, other neurodevelopmental disorders, Bipolar Disorder (BD) and Anxiety Disorders (ADs). When controlled data are unavailable, the authors have included open-label and observational studies. Expert opinion: ED in adult patients with ADHD is a very common and impairing problem that can be treated with stimulants or atomoxetine. ADHD studies in adults with other neurodevelopment disorders are scarce; stimulants seem to be the most effective and safe drugs in treating ADHD symptoms, without worsening the core features of other neurodevelopmental disorders. In patients with ADHD and comorbid BD, the treatment of BD alone may result in residual symptoms of ADHD. Patients should be treated hierarchically: BD should be treated first, while ADHD should be treated combining ADHD medications and mood stabilizers after mood stabilization. The available evidence for treating patients with ADHD and comorbid ADs in adults supports the idea of an anti-anxiety/ADHD-specific treatment association.

Personalized and precision medicine as informants for treatment management of bipolar disorder.

DSM-5 diagnostic categories, defined by a set of psychopathological symptoms are heterogeneous conditions that may include different biological entities, with distinct etiopathogenesis, different courses and requiring different treatment management. For bipolar disorder the major evidences for this lack of validity are the long paths before a proper diagnosis, the inconsistence of treatment guidelines, the long phases of pharmacological adjustment and the low average of long-term treatment response rates. Personalized medicine for mental disorders aims to couple established clinical-pathological indexes with new molecular profiling to create diagnostic, prognostic and therapeutic strategies precisely tailored to each patient. Regarding bipolar disorder, the clinical history and presentation are still the most reliable markers in stratifying patients and guiding therapeutic management, despite the research goes to great lengths to develop new neuropsychological or biological markers that can reliably predict individual therapy effectiveness. We provide an overview of the advancements in personalized medicine in bipolar disorder, with particular attention to how psychopathology, age at onset, comorbidity, course and staging, genetic and epigenetic, imaging and biomarkers can influence treatment management and provide an integration to the conventional treatment guidelines. This approach may offer a new and rational path for the development of treatments for targeted subgroups of patients with bipolar disorder.

Hippocampal subfield volumes and childhood trauma in bipolar disorders.

BACKGROUND: Alterations in hippocampal structure and function are present in bipolar disorder (BD). Childhood trauma is associated with risk for BD, and the several subfields of the hippocampus are differentially sensitive to the effects of stressors of the sort associated with risk for BD. The current study therefore sought to test the hypothesis that childhood trauma may be differentially associated with abnormal hippocampal subfield volumes in BD. METHODS: 104 participants with BD type I (BD-I, n = 56) or BD type II (BD-II, n = 48) and 81 healthy controls (HC) underwent high-resolution structural magnetic resonance neuroimaging. Hippocampal subfield volumes were determined using FreeSurfer. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ). RESULTS: There were significant effects of diagnosis on intracranial volume corrected hippocampal subfield volumes bilaterally as well as a significant interaction between diagnosis and childhood trauma. Hippocampal volumes did not differ between the BD-I and BD-II subgroups but hippocampal volumes were smaller in both groups when compared to HC. There was a significant effect of childhood trauma on bilateral presubiculum volume as well as significant interactions between diagnosis and childhood trauma on bilateral CA1, presubiculum and subiculum volumes, the direction of which differed between individuals with BD (larger) and HC (smaller). LIMITATIONS: Recall bias may influence the reliability of the retrospective assessment of childhood trauma experiences. CONCLUSIONS: Childhood trauma demonstrates differential effects on hippocampal subfield volumes of BD and HC, particularly in hippocampal subfields involved in emotion regulation.

Temperament correlates in adult ADHD: A systematic review☠☠.

BACKGROUND: Attention deficit and hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children, but adult-ADHD is still an under-diagnosed and untreated condition. Treating adult-ADHD is complex and requires effective strategies for ADHD symptoms and comorbidities. Because of its high comorbidity rate with mood disorders and the growing interest in symptoms of emotional dysregulation in these patients, our aim was to collect studies that investigated temperament correlates in adult people with ADHD, to better understand the association between them and the eventual role of temperament as a prognostic-therapeutic marker. METHODS: We performed a systematic review of the literature. We included only studies that measured temperament traits in ADHD adults using the Temperament Evaluation of Memphis, Paris and San Diego-Auto-questionnaire (TEMPS-A) or the Temperament and Character Inventory (TCI). RESULTS: We retrieved 15 papers that used the TCI and 6 papers that used the TEMPS-A. In the TCI studies, ADHD was associated with high scores on Novelty Seeking and Harm Avoidance and low scores on Persistence. For the TEMPS-A studies, ADHD and Bipolar Disorders share some similarities in temperament scores, except for the hyperthymic temperament score. LIMITATIONS: A comparison between the TCI and TEMPS-A results was not possible. The number of papers included was small. Among them, the type of sample, the number of recruited subjects and the ADHD assessment were very different. CONCLUSIONS: The majority of ADHD individuals share temperament traits such as lability, irritability and excessiveness of emotional responses. Further research is needed to better understand whether temperament influences the pharmacological response of ADHD patients and whether temperament scores affect the long-term therapeutic outcome.

Pharmacotherapeutic strategies for the treatment of attention-deficit hyperactivity (ADHD) disorder with comorbid substance-use disorder (SUD).

INTRODUCTION: Substance use disorder (SUD) is very common amongst patients with attention deficit hyperactivity disorder (ADHD). The two disorders share partially overlapping features and SUD in ADHD is characterized by an early age of onset, high likelihood of poly-substance use, increased risk of suicide attempts, more hospitalizations, and scarce treatment adherence. AREAS COVERED: This paper reviews randomized active comparator-controlled or placebo-controlled trials evaluating the use of pharmacotherapy in patients with ADHD and SUD. The authors include open label and observational studies. EXPERT OPINION: Stimulant and non-stimulant treatments should be used to aid ADHD symptomatology in patients with SUD. SUD seems to be less responsive, suggesting a relative independence of the two conditions. For this reason, the association of ADHD-specific drugs and SUD-treatments should be recommended in a large proportion of patients suffering from both disorders. The rate and the quality of ADHD response to specific pharmacological treatments is highly variable, depending on the dose and the duration of the treatment, the age of the patient, and the severity and the chronicity of addiction. Further research is necessary to explore the divergences in treatment response of different ADHD subtypes in different subtypes of SUD.

Psychopathological characteristics and adverse childhood events are differentially associated with suicidal ideation and suicidal acts in mood disorders.

BACKGROUND: Depression is an important risk factor for suicide. However, other dimensions may contribute to the suicidal risk and to the transition from ideas to acts. We aimed to test the relative involvement of hopelessness, temperament, childhood trauma, and aggression in suicide risk in a large sample of patients with mood disorders. METHODS: We assessed 306 patients with major depressive and bipolar disorders for clinical characteristics including hopelessness, temperament, childhood trauma, and aggression. We tested their associations with suicidal ideation and acts using standard univariate/bivariate methods, followed by multivariate logistic regression models. RESULTS: In multivariate analyses, the loss of expectations subscore of the hopelessness scale was associated with lifetime suicidal ideation but not suicide attempt. Childhood emotional abuse, severity of current depression, and female gender were associated with lifetime suicide attempts, whereas hyperthymic temperament was protective. Only hyperthymic temperament differentiated patients with a history of suicidal ideas vs. those with a history of suicide attempt. CONCLUSIONS: Findings support the association of hopelessness with suicidal ideation and point to considering in suicidal acts not only depression, but also childhood emotional abuse, hyperthymic temperament, and gender.

Association between duration of lithium exposure and hippocampus/amygdala volumes in type I bipolar disorder.

BACKGROUND: Prior studies on the effects of lithium on limbic and subcortical gray matter volumes are mixed. It is possible that discrepant findings may be explained by the duration of lithium exposure. We investigated this issue in individuals with type I bipolar disorder (BP-I). METHODS: Limbic and subcortical gray matter volume was measured using FreeSurfer in 60 subjects: 15 with BP-I without prior lithium exposure [no-exposure group (NE)]; 15 with BP-I and lithium exposure < 24 months [short-exposure group (SE)]; 15 with BP-I and lithium exposure > 24 months [long-exposure group (LE)]; and 15 healthy controls (HC). RESULTS: No differences in limbic and subcortical gray matter volumes were found between LE and HC. Hippocampal and amygdalar volumes were larger bilaterally in both LE and HC when compared to NE. Amygdalar volumes were larger bilaterally in SE when compared to NE but did not differ from LE. Hippocampal volumes were smaller bilaterally in SE when compared to LE and HC but did not differ from NE. No between-group differences on subcortical gray matter or other limbic structure volumes were observed. LIMITATIONS: Cross-sectional design and concurrent treatment with other medications limit attribution of between-group differences to lithium exposure alone. CONCLUSIONS: The effect of lithium exposure on limbic and subcortical gray matter volumes appears to be time-dependent and relatively specific to the hippocampus and the amygdala, with short-term effects on the amygdala and long-term effects on both structures. These results support the clinical importance of long-term lithium treatment in BP-I.

Neurobiological Evidence for the Primacy of Mania Hypothesis.

BACKGROUND: Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM) in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi and other collaborators. This hypothesis supports that in bipolar disorder, mania leads to depression, while depression does not lead to mania. OBJECTIVE: To identify evidence in literature that supports or falsifies this hypothesis. METHOD: We searched the medical literature (PubMed, Embase, PsycINFO, and the Cochrane Library) for peer-reviewed papers on the primacy of mania, the default mode function of the brain in normal people and in bipolar disorder patients, and on illusion superiority until 6 June, 2016. Papers resulting from searches were considered for appropriateness to our objective. We adopted the PRISMA method for our review. The search for consistency with PoM was filtered through the neurobiological results of superiority illusion studies. RESULTS: Out of a grand total of 139 records, 59 were included in our analysis. Of these, 36 were of uncertain value as to the primacy of mania hypothesis, 22 favoured it, and 1 was contrary, but the latter pooled patients in their manic and depressive phases, so to invalidate possible conclusions about its consistency with regard to PoM. All considered studies were not focused on PoM or superiority illusion, hence most of their results were, as expected, unrelated to the circuitry involved in superiority illusion. A considerable amount of evidence is consistent with the hypothesis, although indirectly so. LIMITATIONS: Only few studies compared manic with depressive phases, with the majority including patients in euthymia. CONCLUSION: It is possible that humans have a natural tendency for elation/optimism and positive self-consideration, that are more akin to mania; the depressive state could be a consequence of frustrated or unsustainable mania. This would be consistent with PoM.

Changes in serum levels of kynurenine metabolites in paediatric patients affected by ADHD.

This study aims at determining serum levels of tryptophan and other metabolites of the kynurenine pathway in children with attention deficit hyperactivity disorder (ADHD) compared to healthy controls. Such metabolites interact with glutamate receptors in the central nervous system, potentially modulating mechanisms that are pivotal in ADHD and thus potentially representing peripheral biomarkers of the disorder. We measured serum levels of tryptophan and some metabolites of the kynurenine pathway in 102 children with ADHD and 62 healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS). As compared to healthy controls, children with ADHD showed a reduction in serum levels of anthranilic acid (-60%), kynurenic acid (-11.2%), and xanthurenic acid (-12.5%). In contrast, serum levels of tryptophan (+11.0%) and kynurenine (+48.6%) were significantly enhanced, and levels of quinolinic acid were unchanged in children with ADHD. In a logistic regression model, the presence of ADHD was predicted by low anthranilic acid and high tryptophan levels. These findings support the involvement of the kynurenine pathway in the pathophysiology of ADHD and suggest that anthranilic acid and tryptophan levels should be investigated as potential peripheral biomarker for ADHD.

Left nucleus accumbens atrophy in deficit schizophrenia: A preliminary study.

A question that remains to be answered is whether schizophrenia can be characterized by a single etiopathophysiology or whether separate sub-syndromes should be differentiated to define specific mechanisms for each sub-type. Individuals affected by the deficit subtype of schizophrenia (DSZ) display avolitional/amotivational features that respond poorly to conventional treatments. Characterizing DSZ from a neuroanatomical point of view may help clarify this issue and develop new treatment strategies. To determine if DSZ is associated with structural alterations in specific deep grey matter structures linked to its key clinical features, 22 DSZ patients, 22 non-deficit schizophrenia (NDSZ) patients and 22 healthy controls (HC) were recruited for a case-control cross-sectional study. High-resolution magnetic resonance imaging was performed in all subjects and volumes of deep grey matter structures were measured using FreeSurfer. DSZ patients displayed smaller left accumbens volumes compared to both NDSZ patients and HC. Moreover, age and duration of illness were significantly associated with lower volume of the left accumbens in DSZ but not in NDSZ. Findings indicate that DSZ is associated with lower volume of the nucleus accumbens in the dominant hemisphere. This is consistent with the psychopathological features and functional impairments present in DSZ and thus indicates a potential mechanism.