Psychosis Biotypes: Replication and Validation from the B-SNIP Consortium.

Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called "B-SNIP1" with 711 psychosis and 274 healthy persons, and the "replication sample" with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r's from .96-.99) and temporally stable (r's from .76-.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%-89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.

Manía unipolar: un ineludible diagnóstico: revisión de la literatura a propósito de un caso / Unipolar mania: an unavoidable diagnosis: case report and literature review

Resumen Introducción: La manía unipolar (MU) es un trastorno que se comporta de manera distinta al trastorno bipolar-I (TB-I), sin embargo, no es considerado como una entidad independiente por los manuales diagnósticos vigentes, sino que es incluido dentro del diagnóstico de TB-I. Caso clínico: Hombre de 21 años presenta cuadro clínico de 3 meses de evolución caracterizado por ánimo exaltado y síntomas psicóticos congruentes al estado de ánimo. El paciente niega episodios depresivos previos. Se instaura tratamiento con litio y aripiprazol que resulta satisfactorio, sin presentar recurrencias tras 5 años de seguimiento. Revisión de la literatura y discusión: Los manuales diagnósticos describen que para diagnosticar TB-I no se requiere la presencia de un episodio depresivo mayor, lo que implica que pacientes con MU quedan dentro de la misma categoría diagnóstica que pacientes con TB-I. Diferencias entre MU y TB-I han sido demostradas en estudios epidemiológicos, clínicos y genéticos, por lo tanto, incluir pacientes heterogéneos dentro de la misma categoría podría dificultar la interpretación de estudios y limitar los avances en el conocimiento de ambos trastornos. Conclusión: De la revisión de la literatura se sugiere que la MU debe ser reconocida como un diagnóstico independiente. A pesar de su baja prevalencia, al validarlo como tal, en un futuro podríamos contar con mayor cantidad y mejor calidad de datos sobre este. De esta forma se podrá definir de manera más concreta sus características distintivas, y por consiguiente mejorar el abordaje clínico de estos pacientes.

Introduction: Unipolar mania (UM) is a disorder that behaves differently from bipolar-I disorder (BP-I), however, it is not considered an independent entity by current diagnostic manuals, but rather included within the diagnosis of BP-I. Case report: A 21-year-old man presented a 3-month-long episode characterized by exalted mood and mood-congruent psychotic symptoms. The patient denies previous depressive episodes. Treatment with lithium and aripiprazole was established, which was satisfactory, not showing recurrence after 5 years of follow-up. Literature review and discussion: Diagnostic manuals describe that to diagnose BP-I the presence of a major depressive episode is not required, which implies that patients with UM fall into the same diagnostic category as patients with BP-I. Differences between UM and BP-I have been demonstrated in epidemiological, clinical, and genetic studies, therefore, including heterogeneous patients within the same category could hinder the interpretation of studies and limit advances in the knowledge of both disorders. Conclusion: Based on the literature review, it is suggested that UM should be recognized as an independent diagnosis. Despite its low prevalence, by validating it as such, in the future we could have more and better-quality data about this diagnosis. In this way, its distinctive characteristics can be defined more concretely, and therefore improve the clinical approach of these patients.

Identifying subtypes of bipolar disorder based on clinical and neurobiological characteristics.

The ability to classify patients with bipolar disorder (BD) is restricted by their heterogeneity, which limits the understanding of their neuropathology. Therefore, we aimed to investigate clinically discernible and neurobiologically distinguishable BD subtypes. T1-weighted and resting-state functional magnetic resonance images of 112 patients with BD were obtained, and patients were segregated according to diagnostic subtype (i.e., types I and II) and clinical patterns, including the number of episodes and hospitalizations and history of suicide and psychosis. For each clinical pattern, fewer and more occurrences subgroups and types I and II were classified through nested cross-validation for robust performance, with minimum redundancy and maximum relevance, in feature selection. To assess the proportion of variance in cognitive performance explained by the neurobiological markers, multiple linear regression between verbal memory and the selected features was conducted. Satisfactory performance (mean accuracy, 73.60%) in classifying patients with a high or low number of episodes was attained through functional connectivity, mostly from default-mode and motor networks. Moreover, these neurobiological markers explained 62% of the variance in verbal memory. The number of episodes is a potentially critical aspect of the neuropathology of BD. Neurobiological markers can help identify BD neuroprogression.

A Diagnosis and Biotype Comparison Across the Psychosis Spectrum: Investigating Volume and Shape Amygdala-Hippocampal Differences from the B-SNIP Study.

OBJECTIVE: Brain-based Biotypes for psychotic disorders have been developed as part of the B-SNIP consortium to create neurobiologically distinct subgroups within idiopathic psychosis, independent from traditional phenomenological diagnostic methods. In the current study, we aimed to validate the Biotype model by assessing differences in volume and shape of the amygdala and hippocampus contrasting traditional clinical diagnoses with Biotype classification. METHODS: A total of 811 participants from 6 sites were included: probands with schizophrenia (n = 199), schizoaffective disorder (n = 122), psychotic bipolar disorder with psychosis (n = 160), and healthy controls (n = 330). Biotype classification, previously developed using cognitive and electrophysiological data and K-means clustering, was used to categorize psychosis probands into 3 Biotypes, with Biotype-1 (B-1) showing reduced neural salience and severe cognitive impairment. MAGeT-Brain segmentation was used to determine amygdala and hippocampal volumetric data and shape deformations. RESULTS: When using Biotype classification, B-1 showed the strongest reductions in amygdala-hippocampal volume and the most widespread shape abnormalities. Using clinical diagnosis, probands with schizophrenia and schizoaffective disorder showed the most significant reductions of amygdala and hippocampal volumes and the most abnormal hippocampal shape compared with healthy controls. Biotype classification provided the strongest neuroanatomical differences compared with conventional DSM diagnoses, with the best discrimination seen using bilateral amygdala and right hippocampal volumes in B-1. CONCLUSION: These findings characterize amygdala and hippocampal volumetric and shape abnormalities across the psychosis spectrum. Grouping individuals by Biotype showed greater between-group discrimination, suggesting a promising approach and a favorable target for characterizing biological heterogeneity across the psychosis spectrum.

Predicting Long-Term Outcomes in First-Admission Psychosis: Does the Hierarchical Taxonomy of Psychopathology Aid DSM in Prognostication?

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical, dimensional model of psychological symptoms and functioning. Its goals are to augment the use and address the limitations of traditional diagnoses, such as arbitrary thresholds of severity, within-disorder heterogeneity, and low reliability. HiTOP has made inroads to addressing these problems, but its prognostic validity is uncertain. The present study sought to test the prediction of long-term outcomes in psychotic disorders was improved when the HiTOP dimensional approach was considered along with traditional (ie, DSM) diagnoses. We analyzed data from the Suffolk County Mental Health Project (N = 316), an epidemiologic study of a first-admission psychosis cohort followed for 20 years. We compared 5 diagnostic groups (schizophrenia/schizoaffective, bipolar disorder with psychosis, major depressive disorder with psychosis, substance-induced psychosis, and other psychoses) and 5 dimensions derived from the HiTOP thought disorder spectrum (reality distortion, disorganization, inexpressivity, avolition, and functional impairment). Both nosologies predicted a significant amount of variance in most outcomes. However, except for cognitive functioning, HiTOP showed consistently greater predictive power across outcomes-it explained 1.7-fold more variance than diagnoses in psychiatric and physical health outcomes, 2.1-fold more variance in community functioning, and 3.4-fold more variance in neural responses. Even when controlling for diagnosis, HiTOP dimensions incrementally predicted almost all outcomes. These findings support a shift away from the exclusive use of categorical diagnoses and toward the incorporation of HiTOP dimensions for better prognostication and linkage with neurobiology.

Spatial Expression Pattern of ZNF391 Gene in the Brains of Patients With Schizophrenia, Bipolar Disorders or Major Depressive Disorder Identifies New Cross-Disorder Biotypes: A Trans-Diagnostic, Top-Down Approach.

The results generated from large psychiatric genomic consortia show us some new vantage points to understand the pathophysiology of psychiatric disorders. We explored the potential of integrating the transcription output of the core gene underlying the commonality of psychiatric disorders with a clustering algorithm to redefine psychiatric disorders. Our results showed that an extended MHC region was associated with the common factor of schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) at the level of genomic significance, with rs7746199 (P = 4.905e-08), a cis-eQTL to the gene ZNF391, pinpointed as a potential causal variant driving the signals in the region. Gene expression pattern of ZNF391 in the brain led to the emergence of 3 biotypes, independent of disorder. The 3 biotypes performed significantly differently in working memory and demonstrated different gray matter volumes in the right inferior frontal orbital gyrus (RIFOG), with a partial causal pathway arising from ZNF391 to RIFOG to working memory. Our study illustrates the potential of a trans-diagnostic, top-down approach in understanding the commonality of psychiatric disorders.

Categorical differentiation of the unipolar and bipolar disorders.

There has been a longstanding debate as to whether the bipolar disorders differ categorically or dimensionally, with some dimensional or spectrum models including unipolar depressive disorders within a bipolar spectrum model. We analysed manic/hypomanic symptom data in samples of clinically diagnosed bipolar I, bipolar II and unipolar patients, employing latent class analyses to determine if separate classes could be identified. Mixture analyses were also undertaken to determine if a unimodal, bimodal or a trimodal pattern was present. For both a refined 15-item set and an extended 30-item set of manic/hypomanic symptoms, our latent class analyses favoured three-class solutions, while mixture analyses identified trimodal distributions of scores. Findings argue for a categorical distinction between unipolar and bipolar disorders, as well as between bipolar I and bipolar II disorders. Future research should aim to consolidate these results in larger samples, particularly given that the size of the unipolar group in this study was a salient limitation.

SNP Data Science for Classification of Bipolar Disorder I and Bipolar Disorder II.

Bipolar disorder I (BD-I) and bipolar disorder II (BD-II) have specific characteristics and clear diagnostic criteria, but quite different treatment guidelines. In clinical practice, BD-II is commonly mistaken as a mild form of BD-I. This study uses data science technique to identify the important Single Nucleotide Polymorphisms (SNPs) significantly affecting the classifications of BD-I and BD-II, and develops a set of complementary diagnostic classifiers to enhance the diagnostic process. Screening assessments and SNP genotypes of 316 Han Chinese were performed with the Affymetrix Axiom Genome-Wide TWB Array Plate. The results show that the classifier constructed by 23 SNPs reached the area under curve of ROC (AUC) level of 0.939, while the classifier constructed by 42 SNPs reached the AUC level of 0.9574, which is a mere addition of 1.84 percent. The accuracy rate of classification increased by 3.46 percent. This study also uses Gene Ontology (GO) and Pathway to conduct a functional analysis and identify significant items, including calcium ion binding, GABA-A receptor activity, Rap1 signaling pathway, ECM proteoglycans, IL12-mediated signaling events, Nicotine addiction), and PI3K-Akt signaling pathway. The study can address time-consuming SNPs identification and also quantify the effect of SNP-SNP interactions.

Bipolar disorders.

Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10-20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly in low-income and middle-income countries. Targeting medical and psychiatric comorbidity, integrating adjunctive psychosocial treatments, and involving caregivers have been shown to improve health outcomes for people with bipolar disorders. The aim of this Seminar, which is intended mainly for primary care physicians, is to provide an overview of diagnostic, pathogenetic, and treatment considerations in bipolar disorders. Towards the foregoing aim, we review and synthesise evidence on the epidemiology, mechanisms, screening, and treatment of bipolar disorders.

Is it depression or is it bipolar depression?

This review is intended to guide primary care providers in differentiating patients with bipolar depression from those with unipolar depression and inform patient management. Up to 64% of clinical encounters for depression occur in primary care, with misdiagnosis of bipolar depression common in both primary care and psychiatry. Although bipolar disorder is characterized by manic, hypomanic, and depressive episodes, the most common and debilitating symptomatic presentation is depression. Misdiagnosis as unipolar depression is common, often resulting in mistreatment with an unopposed monoamine antidepressant. Antidepressants are often ineffective for treating bipolar depression and may cause detrimental consequences such as treatment-emergent hypomania/mania, rapid cycling, or increased suicidality. Factors that are suggestive of bipolar disorder versus unipolar depression include early-onset depression, frequent depressive episodes, family history of serious mental illness, hypomania/mania symptoms within the depressive episode, and nonresponse to antidepressants. Comorbid medical (e.g., cardiovascular disease, hypertension, obesity) and psychiatric (e.g., attention-deficit/hyperactivity disorder, anxiety disorder, personality disorders, and substance use disorder) conditions are common and contribute to premature mortality for patients with bipolar disorder compared with the general public. Cariprazine, fluoxetine/olanzapine, lurasidone, and quetiapine are approved to treat bipolar depression; only cariprazine and quetiapine are approved to treat both bipolar mania and depression. Primary care providers who can differentiate presenting symptoms of bipolar depression from unipolar depression and offer appropriate treatment options will optimize patient care in clinical practice. Relevant information for this review was identified through a multistep literature search of PubMed using the terms bipolar depression/bipolar disorder plus other relevant terms.

Olfactory markers for depression: Differences between bipolar and unipolar patients.

OBJECTIVES: The aim of the study was to compare olfactory functions between unipolar and bipolar patients according to the thymic states (depressed, euthymic) and determine specific olfactory variations between these different states. METHODS: We recruited 176 participants in 5 groups: depressed bipolar (DB), euthymic bipolar (EB), depressed unipolar (DU), euthymic unipolar (EU), and controls (HC). They were assessed using the Sniffin' sticks threshold and identification tests. Odors' pleasantness, intensity, familiarity and emotion were assessed. Clinical evaluation explored dimensions of depression, mania, anxiety, and anhedonia. RESULTS: Smell identification was lower in DU compared to EU patients and controls. Pleasant odors received lower hedonic rating in DU and DB patients compared to EU and EB patients respectively. Negative correlation was found in EB patients between hedonic rating and social anhedonia. In EU patients hedonic rating was negatively correlated with anxiety-state, and anhedonia. CONCLUSIONS: Odor identification of pleasant odors is altered in both depressive states. Only unipolar patients would recover a regular identification level in symptomatic remission, while bipolar subjects would keep their deficits. Hedonic rating is lower in bipolar depressed patients compared to unipolar ones, and these deficits improve after remission. Hedonic rating of pleasant odors may distinguish bipolar depression from unipolar depression during periods of decompensation and phases of remission. Olfactory assessment may be useful to screen unipolar and bipolar depression, leading to possible future sensory markers in mood disorders.

Utility of TEMPS-A in differentiation between major depressive disorder, bipolar I disorder, and bipolar II disorder.

BACKGROUND: The association between temperament characteristics and mood disorders has gained much attention in recent years. The Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A) is a self-rating scale measuring 5 affective temperament dimensions. In this study, we aimed to clarify whether each affective temperament of TEMPS-A is a differentiating factor between major depressive disorder (MDD), bipolar I disorder (BD-I), and bipolar II disorder (BD-II), and analyzed the utility of TEMPS-A in their differential diagnosis in a clinical setting. METHODS: A total of 346 patients (MDD, n = 176; BD-II, n = 112; BD-I, n = 58) filled out TEMPS-A. To assess the patients' mood state at the time of temperament assessment, Patient Health Questionnaire-9 (PHQ-9) and Young Mania Rating Scale (YMRS) were also conducted. RESULTS: Multivariate logistic regression analysis demonstrated that cyclothymic and anxious temperament scores were significant factors differentiating the diagnosis of BD-I and BD-II from the diagnosis of MDD, and hyperthymic temperament score was a specific factor for the differential diagnosis of BD-I versus the diagnosis of BD-II. LIMITATIONS: All of the patients included in our study received treatment in large general hospitals. Because the nature of the present study was cross-sectional, some MDD subjects in this study might have unrecognized BD-I/BD-II. CONCLUSIONS: Cyclothymic and anxious temperament scores assessed by TEMPS-A might enable differentiation between MDD and BD, and hyperthymic temperament score on TEMPS-A might be useful in distinguishing between BD-I and BD-II.

Towards an ICF Core Set for functioning assessment in severe mental disorders: Commonalities in bipolar disorder, depression and schizophrenia.

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) offers an internationally accepted standard for describing and assessing functioning and disability in any health condition. A specific list of ICF categories, an ICF Core Set (CS), has been developed for bipolar disorder, depression and schizophrenia. The aim of this study was to determine commonalities in the ICF-CSs for these three disorders, and to identify relevant categories for the development of tentative ICF-CSs for severe mental disorders in general. METHODS: The ICF categories of all three mental health conditions were examined and compared. RESULTS: Comparison of the Comprehensive ICF-CSs for the three mental health conditions revealed a set of 34 common categories (i.e., 10 from the Body functions component, 14 from the Activities and participation component, and 10 Environmental factors ). These categories formed the proposed Comprehensive ICF-CS for severe mental disorders. A total of 11 categories were common to the Brief ICF-CSs of the three mental health conditions, and these formed the Brief ICF-CS for severe mental disorders (i.e., 3 from the Body functions component, 6 from the Activities and participation component, and 2 Environmental factors ). All the categories included refer to key aspects of functioning for severe mental disorders. CONCLUSIONS: The proposed ICF-CSs for severe mental disorders may be applicable across a number of psychotic and affective disorders and they should prove useful for mental health services whose care remit covers a range of conditions.

Differential core pharmacotherapy in bipolar I versus bipolar II disorder and European versus American patients not in a syndromal episode.

Assess bipolar disorder subtype and treatment location effects on bipolar disorder core pharmacotherapy. Outpatients not in a syndromal episode referred to the University of Milan and Stanford University Bipolar Disorder Clinics were assessed with SCID for the fourth Edition of the Diagnostic and Statistical Manual of Mood Disorders, and the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation, respectively. Prevalence and clinical correlates of antidepressant, antipsychotic, and mood stabilizer use, in aggregate and individually, were compared in bipolar I (BDI) versus II (BDII) patients in Milan/Stanford and in Milan versus Stanford patients, stratified by subtype. Milan/Stanford pooled BDI versus BDII patients significantly more often took antipsychotic (69.8 versus 44.8%), mood stabilizers (68.6 versus 57.7%), and valproate (40.1 versus 17.5%), and less often took antidepressants (23.1 versus 55.6%) and lamotrigine (9.9 versus 25.2%). Milan versus Stanford patients (stratified by bipolar disorder subtype) significantly more often took antipsychotic (BDI and BDII), antidepressants (BDII), and valproate (BDII), and less often took lamotrigine (BDI). Research regarding bipolar disorder core pharmacotherapy relationships with bipolar subtype and treatment location is warranted to enhance clinical management.

Progression of the functional deficit in a group of patients with bipolar disorder: a cluster analysis based on longitudinal data.

We aimed to examine the trajectory of psychosocial functioning in a sample of euthymic patients with bipolar disorder (BD) throughout a 5-year follow-up. Ninety-nine euthymic bipolar patients and 40 healthy controls (HC) were included. A neurocognitive assessment (17 neurocognitive measures grouped in 6 domains) was carried out at baseline. The split version of the Global Assessment of Functioning scale (GAF-F) and the Functioning Assessment Short Test (FAST) were used to examine psychosocial functioning at baseline (T1), and after a 5-year follow-up (T2). The statistical analysis was performed through repeated measures ANOVA and hierarchical cluster analysis based on the GAF-F and the FAST scores at T1 and T2. Eighty-seven patients (87.9%) were evaluated at T2. The cluster analysis identified two groups of patients. The first group included 44 patients (50.6%) who did not show a progression of the functional impairment (BD-NPI). The second cluster, which included 43 patients (49.4%), was characterized by a progression of the functional impairment (BD-PI). The BD-PI had a higher number of relapses and a higher number of hospitalizations during the follow-up period, as well as worse neurocognitive functioning than the BD-NPI. The repeated measures ANOVA confirmed that the psychosocial performance of BD-NPI is stable while there was a progression of the functional deterioration in BD-PI. The trajectory of the psychosocial functioning of patients with BD is not homogeneous. Our results suggest that in at least one subset of patients with BD, which might account for half of the patients, the disease has a progressive course.

Distinct structural brain circuits indicate mood and apathy profiles in bipolar disorder.

Bipolar disorder (BD) is a severe manic-depressive illness. Patients with BD have been shown to have gray matter (GM) deficits in prefrontal, frontal, parietal, and temporal regions; however, the relationship between structural effects and clinical profiles has proved elusive when considered on a region by region or voxel by voxel basis. In this study, we applied parallel independent component analysis (pICA) to structural neuroimaging measures and the positive and negative syndrome scale (PANSS) in 110 patients (mean age 34.9 ±â€¯11.65) with bipolar disorder, to examine networks of brain regions that relate to symptom profiles. The pICA revealed two distinct symptom profiles and associated GM concentration alteration circuits. The first PANSS pICA profile mainly involved anxiety, depression and guilty feelings, reflecting mood symptoms. Reduced GM concentration in right temporal regions predicted worse mood symptoms in this profile. The second PANSS pICA profile generally covered blunted affect, emotional withdrawal, passive/apathetic social withdrawal, depression and active social avoidance, exhibiting a withdrawal or apathy dominating component. Lower GM concentration in bilateral parietal and frontal regions showed worse symptom severity in this profile. In summary, a pICA decomposition suggested BD patients showed distinct mood and apathy profiles differing from the original PANSS subscales, relating to distinct brain structural networks.

Characterizing functional regional homogeneity (ReHo) as a B-SNIP psychosis biomarker using traditional and machine learning approaches.

BACKGROUND: Recently, a biologically-driven psychosis classification (B-SNIP Biotypes) was derived using brain-based cognitive and electrophysiological markers. Here, we characterized a local functional-connectivity measure, regional homogeneity (ReHo), as a biomarker across Biotypes and conventional DSM diagnoses. METHODS: Whole-brain ReHo measures of resting-state functional MRI were examined in psychosis patients and healthy controls organized by Biotype and by DSM-IV-TR diagnosis (n = 737). Group-level ANOVA and individual-level prediction models using support vector machines (SVM) were employed to evaluate the discriminative characteristics in comparisons of 1) DSM diagnostic groups, 2) Biotypes, to controls, and 3) within-proband subgroups with each other. RESULTS: Probands grouped by Biotype versus controls showed a unique abnormality pattern: Biotype-1 displayed bidirectional ReHo differences in more widespread areas, with higher ReHo in para-hippocampus, fusiform, inferior temporal, cerebellum, thalamus and caudate, plus lower ReHo in the postcentral gyrus, middle temporal, cuneus, and middle occipital cortex; Biotype-2 and Biotype-3 showed lesser and unidirectional ReHo changes. Among diagnostic groups, only schizophrenia showed higher ReHo versus control values in the inferior/middle temporal area and fusiform gyrus. For within-patient comparisons, Biotype-1 showed characteristic ReHo when compared to Biotype-2 and Biotype-3. SVM results more accurately identified Biotypes than DSM diagnoses. CONCLUSION: We characterized patterns of ReHo abnormalities across both Biotypes and DSM sub-groups. Both group-level statistical and machine-learning methods were more sensitive in capturing ReHo deficits in Biotypes than DSM. Overall ReHo is a robust psychosis biomarker.

[Attention-deficit/hyperactivity disorder in adults in the clinical description and classification of Emil Kraepelin]. / Die Aufmerksamkeitsdefizit­/Hyperaktivitätsstörung bei Erwachsenen in der klinischen Beschreibung und der Klassifikation von Emil Kraepelin.

This study presents descriptions of symptoms specific to the adult form of attention-deficit/hyperactivity disorder (ADHD) in the 8th edition of the Textbook on Psychiatry by Emil Kraepelin (1856-1926). To identify whether ADHD is a new, fashionable phenomenon in adults or whether early psychiatrists also saw such patients and how they classified them, this textbook is an essential source. Published between 1905 and 1915, it can be perceived as the culmination and at the same time terminal point of Kraepelin's conceptual and nosological work, which in turn marked the beginning of present-day psychiatric classification. Kraepelin did not perceive ADHD as a psychiatric entity of its own, which is either due to the fact that he saw no necessity to do so or that he did not recognize this. If the latter, Kraepelin may have been misled by the manifold psychiatric comorbidities typical for ADHD, which may have masked ADHD. Kraepelin seems to have grouped patients obviously suffering from the adult form of ADHD into two groups: on the one hand into the so-called basic constitution (Grundzustand) of manic-depressive disorder, which he called manic disposition or constitutional excitement (manische Veranlagung oder konstitutionelle Erregung) and on the other hand into the so-called group of anchorless people (Haltlose), which he perceived as a special form of psychopathic personality. It seems that Kraepelin grouped milder grades of ADHD with predominantly ADHD-associated mood swings into the group of manic disposition while grouping more severe forms, which usually occur together with distinct personality disorders and addictive disorders, into that of anchorless people.

Antipsychotic use in Northern Italian inter-episode bipolar disorder patients: considering both second- and first-generation agents.

Evidence supports increasing antipsychotic use in bipolar disorder, especially second-generation antipsychotics. However, data regarding first-generation antipsychotic contemporary use are limited. We studied 380 Northern Italian bipolar disorder inter-episode patients, grouped according to current antipsychotic use, stratified by bipolar subtype (BDI vs. BDII). Furthermore, we compared first-generation antipsychotic users vs. non-users. In our sample (n = 357), 81.8% were taking antipsychotics (74% second-generation antipsychotics, 24.1% first-generation antipsychotics), with antipsychotic use in BDI significantly more prevalent than in BDII (85.2% vs. 72.0%). Overall, antipsychotic users vs. non-users had higher rates of hypo/manic last episode, lifetime psychiatric hospitalization, psychosis, and current psychotropic use, but lower rates of anxiety disorder main comorbidity and current antidepressant use. First-generation antipsychotic use rates (30.3% in BDI vs. 6.5% in BDII) were associated with more frequently being unpartnered, having elevated first/last episodes, higher lifetime hospitalization, involuntary commitment, psychosis, and psychosocial rehabilitation rates, and more current psychotropic use, but lower Global Assessment Functioning scores and less current antidepressant use. Bipolar disorder patients had robust antipsychotic (second-generation antipsychotic > first-generation antipsychotic) use, consistently with previous reports. FGAs were still prescribed for a substantial group of patients, likely suffering from severe bipolar disorder. Prescriptions need to be monitored to assess their appropriateness and adherence to evidence-based recommendations.