Association of Occupational Dysfunction and Hospital Admissions With Different Polygenic Profiles in Bipolar Disorder.

OBJECTIVE: Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term occupational dysfunction that extends beyond acute mood episodes. It is not known whether these dissimilar outcomes of bipolar disorder are driven by different polygenic profiles. Here, polygenic scores (PGSs) for major psychiatric disorders and educational attainment were assessed for associations with occupational functioning and psychiatric hospital admissions in bipolar disorder. METHODS: A total of 4,782 patients with bipolar disorder and 2,963 control subjects were genotyped and linked to Swedish national registers. Longitudinal measures from at least 10 years of registry data were used to derive percentage of years without employment, percentage of years with long-term sick leave, and mean number of psychiatric hospital admissions per year. Ordinal regression was used to test associations between outcomes and PGSs for bipolar disorder, schizophrenia, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and educational attainment. Replication analyses of hospital admissions were conducted with data from the Bipolar Disorder Research Network cohort (N=4,219). RESULTS: Long-term sick leave and unemployment in bipolar disorder were significantly associated with PGSs for schizophrenia, ADHD, major depressive disorder, and educational attainment, but not with the PGS for bipolar disorder. By contrast, the number of hospital admissions per year was associated with higher PGSs for bipolar disorder and schizophrenia, but not with the other PGSs. CONCLUSIONS: Bipolar disorder severity (indexed by hospital admissions) was associated with a different polygenic profile than long-term occupational dysfunction. These findings have clinical implications, suggesting that mitigating occupational dysfunction requires interventions other than those deployed to prevent mood episodes.

Does NUCB2/Nesfatin-1 Influence Eating Behaviors in Obese Patients with Binge Eating Disorder? Toward a Neurobiological Pathway.

Nesfatin-1 is a new anorexigenic neuropeptide involved in the regulation of hunger/satiety, eating, and affective disorders. We aimed to investigate nesfatin-1 secretion in vitro, in murine adipose cells, and in human adipose fat samples, as well as to assess the link between circulating nesfatin-1 levels, NUCB2 and Fat Mass and Obesity Gene (FTO) polymorphisms, BMI, Eating Disorders (EDs), and pathological behaviors. Nesfatin-1 secretion was evaluated both in normoxic fully differentiated 3T3-L1 mouse adipocytes and after incubation under hypoxic conditions for 24 h. Omental Visceral Adipose tissue (VAT) specimens of 11 obese subjects, and nesfatin-1 serum levels' evaluation, eating behaviors, NUCB2 rs757081, and FTO rs9939609 polymorphisms of 71 outpatients seeking treatment for EDs with different Body Mass Index (BMI) were studied. Significantly higher levels of nesfatin-1 were detected in hypoxic 3T3-L1 cultured adipocytes compared to normoxic ones. Nesfatin-1 was highly detectable in the VAT of obese compared to normal-weight subjects. Nesfatin-1 serum levels did not vary according to BMI, sex, and EDs diagnosis, but correlations with grazing; emotional, sweet, and binge eating; hyperphagia; social eating; childhood obesity were evident. Obese subjects with CG genotype NUCB2 rs757081 and AT genotype FTO rs9939609 polymorphisms had higher nesfatin-1 levels. It could represent a new biomarker of EDs comorbidity among obese patients.

The role of hormonal, metabolic and inflammatory biomarkers on sleep and appetite in drug free patients with major depression: A systematic review.

BACKGROUND: Major depressive disorder (MDD) is a complex and heterogeneous disorder in which clinical symptoms can widely differ among patients. Neurovegetative symptoms, i.e. decreased or increased appetite, changes in body weight and sleep disturbances, described as 'melancholic' or 'atypical' features of a depressive episode, are the most variable symptoms among patients with MDD. We hypothesized biomarkers differences underlying this neurovegetative variability in major depression. METHODS: We systematically reviewed, according to the PRISMA guidelines, the role of specific metabolic, hormonal and inflammatory biomarkers in drug-free MDD patients, that could have neurobiological effects on appetite, weight regulation and circadian rhythms, influencing eating behaviour and sleep patterns. All studies regarding the co-occurrence of disturbed sleep and appetite were examined. RESULTS: Besides the well-known leptin and ghrelin, other biomarkers such as BDNF, VEGF, NPY, orexin, and the recent discovered nesfatin-1 seem to be involved in neurovegetative changes in depressive disorders playing a role in the regulation of affective states, stress reactions and sleep patterns. Interestingly, based on the existing evidence, ghrelin, orexin and nesfatin-1 could be linked both to sleep and appetite regulation in depressed patients. LIMITATIONS: Heterogeneous studies with low sample size. CONCLUSIONS: Despite the wide heterogeneity of results, studies on biomarkers of appetite and sleep in MDD are an interesting field of research to explain the neurobiological substrates of depressive symptoms that deserve further investigation.

A real world study on the genetic, cognitive and psychopathological differences of obese patients clustered according to eating behaviours.

BACKGROUND: Considering that specific genetic profiles, psychopathological conditions and neurobiological systems underlie human behaviours, the phenotypic differentiation of obese patients according to eating behaviours should be investigated. The aim of this study was to classify obese patients according to their eating behaviours and to compare these clusters in regard to psychopathology, personality traits, neurocognitive patterns and genetic profiles. METHODS: A total of 201 obese outpatients seeking weight reduction treatment underwent a dietetic visit, psychological and psychiatric assessment and genotyping for SCL6A2 polymorphisms. Eating behaviours were clustered through two-step cluster analysis, and these clusters were subsequently compared. RESULTS: Two groups emerged: cluster 1 contained patients with predominantly prandial hyperphagia, social eating, an increased frequency of the long allele of the 5-HTTLPR and low scores in all tests; and cluster 2 included patients with more emotionally related eating behaviours (emotional eating, grazing, binge eating, night eating, post-dinner eating, craving for carbohydrates), dysfunctional personality traits, neurocognitive impairment, affective disorders and increased frequencies of the short (S) allele and the S/S genotype. CONCLUSIONS: Aside from binge eating, dysfunctional eating behaviours were useful symptoms to identify two different phenotypes of obese patients from a comprehensive set of parameters (genetic, clinical, personality and neuropsychology) in this sample. Grazing and emotional eating were the most important predictors for classifying obese patients, followed by binge eating. This clustering overcomes the idea that 'binging' is the predominant altered eating behaviour, and could help physicians other than psychiatrists to identify whether an obese patient has an eating disorder. Finally, recognising different types of obesity may not only allow a more comprehensive understanding of this illness, but also make it possible to tailor patient-specific treatment pathways.

Infection and characterization of Toxoplasma gondii in human induced neurons from patients with brain disorders and healthy controls.

Toxoplasma gondii is a protozoan parasite capable of establishing persistent infection within the brain. Serological studies in humans have linked exposure to Toxoplasma to neuropsychiatric disorders. However, serological studies have not elucidated the related molecular mechanisms within neuronal cells. To address this question, we used human induced neuronal cells derived from peripheral fibroblasts of healthy individuals and patients with genetically-defined brain disorders (i.e. childhood-onset schizophrenia with disease-associated copy number variations). Parasite infection was characterized by differential detection of tachyzoites and tissue cysts in induced neuronal cells. This approach may aid study of molecular mechanisms underlying individual predisposition to Toxoplasma infection linked to neuropathology of brain disorders.

Enhanced conversion of induced neuronal cells (iN cells) from human fibroblasts: Utility in uncovering cellular deficits in mental illness-associated chromosomal abnormalities.

The novel technology of induced neuronal cells (iN cells) is promising for translational neuroscience, as it allows the conversion of human fibroblasts into cells with postmitotic neuronal traits. However, a major technical barrier is the low conversion rate. To overcome this problem, we optimized the conversion media. Using our improved formulation, we studied how major mental illness-associated chromosomal abnormalities may impact the characteristics of iN cells. We demonstrated that our new iN cell culture protocol enabled us to obtain more precise measurement of neuronal cellular phenotypes than previous iN cell methods. Thus, this iN cell culture provides a platform to efficiently obtain possible cellular phenotypes caused by genetic differences, which can be more thoroughly studied in research using other human cell models such as induced pluripotent stem cells.