Paternal Western diet causes transgenerational increase in food consumption in Drosophila with parallel alterations in the offspring brain proteome and microRNAs.

Several lines of evidence indicate that ancestral diet might play an important role in determining offspring's metabolic traits. However, it is not yet clear whether ancestral diet can affect offspring's food choices and feeding behavior. In the current study, taking advantage of Drosophila model system, we demonstrate that paternal Western diet (WD) increases offspring food consumption up to the fourth generation. Paternal WD also induced alterations in F1 offspring brain proteome. Using enrichment analyses of pathways for upregulated and downregulated proteins, we found that upregulated proteins had significant enrichments in terms related to translation and translation factors, whereas downregulated proteins displayed enrichments in small molecule metabolic processes, TCA cycles, and electron transport chain (ETC). Using MIENTURNET miRNA prediction tool, dme-miR-10-3p was identified as the top conserved miRNA predicted to target proteins regulated by ancestral diet. RNAi-based knockdown of miR-10 in the brain significantly increased food consumption, implicating miR-10 as a potential factor in programming feeding behavior. Together, these findings suggest that ancestral nutrition may influence offspring feeding behavior through alterations in miRNAs.

Role of Transposable Elements in Genome Stability: Implications for Health and Disease.

Most living organisms have in their genome a sizable proportion of DNA sequences capable of mobilization; these sequences are commonly referred to as transposons, transposable elements (TEs), or jumping genes. Although long thought to have no biological significance, advances in DNA sequencing and analytical technologies have enabled precise characterization of TEs and confirmed their ubiquitous presence across all forms of life. These findings have ignited intense debates over their biological significance. The available evidence now supports the notion that TEs exert major influence over many biological aspects of organismal life. Transposable elements contribute significantly to the evolution of the genome by giving rise to genetic variations in both active and passive modes. Due to their intrinsic nature of mobility within the genome, TEs primarily cause gene disruption and large-scale genomic alterations including inversions, deletions, and duplications. Besides genomic instability, growing evidence also points to many physiologically important functions of TEs, such as gene regulation through cis-acting control elements and modulation of the transcriptome through epigenetic control. In this review, we discuss the latest evidence demonstrating the impact of TEs on genome stability and the underling mechanisms, including those developed to mitigate the deleterious impact of TEs on genomic stability and human health. We have also highlighted the potential therapeutic application of TEs.

GABAergic neuroactive steroids: a new frontier in bipolar disorders?

Neurosteroids are synthesized in the brain and modulate brain excitability. There is increasing evidence of their sedative, anesthetic and antiseizure properties, as well as their influence on mood. Currently neurosteroids are classified as pregnane neurosteroids (allopregnanolone and allotetrahydrodeoxycorticosterone), androstane neurosteroids (androstanediol and etiocholanone) or sulfated neurosteroids (pregnenolone sulfate and dehydroepiandrosterone sulfate). Both preclinical and clinical findings indicate that progesterone derivative neurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone play a role in mood disorders. Clozapine and olanzapine, which were shown to be effective in stabilizing bipolar disorder, elevate pregnenolone levels in rat hippocampus, cerebral cortex, and serum. In lithium-treated mice, the blood levels of allopregnanolone and pregnenolone were elevated compared to control levels. Women diagnosed with bipolar disorder typically show symptomatic exacerbation in relation to the menstrual cycle, and show vulnerability to the onset or recurrence of mood disorders immediately after giving birth, when the levels of neurosteroid derivatives of progesterone drop. Whereas in women who had recovered from bipolar disorder, the plasma concentration of allopregnanolone was elevated compared to either healthy controls or women with major depressive disorder during the premenstrual period. During depressive episodes, blood level of allopregnanolone is low. Treatment with fluoxetine tends to stabilize the levels of neurosteroids in depression. These findings converge to suggest that these steroids have significant mood-stabilizing effect. This hypothesis is consistent with the observation that a number of anticonvulsants are effective therapies for bipolar disorder, a finding also consistent with the antiseizure properties of neurosteroids. Further exploration of action of neuroactive steroids is likely to open new frontiers in the investigation of the etiology and treatment of mood disorders, particularly bipolar disorders.

Bipolar disorders and Wilson's disease.

BACKGROUND: The aim of this study was to determine the risk for Bipolar Disorder (BD) in Wilson's disease (WD) and to measure the impaired Quality of Life (QL) in BD with WD using standardized psychiatric diagnostic tools and a case control design. METHODS: This was a case control study. The cases were 23 consecutive patients with WD treated at the University Hospital in Cagliari, Italy, and the controls were 92 sex- and age-matched subjects with no diagnosis of WD who were randomly selected from a database used previously for an epidemiological study. Psychiatric diagnoses according to DSM-IV criteria were determined by physicians using structured interview tools (ANTAS-SCID). QL was measured by means of SF-12. RESULTS: Compared to controls, WD patients had lower scores on the SF-12 and higher lifetime prevalence of DSM-IV major depressive disorders (OR = 5.7, 95% CI 2.4-17.3) and bipolar disorders (OR = 12.9, 95% CI 3.6-46.3). BD was associated with lower SF-12 in WD patients. CONCLUSIONS: This study was the first to show an association between BD and WD using standardized diagnostic tools and a case control design. Reports in the literature about increased schizophrenia-like psychosis in WD and a lack of association with bipolar disorders may thus have been based on a more inclusive diagnosis of schizophrenia in the past. Our findings may explain the frequent reports of loss of emotional control, hyperactivity, loss of sexual inhibition, and irritability in WD patients. This study was limited by a small sample size.

Psychiatric symptoms and quality of life in systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a rare conjunctive tissue disorder characterized by fibrosis of the skin and internal organs, and vascular obliteration phenomena. Patients with SSc often experience elevated symptoms of psychological distress, determined by the disfiguration, the pain, the fatigue sensation, and the difficult in daily life occupations. The characteristics of the disease may influence the perceived quality of life (QoL) in people with SSc. METHODS: This is a narrative review aiming to define the amount of impairment of Quality of Life in patients with Systemic Sclerosis and the component of this impairment due to depressive or other psychiatric symptoms. The search of the significant articles was carried out in PubMed for the key words "Psychiatric symptoms and Systemic Sclerosis"; "Quality of life and Systemic Sclerosis"; "Depressive Disorders and Systemic Sclerosis". RESULTS: Psychiatric symptoms are frequents in patients with SSc, but pain, fatigue, disability, body changes don't appear to explain the high prevalence of psychiatric comorbidity in SSc. Many studies founded a significant impairment in SSc patients' QoL, and despite the undeniable correlation between physical symptoms and SSc patients' QoL, mental health was found significantly impaired. DISCUSSION: The high rate of depression seems to strictly correlate with poor quality of life, and this finding needs more research to establish the cause of such a correlation. Patients' point of view regarding their health-related QoL could help physicians to enlarge the knowledge about physical and mental correlates of the disease, and to fit therapies as patient required. Particular attention must be given to provide the patient with correct information, in order to mitigate the anxious state on disease course, and to enhance coping skills of the patients.

Schizophrenia: from epidemiology to rehabilitation.

PURPOSE/OBJECTIVE: We discuss recent evidences about schizophrenia (frequency, onset, course, risk factors and genetics) and their influences to some epidemiological myths about schizophrenia diffuse between psychiatric and psychopathology clinicians. The scope is to evaluate if the new acquisitions may change the rehabilitation approaches to schizophrenia modifying the balance about the neurodevelopmental hypothesis of schizophrenia accepting that the cognitive deficits are produced by errors during the normal development of the brain (neurodevelopmental hypothesis) that remains stable in the course of illness and the neurodegenerative hypothesis according of which they derived from a degenerative process that goes on inexorably. RESEARCH METHOD/DESIGN: A review of the literature about epidemiology of schizophrenia has been performed and the contributions of some of these evidence to neurodevelopmental hypothesis and to rehabilitation has been described. RESULTS: It cannot be definitively concluded for or against the neurodevelopmental or degenerative hypothesis, but efforts in understanding basis of schizophrenia must go on. Until now, rehabilitation programs are based on the vulnerability-stress model: supposing an early deficit that go on stable during the life under favorable circumstances. So, rehabilitation approaches (as neuro-cognitive approaches, social skill training, cognitive-emotional training) are focused on the individual and micro-group coping skills, aiming to help people with schizophrenia to cope with environmental stress factors. CONCLUSIONS/IMPLICATIONS: Coping of cognitive deficits in schizophrenia may represents the starting-point for further research on schizophrenia, cohort studies and randomized trials are necessary to defined the range of effectiveness and the outcome of the treatments.

Could hypomanic traits explain selective migration? Verifying the hypothesis by the surveys on sardinian migrants.

INTRODUCTION: A recent survey put forward the hypothesis that the emigration that occurred from Sardinia from the 1960's to the 1980's, selected people with a hypomanic temperament. The paper aims to verify if the people who migrated from Sardinia in that period have shown a high risk of mood disorders in the surveys carried out in their host countries, and if the results are consistent with this hypothesis. METHODS: This is systematic review. RESULTS: In the 1970's when examining the attitudes towards migration in Sardinian couples waiting to emigrate, Rudas found that the decision to emigrate was principally taken by males. Female showed lower self-esteem than male emigrants. A study on Sardinian immigrants in Argentina carried out in 2001-02, at the peak of the economic crisis, found a high risk of depressive disorders in women only. These results were opposite to the findings recorded ten years earlier in a survey on Sardinian immigrants in Paris, where the risk of Depressive Episode was higher in young men only. DISCUSSION: Data point to a bipolar disorder risk for young (probably hypomanic) male migrants in competitive, challenging conditions; and a different kind of depressive episodes for women in trying economic conditions. The results of the survey on Sardinian migrants are partially in agreement with the hypothesis of a selective migration of people with a hypomanic temperament. Early motivations and self-esteem seem related to the ways mood disorders are expressed, and to the vulnerability to specific triggering situations in the host country.

Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks.

Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homologous recombination (HR) pathway by a poorly defined mechanism(s); however, the mechanisms for this inhibition remain unclear. Here we report that hyperthermia decreases H4K16 acetylation (H4K16ac), an epigenetic modification essential for genome stability and transcription. Heat-induced reduction in H4K16ac was detected in humans, Drosophila, and yeast, indicating that this is a highly conserved response. The examination of histone deacetylase recruitment to chromatin after heat-shock identified SIRT1 as the major deacetylase subsequently enriched at gene-rich regions. Heat-induced SIRT1 recruitment was antagonized by chromatin remodeler SMARCAD1 depletion and, like hyperthermia, the depletion of the SMARCAD1 or combination of the two impaired DNA end resection and increased replication stress. Altered repair protein recruitment was associated with heat-shock-induced γ-H2AX chromatin changes and DSB repair processing. These results support a novel mechanism whereby hyperthermia impacts chromatin organization owing to H4K16ac deacetylation, negatively affecting the HR-dependent DSB repair.

Sub-threshold depression and antidepressants use in a community sample: searching anxiety and finding bipolar disorder.

BACKGROUND: To determine the use of antidepressants (ADs) in people with sub-threshold depression (SD); the lifetime prevalence of mania and hypomania in SD and the link between ADs use, bipolarity and anxiety disorders in SD. STUDY DESIGN: community survey. STUDY POPULATION: samples randomly drawn, after stratification from the adult population of municipal records. SAMPLE SIZE: 4999 people from seven areas within six Italian regions. Tools: Questionnaire on psychotropic drug consumption, prescription; Structured Clinical Interview NP for DSM-IV modified (ANTAS); Hamilton Depression Rating Scale (HAM-D); Mood Disorder Questionnaire (MDQ); Short Form Health Survey (SF-12). SD definition: HAM-D > 10 without lifetime diagnosis of Depressive Episode (DE). RESULTS: SD point prevalence is 5.0%. The lifetime prevalence of mania and hypomania episodes in SD is 7.3%. Benzodiazepines (BDZ) consumption in SD is 24.1%, followed by ADs (19.7%). In SD, positive for MDQ and comorbidity with Panic Disorder (PD) or Generalized Anxiety Disorders (GAD) are associated with ADs use, whereas the association between a positive MDQ and ADs use, without a diagnosis of PD or GAD, is not significant. Only in people with DE the well-being (SF-12) is higher among those using first-line antidepressants compared to those not using any medication. In people with SD no significant differences were found in terms of SF-12 score according to drug use. CONCLUSIONS: This study suggests caution in prescribing ADs to people with SD. In people with concomitant anxiety disorders and SD, it should be mandatory to perform a well-designed assessment and evaluate the presence of previous manic or hypomanic symptoms prior to prescribing ADs.

A pattern of cerebral perfusion anomalies between major depressive disorder and Hashimoto thyroiditis.

BACKGROUND: This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion. DESIGN: Analysis of data derived from two separate data banks. SAMPLE: 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25). ASSESSMENT: Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by (99 m)Tc-ECD SPECT. Statistical analysis was done through logistic regression. RESULTS: MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group. CONCLUSION: In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD.

Preference and detrimental effects of high fat, sugar, and salt diet in wild-caught Drosophila simulans are reversed by flight exercise.

High saturated fat, sugar, and salt contents are a staple of a Western diet (WD), contributing to obesity, metabolic syndrome, and a plethora of other health risks. However, the combinatorial effects of these ingredients have not been fully evaluated. Here, using the wild-caught Drosophila simulans, we show that a diet enriched with saturated fat, sugar, and salt is more detrimental than each ingredient separately, resulting in a significantly decreased lifespan, locomotor activity, sleep, reproductive function, and mitochondrial function. These detrimental effects were more pronounced in female than in male flies. Adding regular flight exercise to flies on the WD markedly negated the adverse effects of a WD. At the molecular level, the WD significantly increased levels of triglycerides and caused mitochondrial dysfunction, while exercise counterbalanced these effects. Interestingly, fruit flies developed a preference for the WD after pre-exposure, which was averted by flight exercise. The results demonstrate that regular aerobic exercise can mitigate adverse dietary effects on fly mitochondrial function, physiology, and feeding behavior. Our data establish Drosophila simulans as a novel model of diet-exercise interaction that bears a strong similarity to the pathophysiology of obesity and eating disorders in humans.