S50-01 Depression and bipolar disorder: Is prevention of mania possible? Critical issues on diagnostic criteria

Diagnostic criteria for bipolar disorder in DSM IV require the occurrence of a manic or hypomanic episode. The scant appropriateness of these criteria compared with Kraepelin"s concept of manic depressive insanity has been repeatedly reported and the concept of bipolar spectrum has been proposed for more than 30 years. The negative consequences of pure adherence to operational diagnostic criteria on clinical needs are presented in terms of community epidemiology results and in terms of clinical evidences and the inadequate treatment of depressive and anxiety episodes and the risk of manic switch with antidepressant drugs are discussed.The epidemiological survey conducted in Sesto Fiorentino showed that depressive episodes in patients with subthreshold mania or hypomania were different from the clinical presentation of pure unipolar depressives episodes confirming not only the numeric impact but also qualitative differences between these groups of patients.Our clinical study where predictors of mania have been prospectively evaluated in a trans nosographic sample of outpatients demonstrated that aspects related to bipolarity predicted manic shift regardless of the diagnosis. DSM IV criteria seem not to be able to detect and describe a group of patients relevant both on epidemiological and on clinical level. These findings underline the need of a careful examination of patients treatment and validate the rule of further research in definition of mood disorders boundaries for prevention strategies

Subtelomeric FISH analysis in 76 patients with syndromic developmental delay/intellectual disability

<p>Abstract</p> <p>Background</p> <p>Intellectual disability affects approximately 1 to 3% of the general population. The etiology is still poorly understood and it is estimated that one-half of the cases are due to genetic factors. Cryptic subtelomeric aberrations have been found in roughly 5 to 7% of all cases.</p> <p>Methods</p> <p>We performed a subtelomeric FISH analysis on 76 unrelated children with normal standard karyotype ascertained by developmental delay or intellectual disability, associated with congenital malformations, and/or facial dysmorphisms.</p> <p>Results</p> <p>Ten cryptic chromosomal anomalies have been identified in the whole cohort (13,16%), 8 in the group of patients characterized by developmental delay or intellectual disability associated with congenital malformations and facial dysmorphisms, 2 in patients with developmental delay or intellectual disability and facial dysmorphisms only.</p> <p>Conclusion</p> <p>We demonstrate that a careful clinical examination is a very useful tool for pre-selection of patients for genomic analysis, clearly enhancing the chromosomal anomaly detection rate. Clinical features of most of these patients are consistent with the corresponding emerging chromosome phenotypes, pointing out these new clinical syndromes associated with specific genomic imbalances.</p

A Fe2+-dependent self-inhibited state influences the druggability of human collagen lysyl hydroxylase (LH/PLOD) enzymes

Multifunctional human collagen lysyl hydroxylase (LH/PLOD) enzymes catalyze post-translational hydroxylation and subsequent glycosylation of collagens, enabling their maturation and supramolecular organization in the extracellular matrix (ECM). Recently, the overexpression of LH/PLODs in the tumor microenvironment results in abnormal accumulation of these collagen post-translational modifications, which has been correlated with increased metastatic progression of a wide variety of solid tumors. These observations make LH/PLODs excellent candidates for prospective treatment of aggressive cancers. The recent years have witnessed significant research efforts to facilitate drug discovery on LH/PLODs, including molecular structure characterizations and development of reliable high-throughput enzymatic assays. Using a combination of biochemistry and in silico studies, we characterized the dual role of Fe2+ as simultaneous cofactor and inhibitor of lysyl hydroxylase activity and studied the effect of a promiscuous Fe2+ chelating agent, 2,2'-bipyridil, broadly considered a lysyl hydroxylase inhibitor. We found that at low concentrations, 2,2'-bipyridil unexpectedly enhances the LH enzymatic activity by reducing the inhibitory effect of excess Fe2+. Together, our results show a fine balance between Fe2+-dependent enzymatic activity and Fe2+-induced self-inhibited states, highlighting exquisite differences between LH/PLODs and related Fe2+, 2-oxoglutarate dioxygenases and suggesting that conventional structure-based approaches may not be suited for successful inhibitor development. These insights address outstanding questions regarding druggability of LH/PLOD lysyl hydroxylase catalytic site and provide a solid ground for upcoming drug discovery and screening campaigns

The prevalence of specific phobia by age in an Italian nationwide survey: How much does it affect the quality of life?

Introduction: The study aimed to see if a community survey conducted by clinical interviewers with semi-structured psychiatric interviews shows lifetime prevalence rates of Specific Phobia (SP) similar to those found by surveys carried out by lay interviewers and if the high level of impairment found in SP may be confirmed. Methods: This is a community survey on an Italian nationwide sample randomly selected from registers of municipalities. Tools: semi-structured ANTAS psychiatric interview derived from the SCID-DSM-IV, carried out by clinicians (psychologists or physicians); Short Form Health Survey (SF-12) as a measure of Quality of Life (QoL). Analyses: means of the χ2 test odds ratios were adopted to test several associations regarding SP prevalence. One-way ANOVA was used to compare different groups on attributable burden due to SP and/or other disorders in worsening QoL. Results: The lifetime prevalence of SP was 2.3%. No difference was found by age class. Females showed more than twice the frequency of males (p&lt;0.0001). The disorders showing the closest association with SP were: social phobia (OR=17.53); general anxiety disorder (OR=11.57); anorexia (OR=11.13) and agoraphobia (OR=10.03), but also obsessive compulsive disorders (OR=8.8), eating disorders (OR=7.2), panic disorder (OR=5.9), post-traumatic stress disorder (OR=5.8), and major depressive disorder (OR=4.8) presented an association that achieved statistical significance. The QoL of people with SP and at least one disorder of anxiety, mood or eating in comorbidity, measured as a score at SF12, was worse than controls without SP (p &lt;0.001) but that of people with SP without co-morbidity was not (p = 0.809). Conclusion: An epidemiological study conducted by clinical interviewers through semi-structured interviews appears to re-dimension the impact of SP, at least from the public health perspective. Future prospective studies will better clarify the role of SP in the context of anxiety disorders

The Burden of Comorbidity Between Bipolar Spectrum and Obsessive-Compulsive Disorder in an Italian Community Survey

© 2020 Carta, Fineberg, Moro, Preti, Romano, Balestrieri, Caraci, Dell’Osso, Disciascio, Drago, Hardoy, Roncone, Minerba, Faravelli and Angst. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY: https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background: The impact of the comorbidity between Obsessive-Compulsive Disorder (OCD) and Bipolar Disorder Spectrum (BDS) remains to be clarified. The objective of this study was to examine the lifetime prevalence of OCD, the strength of the association of OCD with comorbid BDS and the role of comorbidity of OCD with BDS in the impairment of health-related quality of life (HRQoL) in an Italian community survey. Methods: The study is a community survey. The sample (N = 2,267; women: 55.3%) was randomly selected after stratification by sex and four age groups from the municipal records of the adult population of one urban, one suburban, and at least one rural area in six Italian regions. Physicians using a semi-structured interview (Advanced Tools and Neuropsychiatric Assessment Schedule, ANTAS-SCID) made Diagnostic and Statistical Manual of Mental Disorders – 4th revision (DSM-IV) diagnoses of OCD, Major Depressive Disorder (MDD) and Bipolar Disorder (BD). HR-QoL was measured by the Health Survey Short Form (SF-12). Lifetime Hypomania and subthreshold hypomania were screened by the Mood Disorder Questionnaire (MDQ). BDS was defined as the sum of people shown to be positive for hypomania by the MDQ—with or without a mood disorder diagnosis—plus people with a BD-DSMIV diagnosis even if negative for hypomania at the MDQ. Results: Overall, 44 subjects were diagnosed with OCD, 6 with MDD and 1 with BD. The lifetime prevalence of OCD was 1.8% in men (n = 18) and 2.0% in women (n = 26). MDD with lifetime subthreshold hypomania (i.e., people screened positive at the MDQ, even without diagnosed mania or hypomania at the interview) was associated with OCD (OR = 18.15, CI 95% 2.45–103.67); MDD without subthreshold hypomania (and screened negative at the MDQ) was not (OR = 2.33, CI 95% 0.69–7.01). People with BDS were strongly associated with OCD (OR = 10.5, CI 95% 4.90–12.16,). People with OCD and BDS showed significantly poorer HR-QoL than people with OCD without BDS (F = 9.492; P < 0.003). Discussion: The study found a strong association between BDS and OCD. BDS comorbid with OCD was associated with more severe impairment of HR-QoL than OCD without comorbid BDS. Identification of symptoms of hypomania, including subthreshold symptoms, may therefore be important in people with OCD as they might predict a course with poorer HR-QoL.Peer reviewedFinal Published versio

Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms

The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may vary. The observation that precursors of amyloid fibrils derived from circulating globular plasma proteins led to huge efforts in trying to elucidate the structural events determining the protein metamorphosis from their globular to fibrillar state. Whereas the process of metamorphosis has inspired poets and writers from Ovid to Kafka, protein metamorphism is a more recent concept. It is an ideal metaphor in biochemistry for studying the protein folding paradigm and investigating determinants of folding dynamics. Although we have learned how to transform both normal and pathogenic globular proteins into fibrillar polymers in vitro, the events occurring in vivo, are far more complex and yet to be explained. A major gap still exists between in vivo and in vitro models of fibrillogenesis as the biological complexity of the disease in living organisms cannot be reproduced at the same extent in the test tube. Reviewing the major scientific attempts to monitor the amyloidogenic metamorphosis of globular proteins in systems of increasing complexity, from cell culture to human tissues, may help to bridge the gap between the experimental models and the actual pathological events in patients

FXS-Like Phenotype in Two Unrelated Patients Carrying a Methylated Premutation of the FMR1 Gene

Fragile X syndrome (FXS) is mostly caused by two distinct events that occur in the FMR1 gene (Xq27.3): an expansion above 200 repeats of a CGG triplet located in the 5′UTR of the gene, and methylation of the cytosines located in the CpG islands upstream of the CGG repeats. Here, we describe two unrelated families with one FXS child and another sibling presenting mild intellectual disability and behavioral features evocative of FXS. Genetic characterization of the undiagnosed sibling revealed mosaicism in both the CGG expansion size and the methylation levels in the different tissues analyzed. This report shows that in the same family, two siblings carrying different CGG repeats, one in the full-mutation range and the other in the premutation range, present methylation mosaicism and consequent decreased FMRP production leading to FXS and FXS-like features, respectively. Decreased FMRP levels, more than the number of repeats seem to correlate with the severity of FXS clinical phenotypes

The Use of Antidepressant Drugs and the Lifetime Prevalence of Major Depressive Disorders in Italy

BACKGROUND: The increased use of antidepressant drugs (ADs) improved the response to the needs of care although some community surveys have shown that subjects without lifetime psychiatric diagnosis (anxiety/depression) used ADs. OBJECTIVES: To evaluate the appropriateness and amount of prescription of psychotropic drugs in people with lifetime diagnosis of Major Depressive Disorder (MDD) by means of community survey with a semi-structured interview as a diagnostic instrument, administered by clinicians. METHODS: STUDY DESIGN: community survey. STUDY POPULATION: samples randomly drawn, after stratification from the adult population of municipal records. Sample size: 4.999 people were drawn in 7 centres of 6 Italian regions. TOOLS: questionnaire on psychotropic drug consumption, prescription, health services utilization; Structured Clinical Interview for DSM-IV modified (ANTAS); Training: interviewers were trained psychologists or medical doctors. RESULTS: 3.398 subjects were interviewed (68% of the recruited sample). The lifetime prevalence of DSM-IV MDD was 4.3% in males and 11.5% in females; antidepressant drugs were taken by 4.7% of subjects, 2.9% male and 5.9% female. 38% of males and 57% of females with lifetime diagnosis of MDD were taking ADs. CONCLUSIONS: Compared with studies using lay interviewers and structured tools the prevalence of the MDD was quite lower; ADs use was higher and tallied well with the data regarding antidepressant sales in Italy; the correspondence between lifetime diagnosis of MDD and ADs use was closer