Dataset Information

Pharmacogenomic Characterization in Bipolar Spectrum Disorders.

ABSTRACT: The holistic approach of personalized medicine, merging clinical and molecular characteristics to tailor the diagnostic and therapeutic path to each individual, is steadily spreading in clinical practice. Psychiatric disorders represent one of the most difficult diagnostic challenges, given their frequent mixed nature and intrinsic variability, as in bipolar disorders and depression. Patients misdiagnosed as depressed are often initially prescribed serotonergic antidepressants, a treatment that can exacerbate a previously unrecognized bipolar condition. Thanks to the use of the patient's genomic profile, it is possible to recognize such risk and at the same time characterize specific genetic assets specifically associated with bipolar spectrum disorder, as well as with the individual response to the various therapeutic options. This provides the basis for molecular diagnosis and the definition of pharmacogenomic profiles, thus guiding therapeutic choices and allowing a safer and more effective use of psychotropic drugs. Here, we report the pharmacogenomics state of the art in bipolar disorders and suggest an algorithm for therapeutic regimen choice.

SUBMITTER: Fortinguerra S

PROVIDER: S-EPMC7022469 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacogenomic Characterization in Bipolar Spectrum Disorders.

Fortinguerra Stefano S Sorrenti Vincenzo V Giusti Pietro P Zusso Morena M Buriani Alessandro A

Pharmaceutics 20191221 1

The holistic approach of personalized medicine, merging clinical and molecular characteristics to tailor the diagnostic and therapeutic path to each individual, is steadily spreading in clinical practice. Psychiatric disorders represent one of the most difficult diagnostic challenges, given their frequent mixed nature and intrinsic variability, as in bipolar disorders and depression. Patients misdiagnosed as depressed are often initially prescribed serotonergic antidepressants, a treatment that ...[more]

PMID: 31877761

Similar Datasets

Project description:The authors sought to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorders in youths at familial risk of bipolar disorder ("at-risk" youths).Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolar parents had a bipolar spectrum disorder. Over 8 years, 14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder). Measures collected at baseline and follow-up were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors of new-onset bipolar spectrum disorders.Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum disorders were baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<0.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed a bipolar spectrum disorder, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrum disorder in part through increased manic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was also significantly associated with an increased risk of conversion. While youths without anxiety/depression, affective lability, and mania (and with a parent with older age at mood disorder onset) had a 2% predicted chance of conversion to a bipolar spectrum disorder, those with all risk factors had a 49% predicted chance of conversion.Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum disorders in at-risk youths. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.

Project description:BackgroundCurrent operational diagnostic systems have substantial limitations for lifetime diagnostic classification of bipolar spectrum disorders. Issues include: (1) It is difficult to operationalize the integration of diverse episodes of psychopathology, (2) Hierarchies lead to loss of information, (3) Boundaries between diagnostic categories are often arbitrary, (4) Boundaries between categories usually require a major element of subjective interpretation, (5) Available diagnostic categories are relatively unhelpful in distinguishing severity, (6) "Not Otherwise Specified (NOS)" categories are highly heterogeneous, (7) Subclinical cases are not accommodated usefully within the current diagnostic categories. This latter limitation is particularly pertinent in the context of the increasing evidence for the existence of a broader bipolar spectrum than has been acknowledged within existing classifications.MethodWe have developed a numerical rating system, the Bipolar Affective Disorder Dimension Scale, BADDS, that can be used as an adjunct to conventional best-estimate lifetime diagnostic procedures. The scale definitions were informed by (a) the current concepts of mood syndrome recognized within DSMIV and ICD10, (b) the literature regarding severity of episodes, and (c) our own clinical experience. We undertook an iterative process in which we initially agreed scale definitions, piloted their use on sets of cases and made modifications to improve utility and reliability.ResultsBADDS has four dimensions, each rated as an integer on a 0 - 100 scale, that measure four key domains of lifetime psychopathology: Mania (M), Depression (D), Psychosis (P) and Incongruence (I). In our experience it is easy to learn, straightforward to use, has excellent inter-rater reliability and retains the key information required to make diagnoses according to DSMIV and ICD10.ConclusionsUse of BADDS as an adjunct to conventional categorical diagnosis provides a richer description of lifetime psychopathology that (a) can accommodate sub-clinical features, (b) discriminate between illness severity amongst individuals within a single conventional diagnostic category, and (c) demonstrate the similarity between the illness experience of individuals who have been classified into different disease categories but whose illnesses both fall near the boundaries between the two categories. BADDS may be useful for researchers and clinicians who are interested in description and classification of lifetime psychopathology of individuals with disorders lying on the bipolar spectrum.

Project description:Objectives: Bipolar disorder (BD) is a debilitating illness that often starts at an early age. Prevention of first and subsequent mood episodes, which are usually preceded by a period characterized by subthreshold symptoms is important. We compared demographic and clinical characteristics including severity and duration of subsyndromal symptoms across adolescents with three different bipolar-spectrum disorders. Methods: Syndromal and subsyndromal psychopathology were assessed in adolescent inpatients (age = 12-18 years) with a clinical mood disorder diagnosis. Assessments included the validated Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P). We compared phenomenology across patients with a research consensus conference-confirmed DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnoses of BD-I, BD-not otherwise specified (NOS), or mood disorder (MD) NOS. Results: Seventy-six adolescents (age = 15.6 ± 1.4 years, females = 59.2%) were included (BD-I = 24; BD-NOS = 29; MD-NOS = 23) in this study. Median baseline global assessment of functioning scale score was 21 (interquartile range = 17-40; between-group p = 0.31). Comorbidity was frequent, and similar across groups, including disruptive behavior disorders (55.5%, p = 0.27), anxiety disorders (40.8%, p = 0.98), and personality disorder traits (25.0%, p = 0.21). Mania symptoms (most frequent: irritability = 93.4%, p = 0.82) and depressive symptoms (most frequent: depressed mood = 81.6%, p = 0.14) were common in all three BD-spectrum groups. Manic and depressive symptoms were more severe in both BD-I and BD-NOS versus MD-NOS (p < 0.0001). Median duration of subthreshold manic symptoms was shorter in MD-NOS versus BD-NOS (11.7 vs. 20.4 weeks, p = 0.002) and substantial in both groups. The most used psychotropics upon discharge were antipsychotics (65.8%; BD-I = 79.2%; BD-NOS = 62.1%; MD-NOS = 56.5%, p = 0.227), followed by mood stabilizers (43.4%; BD-I = 66.7%; BD-NOS = 31.0%; MD-NOS = 34.8%, p = 0.02) and antidepressants (19.7%; BD-I = 20.8%; BD-NOS = 10.3%; MD-NOS = 30.4%). Conclusions: Youth with BD-I, BD-NOS, and MD-NOS experience considerable symptomatology and are functionally impaired, with few differences observed in psychiatric comorbidity and clinical severity. Moreover, youth with BD-NOS and MD-NOS undergo a period with subthreshold manic symptoms, enabling identification and, possibly, preventive intervention of those at risk for developing BD or other affective episodes requiring hospitalization.

Dataset Information

Pharmacogenomic Characterization in Bipolar Spectrum Disorders.

Publications

Pharmacogenomic Characterization in Bipolar Spectrum Disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets