Dimensional endophenotypes in bipolar disorder: Affective dysregulation and psychosis proneness

Abstract

Background The clinical phenotype of bipolar disorder (BPD) is heterogeneous and the genetic architecture of the disorder is complex and not well understood. Given these complications, it is possible that the identification of intermediate phenotypes (“endophenotypes”) will be useful in elucidating the complex genetic mechanisms that result in the disorder. The examination of unaffected relatives is critical in determining whether a particular trait is genetically-relevant to BPD. However, few dimensional traits related to BPD have been assessed in unaffected relatives of patients. Methods We assessed affective temperament and schizotypy in 55 discordant sibling pairs and 113 healthy controls (HCs) using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire version (TEMPS-A) to assess affective temperament and the Schizotypal Personality Questionnaire (SPQ) to assess schizotypy. Results BPD patients scored significantly higher than HCs on all subscales of the SPQ and on all but one subscale (hyperthymic) of the TEMPS-A (all p <0.01). Siblings demonstrated scores that were significantly intermediate to patients and HCs on the anxious subscale of the TEMPS-A and on the interpersonal deficits and disorganized subscales of the SPQ. Limitations We did not investigate the BPD spectrum as most patients were diagnosed with BPD I (n = 47). Most of the patients had experienced psychosis (n = 42) and so we were unable to examine whether psychosis status impacted upon affective temperament or schizotypy in patients or their siblings. Conclusion These data suggest that schizotypy and affective temperament represent dimensional traits that are likely to underlie the genetic risk for BPD.

Autistic and schizotypal traits and global functioning in bipolar I disorder

“…When adjusting for demographic and lifetime clinical variables (see Table 2) the differences among the groups became non-significant Note, the sample sizes of the adjusted models are smaller due to missing data. had elevated rates of schizotypy compared to healthy controls, as measured by the Schizotypal Personality Questionnaire (Mahon et al, 2013). Participants' unaffected siblings scored intermediately, suggesting that schizotypy is a dimensional trait that contributes to the genetic risk for BD (Mahon et al, 2013).…”

“…had elevated rates of schizotypy compared to healthy controls, as measured by the Schizotypal Personality Questionnaire (Mahon et al, 2013). Participants' unaffected siblings scored intermediately, suggesting that schizotypy is a dimensional trait that contributes to the genetic risk for BD (Mahon et al, 2013). This study's second objective was to examine the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD.…”

“…Indeed, BD has a number of genetic, symptomatological and epidemiological overlaps with SSD (Laursen, Agerbo, & Pedersen, 2009;Lichtenstein et al, 2009;Murray et al, 2004), and psychosis has been recognised as an important dimension in the psychopathology of BD (van Os & Kapur, 2009). In addition, schizotypy, which encompasses a set of personality traits that reflect subclinical expression of schizophrenia (Ettinger et al, 2015), is recognised as genetically related to SSD and is considered an endophenotype common to both SSD and BD (Ettinger, Meyhofer, Steffens, Wagner, & Koutsouleris, 2014;Mahon, Perez-Rodriguez, Gunawardane, & Burdick, 2013;Schurhoff, Laguerre, Szoke, Meary, & Leboyer, 2005). Schizotypy has been reported at elevated rates in individuals with BD compared to healthy controls, although this was conducted in a relatively small BD sample (N=92) (Heron et al, 2003).…”

Comparison of Schizotypal Characteristics of Bipolar Patients and Their Healthy Siblings

“…Bipolar bozukluğu olan bireylerle ilişkili olabilecek diğer bir mizaç özelliği ise tuhaf, irritabl, sosyal olarak izole ve hipersensitif reaksiyonların olduğu şizotipidir (8,9) . BPB hastaları ve yakınlarında sağlıklı kontrollere göre şizotipi oranlarının arttığını gösteren kanıtlar bulunmaktadır (8,10) . BPB hastalarının yaklaşık %50-70'inde duygudurum epizodları sırasında psikotik özellikler yaşadığı bildirilmektedir, bu yüzden BPB tanılı bireylerde şizotipi özelliklerinin yüksek olması beklenebilir (8,11) .…”

“…Bir çalışmada şizofreni ve BPB yakınlarının psikoz yatkınlığında farklılık görülme-diği bildirilmiştir (12) . Ancak bu çalışmada psikotik özellikli atağı olan BPB tanılı hastaların yakınlarında psikoz öyküsü olmayanların yakınlarına göre psikoz yatkınlığının arttığı gözlenmiştir (8,12) . Mahon ve ark.…”