Search

Background Males have a lower prevalence of depression than females and testosterone may be a contributing factor. A comparison of opposite-sex and same-sex twins can be used indirectly to establish the role of prenatal testosterone exposure and the risk of depression. We therefore aimed to explore differences in depression risk using opposite-sex and same-sex twins. Methods We included 126 087 opposite-sex and same-sex twins from the Danish Twin Registry followed in nationwide Danish registers. We compared sex-specific incidences of depression diagnosis and prescriptions of antidepressants between opposite-sex and same-sex twins using Cox proportional hazard regression. Results During follow-up, 2664 (2.1%) twins were diagnosed with depression and 19 514 (15.5%) twins had purchased at least one prescription of antidepressants. First, in male twins, we found that the opposite-sex male twins had the same risk of depression compared to the same-sex male twins {hazard ratio (HR) = 1.01 [95% confidence interval (CI) 0.88-1.17)]}. Revealing the risk of use of antidepressants, the opposite-sex male twins had a slightly higher risk of 4% (HR = 1.04 (95% CI 1.00-1.11)) compared with the same-sex male twins. Second, in the female opposite-sex twins, we revealed a slightly higher, however, not statistically significant risk of depression (HR = 1.08 (95% CI 0.97-1.29)) or purchase of antidepressants (HR = 1.01 (95% CI 0.96-1.05)) when compared to the same-sex female twins. Conclusions We found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life.

Background: Bipolar disorder (BD), and especially the mania phenotype, is characterized by heightened reward responsivity and aberrant reward processing. In this longitudinal fMRI study, we investigated neuronal response during reward anticipation as the computed expected value (EV) and outcome evaluation as reward prediction error (RPE) in recently diagnosed patients with BD. Methods: Eighty remitted patients with BD and 60 healthy controls (HC) underwent fMRI during which they performed a card guessing task. Of these, 41 patients and 36 HC were re-scanned after 16 months. We compared reward-related neural activity between groups at baseline and longitudinally and assessed the impact of mood relapse. Results: Patients showed lower RPE signal in areas of the ventrolateral prefrontal cortex (vlPFC) than HC. In these regions, the HC showed decrease in RPE signal over time, which was absent in patients. Patients further exhibited decreased EV signal in the occipital cortex across baseline and follow-up. Patients who remained in remission showed normalization of the EV signal at follow-up. Baseline activity in the identified regions was not associated with subsequent relapse. Limitations: Follow-up scans were only available in a relatively small sample. Medication status, follow-up time and BD illness duration prior to diagnosis varied. Conclusions: Lower RPE signal in the vlPFC in patients with BD at baseline and its lack of normative reduction over time may represent a trait marker of dysfunctional reward-based learning or habituation. The increase in EV signal in the occipital cortex over time in patients who remained in remission may indicate normalization of reward anticipation activity.

Pregnancy and childbirth are among the strongest risk factors for depression but the neurocognitive mechanisms underlying this enhanced risk are unknown. This study investigated emotional and non-emotional cognition in 57 pregnant women with or without an affective disorder during their third trimester, and the association between cognitive biases and subsequent postpartum depression (PPD). Of the pregnant women, 22 had a diagnosis of unipolar disorder (UD) and seven of bipolar disorder (BD) in full or partial remission, while 28 had no history of affective disorder. We included a control group of 29 healthy non-pregnant women. First, participants were interviewed, completed non-emotional and emotional cognitive tests and lastly filled out questionnaires. The participants were assessed two times after birth: at a home visit shortly after birth, and with a telephone interview to assess PPD in the first six months after birth. Healthy pregnant women rated infant cries less negatively than non-pregnant women, possibly reflecting preparation for motherhood. Pregnant women with UD exhibited a negative bias in ratings of infant cries, whereas pregnant women with BD showed a positive bias in ratings of infant happy faces and recognition of adult facial expressions. Across all pregnant women, more negative ratings of infant cries were associated with enhanced risk of PPD. Negatively biased perception of infant cries during pregnancy may thus signal vulnerability toward PPD.