Pre- and perinatal hypoxia associated with hippocampus/amygdala volume in bipolar disorder

Abstract

BackgroundPre- and perinatal adversities may increase the risk for schizophrenia and bipolar disorder. Hypoxia-related obstetric complications (OCs) are associated with brain anatomical abnormalities in schizophrenia, but their association with brain anatomy variation in bipolar disorder is unknown.MethodMagnetic resonance imaging brain scans, clinical examinations and data from the Medical Birth Registry of Norway were obtained for 219 adults, including 79 patients with a DSM-IV diagnosis of bipolar disorder (age 29.4 years, s.d. = 11.8 years, 39% male) and 140 healthy controls (age 30.8 years, s.d. = 12.0 years, 53% male). Severe hypoxia-related OCs throughout pregnancy/birth and perinatal asphyxia were each studied in relation to a priori selected brain volumes (hippocampus, lateral ventricles and amygdala, obtained with FreeSurfer), using linear regression models covarying for age, sex, medication use and intracranial volume. Multiple comparison adjustment was applied.ResultsPerinatal asphyxia was associated with smaller left amygdala volume (t = −2.59, p = 0.012) in bipolar disorder patients, but not in healthy controls. Patients with psychotic bipolar disorder showed distinct associations between perinatal asphyxia and smaller left amygdala volume (t = −2.69, p = 0.010), whereas patients with non-psychotic bipolar disorder showed smaller right hippocampal volumes related to both perinatal asphyxia (t = −2.60, p = 0.015) and severe OCs (t = −3.25, p = 0.003). No associations between asphyxia or severe OCs and the lateral ventricles were found.ConclusionsPre- and perinatal hypoxia-related OCs are related to brain morphometry in bipolar disorder in adulthood, with specific patterns in patients with psychotic versus non-psychotic illness.

Stereological investigation of the posterior hippocampus in affective disorders

“…These alterations may be generated during a perinatal neurodevelopmental period. During this period, severe obstetric complications and perinatal asphyxia have been reported to be related to smaller hippocampal volumes in patients with non-psychotic BD (Haukvik et al 2014), whereas patients with psychotic features were exposed to maternal serological influenza as a risk factor (Canetta et al 2014). CA1 receives input from CA2/3 and projects to the subiculum, where a higher number of neurons indicates the same pathophysiology as in CA1.…”

In Vivo Hippocampal Subfield Volumes in Schizophrenia and Bipolar Disorder

“…Diagnostic differences in total hippocampal formation volumes were studied using the same model, with the hippocampal formation as the dependent variable. In concordance with previous studies by our group, we performed subgroup analyses on patients within the bipolar spectrum [psychotic vs. nonpsychotic bipolar disorder (41) and bipolar I vs. bipolar II disorder (2)]. …”

Neuropathological and neuromorphometric abnormalities in bipolar disorder: View from the medial prefrontal cortical network

“…Similarly, a linear relationship between birth weight and the risk for BD as well as other psychiatric disorders was found (Abel et al, 2010), and children delivered by cesarean section had a 2.5-fold greater risk for BD in a large population-based register (Chudal et al, 2013). A recent study that reported an association between perinatal hypoxia and reduced left amygdala and right hippocampal volumes in psychotic and non-psychotic BD subjects, respectively, raises the possibility that perinatal complications increase the risk for developing BD by impacting key circuits involved in the regulation of emotion (Haukvik et al, 2013).…”