Postpartum depression (PPD) is a mood disorder that affects women during pregnancy or in the first year after giving birth. Characterized by constant feelings of sadness, anxiety, and fatigue, it severely affects a mother’s ability to care for herself and her newborn. It’s very different from the “baby blues,” which usually resolves within a few weeks of giving birth.
The main causes of PPD are multifaceted. Hormonal changes during pregnancy and after pregnancy play a major role, because the levels of estrogen and progesterone increase significantly during pregnancy and decrease significantly after childbirth. This hormonal rollercoaster eventually affects mood and emotional stability.
Additionally, genetics make some women more susceptible to PPD. Environmental factors such as stress, lack of sleep, and the physical demands of caring for a newborn can contribute to the development of this condition. These elements create the perfect storm that leads to PPD.
When these factors come together, they disrupt the normal functioning of the brain. Hormonal imbalances affect the neurotransmitter systems responsible for controlling mood and emotions. Now, researchers are trying to understand how the human brain changes and adapts during this period in order to help new mothers manage their situation better.
Brain structure of women with postmenopausal depression
Research published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging aims to identify neurobiological differences between women with and without PPD. The authors focused specifically on the basal ganglia, a group in the brain associated with emotion, reward, and decision-making processes, as well as the effects of polygenic risk factors (PRS) of estradiol on brain morphology.1
The study involved 64 mothers diagnosed with major depressive disorder (MDD) – 30 with a history of PPD and 34 without – among a larger group of 219 patients in Milan. To compare brain structure between the two groups, the team used voxel-based morphometric analysis to study the volume of gray matter in specific regions of the basal ganglia.
The group with a history of PPD was found to have significantly larger gray matter volumes in bilateral clusters involving the putamen, pallidum, caudate, and thalamus. This structural difference indicates that the basal ganglia are affected in PPD. It has been shown to play an important role in pathophysiology and to have a large number of estrogen receptors for hormonal changes.2
Additionally, the study found that estradiol PRSs interacted differently with brain volumes based on PPD history.3 Specifically, higher estradiol PRSs were associated with increased gray matter volume in basal ganglia clusters in women with PPD. In contrast, women without PPD showed a negative correlation between estradiol PRS and gray matter volumes in these regions.4
Effects of estradiol on brain function
The study explored how estradiol levels affect basal ganglia structure and function. For context, estradiol affects gene expression, dendritic spine density, and neurotransmitter function in these brain regions.5 These pathways may contribute to the observed structural differences, suggesting that hormonal changes during the peripartum period trigger or exacerbate stress symptoms in susceptible women.
Moreover, the involvement of the basal ganglia in emotion regulation and decision-making provides a functional context for the observed structural differences. Altered basal ganglia structure and function have been linked to MDD in previously published studies, suggesting that these regions play a role in the development of depression.6
Overall, the study sheds new light on how hormonal and genetic factors interact to influence brain structure and function in the context of PPD. The identification of large gray matter masses in certain regions of the basal ganglia among women with PPD indicates the importance of considering both hormonal sensitivity and genetic predisposition in the diagnosis and treatment of this condition.7
Additional neurobiological changes occur during the peripartum period
In a meta-analysis published in Social Cognitive and Affective Neuroscience, researchers explored the significant changes that occur in women’s brains during pregnancy and after childbirth. In particular, they focused on understanding how hormonal changes, immune system adjustments, sleep disturbances and increased stress levels affect women’s mental health and brain structure.8
After comparing pregnant and postpartum women with non-pregnant women, the findings show that more than a quarter of women experience symptoms of depression during this period. Also, symptoms are associated with significant changes in brain structure and function. These include hormonal and immune system changes, as well as sleep deprivation and increased caregiving responsibilities after childbirth.9
Researchers have found that during the peripartum period (the period just before and after childbirth)10), women undergo significant structural changes in their brains. In particular, gray matter volume decreased, particularly in the hippocampus, a region critical to memory and learning.
Additionally, the amygdala, which is involved in processing emotions, is altered. These changes are not only temporary, but also extend immediately after childbirth.11
Hormonal changes play an important role in these brain changes. The drop in estrogen and progesterone levels after childbirth causes many chemical reactions in the brain, leading to mood swings and increased susceptibility to depression. These hormones are very important to maintain pregnancy, and their rapid decline affects different brain regions responsible for emotional control and cognitive functions.12
During pregnancy, the immune system is highly regulated to protect the mother and fetus. This balance affects the brain by changing the function of immune cells that influence neurodevelopmental processes. Disruption of immune function contributes to structural changes in the brain and increases the risk of depression symptoms.13
Lack of sleep is another major factor contributing to neurobiological changes. Many new mothers experience poor sleep quality or insufficient sleep duration, which affects the amygdala, causing it to become more alert and emotional. This heightened response leads to heightened emotional intensity and volatility, which further exacerbates symptoms of depression and anxiety.14
Psychosocial stress resulting from the challenges of caregiving and adapting to motherhood also affects brain structure. Chronic stress causes changes in brain regions involved in reward processing and decision making, such as the striatum and prefrontal cortex. These changes disrupt cognitive functions such as memory and information processing, making it difficult for new mothers to cope with daily responsibilities.15
Brain structural abnormalities have been found in postpartum depression
In another study published in Behavioral Brain Research, a group examined the differences in brain structure between women who experience PPD and those who do not. The study focused on examining both cortical and subcortical brain regions, involving 29 women with PPD and 23 healthy postpartum women as a control group. All participants were right-handed between the ages of 20 and 40 and one to two months postpartum.16
According to the study, women with PPD showed increased thickness in several specific brain regions. Specifically, there was a significant increase in the cortical thickness of the left superior frontal gyrus, cuneus, right lingual gyrus, and facetiform gyrus compared to a group of healthy postpartum women.17 Additionally, these women showed regional inflation in the right pallidum, a subcortical structure involved in emotion regulation and reward processing.
Going deeper into the findings, the study showed that depression was significantly higher in the PPD group than in the healthy group, indicating more severe depressive symptoms.18 Interestingly, there was no significant difference in the local gyrification index—another tool for measuring cortical morphology—between the two groups, suggesting that some aspects of brain curvature were not affected by PPD.19
The increased cortical thickness in the affected regions indicates significant changes in areas responsible for cognitive control, emotional control, and visual processing. For example, the left superior frontal gyrus is key to executive functions, including decision making and emotion regulation.
Meanwhile, the cuneus and facetiform gyrus are critical for processing visual information and recognizing facial emotion, which is important for social interactions and bonding with the infant.20
Moreover, the study indicated that regional inflation in the right pallidum is related to the limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuit. This circuit plays an important role in regulating emotions and processing rewards. A problem in the pallidum leads to symptoms such as lack of motivation, inability to feel happy and constant negative thoughts – all of which are common in PPD.
Importantly, pallidum enlargement in women with PPD is associated with difficulties in responding to infant stimuli, which in turn affects maternal behavior.21
Four ways to help mothers manage postpartum stress
Dramatic hormonal changes, as well as stress during pregnancy and after childbirth, inevitably cause significant changes in the structure and function of the mother’s brain. Understanding and preparing for these changes can help support their mental health during this critical time. To manage the symptoms, here are practical strategies I recommend.
1. Prioritize sleep and recovery – Lack of sleep has a significant impact on brain regions involved in emotional regulation and general cognitive functions. Make sleep a priority by coordinating with family members to get seven to eight hours of rest while you help care for the baby. Read on for tips on how to improve your sleep quality.”How sleep deprivation affects cognitive performance and learning.”
2. Engage in regular, moderate-intensity exercise Once you can, I encourage you to go for a regular walk outside. When you start moving again, your body will suffer from depression, sarcopenia and overall death in a dose-dependent manner. Exercising with a friend or group is best because it adds an element of social support compared to exercising alone.
3. Support your diet with brain-boosting foods – Reduce your intake of stimulants, such as refined sugars and vegetable oils, which affect brain function. Focus on foods rich in the B vitamin family, as this group of nutrients is critical for mental health and emotional regulation.
4. Improving hormonal balance Focus on supporting progesterone production to counter the rapid fall in hormones after childbirth. Getting enough sun exposure supports the production of vitamin D, which works synergistically with progesterone for brain function. For proper administration of progesterone, read my detailed instructions below.
