Borderline personality disorder (BPD) is a complex mental health condition characterized by difficulties with emotion regulation, impulsivity, and instability in relationships and self-image. BPD can significantly impact a person’s quality of life and lead to strained personal relationships, emotional distress, and impulsive behaviors. While the causes of BPD are not fully understood, research suggests that both genetic and environmental factors play a role. In particular, abnormalities in certain brain regions and neurotransmitter systems seem to underlie many of the symptoms of BPD. Understanding what happens in the brain may lead to more targeted and effective treatments for this challenging disorder.
Brain Regions Implicated in BPD
Prefrontal Cortex
The prefrontal cortex, located in the front part of the brain, is responsible for complex cognitive functions like planning, decision-making, impulse control, and emotional regulation. Imaging studies show that individuals with BPD tend to have reduced gray matter volume and activity in the prefrontal cortex compared to healthy controls. This deficit may contribute to the impulsivity, emotional dysregulation, and unstable sense of self seen in BPD.
Amygdala
The amygdala is an almond-shaped structure deep in the brain that is critical for processing emotions, fear responses, and emotional memories. In people with BPD, the amygdala tends to be hyperactive and overly reactive to even minor emotional triggers. This may lead to more intense emotional reactions and greater likelihood of perceiving neutral stimuli as threats. The amygdala has extensive connections with the prefrontal cortex, so abnormalities in both regions may lead to problems regulating emotions.
Hippocampus
The hippocampus is located in the temporal lobe and is involved in memory formation and integration of emotional memories. Individuals with BPD often have a smaller hippocampus, which could impact explicit memory and influence emotional dysregulation. The hippocampus likely interacts extensively with the amygdala as part of the limbic system.
Anterior cingulate cortex
The anterior cingulate cortex (ACC) detects errors, monitors conflicts, and regulates emotional responses. Imaging studies show the ACC is often less active in people with BPD compared to healthy individuals. This underactivity may relate to some clinical features of BPD like impulsivity, emotional instability, and self-harm behaviors.
Neurotransmitter Systems
In addition to abnormalities in specific brain regions, alterations in certain neurotransmitters are also believed to play a role in BPD. Neurotransmitters are chemical messengers that allow communication between nerve cells. The main neurotransmitter systems potentially involved in BPD include:
Serotonin
Serotonin regulates mood, impulse control, aggression, and sleep. Many studies indicate that abnormal serotonin function, particularly excessive reactivity of serotonin receptors, contributes to symptoms of impulsivity and emotional dysregulation in BPD. Certain medications used to treat BPD like SSRIs target the serotonin system.
Dopamine
Dopamine is critical for reward, motivation, attention, and body movement. Some research has found that dopamine activity may be naturally lower in those with BPD. This could relate to feelings of emptiness, anxiety, depression, and self-harm tendencies seen in BPD.
Oxytocin
Oxytocin is sometimes called the “love hormone” and is involved in social bonding, intimacy, and trust. Individuals with BPD often have difficulty establishing stable relationships. Lower oxytocin levels may play a role in challenges with trust and sociability. However, more research is needed in this area.
Glutamate
Glutamate is the most abundant excitatory neurotransmitter in the brain and is involved in cognitive functions, learning, and memory. Subtle alterations in the glutamate system may relate to emotional and behavioral dysregulation in BPD. Glutamate seems to interact closely with the serotonin and dopamine systems as well.
Brain Network Connectivity
In addition to looking at specific brain regions, researchers are also examining how different networks in the brain connect and communicate with each other, also called functional connectivity. Several brain networks seem to function abnormally in BPD.
Default mode network (DMN)
The DMN involves medial prefrontal areas and is active during internal thoughts and reflections about oneself or others. Those with BPD tend to have weaker connections within the DMN. This could impact sense of self and contribute to unstable identity.
Salience network
This network detects emotional and sensory stimuli and shifts attention toward the most salient internal and external cues. Individuals with BPD often exhibit hyperactivity in the salience network, which may explain sensitivity to emotions.
Central executive network (CEN)
The CEN includes dorsolateral prefrontal regions and helps regulate attention, thoughts, and actions. Studies reveal impaired communication between the CEN and emotional processing regions like the amygdala in people with BPD. This miscommunication may underpin poor impulse control.
Overall, abnormalities within specific brain networks and between different networks are likely involved in many BPD symptoms. Future research on brain connectivity could uncover new treatment targets.
Neuroendocrine Factors
In addition to changes in neurotransmitters and neural networks, there is some evidence that hormones and the hypothalamic-pituitary-adrenal (HPA) axis may be dysregulated in BPD.
HPA axis
The HPA axis controls reactions to stress and involves the hypothalamus, pituitary gland, and adrenal glands. Those with BPD tend to have enhanced HPA axis activity, which may relate to hypersensitivity to stress.
Oxytocin
As mentioned previously, the hormone oxytocin may be abnormally low in people with BPD. This could contribute to interpersonal problems and challenges establishing intimacy or trust.
Estrogen
Females with BPD tend to have unusually high levels of estrogen. Fluctuating estrogen could potentially impact serotonin and oxytocin function and may relate to menstrual cycle influences on BPD symptoms in some women. However, more research is needed.
Structural Brain Changes
In addition to differences in activation patterns, connectivity, and neurochemistry, several structural brain changes have been observed in BPD compared to healthy controls:
– Reduced gray matter volume in prefrontal cortex, temporal lobe, and hippocampus
– Smaller amygdala and hippocampal size
– Ventricular enlargement
– Reduced white matter integrity
– Thinning of the cerebral cortex
It is unclear whether these structural changes predispose to BPD or if they are a consequence of living with the disorder. Both genetic and environmental factors likely contribute to brain differences.
Genetic and Environmental Influences
BPD is around five times more common in first-degree biological relatives of those with the disorder, indicating a strong genetic component. Specific genes involved in serotonin, dopamine, and oxytocin function have been implicated. However, no single “BPD gene” has been discovered, suggesting complex polygenic influences.
Environmental factors like childhood trauma and abuse also clearly play a role. Childhood adversity may epigenetically alter expression of genes involved in HPA axis, neurotransmitter, and brain development. It remains unclear exactly how genetic, epigenetic, and environmental influences interact and lead to brain changes in BPD. This is an active area of research.
Neurodevelopmental Factors
In addition to genetics and childhood experiences, initial abnormal brain development may contribute to BPD in some cases. Preterm birth, prenatal trauma, and complications during birth resulting in oxygen deprivation have been linked to increased BPD risk. These early developmental issues could impact structural and functional brain connectivity. Some theorists conceptualize BPD as a subtle neurodevelopmental disorder.
Sex Differences
BPD is diagnosed around three times more often in females compared to males. This has prompted questions around whether male and female brains differ in how BPD manifests. However, clear sex differences have not been established. While estrogen may play a role in women, testosterone does not seem to influence BPD in men. The underlying neurobiology is likely quite similar in both sexes. Social and diagnostic factors probably account for most of the gender difference in diagnosis rates.
Neuroprogression
Some research indicates that structural and functional brain changes in BPD may worsen over time, a process sometimes called “neuroprogression”. While not conclusive, longitudinal studies show GM volume reductions and CSF increases occur over time in BPD, potentially reflecting ongoing neural degeneration. However, with therapy, it may be possible to halt or reverse negative neuroprogressive changes.
Brain Changes with Treatment
Interestingly, certain brain changes observed in BPD seem to normalize with effective psychotherapy and medication treatment. For example, increases in prefrontal and temporal lobe gray matter and strengthened connectivity in limbic brain networks can occur alongside clinical improvement. Brain plasticity likely underlies these therapy-induced neural changes. Identifying specific neurobiological treatment targets could optimize outcomes.
| Brain Region | Abnormality in BPD |
|---|---|
| Prefrontal cortex | Reduced gray matter volume and activity |
| Amygdala | Hyperactive and overreactive |
| Hippocampus | Smaller in size |
| Anterior cingulate cortex | Underactive |
Conclusion
In summary, BPD is characterized by abnormalities in brain structure and function that likely arise from a combination of genetic vulnerabilities and environmental exposures, especially childhood adversity. Key brain regions implicated include the prefrontal cortex, amygdala, hippocampus, and anterior cingulate cortex. Dysregulation in serotonin, dopamine, oxytocin, and the HPA axis also play a role. Looking at connections between brain networks reveals further alterations underlying BPD symptoms. Ongoing research on the neurobiology of BPD may uncover new treatment targets and improve diagnosis and prevention. While current treatments can help normalize some neural changes, greater understanding of what happens in the brain in this disorder is needed.
