Bipolar disorder (BD) is a mood disorder characterized by shifts in energy, mood, and activity levels, cycling between periods of mania or hypomania and depression. While the symptoms are defined by mood and behavior, the root cause of these shifts is deeply physiological, involving measurable differences in brain structure, function, and chemistry. Understanding what a bipolar brain looks like requires examining the underlying biological landscape, which reveals specific changes in neural anatomy and communication pathways that contribute to the disorder’s erratic nature.
Changes in Physical Structure
The brains of individuals with bipolar disorder often exhibit anatomical differences when examined using neuroimaging techniques like Magnetic Resonance Imaging. One of the most consistent findings is a reduction in gray matter volume (GMV) and thickness in specific cortical regions. This gray matter is composed primarily of neuronal cell bodies and is crucial for processing information, making decisions, and regulating emotions.
Volume reduction is frequently observed in the prefrontal cortex (PFC), particularly in areas like the subgenual PFC, which is heavily implicated in emotional regulation and complex executive functions. A smaller PFC volume may reflect impaired neuronal health or connectivity, which can diminish the brain’s capacity for cognitive control over intense emotional states. Furthermore, studies have documented decreased gray matter volume in the hippocampus, a structure central to memory and stress response. The amygdala, a subcortical region that processes fear and emotional salience, shows mixed findings, indicating structural irregularity in this emotional accelerator of the brain.
Altered Functional Connectivity
Beyond static structure, the functional communication between different brain regions is altered in bipolar disorder. This involves a breakdown in the cooperative signaling of neural networks responsible for integrating emotional and cognitive processes. A key finding is the dysregulation of the fronto-limbic circuit, where control centers in the frontal lobe fail to adequately modulate emotional centers deep within the limbic system.
The prefrontal cortex acts like a cognitive “brake,” attempting to dampen the intense activity of the amygdala and other limbic structures that act as the emotional “accelerator”. In BD, this top-down control is often diminished, leading to hyperactive emotional responses and mood instability. Disruptions are also seen in the default mode network (DMN) and the salience network (SN). A decreased negative correlation, or anti-correlation, between the DMN and SN suggests an impaired ability to switch efficiently between internally focused thought and external task focus. This functional dysconnectivity may contribute to the cognitive challenges and attention difficulties experienced during both manic and depressive phases.
The Role of Chemical Signaling
The functional and structural alterations are closely linked to an imbalance in the brain’s internal chemical messengers, known as neurotransmitters. Dopamine, associated with reward and motivation, is particularly implicated, with elevated activity hypothesized to drive the heightened energy, impulsivity, and euphoria seen during manic episodes. Conversely, reduced dopamine function contributes to the apathy, low motivation, and persistent sadness characteristic of the depressive phase. Serotonin, a broad regulator of mood, sleep, and appetite, is also often dysregulated, with low levels being a common feature of depressive symptoms.
The balance between excitation and inhibition is compromised through the amino acid neurotransmitters glutamate and gamma-aminobutyric acid (GABA). Glutamate, the brain’s main excitatory signal, may be overactive in areas like the prefrontal cortex during mania, leading to racing thoughts and emotional highs. Meanwhile, GABA, the primary inhibitory signal, shows reduced function in some patients, which can result in a loss of inhibitory control and contribute to manic symptoms.
Applying Biological Understanding to Treatment
Understanding the bipolar brain’s biology provides the rationale for pharmacological treatments, which aim to restore chemical and cellular stability. Mood stabilizers like lithium work at a fundamental level by modulating the abnormal intracellular signaling pathways identified in the disorder. Lithium, for example, is known to inhibit enzymes like Glycogen Synthase Kinase-3 beta (GSK-3 beta), which is involved in regulating cell survival and neuroplasticity.
By inhibiting GSK-3 beta, lithium promotes neuroprotection and enhances the brain’s ability to form new connections, potentially counteracting the gray matter volume reductions observed in the PFC and hippocampus. Furthermore, these medications directly influence the imbalanced neurotransmitter systems, such as by decreasing the excessive excitatory glutamatergic signaling and enhancing the inhibitory effects of GABA. This dual action helps stabilize the neural networks, allowing for better emotional and cognitive regulation.