Will neuroimaging revolutionize the diagnosis of PMDD?

It takes an average of 20 years for women to be accurately diagnosed with PMDD.

Premenstrual Dysphoric Disorder (PMDD) is a severe form of Premenstrual Syndrome, affecting 5 - 8% of all women. It is currently classified in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as a Depressive disorder and is defined as a “cyclical recurrence of distressing or impairing affective symptoms.” It involves a range of physical and mental premenstrual symptoms but is particularly characterized by an abnormal response in the brain towards a normal monthly change in hormone levels post-ovulation, resulting in significant distress and functional impairment.

Despite its impact, it takes an average of 20 years for women to be accurately diagnosed with PMDD. The diagnosis is fraught with unique challenges, which include:

• It is cyclical in nature: PMDD symptoms are tied to the menstrual cycle, typically emerging in the luteal phase and subsiding with menstruation. This pattern presents diagnostic difficulties due to the transient and inconsistent presence of symptoms. Clinicians typically need to observe and record symptoms over multiple menstrual cycles to discern a consistent PMDD pattern, a process that can be extensive and time-consuming.
• It is similar to other mood disorders: PMDD shares many clinical features with other mood disorders like Major Depressive Disorder and Generalized Anxiety Disorder, including mood swings, irritability, and depressive states. This overlap in symptomatology often leads to misdiagnosis or the belief that PMDD symptoms are merely an exacerbation of a pre-existing mood disorder.
• It relies on self-reported symptoms: Diagnosing PMDD heavily depends on the patient's self-reported symptoms. This approach is inherently subjective and prone to inaccuracies. Fluctuations in cognitive and emotional states throughout the menstrual cycle can lead to recall bias and inconsistent symptom documentation, further complicating an accurate diagnosis.

These challenges are made worse by the absence of biomarker-based diagnostic tests for PMDD, such as blood tests or imaging scans. Consequently, women experiencing PMDD symptoms often face misdiagnosis, underdiagnosis, and invalidation.

How is PMDD currently diagnosed?

Because PMDD is listed in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as a separate entity under Depressive disorders, there are tools to diagnose it. Clinicians often use the following self-reported screening test to determine a diagnosis.

Criterion A - At least 5 of the following 11 symptoms (including at least 1 of the first 4 listed) should be present:

• Markedly depressed mood, feelings of hopelessness, or self-deprecating thoughts
• Marked anxiety, tension, feelings of being “keyed up” or “on edge”
• Marked affective lability
• Persistent and marked anger or irritability or increased interpersonal conflicts
• Decreased interest in usual activities (eg, work, school, friends, and hobbies)
• Subjective sense of difficulty in concentrating
• Lethargy, easy fatigability, or marked lack of energy
• Marked change in appetite, overeating, or specific food cravings
• Hypersomnia or insomnia
• A subjective sense of being overwhelmed or out of control
• Other physical symptoms, such as breast tenderness or swelling, headaches, joint or muscle pain, a sensation of bloating, or weight gain.

Criterion B - symptoms severe enough to interfere significantly with social, occupational, sexual, or scholastic functioning.

Criterion C - symptoms discretely related to the menstrual cycle and must not merely represent an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, dysthymic disorder, or a personality disorder (although the symptoms may be superimposed on those of these disorders).

Criterion D - criteria A, B, and C are confirmed by prospective daily ratings during at least 2 consecutive symptomatic menstrual cycles. The diagnosis may be made provisionally before this confirmation.

The promise of neuroimaging

Neuroimaging represents a cutting-edge frontier in medical diagnostics, offering a window into the complex workings of the brain. This technology, which encompasses various techniques like functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) scans, has the potential to revolutionize the diagnosis of mental health conditions. In essence, neuroimaging allows for the non-invasive visualization of brain activity and structural changes, providing vital insights into the underlying neural variations of mood disorders.

Functional MRI, for instance, measures brain activity by detecting changes associated with blood flow, offering insights into which areas of the brain are more active during certain tasks or states. PET scans, on the other hand, utilize a small amount of radioactive material to reveal functional processes in the brain, such as glucose metabolism, indicating areas of increased neuronal activity. Through these sophisticated techniques, neuroimaging could potentially identify unique biomarkers specific to PMDD, thereby providing an objective and reliable basis for its diagnosis. This is particularly crucial given the subjective nature of PMDD symptom reporting and the absence of current biomarker-based diagnostic tests.

The application of neuroimaging in the realm of depression diagnosis is a testament to its potential in understanding and diagnosing mood disorders. In depression, neuroimaging has been instrumental in uncovering specific brain changes, particularly in regions like the prefrontal cortex and the amygdala. The prefrontal cortex, responsible for complex behavioural and emotional processes, often shows altered activity in individuals with depression, reflecting the disorder's impact on mood regulation and decision-making. Similarly, changes in the amygdala, a region central to emotional processing, have been linked to the heightened emotional responses characteristic of depression.

These neuroimaging findings have not only deepened the scientific community's understanding of the pathophysiology of depression but have also opened new avenues for targeted treatments. By identifying the specific neural circuits and regions implicated in depression, researchers and clinicians can develop more precise therapeutic interventions, moving towards personalized medicine approaches in mental health care.

The future of PMDD diagnosis

In a groundbreaking study that was published in October 2023, neuroscientists Elizabeth Rizor and Viktoriya Babenko of the University of California Santa Barbara showed structural, brain-wide changes during menstruation. This study is not the first of its kind to explore the effects of the menstrual cycle and hormonal fluctuations on brain structure and activity.

A study by Li et al. (2021), demonstrated that hormonal fluctuations are more than mere statistical observations; they significantly impact brain function, and consequently, mood and cognition. Specifically, the prefrontal cortex - a critical region for emotional regulation and cognitive processing - shows reduced responsiveness to emotional stimuli during this phase. This effect is more pronounced in women with PMDD, closely resembling patterns seen in depression.

Furthermore, the luteal phase is marked by distinct changes in brain wave activity. Research by Baehr et al. (2004) found that alpha waves, which are instrumental in mood regulation, exhibit notable imbalance or asymmetry during this phase.

It is becoming increasingly evident that the brain's response to hormonal changes offers key insights into PMDD. Identifying specific brain activity patterns or structural changes through neuroimaging could provide a crucial objective diagnostic tool for this complex condition.

The potential of neuroimaging in reshaping the diagnostic approach to PMDD is immense. By offering objective and quantifiable insights into brain function, it could significantly shorten the lengthy process of diagnosis for many women, paving the way for timely and effective treatment. As research in this field advances, neuroimaging is poised to become a fundamental tool in both the diagnosis and management of PMDD, providing objective clarity to a condition that has been traditionally mired in subjective assessments.