What Are Potential Biomarkers and Therapeutic Targets for Obsessive Compulsive Disorder?

What you need to know

• Brain-derived neurotrophic factor (BDNF), dopamine beta-hydroxylase (DBH), and malondialdehyde (MDA) show promise as potential biomarkers for obsessive compulsive disorder (OCD).
• These molecules may also serve as therapeutic targets for developing new OCD treatments.
• More research is needed to confirm their utility as biomarkers and targets, especially in larger clinical studies.

Identifying biomarkers for OCD

Obsessive compulsive disorder (OCD) is a complex psychiatric condition characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). While current treatments like cognitive behavioral therapy and serotonin reuptake inhibitors can help many patients, some do not respond adequately. Identifying reliable biomarkers could improve diagnosis, predict treatment response, and lead to new therapeutic approaches.

This review examines evidence for three promising biomarker candidates in OCD:

1. Brain-derived neurotrophic factor (BDNF)
2. Dopamine beta-hydroxylase (DBH)
3. Malondialdehyde (MDA)

Brain-derived neurotrophic factor (BDNF)

BDNF is a protein that supports the growth and survival of neurons. It plays important roles in learning, memory, and mood regulation. Several studies have found altered BDNF levels in OCD patients compared to healthy controls.

Measuring BDNF

BDNF can be measured in blood serum or plasma samples using techniques like enzyme-linked immunosorbent assay (ELISA). Some key considerations for BDNF measurement include:

• Serum samples are preferred over plasma
• The type of anticoagulant used and sample processing methods can affect results
• BDNF can also be measured in cerebrospinal fluid, though this is more invasive

BDNF findings in OCD

Studies have reported:

• Lower blood BDNF levels in OCD patients compared to controls
• Increased BDNF levels after treatment with OCD medications
• Associations between certain BDNF gene variants and OCD risk or severity

However, results have been mixed across different patient populations. More research is needed to confirm BDNF’s utility as an OCD biomarker.

Dopamine beta-hydroxylase (DBH)

DBH is an enzyme that converts dopamine to norepinephrine. Both of these neurotransmitters are involved in the brain circuits affected in OCD.

Measuring DBH

DBH activity can be measured in cerebrospinal fluid or blood samples. Common methods include:

• Spectrophotometric assays
• High-performance liquid chromatography (HPLC)
• Measuring DBH metabolites like homovanillic acid

However, DBH measurement faces some technical challenges that need to be addressed to improve reliability.

DBH findings in OCD

Preliminary studies have found:

• Elevated serum DBH levels in untreated OCD patients
• Genetic variants of DBH associated with OCD risk

But larger studies are still needed to validate these findings.

Malondialdehyde (MDA)

MDA is a marker of oxidative stress, which may play a role in OCD pathology. It is produced when free radicals damage lipids in cell membranes.

Measuring MDA

MDA can be measured in blood, urine, or cerebrospinal fluid samples. Common techniques include:

• Spectrophotometric assays
• HPLC
• Mass spectrometry

MDA findings in OCD

Multiple studies have reported:

• Higher blood MDA levels in OCD patients compared to controls
• Correlations between MDA levels and OCD symptom severity

A recent meta-analysis confirmed significantly elevated MDA in OCD across studies. This makes it one of the more promising biomarker candidates.

Potential as therapeutic targets

Beyond their use as biomarkers, BDNF, DBH, and MDA pathways may offer new therapeutic targets for OCD:

• BDNF-enhancing drugs could potentially improve neuroplasticity and alleviate symptoms
• Modulating DBH activity may help normalize dopamine/norepinephrine signaling
• Antioxidant approaches targeting oxidative stress and MDA production are being explored

Some existing and experimental OCD treatments may already work in part by affecting these pathways. For example:

• Deep brain stimulation can increase BDNF levels
• The antidepressant agomelatine may boost BDNF while reducing oxidative stress
• N-acetylcysteine, an antioxidant, shows promise for reducing OCD symptoms

Other emerging areas

The review also highlights two other areas of interest for OCD biomarkers and treatment:

Circadian rhythm disruption

OCD often involves sleep disturbances and altered melatonin levels. Targeting the circadian system, for instance with agomelatine, may offer therapeutic benefits.

Insulin signaling

There appears to be a bidirectional relationship between OCD and insulin-related metabolic disorders. Drugs that modulate insulin signaling, like metformin, are being investigated for OCD.

Conclusions

• BDNF, DBH, and MDA show promise as potential biomarkers for diagnosing OCD and monitoring treatment response.
• These molecules and their associated pathways may also serve as targets for developing new OCD therapies.
• Larger clinical studies are still needed to validate their utility as biomarkers and therapeutic targets.
• Emerging areas like circadian rhythm modulation and insulin signaling offer additional avenues to explore in OCD research and treatment.