Obsessive Compulsive Disorder (OCD)

A multidimensional disorder

Obsessive compulsive disorder (OCD) is a complex mental health condition that affects about 3% of the population worldwide. It is characterised by recurrent and persistent thoughts (obsessions) that lead individuals to engage in excessive repetitive behaviours or mental acts (compulsions) - such as washing, checking or counting – as a way to alleviate anxiety. The World Health Organisation has recognised OCD as one of the top 10 most debilitating illnesses by lost income and decreased quality of life. Indeed, it's embarrassing, time-consuming and painful characteristics interfere with sufferers' daily actions and impact most aspects (health, professional, social, relationship) of their lives without them being able to control it. Often referred to as the secret illness, OCD is poorly recognised and under-treated – it currently takes between 7 and 17 years to receive proper diagnosis and care.

OCD is a multidimensional disorder as it has different spheres of obsessions/compulsions: 

1. Contamination with obsessions about dirt/germs and excessive cleaning, washing etc. 
2. Symmetry/ordering with repeating or counting compulsions
3. Responsibility/fear of harm with checking compulsions
4. Unacceptability/taboo thoughts with violent, aggressive, sexual, religious obsessions and reassurance-seeking rituals

Sufferers can have one or several combined spheres of these symptoms. Additionally, OCD is frequently comorbid with other conditions such as anxiety disorders, depression, Tourette syndrome, tic disorders, anorexia and suicidal behaviours.

Although a serious mental health disorder, it is common to hear jokingly, 'I am a little bit OCD' – which is actually a reference to obsessive-compulsive symptoms (OCS), a very normal personality trait that doesn't affect the quality of life and is often used to describe organised or neat people or daily habits. While OCS is relatively common in the general population (13 to 38%), only a small proportion of these individuals meet the criteria for a formal OCD diagnosis, demonstrating the need to differentiate OCD from OCS.

OCD is usually diagnosed by its debilitating, uncontrollable aspect and time-consuming component (more than one hour per day). Some people with OCD are engaged in rituals for much of their waking life and cannot leave their homes.

Risk factors

People of any age, sex, ethnicity, social and economic circumstances can develop OCD. However, some key risk factors for OCD are:

• Traumatic episodes or stressful events
• Infections (bacteria/viruses) or injury
• Nutritional deficiency, such as omega-3, vitamin B12, vitamin D
• Genetics – genetic influences in the range of 27-65%. Biological parents and siblings of people with OCD have a 4-20 fold increased risk of having it too.

Genetics

Numerous studies have shown that genetics play a significant role in the development of OCD.

No single gene is solely responsible for OCD, hence it is a consider a polygenic disorder. As research continues to unravel the genetic underpinnings of OCD, it creates opportunities for more targeted treatments and interventions that could improve the lives of those affected by this debilitating disorder.

Neurotransmitter systems

Genetic variants linked to OCD often influence the functioning of neurotransmitters such as serotonin, dopamine and GABA, impacting communication between brain cells and therefore affecting mood, anxiety, and behaviour regulation.

Serotonin

Serotonin, or 5-HT, is associated with well-being and is popularly called the 'happiness neurotransmitter'. Several aspects of the serotonin lifecycle can be impaired - synthesis, response/sensitivity and metabolism - and create an imbalance. Low serotonin levels, due to SNPs or other factors, is a common biochemical characteristic of OCD patients.

Serotonin synthesis starts with the essential amino acid tryptophan, hence reduced availability of tryptophan can be a significant factor in OCD. Tryptophan is converted to 5-HTP by the enzyme tryptophan-5-hydroxylase, which exists in two different forms, TPH2 in the brain and TPH1 in the digestive system. This conversion can be slowed due to genetic variations on TPH1 and TPH2, insufficiency of a cofactor BH4 (impacted by availability of methyl-folate) or vitamin D deficiency, which is why VDR (Vitamin D Receptor) SNPs are tested. The second step is the conversion of 5-HTP to serotonin, which is dependent on vitamin B6 (PLP form), zinc and magnesium.

Tryptophan steal

Raised cortisol levels due to stress (exacerbated by an FKBP5 SNP), or inflammation resulting from infection or injury (and worsened by SNPs on IFNG (interferon gamma) and TNF (tumour necrosis factor) can cause tryptophan to be redirected to the kynurenic pathway, so called 'tryptophan steal'. Omega-3 fatty acids (from oily fish) and other anti-inflammatory foods (such as curcumin) can inhibit the kynurenine pathway, and thus be beneficial.

Serotonin receptors

Serotonin receptors are the 'biggies' in this pathway. HTR1A (alternative name 5-HT1A) and HTR2A (5-HT2A) are activated by serotonin and control the release of a number of excitatory and inhibitory neurotransmitters, including acetylcholine, adrenaline, dopamine, glutamate, noradrenaline and as well as the hormones corticotropin, cortisol, prolactin and vasopressin. They are the target of many drugs, including antidepressants, antipsychotics and anti-migraine agents. 

Receptors are supposed to enable adaptation to certain conditions. SNP on genes that code for the receptors can mean they are not as adaptable, and the response to serotonin will be different.

HTR1A and HTR2A receptors have a balancing, or opposite, effects. 

HTR1A is a pre-synaptic inhibitory autoreceptor, which inhibits serotonin release when serotonin is high. A SNP associated with higher activity is detrimental because it inhibits serotonin at a lower threshold. This can result in significantly lower levels of serotonin and increased anxiety and impulsivity, as well as antisocial behaviour. This receptor is also upregulated by stress and chronic pain.

This HTR1A SNP has also been associated with OCD, increased fear, stress response and a worse response to antidepressants. SSRIs block the reuptake of serotonin in the synapse as well as activate this HTR1A receptor. Individuals with this SNP experience more negative feedback and more inhibition of serotonin release, which is why antidepressants can be worse at first for them. However, over time (days to weeks, depending on the individual), the receptors are desensitised by the SSRIs, eventually resulting in less inhibition, which is why it can take longer for these medications to work.

In contrast, HTR2A is a post-synaptic excitatory receptor which promotes serotonin effects and functions. The SNP is associated with over-sensitivity to serotonin - and the receptor reacts by blocking the serotonin cascade (a kind of 'serotonin resistance' effect) - limiting serotonin effect, and resulting in symptoms of low serotonin. This has been associated with juvenile and severe OCD and more risk of antidepressant resistance.

For individuals with this SNP, low-dose SSRIs might be more efficient than high doses – which could exaggerate the dysfunction.

In general, serotonin sensitivity can be increased with St. John's Wort, saffron and omega-3.

Serotonin Metabolism

Serotonin metabolism (breakdown, or removal) is also important for balance. Serotonin can be used as a substrate for melatonin synthesis (needed for sleep) or can be metabolised by MAOA (monoamine oxidase A), resulting in an aldehyde, which is then detoxified by ALDH (aldehyde dehydrogenase). 

A SNP on MAOA slows down the metabolism of serotonin, which can be beneficial or detrimental depending on the context of high/low serotonin levels. Slow metabolism of serotonin can contribute to higher levels, which could be detrimental if serotonin is high in the first place (and in combination with SSRIs, while fast metabolism can drain serotonin too quickly and risk low serotonin and symptoms such as depression, anxiety and OCD.

Dopamine Lifecycle

Another biochemical characteristic of OCD is high dopamine and adrenaline. S. Kim & C. Kim, 2006 state that "evidence from neuroanatomical and pharmacological data suggests that the dopaminergic neurotransmitter system may also be implicated in mediating OCD."

The catechol-O-methyltransferase (COMT) gene is involved in the breakdown of amine neurotransmitters like dopamine and noradrenaline. Genetic variations in COMT have been associated with altered dopamine levels in the brain. In fact, a SNP leading to a lower COMT enzymatic activity (Met158) has been linked to higher dopamine levels and a slightly increased risk of OCD.

Adrenaline is the hormone and neurotransmitter responsible for increasing blood flow. This is particularly important in the 'fight or flight' response. Excess adrenaline can cause tachycardia, cardiac arrhythmia, hypertension, anxiety and panic attacks. SNPs on adrenergic receptors (ADRB1 and ADRB2) confer increased sensitivity to to adrenaline and noradrenaline and a greater stress response, a contributing factor to OCD and other anxiety disorders..

GABA

GABA, gamma-aminobutyric acid, is the major inhibitory neurotransmitter in the brain. It decreases a neuron's action potential or excitability at a synapse level. GABA is critical for relaxation, improves memory and mood, relieves anxiety, promotes sleep, moderates blood pressure, and influences catecholamine release and cytokine and hormone production. Disruption of GABA neurotransmission can contribute to many neurological diseases, including epilepsy, general anxiety disorder or OCD. The level (amount) of GABA and number of receptors can be impacted by genetic variance,

Glutamate is the major excitatory neurotransmitter with opposite effects to GABA. It is also the precursor from which GABA is made.

Vitamin B6 is a major cofactor of GABA synthesis, and ALPL is the gene that codes the enzyme responsible for breaking it down. A SNP on ALPL is associated with faster clearance of vitamin B6 (hence lower B6 status) and potentially lower GABA levels. Good sources of B6 include organ meats, pork, chicken, tuna, salmon, chickpeas, sweet potatoes, hazelnuts and bananas.

A SNP on GABRA2 (GABA receptor) is associated with to lower activity and therefore reduced sensitivity to GABA. L-theanine and rosmarinic acid (found in rosemary, lemon balm, sage, thyme and peppermint) can help inhibit removal of GABA, thereby supporting levels.

Inflammation

Finally, inflammation – and, more specifically, neuroinflammation – has been identified as a significant contributor to OCD. SNPS on genes such as CRP, IFNG, IL6 and TNF are linked to higher activity and more inflammation. Including anti-inflammatory foods such as green tea, omega-3, curcumin, and brassicas in the diet can help to reduce neuroinflammation.

Reactive oxygen species (commonly called ROS) also participate in inflammation. Several genes have been identified as the antioxidant cascade - SOD2, CAT and GPX1. The first step of the antioxidant defence mechanism is led by SOD2, which transforms superoxide into hydrogen peroxide and oxygen. A SNP on this gene can reduce SOD2 activity, leading to more oxidative stress and increased risk of free radical damage. Manganese is the primary cofactor for SOD2.

In the second step, CAT and GPX1 convert hydrogen peroxide into oxygen and water. Polymorphisms on these genes reduce their antioxidant activity, too and increase ROS levels. Their cofactors are manganese (for CAT), selenium and glutathione (for GPX1).

Lifecode Gx® Reports

Having genetic predisposition to OCD does not guarantee that someone will develop the disorder. As explained earlier in this article, environmental factors, such as childhood trauma, stressful life events, infections and nutritional deficiencies/diet, can interact with genetic weaknesses to trigger the onset of OCD symptoms.

The DNA reports featured in this article are the Nervous System, and the Metabolics reports.

If you’d like to know more about OCD and how to use our reports, feel free to watch our OCD and Nutrigenomics snapshot video.