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Case Study: Mary, a 40-Year-Old female Struggling with Obsessive Compulsive Disorder and Depression

While all case studies are based on actual patients, significant aspects of the case have been changed to conceal the patient’s original identity.

Initial Presentation

Mary was a high-functioning business executive with an accomplished career. She was married with two children and tried to maintain a healthy work-life balance. In her early thirties, long-standing dysthymia worsened into depression. While she had a history of rituals and routines that were strongly suggestive of obsessive-compulsive disorder (OCD) since adolescence, she didn’t discuss them with her doctor and her initial diagnosis and treatment focused solely on her depressive symptoms. After attempting numerous selective serotonergic reuptake inhibitors that provided minimal relief, she was finally switched to bupropion which helped alleviate her depression, but had no impact on her OCD.

As her work-stress levels increased, her OCD symptoms worsened even though her depression was reasonably well controlled on the bupropion. Due to her concerns about the disruptive nature of the intrusive routines and obsessive thoughts, she sought help from our clinic. Upon intake, she acknowledged that she had a family history of depression.

Initial relevant labs

  • Genomind genetic testing: homozygous for a single nucleotide polymorphism (SNP) of the methylenetetrahydrofolate reductase (MTHFR) enzyme at position 677 with a C to T substitution
  • B12 low normal at 283 pg/mL
  • Elevated homocysteine levels at 17.3 mcmol/L

Initial Treatment

  • Continue bupropion
  • SeroPlus, 1 cap twice daily
  • NAC, 1200 mg twice daily
  • Methylfolate, 3 mg once daily
  • Sublingual B12, 1 mg twice daily

Explanation

Since the bupropion was helping with depressive symptoms, it was maintained as a part of Mary’s treatment. To focus on the OCD, SeroPlus, a product that contains 5-HTP, inositol, taurine and other cofactors necessary for serotonin synthesis was prescribed. 5-HTP has been shown to help treat moderate to severe OCD symptoms (Yousefzadeh 2020). It works as a direct precursor for serotonin synthesis that can cross the blood-brain barrier.

Inositol is a precursor to the “second messenger system” in cellular signal transduction (Levine 1997). In other words, when serotonin binds to a cellular receptor, it activates the second messenger system to relay the serotonin-signal inside the cell. As such, inositol is critical for helping to relay serotonin signals in order to initiate the proper cellular response. While more research is needed, some clinical trial evidence has found benefits with inositol for OCD, depression and panic attacks (Fux 1996).

As a supplement, the amino acid taurine can stimulate gamma aminobutyric acid receptors which may also help to reduce anxiety symptoms. While not directly studied in OCD, tic disorders are a common OCD comorbidity. In a clinical trial of taurine for patients with tic disorders, taurine was found to reduce symptoms more effectively than placebo (Ding 2020). Interestingly, taurine has even been shown to be helpful in treating first episode psychosis (O’Donnell 2016).

Further studies also support the use of N-acetylcysteine (NAC) for OCD treatment. NAC is a precursor to glutathione, one of the body’s main antioxidants. In addition, it has effects on reducing the excitatory neurotransmitter glutamate (Berk 2013). Research suggests that excess glutamate may be an underlying factor that can contribute to OCD (Biria 2023). A meta-analysis from 2021 found that NAC shows promise for reducing symptoms in OCD patients (Hadi 2021).

Studies have also found that homocysteine, a neurotoxic amino acid, may be higher in patients with OCD and could be related to the pathology of the condition in some patients (Türksoy 2014). Homocysteine is known to be higher for individuals with MTHFR mutations, like Mary, especially when homozygous (Colson 2017). MTHFR mutations disrupt the processing of folic acid into the active form needed by the body. As a supplement, methylfolate bypassess the MTHFR enzyme, providing a form of folate that can cross the blood-brain barrier, effectively lowering homocysteine levels.

Vitamin B12 is also a necessary cofactor to metabolize homocysteine. And while Mary’s serum B12 levels were in the “normal” lab range, research clearly suggests that patients can still have B12 deficiencies with serum B12 levels up to 400 pg/mL (Hermann 2005). And this doesn’t take into account subclinical deficiency or potential problems with lower levels in the central nervous system, which may still be present in patients with “normal” serum B12.

Follow-up Presentation

Over the next few months, Mary’s symptoms slowly improved. Her need to engage in ritualistic behaviors became more manageable. The stress from the OCD symptoms decreased as she developed more control. However, even with the improvements, she continued to have challenges around obsessive thoughts.

Follow-up Testing

  • Homocysteine 8.7 mcmol/L

Follow-up Treatment

  • Inositol as needed for obsessive thoughts ½ tsp in water

Explanation for Follow-up Treatment

In the clinical trials of inositol, dosing is often quite high, around 15 grams per day. Providing additional inositol on an as-needed basis allowed Mary to have another tool to help reign in her obsessive thoughts, rather than engaging in the ritualistic behaviors they demanded.

Additional Follow-up

As Mary continued on the supplements, she found the control that she needed to function normally on a day-to-day basis. She was thrilled to no longer be at the mercy of her OCD obsessions and compulsions.

Case Summary

Elevations of homocysteine due to an increased need for vitamin B12, folate or both can contribute to mental-emotional symptoms. In Mary’s case, the OCD appeared to have roots in SNPs of the MTHFR gene needed for converting folic acid into active folate. By supplementing around the MTHFR gene using methylfolate, the impact of the MTHFR SNPs was effectively mitigated and her symptoms improved. Additional support for decreasing healthy homocysteine levels with supplemental B12 likely provided further benefits. Moreover, by supporting serotonin production and transmission with 5-HTP, inositol and other necessary cofactors, she was able to bring her condition under much better control, allowing for normal day-to-day function.

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References

Biria M, Banca P, Healy MP, et al. Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls. Nat Commun. 2023;14(1):3324. Published 2023 Jun 27. doi:10.1038/s41467-023-38695-z

Colson NJ, Naug HL, Nikbakht E, Zhang P, McCormack J. The impact of MTHFR 677 C/T genotypes on folate status markers: a meta-analysis of folic acid intervention studies. Eur J Nutr. 2017;56(1):247-260. doi:10.1007/s00394-015-1076-x

Ding L, Yang Z, Liu G, et al. Safety and efficacy of taurine as an add-on treatment for tics in youngsters. Eur J Neurol. 2020;27(3):490-497. doi:10.1111/ene.14107

Fux M, Levine J, Aviv A, Belmaker RH. Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry. 1996;153(9):1219-1221. doi:10.1176/ajp.153.9.1219

Hadi F, Kashefinejad S, Kamalzadeh L, Hoobehfekr S, Shalbafan M. Glutamatergic medications as adjunctive therapy for moderate to severe obsessive-compulsive disorder in adults: a systematic review and meta-analysis. BMC Pharmacol Toxicol. 2021;22(1):69. Published 2021 Nov 4. doi:10.1186/s40360-021-00534-6

Herrmann W, Obeid R, Schorr H, Geisel J. The usefulness of holotranscobalamin in predicting vitamin B12 status in different clinical settings. Curr Drug Metab. 2005;6(1):47-53. doi:10.2174/1389200052997384

Levine J. Controlled trials of inositol in psychiatry. Eur Neuropsychopharmacol. 1997;7(2):147-155. doi:10.1016/s0924-977x(97)00409-4

O’Donnell CP, Allott KA, Murphy BP, et al. Adjunctive Taurine in First-Episode Psychosis: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study. J Clin Psychiatry. 2016;77(12):e1610-e1617. doi:10.4088/JCP.15m10185

Yousefzadeh F, Sahebolzamani E, Sadri A, et al. 5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control. Int Clin Psychopharmacol. 2020;35(5):254-262. doi:10.1097/YIC.0000000000000321