A new approach for the treatment of subthreshold bipolar disorders: Targeted high dose levothyroxine and repetitive transcranial magnetic stimulation for mitochondrial treatment

Zamar, Andy; Lulsegged, Abbi; Kouimtsidis, Christos

doi:10.3389/fpsyt.2022.976544

Cited by 5 publications

(3 citation statements)

References 63 publications

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“…We do, however, argue that the presence of a DiO1 variant might play a greater role in protecting the periphery from the effects of high-dose levothyroxine, which has been shown in many studies [16], including the cohorts treated by the authors [18,19]. These mutations explain the disease model and mitochondrial dysfunction, as well as the model the authors published for the disease [26].…”

Section: Discussionmentioning

confidence: 80%

Towards the First Biomarker Test for Bipolar Spectrum Disorder: An Evaluation of 199 Patients in an Outpatient Setting

Zamar

Mohamed

Lulsegged³

et al. 2023

JPM

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Bipolar spectrum disorder seems to be challenging to diagnose, particularly unspecified or subthreshold types. The delay in diagnosis in the UK for bipolar I and II types is a staggering 10–13 years, with only 15% correctly diagnosed without delay. In the USA, the delay is 6–8 years, and there is a 60% incorrect diagnosis rate. The HCL-32 questionnaire is adequate, but not sufficient by itself, and patients may find it difficult to complete, particularly if they are unwell. We have investigated a biomarker test which can be used in day-to-day clinical practice to assist diagnosis. We evaluated 199 patients diagnosed with ICD-10 bipolar I, II, and unspecified disorders, using the HCL-32 questionnaire with a cut-off point of 14 and above, supplemented by history taking and examination using the principles of the CIDI 3, interviews of relatives, and longitudinal mood charts where available. The results were compared to the general population and a sample of patients diagnosed with recurrent depression for assessment of sensitivity and specificity. We evaluated four mutations of SLCO1C1, DiO1, and two DiO2alleles as potential biomarkers for bipolar spectrum disorder, and identified three mutations that exhibited high sensitivity, with rates of up to 87% and specificity of up to 46% in distinguishing bipolar spectrum disorders from recurrent depressive disorder. Additionally, mutations in SLCO1C1 and DiO1 exhibited a sensitivity of up to 86% and a specificity of up to 60% in detecting bipolar spectrum disorder compared to the general population within a clinical setting. These biomarkers have the potential to be used as a diagnostic test that is not open to subjective interpretation and can be administered even if patients are very unwell, requiring, though, the patient’s consent. Further studies confirming these results are needed to compare the validity of using individual or a best combination of single nucleotide polymorphisms to identify bipolar spectrum disorders, particularly subthreshold presentations, and to differentiate them from other mood disorders such as major depression and recurrent depressive disorder.

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Section: Discussionmentioning

confidence: 80%

Towards the First Biomarker Test for Bipolar Spectrum Disorder: An Evaluation of 199 Patients in an Outpatient Setting

Zamar

Mohamed

Lulsegged³

et al. 2023

JPM

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“…[93,94]. What's more, supraphysiological doses of TH also appeared to be an excellent option for BD treatment [95,96]. The reason maybe that BD has mitochondrial dysfunction and low ATP cellular state, while the uptake of TH in the cell is energy dependent.…”

Section: Treatment Of Bdmentioning

confidence: 99%

Thyroid hormone levels in patients with bipolar disorder: A systematic review and meta- analysis

Liu,

Chen,

et al. 2023

Preprint

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Purpose To investigate the difference of serum thyroid hormone (TH) levels in bipolar disorder (BD) during different mood episodes (depression and mania) compared with healthy control (HC) and among different mood episodes. Methods We systematically searched the electronic databases for studies on the relationship between BD and TH levels. The random effects model and the standardized mean difference were used to combine the effect sizes. Results Serum T3 (standard mean difference [SMD]: -0.52, 95% confidence interval [CI]: -0.86 to -0.18, P = 0.00), FT3 (SMD: -0.55, 95%CI: -1.06 to -0.04, P = 0.04) decreased significantly in BD-depression compared with HC. Serum TSH(SMD: 0.20, 95%CI: 0.04 to 0.36, P = 0.02), FT4 (SMD: 0.42, 95%CI: 0.17 to 0.66, P = 0.00) increased significantly and T3 (SMD: −0.73, 95%CI: −1.37 to -0.08, P = 0.03) decreased significantly in BD-mania compared with HC; FT4 (SMD: 0.85, 95%CI: 0.56 to 1.13, P = 0.00) increased significantly in males; TSH (SMD: 0.49, 95%CI: 0.21 to 0.78, P = 0.00) increased significantly, T3 (SMD: -0.57, 95%CI: -0.86 to -0.29, P = 0.00) and T4 (SMD: -0.68, 95%CI: -1.34 to -0.01, P = 0.05) decreased significantly in females. Serum T3 (SMD: 0.29, 95%CI: 0.12 to 0.46, P = 0.00), FT3(SMD: 0.55, 95%CI: 0.28 to 0.81, P = 0.00) increased significantly in BD-mania than in BD-depression. Conclusion Serum T3 and FT3 levels decreased significantly in BD-depression compared with HC. Serum TSH, FT4 levels increased significantly and T3 level decreased significantly in BD-mania compared with HC. Serum T3, FT3 levels increased significantly in BD-mania than in BD-depression. The fascinating thing was that gender differences may affect the compensatory secretion of BD-mania anterior pituitary hormone. Trial registration number and date of registration for prospectively registered trials No. CRD42022378530 (4 December 2022)

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“…Neuroplasticity can be induced by both rTMS (Lenz et al, 2016) and tDCS (Ranieri et al, 2012), and we recently found evidence of increased neuroplastic changes in the rat brain after a single treatment of TILS (Wade et al, 2023). The induction of neuroplasticity by these methodologies may be one key mechanism by which they have a therapeutic effect in bipolar disorder (Zamar et al, 2022;D'Urso et al, 2023). rTMS, tDCS, and TILS also show promise in treating age-related cognitive decline (Vargas et al, 2017;Cai et al, 2019;Phipps et al, 2021).…”

Section: Comparison Of Tils With Non-invasive Magnetic and Electrical...mentioning

confidence: 99%

Prefrontal photobiomodulation produces beneficial mitochondrial and oxygenation effects in older adults with bipolar disorder

O’Donnell,

Barrett,

O’Connor

et al. 2023

Front. Neurosci.

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There is growing evidence of mitochondrial dysfunction and prefrontal cortex (PFC) hypometabolism in bipolar disorder (BD). Older adults with BD exhibit greater decline in PFC-related neurocognitive functions than is expected for age-matched controls, and clinical interventions intended for mood stabilization are not targeted to prevent or ameliorate mitochondrial deficits and neurocognitive decline in this population. Transcranial infrared laser stimulation (TILS) is a non-invasive form of photobiomodulation, in which photons delivered to the PFC photo-oxidize the mitochondrial respiratory enzyme, cytochrome-c-oxidase (CCO), a major intracellular photon acceptor in photobiomodulation. TILS at 1064-nm can significantly upregulate oxidized CCO concentrations to promote differential levels of oxygenated vs. deoxygenated hemoglobin (HbD), an index of cerebral oxygenation. The objective of this controlled study was to use non-invasive broadband near-infrared spectroscopy to assess if TILS to bilateral PFC (Brodmann area 10) produces beneficial effects on mitochondrial oxidative energy metabolism (oxidized CCO) and cerebral oxygenation (HbD) in older (≥50 years old) euthymic adults with BD (N = 15). As compared to sham, TILS to the PFC in adults with BD increased oxidized CCO both during and after TILS, and increased HbD concentrations after TILS. By significantly increasing oxidized CCO and HbD concentrations above sham levels, TILS has the potential ability to stabilize mitochondrial oxidative energy production and prevent oxidative damage in the PFC of adults with BD. In conclusion, TILS was both safe and effective in enhancing metabolic function and subsequent hemodynamic responses in the PFC, which might help alleviate the accelerated neurocognitive decline and dysfunctional mitochondria present in BD.

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A new approach for the treatment of subthreshold bipolar disorders: Targeted high dose levothyroxine and repetitive transcranial magnetic stimulation for mitochondrial treatment

Cited by 5 publications

References 63 publications

Towards the First Biomarker Test for Bipolar Spectrum Disorder: An Evaluation of 199 Patients in an Outpatient Setting

Towards the First Biomarker Test for Bipolar Spectrum Disorder: An Evaluation of 199 Patients in an Outpatient Setting

Thyroid hormone levels in patients with bipolar disorder: A systematic review and meta- analysis

Prefrontal photobiomodulation produces beneficial mitochondrial and oxygenation effects in older adults with bipolar disorder

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