Scholarlink

Introduction <p>Mitochondria generate energy in the form of adenosine triphosphate (ATP), integral in regulating cellular activities. Pathogenic variants in mitochondrial DNA occur when excess free radicals are produced during abnormal electron transport, causing cumulative oxidative stress and decline in mitochondrial function. The brain is particularly susceptible to oxidative damage due to its high oxygen consumption and low levels of antioxidant enzymes. This predisposes to neuropsychiatric manifestations, which may be exacerbated by psychotropics that further impair mitochondrial function.</p> Objectives <p>To highlight clinical clues that distinguish primary psychiatric disorders from neuropsychiatric manifestations of mitochondrial disease, and to outline key prescribing principles in this context.</p> Methods <p>Non-systematic review of the literature and report of a case study.</p> Results <p>We present a 59-year-old Chinese lady with papillary thyroid cancer, congenital alopecia and eczema, treated for schizophrenia and OCD for over 30 years before a diagnosis of possible TK2-related mitochondrial DNA depletion myopathy—the first reported case with neuropsychiatric features. Her psychiatric symptoms included contamination obsessions, cleaning compulsions, elementary auditory hallucinations, and negative symptoms, remaining stable on low-dose risperidone and fluoxetine without relapses. In 2023, she developed post-operative drowsiness and desaturation, with physical examination showing oculopharyngeal weakness and proximal myopathy. CK &gt; 10,000, aldolase 96.6, EMG with myopathic changes, and biopsy suggested mitochondrial myopathy. Genetic testing revealed two TK2 variants, also present in her sister. Despite months of psychotropic non-compliance, she reported only intermittent hallucinations without OCD relapse.</p> Conclusions <p>Differentiating primary psychiatric disorders from neuropsychiatric symptoms of mitochondrial disease is crucial, as some psychotropics may worsen mitochondrial function. Literature reveals no clear guidelines and conflicting recommendations. Three predictors of organic pathology include: (a) multi-organ involvement, (b) cognitive impairment with negative symptoms, and (c) well-controlled symptoms on low-dose psychotropics. The absence of pharmacological guidelines highlights the need for research on psychotropic–mitochondrial interactions and potential adjunctive antioxidant or mitochondrial-targeted therapies. Meanwhile, safe prescribing should follow the principles of ‘start low, go slow’ with careful titration.</p> Clinical trial number <p>Not applicable.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

First case of schizophrenia and OCD in TK2-related mitochondrial DNA depletion myopathy: a case report

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月10日

查看全文
  • Shu Hui Ngoh,
  • Alakananda Gudi

摘要

Introduction

Mitochondria generate energy in the form of adenosine triphosphate (ATP), integral in regulating cellular activities. Pathogenic variants in mitochondrial DNA occur when excess free radicals are produced during abnormal electron transport, causing cumulative oxidative stress and decline in mitochondrial function. The brain is particularly susceptible to oxidative damage due to its high oxygen consumption and low levels of antioxidant enzymes. This predisposes to neuropsychiatric manifestations, which may be exacerbated by psychotropics that further impair mitochondrial function.

Objectives

To highlight clinical clues that distinguish primary psychiatric disorders from neuropsychiatric manifestations of mitochondrial disease, and to outline key prescribing principles in this context.

Methods

Non-systematic review of the literature and report of a case study.

Results

We present a 59-year-old Chinese lady with papillary thyroid cancer, congenital alopecia and eczema, treated for schizophrenia and OCD for over 30 years before a diagnosis of possible TK2-related mitochondrial DNA depletion myopathy—the first reported case with neuropsychiatric features. Her psychiatric symptoms included contamination obsessions, cleaning compulsions, elementary auditory hallucinations, and negative symptoms, remaining stable on low-dose risperidone and fluoxetine without relapses. In 2023, she developed post-operative drowsiness and desaturation, with physical examination showing oculopharyngeal weakness and proximal myopathy. CK > 10,000, aldolase 96.6, EMG with myopathic changes, and biopsy suggested mitochondrial myopathy. Genetic testing revealed two TK2 variants, also present in her sister. Despite months of psychotropic non-compliance, she reported only intermittent hallucinations without OCD relapse.

Conclusions

Differentiating primary psychiatric disorders from neuropsychiatric symptoms of mitochondrial disease is crucial, as some psychotropics may worsen mitochondrial function. Literature reveals no clear guidelines and conflicting recommendations. Three predictors of organic pathology include: (a) multi-organ involvement, (b) cognitive impairment with negative symptoms, and (c) well-controlled symptoms on low-dose psychotropics. The absence of pharmacological guidelines highlights the need for research on psychotropic–mitochondrial interactions and potential adjunctive antioxidant or mitochondrial-targeted therapies. Meanwhile, safe prescribing should follow the principles of ‘start low, go slow’ with careful titration.

Clinical trial number

Not applicable.