East Asian Arch Psychiatry 2024;34:43-4 | https://doi.org/10.12809/eaap2348

CASE REPORT

Sulagna Mallik, Rajeev Ranjan, Kumar Gourav, Kritika Aggarwal

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Key words: Bipolar disorder; Muscular dystrophy, Duchenne

Sulagna Mallik, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India
Rajeev Ranjan, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India
Kumar Gourav, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India
Kritika Aggarwal, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India

Address for correspondence: Dr Sulagna Mallik, Department of Psychiatry, All India Institute of Medical Sciences, Patna, India 801507. Email: sulagnamallik2014@gmail.com

Submitted: 26 October 2023; Accepted: 11 January 2024

Duchenne muscular dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophies. It is caused by a mutation in the dystrophin gene, leading to progressive muscular degeneration and weakness. It is inherited as an X-linked recessive trait, mostly located on chromosome Xp21; however, approximately 30% of cases are de novo mutations. Mutations lead to limited production of the dystrophin protein, which results in loss of myofibres and progressive replacement of muscle with connective tissue and fat.¹ Children with DMD have difficulty walking, whereas increased steroid intake can result in depressed mood or attention deficit hyperactivity disorder.²

Paediatric bipolar disorder (PBD), which is defined as onset before the age of 18 years, is characterised by episodes of mania or hypomania and depression. A manic episode includes a period of at least 1 week during which the person is in an abnormally and persistently elevated or irritable mood.³ Those with PBD display impaired signal communication in neural networks critical to processing faces and emotional stimuli. Both the fusiform gyrus and posterior cingulate are associated with the visual processing of facial expressions. The parahippocampal gyrus is implicated in emotional and cognitive learning, specifically associating stimuli with affective meaning.⁴ Dystrophin is expressed in the brain and the retina but at relatively lower levels, which explains some of the central nervous system manifestations of DMD.⁵ Animal models have shown that dystrophin gene deficiency in the hippocampus leads to hypoxia and that a 50% shrinkage of neurons in the cerebral cortex results in impairment in short-term memory and passive avoidance reflex. There is a potential mechanism by which DMD could contribute to the development of PBD owing to under-development of the hippocampus, although evidence connecting the two conditions in humans is lacking. We report a rare case of PBD in the presence of DMD in a 10-year-old boy.

Four days prior to his presentation, he had experienced sleep disturbances with frequent breaks during sleep and early waking. He was observed to be more active and verbose than usual. He was very difficult to interrupt when talking and became irritable if anyone attempted to do so. He boasted about his ability to communicate with God and solve all his problems on his own. He appeared more religious than before and told his parents to pray to Hindu deities so that he could solve all of their problems. His mother heard him repeatedly chanting mantra and conducting a Puja. His mother reported that he was previously a quiet and obedient child and would not speak so confidently. He kept asking for food every 2 hours. He appeared happy and smiling even when his parents were scolding him. His sleep remained disturbed, but he appeared rested during the day.

In April 2023, a 10-year-old boy was brought to the emergency department and admitted by our psychiatry team. He was not formally educated and was residing in rural area. He had a slow-to-warm premorbid temperament. His medical history included early preterm delivery, neonatal jaundice, a femoral fracture when he was 2 years old, and a fracture and malunion of the tibia when he was 2.5 years old. He was diagnosed with DMD at the age of 4 years but was prescribed no medication. There was also a family history of DMD in a younger brother.

After assessment, he was diagnosed as having mania and prescribed olanzapine 5 mg/day and clonazepam 5 mg/day after a discussion with the paediatric neurology team. The olanzapine was titrated up to 10 mg/day, and he was monitored for adverse effects such as extrapyramidal symptoms. His sleep and craving for food conditions improved, and his Young Mania Rating Scale score improved from 32 to 8. He was discharged on olanzapine 7.5 mg/day. One week later, the talkativeness and sleep disturbances had recurred; the olanzapine was therefore increased to and maintained at 10 mg/day.

Although comorbidities are common in cases of PBD, our patient did not have any history of florid psychopathology or externalising behaviours. The behavioural symptoms were of sudden onset and receded quickly after commencing olanzapine, unlike in other cases of PBD.

Children with DMD often have cognitive deficits. The dystrophin protein is encoded by the dystrophin gene, which represents around 0.1% of genetic makeup of human beings. Dystrophin is mainly involved in calcium metabolism and cell necrosis.⁶ It also has a role in maintaining the integrity of the lipid bilayer. In cases of dystrophin deficiency, the cell membrane is more easily disrupted by mechanical or chemical stresses, causing an influx of extracellular proteins and calcium ions.⁷

In dystrophin-deficient mice, the number and the size of gamma-aminobutyric acid (GABA)A clusters are markedly reduced in the hippocampus but not in the striatum, whereas the number (not the size) of GABAA clusters is markedly reduced in both the cerebellum and hippocampus.⁸ In patients with bipolar disorder, there are reduced hippocampal volume and verbal memory deficits.⁹ Abnormalities in hippocampal plasticity have been implicated in the neuropathology of mood disorders. Similarly, abnormalities in markers of cell density have been found in the hippocampus before the onset of the bipolar disorder,10 which may reflect early dysfunctions in cell growth and plasticity. GABA dysfunctions are mostly noted in the parieto-occipital cortex. GABAergic interneurons provide both inhibitory and disinhibitory modulation of cortical and hippocampal circuits and contribute to the generation of oscillatory rhythms, discriminative information processing, and the gating of sensory information within the corticolimbic system. Under pathological conditions, there is an excessive discharge of excitatory activity emanating from the amygdala, which projects massively to layer II of the anterior cingulate cortex and sectors CA3 and CA2 of the hippocampus.¹⁰ However, there is no association between defective GABAA neurotransmission in the hippocampus in DMD and defective GABA neurotransmission in the hippocampus in bipolar disorder.

Our patient could have been predisposed to PBD in the presence of the organic pathology of DMD. However, the absence of a similar history in his brother, who also had DMD, lends weight to the co-occurrence of both illnesses being coincidental. Psychosocial stressors may have contributed to the development of PBD. DMD has been reported to cause anxiety and depression, but no case involving mania has been reported. Further neurobiological studies to investigate whether DMD can contribute to the development of PBD are warranted.

All authors designed the study, acquired the data, analysed the data, drafted the manuscript, and critically revised the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

All data generated or analysed during the present study are available from the corresponding author on reasonable request.

The patient was treated in accordance with the tenets of the Declaration of Helsinki. The patient provided written informed consent for all treatments and procedures and for publication.

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