Beyond the Ice Bucket: A Research-Based Examination of ALS and Its Overlap with Mental Disease

The Ice Bucket Challenge, a viral social media campaign that surged in 2014, placed Amyotrophic Lateral Sclerosis (ALS) in the global spotlight. Though originally celebrated for its ability to raise over $115 million for ALS research, the challenge faded from public discourse as its trend subsided. In 2025, however, a new wave of advocacy—driven by youth and mental health organizations—has reawakened interest in the disease. But ALS is not simply a “motor neuron disease,” nor is it isolated from the broader landscape of mental and neurological disorders. This essay seeks to explore ALS in its biological complexity, emphasize its often-overlooked cognitive and psychiatric components, and examine the shared mechanisms between neurodegenerative and mental diseases. It also argues that the convergence of ALS and mental health advocacy offers an urgent and necessary reimagining of how we understand illness, stigma, and interdisciplinary care.

Amyotrophic Lateral Sclerosis is a rare, progressive neurodegenerative disease affecting upper and lower motor neurons—nerve cells responsible for controlling voluntary muscle movement. As these neurons degenerate, patients experience muscle weakness, spasticity, dysphagia (difficulty swallowing), and eventually respiratory failure. The average life expectancy following diagnosis is 3 to 5 years, although certain variants, such as the C9orf72-associated form, may progress differently (Hardiman et al., 2017).

Approximately 90% of ALS cases are sporadic, while 10% are familial, often linked to mutations in genes such as SOD1, TARDBP, FUS, and C9orf72 (Taylor et al., 2016). Historically, ALS was conceptualized as a disease that left patients’ cognitive faculties intact. However, contemporary research demonstrates that cognitive and behavioral impairments are present in up to 50% of ALS cases, with 15%–20% developing comorbid frontotemporal dementia (FTD) (Phukan et al., 2012). This radically shifts how the disease must be understood—not just as a physical illness, but one deeply entwined with psychological and neurological complexity.

The discovery of a continuum between ALS and FTD has challenged the clinical orthodoxy of the disease as purely motor. Cognitive deficits, particularly in executive function, verbal fluency, and social cognition, are common. Behavioral disturbances—ranging from apathy and emotional blunting to disinhibition—have also been documented. Such symptoms mirror those observed in major psychiatric illnesses, thereby complicating the patient’s journey and care (Elamin et al., 2011).

Psychiatric comorbidities such as depression, anxiety, and even suicidality are prevalent in ALS populations. Notably, these symptoms are not simply reactions to diagnosis or physical decline; they may stem from the same neural disruptions affecting motor pathways. The shared neurobiological substrate includes TDP-43 proteinopathy, glutamate excitotoxicity, oxidative stress, and neuroinflammation—mechanisms also implicated in conditions such as schizophrenia and bipolar disorder (Vucic et al., 2013; Sekar et al., 2016).

The conventional division between “neurological” and “psychiatric” illness is increasingly viewed as artificial. The rise of systems neuroscience and genomics has revealed significant overlap in pathophysiological mechanisms. For instance, genome-wide association studies (GWAS) have shown that the C9orf72 gene, a major contributor to ALS, is also linked to increased risk for psychiatric disorders like depression and schizophrenia (Renton et al., 2014).

Moreover, both neurodegenerative and psychiatric diseases exhibit dysregulation of neural connectivity, loss of synaptic plasticity, microglial activation and chronic inflammation, and disruption of RNA metabolism and protein clearance. Such findings underscore the need for an integrative, rather than compartmentalized, approach to brain disease—one that situates ALS within a broader spectrum of mental and neurological disorders. Understanding ALS through this interdisciplinary lens allows for more holistic diagnostics and therapeutics that address the full scope of patient suffering.

Despite notable research progress, ALS remains incurable. FDA-approved treatments like riluzole and edaravone provide only modest delays in progression. Experimental approaches—including antisense oligonucleotides (e.g., tofersen), stem cell therapies, and neuroimmune modulators—are in clinical trials (Miller et al., 2022).

Yet treatment must move beyond pharmacology. Psychiatric symptoms, cognitive decline, and existential distress often go unaddressed in ALS care, exacerbated by communication barriers, diagnostic overshadowing, and stigma. Ethical dilemmas surrounding assisted dying, ventilator withdrawal, and mental capacity demand a psychosocial framework rooted in empathy and patient autonomy (Oliver et al., 2016).

This is where youth-driven advocacy plays a pivotal role. By integrating neuroscience with emotional storytelling and mental health education, campaigns like the revived Ice Bucket Challenge offer more than fundraising—they foster cultural transformation. Youth can normalize difficult conversations, elevate patient voices, and demand systems that treat the mind and brain as inseparable.

ALS is not merely a rare motor disease—it is a window into the fundamental interconnectedness of neurobiology, mental health, and social advocacy. As young leaders reignite the Ice Bucket Challenge in 2025, they do so not only in memory of those lost to ALS but in solidarity with all who suffer from invisible neurological and psychiatric pain.

Bridging the gaps between these domains will require more than scientific progress—it will demand cultural humility, interdisciplinary collaboration, and continued advocacy from the next generation. In doing so, we may finally move toward a future where diseases of the brain are no longer siloed but understood as shared human challenges deserving of empathy, innovation, and collective action.

REFERENCES

Elamin, M., Phukan, J., Bede, P., Jordan, N., Byrne, S., Pender, N., ... & Hardiman, O. (2011). Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology, 76(14), 1263–1269.

Hardiman, O., Al-Chalabi, A., Chio, A., Corr, E. M., Logroscino, G., Robberecht, W., ... & van den Berg, L. H. (2017). Amyotrophic lateral sclerosis. Nature Reviews Disease Primers, 3, 17071.

Miller, T. M., Cudkowicz, M. E., Genge, A., Shaw, P. J., Sobue, G., Bucelli, R. C., ... & Vucic, S. (2022). Phase 3 Trial of Tofersen for SOD1 ALS. New England Journal of Medicine, 387(12), 1099-1110.

Oliver, D., Borasio, G. D., & Johnston, W. (2016). Palliative Care in Amyotrophic Lateral Sclerosis: From Diagnosis to Bereavement. Oxford University Press.

Phukan, J., Pender, N. P., & Hardiman, O. (2007). Cognitive impairment in amyotrophic lateral sclerosis. The Lancet Neurology, 6(11), 994–1003.

Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., ... & Traynor, B. J. (2014). A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron, 72(2), 257-268.

Sekar, A., et al. (2016). Schizophrenia risk from complex variation of complement component 4. Nature, 530(7589), 177–183.

Taylor, J. P., Brown, R. H., & Cleveland, D. W. (2016). Decoding ALS: from genes to mechanism. Nature, 539(7628), 197–206.

Vucic, S., Nicholson, G. A., & Kiernan, M. C. (2013). Cortical hyperexcitability may precede the onset of familial ALS. Brain, 131(6), 1540–1550.