Psychiatric Perspectives on Juvenile Huntington’s Disease
Joshua R. Smith, MD, is Assistant Professor of Psychiatry and Behavioral Sciences in the Division of Child and Adolescent Psychiatry at Vanderbilt University Medical Center.
I have been a practicing psychiatrist for eight years, three of which have been at Vanderbilt University Medical Center. In the last two years, I founded a clinic focused on psychiatric care for individuals with neurodevelopmental conditions.
During this time, I’ve come to appreciate the profound impact that rapid identification and treatment of psychiatric symptoms can have on those with comorbid neurodevelopmental conditions such as JHD. However, identifying a neurodevelopmental condition as a potential cause of psychiatric symptoms may lead to patients being unable to find a collaborative team of providers willing to address all aspects of clinical care.
In my clinic, I have seen significant improvements in the quality of life for children and adults with neurodevelopmental conditions, when care is addressed collaboratively between neurology, medicine, and psychiatry. Given these observations, I offer the following summary of psychiatric care in JHD with the hope that it will lead to further collaboration, research, and enhanced clinical care for this underserved population.
Huntington’s disease (HD) is a condition that embodies at the interface of neurology, psychiatry, and genetics. There has been growing evidence of HD as a neurodevelopmental disorder, especially when presenting before age twenty-one or ten, defined as juvenile HD (JHD) and childhood-onset HD (COHD).1 In JHD and COHD, psychiatric symptoms may present before motor abnormalitie, and are often identified retrospectively.2 The most common psychiatric symptoms in JHD are impulsivity, aggression, and oppositional behaviors. Patients may also experience suicidal ideation, psychosis, and depression, however, these are less common.2
Diagnostically, these psychiatric symptoms are non-specific. They may occur in a myriad of primary psychiatric conditions, including, but not limited to, the following: depression, bipolar disorder, and schizophrenia. The challenge of diagnosis is further complicated when occurring in children, as symptoms of irritability, impulsivity, and oppositionality are common in many pediatric psychiatric conditions.3–5 Thus, a family and developmental history is critical in assessing a child or an adult when prodromal HD is on the differential.
For a teenager or young adult presenting with an acute change in behavior, a medical workup is often indicated to rule out an identifiable cause. The most well-described and evidence-based recommendations include first-break psychosis6 and autoimmune encephalitis, which include brain MRI in the diagnostic workup.7 Of note, a brain MRI may be of diagnostic utility when there is a concern for JHD, as case reports of patients as young as eight years of age have shown atrophy of caudate nuclei and putamen.8
Genetic testing in psychiatry is most often recommended for neurodevelopmental conditions such as autism and intellectual disability, which are most often diagnosed in childhood.9 However, given that JHD symptoms begin in adolescence or young adulthood, genetic testing should be considered if JHD is on the diagnostic differential based on family and/or developmental history. In summary, when an acute behavioral change occurs in children, adolescents, and young adults, genetic testing and/or a brain MRI to aid in diagnosis may be indicated based on developmental and family histories.
Regarding psychopharmacologic interventions, there are currently no FDA-approved treatments for psychiatric comorbidities in HD. Thus, current practice is developed from expert opinions and research investigating the treatment of psychiatric conditions in the absence of HD.10
As the most common symptoms of JHD are aggression, impulsivity, and irritability, antipsychotics are likely often used to treat behavioral symptoms and manage motor symptomology. In such instances, atypical antipsychotics are preferred due to their improved side effect profile relative to typical antipsychotics. Moreover, consideration of the sedating side effect profile of low-potency antipsychotics versus the increased risk of hyperprolactinemia with high-potency antipsychotics is warranted.2,11 If mood stabilization is required to address irritability, anti-epileptic mood stabilizers such as valproic acid and lamotrigine should be first considered due to the elevated risk of epilepsy in HD.10
Lastly, serotonin reuptake inhibitors (SSRIs) are the preferred treatment of anxiety, depression, and apathy for individuals with HD. However, the risk of an acute worsening of irritability after SSRI initiation and SSRI-induced mania should be reviewed with patients and families.
1 van der Plas E, Schultz JL, Nopoulos PC. The Neurodevelopmental Hypothesis of Huntington’s Disease. J Huntingtons Dis. 2020;9(3):217-229. doi:10.3233/JHD-200394
2 Quigley J. Juvenile Huntington’s Disease: Diagnostic and Treatment Considerations for the Psychiatrist. Curr Psychiatry Rep. 2017;19(2):9. doi:10.1007/s11920-017-0759-9
3 Birmaher B, Brent D. Practice Parameter for the Assessment and Treatment of Children and Adolescents With Depressive Disorders. Journal of the American Academy of Child & Adolescent Psychiatry. 2007;46(11):1503-1526. doi:10.1097/chi.0b013e318145ae1c
4 McClellan J, Kowatch R, Findling RL. Practice Parameter for the Assessment and Treatment of Children and Adolescents With Bipolar Disorder. Journal of the American Academy of Child & Adolescent Psychiatry. 2007;46(1):107-125. doi:10.1097/01.chi.0000242240.69678.c4
5 McClellan J, Stock S. Practice Parameter for the Assessment and Treatment of Children and Adolescents With Schizophrenia. Journal of the American Academy of Child & Adolescent Psychiatry. 2013;52(9):976-990. doi:10.1016/j.jaac.2013.02.008
6 Skikic M, Arriola JA. First Episode Psychosis Medical Workup. Child and Adolescent Psychiatric Clinics of North America. 2020;29(1):15-28. doi:10.1016/j.chc.2019.08.010
7 Tanguturi YC, Hanzlik E, Pagano L, Cundiff AW, Graham TB, Fuchs DC. Anti-NMDAR Encephalitis: Multidisciplinary Development of a Clinical Practice Guideline. Hosp Pediatr. 2021;11(11):1295-1302. doi:10.1542/hpeds.2021-005882
8 Arraj P, Robbins K, Dengle Sanchez L, Veltkamp DL, Pfeifer CM. MRI findings in juvenile Huntington’s disease. Radiol Case Rep. 2020;16(1):113-115. doi:10.1016/j.radcr.2020.10.041
9 Savatt JM, Myers SM. Genetic Testing in Neurodevelopmental Disorders. Frontiers in Pediatrics. 2021;9. Accessed February 20, 2023.
10 Anderson KE, van Duijn E, Craufurd D, et al. Clinical Management of Neuropsychiatric Symptoms of Huntington Disease: Expert-Based Consensus Guidelines on Agitation, Anxiety, Apathy, Psychosis and Sleep Disorders.
J Huntingtons Dis. 2018;7(3):355-366. doi:10.3233/JHD-180293
11 Siafis S, Tzachanis D, Samara M, Papazisis G. Antipsychotic Drugs: From Receptor-binding Profiles to Metabolic Side Effects. Curr Neuropharmacol. 20