Psychiatric comorbid conditions in a clinic population of 241 patients with tuberous sclerosis complex
Introduction
Tuberous sclerosis complex (TSC) is a genetic disease that can manifest itself as hamartomatous growths throughout the body. The most frequently involved organs include the brain, skin, kidneys, heart, eyes, and lungs [1]. Disease-causing mutations have been identified in the TSC1 gene on chromosome 9q34 and the TSC2 gene on chromosome 16p13.3 [2], [3]. In addition to the physical manifestations of the disease, psychiatric comorbidities have been reported at widely varying frequencies. This discrepancy may stem from the variety of measurement techniques utilized, from inter-rater variability between physicians, or from any of the many confounding factors secondary to the disease, such as the impact of epilepsy, cognitive impairment, autism spectrum disorder or pervasive developmental disorder (PDD), seizure medication side effects, or a history of epilepsy surgery.
The rate of psychiatric comorbidity in TSC, while often variable, is consistently high. The four comorbidities reported at the highest rates are depression, anxiety, attention deficit hyperactivity disorder (ADHD), and aggressive/disruptive behaviors (Table 1) [4], [5], [6], [7], [8], [9], [10], [11], [12]. Additional comorbidities previously reported include schizophrenia, Capgras’ syndrome, psychosis, auditory hallucinations, mania, anorexia nervosa, and alcoholism [5], [13], [14], [15], [16], [17].
The present study was designed to assess the frequency of the following psychiatric symptom groups across a clinic population of 241 children and adults with TSC: mood disorders, anxiety disorders, thought disorders, ADHD, aggressive/disruptive behavior disorders, and substance abuse disorders. Relationships were then investigated between these findings and various aspects of the disease.
Section snippets
Patients
All 241 patients meeting clinical criteria for TSC and seen by a single neurologist (EAT) between October 31, 1996 and February 2, 2007, were included in this retrospective chart review [1]. A single researcher (DAM) performed the initial screen of all available medical records for these patients, with subsequent review by a single psychiatrist (PN). 43 of these patients were referred to and seen by at least one of two psychiatrists (ND, PN) affiliated with the TSC clinic: 17 by one (ND), 15 by
TSC clinic population
The average age of our TSC population of 241 patients was 20 years (range eight months to 63.4 years). 118 (49%) were male and 123 (51%) were female. Of cases where history was available, 208 (87%) had a history of epilepsy, 141 (59%) had a history of intractable epilepsy, and 92 (39%) had a history of infantile spasms. Mutational analysis was available on 191 (79%) of these patients. In this group, 50 (26%) had a TSC1 mutation, 106 (56%) had a TSC2 mutation, one (1%) had both, and 34 (18%) had
Discussion
The overall rate of 66% of patients in our population qualifying for at least one psychiatric symptom group represents the substantial magnitude of psychiatric comorbidity in TSC. The challenge will be to determine the underlying causes of these symptoms. Can they be explained by the molecular or morphological underpinnings of the disease? Or are they more likely attributable to some confounding factor(s)? Most importantly, what can be done to minimize the effects of these issues on patients’
Conflict of interest statement
The authors report no conflicts of interest.
Acknowledgment
This study was supported by the Carol and James Herscot Center for Tuberous Sclerosis Complex.
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