Schizophrenia or Neurodegenerative Disease Prodrome? Outcome of a First Psychotic Episode in a 35-Year-Old Woman

Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Psychosomatics (Impact Factor: 1.86). 01/2012; 53(3):280-4. DOI: 10.1016/j.psym.2011.04.005
Source: PubMed


C ontrary to common clinical assumptions, neurode-generative disease can begin as early as the third decade of life, and some of these young patients present with isolated neuropsychiatric rather than cognitive symp-toms. These cases can exemplify the diagnostic overlap between psychiatric and neurological disease, as well as the procedural gaps that sometimes occur between psychi-atric and neurological clinical services. While technically these patients present with a psychiatric disorder, the cause of their symptoms is a specific neuropathologic disease that in many cases may be identifiable by genetic testing or a careful family history. Symptomatic and even disease-modifying treatments for some of these neurodegenerative diseases are currently in clinical trials and, thus, it is becoming increasingly urgent that clinicians recognize these "zebras" early in the disease process. Retrospective examination of these patients' clinical course may yield important information to improve diagnostic accuracy in the future. We report the case of a young woman who was initially diagnosed with schizophrenia in her 30s, but was found to have a rare genetic mutation in a -related gene, which together with a specific pattern of brain atrophy, pre-dict a 3R -opathy, i.e., frontotemporal lobar degeneration (FTLD) with Pick's neuropathology. 1 This suggests that the more appropriate clinical diagnosis for this patient was be-havioral variant frontotemporal dementia (bvFTD), a diag-nosis that could have led to an entirely different clinical care plan.

Download full-text


Available from: Joshua D Woolley, Apr 25, 2014
53 Reads
  • Source
    • "Johnson and colleagues reported psychotic features in one patient with a valosin-containing protein gene VCP mutation [34]. Psychosis has only infrequently been reported in families with microtubule-associated protein tau gene MAPT mutations [35,36]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Earlier reports of chromosome 9p-linked frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS) kindreds observed psychosis as a prominent feature in some patients. Since the discovery of chromosome 9 open reading frame 72 (C9orf72) hexanucleotide expansions as a cause of FTD and ALS, research groups and consortia around the world have reported their respective observations of the clinical features associated with this mutation. We reviewed the recent literature on C9orf72-associated FTD and ALS with focus on the neuropsychiatric features associated with this mutation, as well as the experience at University of California, San Francisco. The results and methodologies varied greatly across studies, making comparison of results challenging. Four reports found that psychotic features (particularly delusions) were frequent among mutation carriers, particularly when present early during the disease course, suggesting that this symptom category may be a marker for the mutation. Disinhibition and apathy were the most commonly reported early behavioral symptoms, but these may not be helpful in distinguishing carriers and noncarriers because of the symptoms' frequency in sporadic behavioral variant FTD. Other neuropsychiatric features were reported in different frequencies across studies, suggesting either a similar behavioral phenotype in carriers and noncarriers or reflecting the heterogeneity in clinical presentation of behavioral variant FTD due to C9orf72 expansions. Further studies with larger cohorts will be necessary to determine the neuropsychiatric presentation associated with this mutation.
    Alzheimer's Research and Therapy 10/2012; 4(5):38. DOI:10.1186/alzrt141 · 3.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The clinical, neuropsychiatric and neuroimaging features of patients who carry the important new C9ORF72 mutation are discussed in this special series of Alzheimer's Research & Therapy. First reported in November 2011, the C9ORF72 mutation is the most common mutation associated with both frontotemporal dementia and amyotrophic lateral sclerosis in the Western hemisphere and Europe. It is a gene with strong penetrance, and the vast majority of subjects with the C9ORF72 mutation die from a neurodegenerative condition. The most common clinical manifestation of disease in gene carriers is behavioral variant frontotemporal dementia. An extremely long hexanucleotide repeat (usually greater than 400), appears to lead to ribonucleic acid aggregates within the nucleus and suppression of gene expression. Finding therapies for C9ORF72 will be difficult and require novel therapeutic approaches that involve suppression of the expression of the C9ORF72 repeat.
    Alzheimer's Research and Therapy 02/2013; 5(1):7. DOI:10.1186/alzrt161 · 3.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia is a relatively common disorder diagnosed by the presentation of psychotic symptoms in the absence of identifiable neurologic or other organic cause. Frontotemporal dementia (FTD) is a relatively rare progressive neurodegenerative disorder that can present with a multitude of cognitive and behavioral symptoms including psychosis. At times, this phenotypic overlap can mean that schizophrenia and FTD are 2 possibilities in the differential diagnosis of a psychotic presentation. In this article, we systematically review the literature on the relationship between schizophrenia and FTD including case reports that highlight the potential for diagnostic confusion, clinical studies examining the relationship between the disorders, and the molecular evidence of shared pathophysiologic mechanisms. Although a relationship between the disorders is not definitively supported by the current literature, we identify the characteristics of a psychotic presentation that should alert the clinician to the possibility of FTD and describe the areas where further research is needed to clarify the pathophysiologic relationship.
    Journal of Geriatric Psychiatry and Neurology 06/2013; 26(3). DOI:10.1177/0891988713490992 · 2.24 Impact Factor
Show more