title: Increased symptoms of attention deficit hyperactivity disorder and major depressive disorder symptoms in Nail-patella syndrome: potential association with LMX1B loss-of-function.
abstract: Nail-Patella syndrome (NPS) is an autosomal dominant disorder that is the result of heterozygous loss-of-function mutations in LMX1B, coding for a LIM homeobox (LIM-HD) transcription factor. Analyses of lmx1b mutant mice have revealed the role of Lmx1b in the development of mesencephalic dopaminergic neurons and the serotonergic system; these areas have been linked with symptoms of attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD). Fifty adults (38 females, 12 males) with NPS completed the Conners' Adult ADHD Rating Scales-Self-report: Long Version (CAARS) and Beck Depression Inventory-II (BDI-II). The objective was to describe the neurobehavioral phenotype of these subjects and examine possible relationships between neurobehavioral symptoms and NPS. Elevated levels of DSM-IV-TR ADHD Inattentive symptoms were reported on the CAARS by 22% of the NPS sample. The BDI-II Total score was elevated for 40% of the NPS sample. There was a significant increase in the odds of an elevated BDI-II Total score when any of the three CAARS scales were elevated (odds ratios ranging from 11.455 to 15.615). The CAARS and BDI-II did not significantly differ with gender, age, or education level. There was no significant association between genetic mutation-predicted protein status and elevations on CAARS or BDI-II. Individuals with NPS reported co-occurring symptoms of ADHD and MDD, with higher levels of co-occurrence than reported in the literature for the general population. The co-occurrence of these symptoms may be related to mesencephalic dopaminergic neurologic pathway abnormalities that are a consequence of LMX1B loss of function.
authors.affiliation: Department of Psychiatry, Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: López-Arvizu
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Sparrow
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Strube
authors.forename: Chris
authors.initials: C
authors.lastname: Slavin
authors.forename: Caroline
authors.initials: C
authors.lastname: DeOleo
authors.forename: Justin
authors.initials: J
authors.lastname: James
authors.forename: Julie
authors.initials: J
authors.lastname: Hoover-Fong
authors.forename: Iain
authors.initials: I
authors.lastname: McIntosh
authors.forename: Elaine
authors.initials: E
authors.lastname: Tierney
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications* / Q000235:genetics*; D004252:DNA Mutational Analysis; D003710:Demography; D003865:Major Depressive Disorder / Q000150:complications* / Q000235:genetics; D004493:Education; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D008875:Middle Aged; D009261:Nail-Patella Syndrome / Q000150:complications* / Q000235:genetics*; D016017:Odds Ratio; D057566:Self Report; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors