Assessment of parent-of-origin effect in familiesunlineally affected with panic disorder-agoraphobia

Abstract

While the mode of transmission of psychiatric disorders remains elusive new paradigms to investigate the genetics of mental illnesses + Kennedy 0884# are sug! gested by the recent _ndings reported by some but not studies of bipolar illness and schizophrenia McMa! hon et al[ 0884^ Petronis + Kennedy 0884# of tri! nucleotide repeat TNR# ampli_cations i[e[ genetic mutations where quantitative changes in phenotype cor! respond to the size of the expansion of one group of simple trinucleotides repeats# the related phenomena of anticipation i[e[ the decrease of age at onset or the increase in severity in successive generations# and parent! of!origin e}ect i[e[ di}erential expression of diseases alleles depending on whether the genetic material has come from the mother or the father#[ Our recent _nding of anticipation of age at onset of _rst panic attack and of panic disorder!agoraphobia PDA# et al 0887# led us to assess the possible presence of a parent!of!origin e}ect in the same set of pedigrees[ This investigation is based on a family study of thirty! eight unilineal multigenerational families with multiple subjects with PDA taken from a study group of 440 consecutive outpatients[ This was an extension of a pre! vious study group with the original recruitment and methods unchanged et al[ 0884^ Battaglia et al[ 0887#[ Direct interviews with 54) of all living _rst! and second!degree relatives n 212# were and 61) of all a}ected relatives were directly interviewed while family histories from multiple informants were obtained for the remaining subjects n 063#[ In addition to the transmission of disease!related tri! nucleotide repeats from a parent to his:her o}spring Paulson + Fischbeck 0885# an observed parent!of! origin e}ect can derive from mitochondrial inheritance Hall et al[ 0889# and genomic imprinting Skuse et al[ 0886#[