Association of Apolipoprotein E ε4 (ApoE ε4) Homozygosity with Psychiatric Behavioral Symptoms

Abstract

To examine the relationship between apolipoprotein E ε4 (ApoE ε4) and psychiatric symptoms, we compared ε4/ε4, ε3/ε3, and ε3/ε4 subjects. 659 outpatients with memory complaints underwent comprehensive neuropsychiatric assessment interview and neurological examination and ApoE genotyping: 98 were ε4/ε4. 18.4% (n = 18) ε4/ε4, 19.3% (n = 45) ε3/ε4, and 5.4% (n = 14) ε3/ε3 presented with symptoms of anxiety (p = 0.00001). ε4/ε4 patients with mild cognitive impairment (MCI; p < 0.0001) and those with Alzheimer's disease with late onset (p = 0.0175) were the most frequently affected. For anxiety, there were no gender dependent differences in the two homozygous groups, however, in the ε3/ε4 group, anxiety symptoms were evident in 7.3% (n = 8) of the male versus 30.1% (n = 37) of the female ε3/ε4 heterozygotes (p < 0.0001). Depression was found in 20.4% (n = 20) ε4/ε4 and 21.0% (n = 49) ε3/ε4 compared to 17.1% (n = 44) ε3/ε3 (p = 0.5181). Visual hallucinations were reported in 5.1% (n = 5) ε4/ε4 as opposed to 3.8% (n = 9) ε3/ε4 and 2.3% (n = 6) ε3/ε3 (p = 0.5278). We have seen a higher association of anxiety with the ApoE ε4 allele across all stages of disease and what may be a dosing effect in the early stage (MCI) for this ostensible risk, since we see a significantly higher frequency in the ApoE ε4 homozygotes when compared to the heterozygotes.

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Anxiety is associated with increased risk of dementia in older Swedish twins

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“…23 There may be differences in neuropsychiatric symptoms observed in patients who are homozygous for the APOE E4 allele as opposed to heterozygous. Michels et al 24 found that patients who were homozygous for the APOE E4 allele had the highest rates of anxiety, higher rates of depression than those who did not carry the E4 allele, and higher rates of hallucinations than those who were either heterozygous or did not carry the allele. Van der Flier et al 25 also noted that there may be a dose effect of the E4 allele, finding that those patients who were homozygous for the E4 allele were more likely to have delusions and agitation/aggression.…”