Apolipoprotein E-ε4 allele predicts escalation of psychotic symptoms in late adulthood

Jonas, Katherine; Clouston, Sean; Li, Kaiqiao; Fochtmann, Laura J.; Lencz, Todd; Malhotra, Anil K.; Cicero, David C.; Bromet, Evelyn J.; Kotov, Roman

doi:10.1016/j.schres.2018.12.010

Cited by 10 publications

(10 citation statements)

References 63 publications

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“…Recent meta-analyses and longitudinal analyses have suggested APOE-ε4 as an age-related risk factor for aggressive hallucinations and delusions, and as having an age-mediated pathophysiological role in schizophrenia. This finding could support those individuals with the APOE-ε4 allele being treated with more intensive monitoring and additional interventions in mid-to-late life [ 65 ]. However, these results need to be replicated in other clinical studies.…”

Section: Precision Medicine In Late-onset Psychosismentioning

confidence: 79%

Clinical Approaches to Late-Onset Psychosis

Kim

Jeon

Myung

et al. 2022

JPM

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Psychosis can include schizophrenia, mood disorders with psychotic features, delusional disorder, active delirium, and neurodegenerative disorders accompanied by various psychotic symptoms. Late-onset psychosis requires careful intervention due to the greater associated risks of secondary psychosis; higher morbidity and mortality rates than early-onset psychosis; and complicated treatment considerations due to the higher incidence of adverse effects, even with the black box warning against antipsychotics. Pharmacological treatment, including antipsychotics, should be carefully initiated with the lowest dosage for short-term efficacy and monitoring of adverse side effects. Further research involving larger samples, more trials with different countries working in consortia, and unified operational definitions for diagnosis will help elaborate the clinical characteristics of late-onset psychosis and lead to the development of treatment approaches.

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Section: Precision Medicine In Late-onset Psychosismentioning

confidence: 79%

Clinical Approaches to Late-Onset Psychosis

Kim

Jeon

Myung

et al. 2022

JPM

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“…By comparing the above studies, we speculate that these different results between our current study and other studies may be partly due to differences in population, sample composition, type of schizophrenia, and synergy/interaction effects with other variants. Also, the age of patients could be a potential reason, and a meta-analysis indicated that ApoE -ε4 may play an age-mediated pathophysiological role in schizophrenia [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

“…One possible reason for this is that the combined effect of rs429358 and rs7412, but not rs429358 alone, has a significant effect on the PANSS score of patients with schizophrenia. Furthermore, a longitudinal study found that ApoE -ε4 predicted worsening severity of hallucinations and delusions in patients with schizophrenia in late adulthood [ 63 ]. Hence, it is worth to perform a follow-up study between ApoE rs429358 and subsequent PANSS scores.…”

Section: Discussionmentioning

confidence: 99%

Association between clinical symptoms and apolipoprotein A1 or apolipoprotein B levels is regulated by apolipoprotein E variant rs429358 in patients with chronic schizophrenia

Rao

Meng

et al. 2021

Ann Gen Psychiatry

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Background The apolipoprotein E (ApoE) gene polymorphisms are correlated with blood lipid levels and several neuropsychiatric symptoms. Therefore, this study aimed to examine whether the ApoE rs429358 affected the development and clinical symptoms of schizophrenia and to explore the relationship between apolipoproteins levels and clinical symptoms. Methods The ApoE rs429358 was genotyped using a case–control design. The Positive and Negative Syndrome Scale (PANSS) was employed to evaluate the psychopathology of all patients. Results A total of 637 patients with schizophrenia and 467 healthy controls were recruited. We found no significant differences in the genotype and allele distribution between the patient and control groups. A significant correlation between PANSS negative symptoms and ApoA1 levels (p = 0.048) or ApoB levels (p = 0.001) was found in patients with schizophrenia, which was also confirmed by linear regression analyses (p = 0.048 vs. p = 0.001). Interestingly, only in the T homozygote group, ApoA1 and ApoB levels were predictors of the PANSS negative symptom score (p = 0.008 vs. p = 0.012), while in the C allele carrier group, no correlation was observed. Conclusions This study found that the levels of ApoA1 and ApoB were negatively associated with negative symptoms of patients with schizophrenia. Furthermore, the association between ApoA1 or ApoB levels and psychopathology of schizophrenia was regulated by ApoE rs429358.

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“…APOE ε3 is the most frequent allele, whereas the ε4 allele is the most common genetic risk factor for AD, leading to an earlier onset of the disease as well [ 88 ]. Furthermore, APOE ε4 has been linked to hallucinations and delusions in AD patients [ 89 ], and may be also an age-related risk factor for the worsening of delusions and hallucinations in patients with schizophrenia [ 90 ]. In PD, the APOE ε4 allele has been also associated with earlier disease onset [ 91 , 92 ] and a greater risk of dementia [ 93 ], although there is also evidence that does not confirm these relationships [ 92 , 94 ].…”

Section: Genetic Architecture Of Psychosis In Parkinson’s Diseasementioning

confidence: 99%

Psychosis in Parkinson’s Disease: A Lesson from Genetics

Angelopoulou

Bougea

Papageorgiou

et al. 2022

Genes

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Psychosis in Parkinson’s disease (PDP) represents a common and debilitating condition that complicates Parkinson’s disease (PD), mainly in the later stages. The spectrum of psychotic symptoms are heterogeneous, ranging from minor phenomena of mild illusions, passage hallucinations and sense of presence to severe psychosis consisting of visual hallucinations (and rarely, auditory and tactile or gustatory) and paranoid delusions. PDP is associated with increased caregiver stress, poorer quality of life for patients and carers, reduced survival and risk of institutionalization with a significant burden on the healthcare system. Although several risk factors for PDP development have been identified, such as aging, sleep disturbances, long history of PD, cognitive impairment, depression and visual disorders, the pathophysiology of psychosis in PD is complex and still insufficiently clarified. Additionally, several drugs used to treat PD can aggravate or even precipitate PDP. Herein, we reviewed and critically analyzed recent studies exploring the genetic architecture of psychosis in PD in order to further understand the pathophysiology of PDP, the risk factors as well as the most suitable therapeutic strategies.

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Apolipoprotein E-ε4 allele predicts escalation of psychotic symptoms in late adulthood

Cited by 10 publications

References 63 publications

Clinical Approaches to Late-Onset Psychosis

Clinical Approaches to Late-Onset Psychosis

Association between clinical symptoms and apolipoprotein A1 or apolipoprotein B levels is regulated by apolipoprotein E variant rs429358 in patients with chronic schizophrenia

Psychosis in Parkinson’s Disease: A Lesson from Genetics

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