Psychiatric comorbidity in relation to clinical characteristics of epilepsy: A retrospective observational study

Revdal, Eline; Kolstad, Bjørn Patrick; Winsvold, Bendik Slagsvold; Selmer, Kaja Kristine; Morken, Gunnar; Brodtkorb, Eylert

doi:10.1016/j.seizure.2023.06.011

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…There is, however, a high variability in behavioral outcomes, distributing into resilient and vulnerable populations in which there is an increased vulnerable population in epileptic mice with HPA axis dysfunction ( Kcc2 / Crh KO mice). Interestingly, the impact of HPA axis dysfunction on comorbid behavioral deficits in chronically epileptic mice is more pronounced in females compared with males, which is consistent with the evidence that there is an increased incidence of psychiatric comorbidities in women with epilepsy ( Gaus et al, 2015 ; Zhu et al, 2022 ; Revdal et al, 2023 ).…”

Section: Discussionsupporting

confidence: 86%

Hypothalamic–Pituitary–Adrenal Axis Dysfunction Elevates SUDEP Risk in a Sex-Specific Manner

Basu,

Antonoudiou,

Weiss

et al. 2024

eNeuro

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Epilepsy is often comorbid with psychiatric illnesses, including anxiety and depression. Despite the high incidence of psychiatric comorbidities in people with epilepsy, few studies address the underlying mechanisms. Stress can trigger epilepsy and depression. Evidence from human and animal studies support that hypothalamic-pituitary-adrenal (HPA) axis dysfunction may contribute to both disorders as well as their comorbidity (Kanner, 2003). Here, we investigate if HPA axis dysfunction may influence epilepsy outcomes and psychiatric comorbidities. We generated a novel mouse model (Kcc2/CrhKO mice) lacking the K+/Cl-co-transporter, KCC2, in corticotropin-releasing hormone (CRH) neurons, which exhibit stress- and seizure-induced HPA axis hyperactivation (Melon et al., 2018). We used theKcc2/CrhKO mice to examine the impact on epilepsy outcomes, including seizure frequency/burden, comorbid behavioral deficits, and SUDEP risk. We found sex differences in HPA axis dysfunction's effect on chronically epileptic KCC2/Crh KO mice seizure burden, vulnerability to comorbid behavioral deficits, and SUDEP. Suppressing HPA axis hyperexcitability in this model using pharmacological or chemogenetic approaches decreased SUDEP incidence, suggesting that HPA axis dysfunction may contribute to SUDEP. Altered neuroendocrine markers were present in SUDEP cases compared to people with epilepsy or individuals without epilepsy. Together, these findings implicate HPA axis dysfunction in the pathophysiological mechanisms contributing to psychiatric comorbidities in epilepsy and SUDEP.Significance StatementOur work provides new insight into a potential novel pathophysiological mechanism contributing to psychiatric illnesses and SUDEP in epilepsy patients, implicating HPA axis dysfunction in negative outcomes associated with epilepsy. This study is the first to link HPA axis dysfunction to SUDEP risk. Chronically epileptic male mice with exaggerated HPA axis dysfunction had increased SUDEP incidence. The translational relevance of these findings is supported by neuroendocrine abnormalities observed in postmortem samples from individuals that died of SUDEP. These data suggest that neuroendocrine mechanisms should be further explored in psychiatric comorbidities in epilepsy and SUDEP risk. Further, neuroendocrine markers may be a biomarker for SUDEP risk.

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Section: Discussionsupporting

confidence: 86%

Hypothalamic–Pituitary–Adrenal Axis Dysfunction Elevates SUDEP Risk in a Sex-Specific Manner

Basu,

Antonoudiou,

Weiss

et al. 2024

eNeuro

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“…This might suggest a more critical role for intrinsic (genetically based) susceptibility factors. This hypothesis is also corroborated by the lower age of seizure onset in persons with focal epilepsy with comorbidities compared to those without [46].…”

Section: Discussionmentioning

confidence: 66%

“…Although the prevalence of behavioural and psychiatric comorbidities generally increases in persons with intellectual disability [43], growing evidence supports the view that the link between epilepsy and neurobehavioral impairments is based on specific neurobiological mechanisms [44], including changes in neurotransmitters/neuromodulators, hypothalamic-pituitary adrenal axis dysfunction, network dysfunction, altered neurogenesis, neurotrophic factors, and neuroinflammation [45]. The complex relationship between epilepsy and its neurobehavioural comorbidities is further suggested by one retrospective observational study in Norway, highlighting how the prevalence of these comorbidities is similar in focal and generalized epilepsies, but significantly higher in focal epilepsy of unknown cause compared to lesional epilepsy, and independent of seizure control [46]. This might suggest a more critical role for intrinsic (genetically based) susceptibility factors.…”

Section: Discussionmentioning

confidence: 99%

Genetic Epilepsies and Developmental Epileptic Encephalopathies with Early Onset: A Multicenter Study

Cavirani,

Spagnoli,

Caraffi

et al. 2024

IJMS

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The genetic causes of epilepsies and developmental and epileptic encephalopathies (DEE) with onset in early childhood are increasingly recognized. Their outcomes vary from benign to severe disability. In this paper, we wished to retrospectively review the clinical, genetic, EEG, neuroimaging, and outcome data of patients experiencing the onset of epilepsy in the first three years of life, diagnosed and followed up in four Italian epilepsy centres (Epilepsy Centre of San Paolo University Hospital in Milan, Child Neurology and Psychiatry Unit of AUSL-IRCCS di Reggio Emilia, Pediatric Neurology Unit of Vittore Buzzi Children’s Hospital, Milan, and Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia). We included 168 patients (104 with monogenic conditions, 45 with copy number variations (CNVs) or chromosomal abnormalities, and 19 with variants of unknown significance), who had been followed up for a mean of 14.75 years. We found a high occurrence of generalized seizures at onset, drug resistance, abnormal neurological examination, global developmental delay and intellectual disability, and behavioural and psychiatric comorbidities. We also documented differing presentations between monogenic issues versus CNVs and chromosomal conditions, as well as atypical/rare phenotypes. Genetic early-childhood-onset epilepsies and DEE show a very wide phenotypic and genotypic spectrum, with a high risk of complex neurological and neuropsychiatric phenotypes.

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“…Anxiety and depression are recognised as two of the most common psychiatric co-morbidities in epilepsy [1] with estimates of approximately one in four people suffering from anxiety and 15 % suffering from mood disorders [2] . Depression has a bidirectional relationship with epilepsy [3] and low mood precedes the diagnosis of epilepsy for many [4] .…”

Section: Introductionmentioning

confidence: 99%

Psychiatric comorbidity in relation to clinical characteristics of epilepsy: A retrospective observational study

Cited by 6 publications

References 39 publications

Hypothalamic–Pituitary–Adrenal Axis Dysfunction Elevates SUDEP Risk in a Sex-Specific Manner

Hypothalamic–Pituitary–Adrenal Axis Dysfunction Elevates SUDEP Risk in a Sex-Specific Manner

Genetic Epilepsies and Developmental Epileptic Encephalopathies with Early Onset: A Multicenter Study

Using the hospital anxiety and depression scale in people with epilepsy: Is overlapping symptomatology a problem?

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