Association of telomere length and mitochondrial DNA copy number with risperidone treatment response in first-episode antipsychotic-naïve schizophrenia

Abstract

Accumulating evidence indicates a putative association of telomere length and mitochondrial function with antipsychotics response in schizophrenia (SCZ). However, pharmacological findings were limited and no previous work has assessed this in a prospective longitudinal study. This study assessed telomere length and mitochondrial DNA copy number in first-episode antipsychotic-naïve SCZ patients with 8-week risperidone treatment to evaluate the association between these biomarkers and clinical treatment response. We recruited 137 first-episode antipsychotic-naive SCZ patients (and 144 controls) at baseline and 89 patients completed the 8-week follow-up. Patients, completed follow-up, were divided into Responders (N = 46) and Non-Responders (N = 43) according to the percentage of symptoms improvement. Linear regression analyses show that SCZ patients had significantly lower mtDNA copy number (β = −0.108, p = 0.002), and no alteration of telomere length when compared with healthy controls. In addition, compared with Non-Responders, Responders had significantly lower mtDNA copy number (β = −0.178, p = 0.001), and longer telomere length (β = 0.111, p = 0.071) before the 8-week treatment. After treatment, Responders persisted lower mtDNA copy number comparing with No-Responders (partial η2 = 0.125, p = 0.001). These findings suggest that telomere length and mtDNA copy number may hold the potential to serve as predictors of antipsychotic response of SCZ patients.

Leukocyte telomere length: Effects of schizophrenia, age, and gender

“…However, one large study reported longer LTL in schizophrenia than in HCs (Nieratschker et al, 2013). Yet other studies have detected no difference in LTL between individuals with schizophrenia and HCs (Li et al, 2015;Malaspina et al, 2014;Mansour et al, 2011). Reasons for discrepancies in findings among these studies are not known, but may include inadequate sample sizes, differing gender distributions, quality of diagnostic evaluations, nature of the comparison sample, chronicity and severity of illness, medical illnesses, medication history, and history of treatment responsiveness, along with demographic and lifestyle factors such as age, diet, body-mass index (BMI), exercise, and tobacco use.…”

“…Thus far, cross-sectional studies have reported mixed results. Several investigations found shorter LTL in persons with schizophrenia than in healthy comparison subjects (HCs) (Fernandez-Egea et al, 2009;Kao et al, 2008) or at least in subgroups of individuals with more chronic, severely psychotic, or treatment-resistant illness (Kota et al, 2015;Li et al, 2015;Rao et al, 2016;Yu et al, 2008) (but see (Lin, 2015)), possibly suggesting accelerated biological aging Kirkpatrick et al, 2008). However, one large study reported longer LTL in schizophrenia than in HCs (Nieratschker et al, 2013).…”

Leukocyte Telomere Length Predicts SSRI Response in Major Depressive Disorder: A Preliminary Report

“…However, few studies have investigated the association between LTL and psychopharmacological outcomes. To date, only three studies (one in bipolar disorder and two in schizophrenia) have examined the relationship between LTL and treatment response to psychiatric medications [18–20], two of which assessed clinical treatment outcomes retrospectively [18, 19]. Martinsson et al [18] retrospectively assessed lithium response in 121 patients with bipolar disorder and found that lithium non-responders had significantly shorter LTL than responders.…”

“…Yu et al [19] retrospectively assessed clinical response to antipsychotics in a group of 68 inpatients with schizophrenia, and found that poorer treatment response was associated with shorter LTL. Li et al [20] assessed telomere length in 89 first-episode, antipsychotic-naïve patients with schizophrenia prior to beginning eight weeks of open-label risperidone treatment, and found that poorer treatment response (<50% symptom improvement after treatment) had shorter LTL. Additionally, a placebo-controlled study by Rasgon et al [21] examined LTL as a predictor of antidepressant response to the addition of Pioglitazone (a peroxisome proliferator-activated receptor [PPAR-γ] agonist) in 42 patients with unremitted MDD who were already attempting to treat their depression with another medication(s).…”

Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and Medication Influence

“…In peripheral samples such as blood, mtDNA copy number has been observed to be decreased in first-episode neuroleptic-naïve subjects with SZ [19]. In addition, differences in copy number were observed between risperidone responders and nonresponders, i.e.…”