Mental health conditions in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVES: The reported prevalence of mental health conditions (MHCs) in people with systemic lupus erythematosus (SLE) ranges widely. Whether MHCs are associated with increased risk of SLE or the outcomes of the disease is unclear. This paper aimed to conduct an umbrella and updated meta-analysis of MHCs in people with SLE and to identify whether MHCs are associated with the risk of SLE or patient outcomes. METHODS: We comprehensively searched PubMed, Web of Science, and Embase databases to identify relevant studies published before June 2023. Random-effect models were used to calculate the pooled prevalence and risk ratios for each MHC. RESULTS: 203 studies with 1485094 individuals were included. The most MHCs observed in patients with SLE were sleep disturbance (59.7% [95% CI, 52.4%-66.8%]) among adults and cognitive dysfunction (63.4% [95% CI, 46.9%-77.9%]) among children. We found that depressive disorders (RR = 2.30, 95% CI = 1.94-2.75) and posttraumatic stress disorder (RR = 1.93, 95% CI = 1.61-2.31) in the general population were significantly associated with an increased likelihood of developing SLE. Furthermore, concurrent MHCs were linked to unfavorable outcomes in patients with SLE, such as decreased quality of life, increased risk of unemployment, and other somatic comorbidities. CONCLUSION: Our study demonstrated a high prevalence of MHCs among patients with SLE. Individuals with pre-existing mental disorders exhibited an elevated susceptibility to developing SLE, and patients presenting with MHCs were at increased risk of experiencing suboptimal health and functional outcomes. Therefore, evaluating and preventing MHCs should be considered as an integral component of the comprehensive treatment strategy for SLE.

Virtual reality-based cognitive-behavioural therapy for the treatment of anxiety in patients with acute myocardial infarction: a randomised clinical trial.

Background: The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction (AMI), significantly disrupting their recovery. Providing timely and easily accessible psychological interventions using virtual reality-based cognitive-behavioural therapy (VR-CBT) could potentially improve both acute and long-term symptoms affecting their mental health. Aims: We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit (ICU) during the acute stage of their illness. Methods: In this single-blind randomised clinical trial, participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February 2023. Patients who were Han Chinese aged 18-75 years were randomly assigned (1:1) via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support, or the control group to receive standard mental health support only. VR-CBT consisted of four modules and was delivered at the bedside over a 1-week period. Assessments were done at baseline, immediately after treatment and at 3-month follow-up. The intention-to-treat analysis began in June 2023. The primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale (HAM-A). Results: Among 148 randomised participants, 70 were assigned to the VR-CBT group and 78 to the control group. The 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention (Cohen's d=-1.27 (95% confidence interval (CI): -1.64 to -0.90, p<0.001) and 3-month follow-up (Cohen's d=-0.37 (95% CI: -0.72 to -0.01, p=0.024). Of the 70 participants who received VR-CBT, 62 (88.6%) completed the entire intervention. Cybersickness was the main reported adverse event (n=5). Conclusions: Our results indicate that VR-CBT can significantly reduce post-AMI anxiety at the acute stage of the illness; the improvement was maintained at the 3-month follow-up. Trial registration number: The trial was registered at www.chictr.org.cn with the identifier: ChiCTR2200066435.

Painful physical symptoms and antidepressant treatment outcome in depression: a systematic review and meta-analysis.

BACKGROUND: Painful physical symptoms (PPS) are highly prevalent in patients with major depressive disorder (MDD). Presence of PPS in depressed patients are potentially associated with poorer antidepressant treatment outcome. We aimed to evaluate the association of baseline pain levels and antidepressant treatment outcomes. METHODS: We searched PubMed, Embase and Cochrane Library databases from inception through February 2023 based on a pre-registered protocol (PROSPERO: CRD42022381349). We included original studies that reported pretreatment pain measures in antidepressant treatment responder/remitter and non-responder/non-remitter among patients with MDD. Data extraction and quality assessment were performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses by two reviewers independently. The primary outcome was the difference of the pretreatment pain levels between antidepressant treatment responder/remitter and non-responder/non-remitter. Random-effects meta-analysis was used to calculate effect sizes (Hedge's g) and subgroup and meta-regression analyses were used to explore sources of heterogeneity. RESULTS: A total of 20 studies were included. Six studies reported significantly higher baseline pain severity levels in MDD treatment non-responders (Hedge's g = 0.32; 95% CI, 0.13-0.51; P = 0.0008). Six studies reported the presence of PPS (measured using a pain severity scale) was significantly associated with poor treatment response (OR = 1.46; 95% CI, 1.04-2.04; P = 0.028). Five studies reported significant higher baseline pain interference levels in non-responders (Hedge's g = 0.46; 95% CI, 0.32-0.61; P < 0.0001). Four studies found significantly higher baseline pain severity levels in non-remitters (Hedge's g = 0.27; 95% CI, 0.14-0.40; P < 0.0001). Eight studies reported the presence of PPS significantly associated with treatment non-remission (OR = 1.70; 95% CI, 1.24-2.32; P = 0.0009). CONCLUSIONS: This study suggests that PPS are negatively associated with the antidepressant treatment outcome in patients with MDD. It is possible that better management in pain conditions when treating depression can benefit the therapeutic effects of antidepressant medication in depressed patients.

Association between sleep duration, sleep quality, bedtime and myopia: A systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis to investigate the links between different sleep characteristics and risk of myopia. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, PsycINFO, Wanfang, and CNKI were searched from inception to August 26, 2022, without any language restriction. Cross-sectional, case-control, or cohort studies that explored the association between sleep duration, sleep quality, bedtime, and myopia were included. NIH quality assessment tools were used to assess the methodological quality of included studies. Random-effect or fixed-effect models were used to pool the associations according to whether there is heterogeneity. RESULTS: A total of 31 studies with 205 907 participants were included in the final analysis (25 studies reporting sleep duration; four studies examining sleep quality and six studies evaluating bedtime). Compared to reference sleep duration, sufficient sleep duration (OR = 0.63, 95% CI = 0.51-0.78) was associated with a lower risk of myopia, and short sleep duration (OR = 1.66, 95% CI = 1.14-2.42) was associated with a higher risk of myopia. In addition, poor sleep quality (OR = 1.24, 95% CI = 1.05-1.47) was associated with a higher risk of myopia while late bedtime (OR = 1.30, 95% CI = 0.96-1.75) was not significantly associated with an increased risk of myopia. CONCLUSIONS: Alteration in sleep duration and sleep quality may influence the risk of myopia. Well-designed cohort studies are needed in future investigations to identify a causal relationship between different sleep characteristics and myopia.

Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis.

Predicting antidepressant treatment response has been a clinical challenge for major depressive disorder (MDD). The inflammation hypothesis of depression suggests that cytokines play a key role in the pathophysiology of MDD and alterations in peripheral cytokine levels are associated with antidepressant treatment outcome. Present meta-analysis aimed to examine the association between baseline peripheral cytokine levels and the response to antidepressant treatment and to evaluate whether changes of cytokine levels were associated with the response to antidepressant treatment in patients with MDD. Human-based studies published in any language in peer-reviewed journals were systematically searched from the PubMed, Embase and Web of Science databases, from inception up to October 2018. The search terms included cytokine, depressive disorder and antidepressant and their synonyms. Case-control or case-case studies reporting on levels of IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, CRP, TNF-α, IFN-γ, GM-CSF, MIP-1α, and Eotaxin-1 in patients with MDD based on validated depression scales both before and after antidepressant treatment were included. Of 7408 identified records, 44 studies met inclusion. Standardized mean differences in each cytokine were evaluated, and random-effects meta-analyses were performed. MDD patients who responded to antidepressant treatment had lower baseline IL-8 levels than the nonresponders (Hedge's g = -0.28; 95%CI, -0.43 to -0.13; P = 0.0003; FDR = 0.004). Antidepressant treatment significantly decreased levels of TNF-α (Hedge's g = 0.60; 95%CI, 0.26-0.94; P = 0.0006; FDR = 0.004) only in responders, and responders showed significantly more decreased TNF-α levels compared with nonresponders (P = 0.046). These findings suggested that alterations in peripheral cytokine levels were associated with antidepressant treatment outcomes in MDD. Further investigations are warranted to elucidate sources of heterogeneity and examine the potentiality of using inflammatory cytokines as novel predictive markers for the pharmacological treatment of MDD.

A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression.

Predicting antidepressant response has been a clinical challenge for mood disorder. Although several genome-wide association studies have suggested a number of genetic variants to be associated with antidepressant response, the sample sizes are small and the results are difficult to replicate. Previous animal studies have shown that knockout of the serotonin receptor 7 gene (HTR7) resulted in an antidepressant-like phenotype, suggesting it was important to antidepressant action. In this report, in the first stage, we used a cost-effective pooled-sequencing strategy to sequence the entire HTR7 gene and its regulatory regions to investigate the association of common variants in HTR7 and clinical response to four selective serotonin reuptake inhibitors (SSRIs: citalopram, paroxetine, fluoxetine and sertraline) in a retrospective cohort mainly consisting of subjects with bipolar disorder (n = 359). We found 80 single-nucleotide polymorphisms (SNPs) with false discovery rate < 0.05 associated with response to paroxetine. Among the significant SNPs, rs7905446 (T/G), which is located at the promoter region, also showed nominal significance (P < 0.05) in fluoxetine group. GG/TG genotypes for rs7905446 and female gender were associated with better response to two SSRIs (paroxetine and fluoxetine). In the second stage, we replicated this association in two independent prospective samples of SSRI-treated patients with major depressive disorder: the MARS (n = 253, P = 0.0169) and GENDEP studies (n = 432, P = 0.008). The GG/TG genotypes were consistently associated with response in all three samples. Functional study of rs7905446 showed greater activity of the G allele in regulating expression of HTR7. The G allele displayed higher luciferase activity in two neuronal-related cell lines, and estrogen treatment decreased the activity of only the G allele. Electrophoretic mobility shift assay suggested that the G allele interacted with CCAAT/enhancer-binding protein beta transcription factor (TF), while the T allele did not show any interaction with any TFs. Our results provided novel pharmacogenomic evidence to support the role of HTR7 in association with antidepressant response.

Publisher Correction: Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ambient fine particulate matter is associated with increased emergency ambulance dispatches for psychiatric emergencies.

AIMS: As a top ambient pollutant in urban area, fine particulate matter (PM2.5) has been associated with the occurrence and deterioration of many medical conditions, while limited studies have observed the association with psychiatric conditions. This study aimed to investigate the association between short-term PM2.5 exposure and psychiatric emergency events, and further explored the variation by age, sex and seasonal patterns, which have been suggested to be associated with both psychiatric risk and pollutant toxicity. METHODS: We used time-series analysis to investigate the association between short-term exposure of PM2.5 and emergency ambulance dispatches for psychiatric emergencies (EPE) (n = 158634) in Beijing, one of the top polluted cities in China during the study period between 2008 and 2014. Stratified analyses were conducted to examine the effects of age, sex and seasonal pattern. RESULTS: Every 10 µg/m3 increase of the PM2.5 concentration was associated with a 0.12% increase of the same-day overall EPE (95% CI: 0.03-0.22%, p = 0.013) and a 0.12% increase of the suicide-related EPE at lag 2 (95%CI: 0.01-0.24%, p = 0.041). The associations remained when adjusted for sunlight duration. An age effect was observed where children (age <18) showed a higher risk of suicide-related EPE after PM2.5 exposure compared to adults (18 ≤ age≤64). We did not observe evidence of effect modification by sex and season based on the results of stratified analysis. CONCLUSIONS: We found a positive association between acute PM2.5 exposure and increased psychiatric emergency presentations indicated by emergency ambulance dispatches data. Children were more vulnerable and might develop psychiatric problems including those leading to suicide. Public awareness of the health risks of PM2.5 is important to strengthen current efforts to reduce emissions.

Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment.

Mitochondrial pathology has been implicated in the pathogenesis of psychotic disorders. A few studies have proposed reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder type I, compared to healthy controls. However, it is unknown if mtDNA copy number alteration is driven by psychosis, comorbidity or treatment. Whole blood mtDNA copy number was determined in 594 psychosis patients and corrected for platelet to leukocyte count ratio (mtDNAcnres). The dependence of mtDNAcnres on clinical profile, metabolic comorbidity and antipsychotic drug exposure was assessed. mtDNAcnres was reduced with age (ß = -0.210, p < 0.001), use of clozapine (ß = -0.110,p = 0.012) and risperidone (ß = -0.109,p = 0.014), dependent on prescribed dosage (p = 0.006 and p = 0.026, respectively), and the proportion of life on treatment (p = 0.006). Clozapine (p = 0.0005) and risperidone (p = 0.0126) had a reducing effect on the mtDNA copy number also in stem cell-derived human neurons in vitro at therapeutic plasma levels. For patients not on these drugs, psychosis severity had an effect (ß = -0.129, p = 0.017), similar to age (ß = -0.159, p = 0.003) and LDL (ß = -0.119, p = 0.029) on whole blood mtDNAcnres. Further research is required to determine if mtDNAcnres reflects any psychosis-intrinsic mitochondrial changes.

Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.

Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids.

Stress, depressive status and telomere length: Does social interaction and coping strategy play a mediating role?

BACKGROUND: Telomeres have been reported to be shorter in individuals exposed to psychosocial stress and in those with depression. Since negative environmental stress is a risk factor for depression, the present study tested whether stressors in childhood (CA) and recent adulthood (NLE) predicted telomere attrition directly and/or indirectly through individuals' depressive status 3-6 years before TL measurement; and then if social interaction and coping strategies in adulthood influenced the relationship between depressive status and TL. METHODS: Participants were 337 individuals with a recent depression diagnosis and 574 screened controls that derived from a longitudinal population-based cohort study conducted in Stockholm, Sweden. Relative TL was determined using qPCR. Relationships between the key variables stressors, depressive status, social interaction, coping strategies and TL were explored by path analysis in males and females, adjusting for age. RESULTS: The key variables were correlated in expected directions. In females, depressive status and age had direct negative effects on TL (p < 0.05) and both CA (p = 0.025) and NLE (p < 0.003) had indirect negative effects on TL. For males, the effects of stressors and depressive status on TL were mediated by social interaction (p = 0.005) and the coping strategy worry (p = 0.005). In females, no mediation effect of social interaction and coping strategy was detected. LIMITATIONS: Only little of the TL variation was explained by the models. The environmental stress information was limited. CONCLUSION: Our findings propose gender-specific paths from environmental stressors through depressive status, social interaction and coping strategy to TL.

Interleukin-6 and depressive symptom severity in response to physical exercise.

Elevated IL-6 has been implicated in depression. The anti-inflammatory effects of exercise may be associated with its clinical efficacy for depression. We determined if serum IL-6 levels were altered by 12 weeks of physical exercise, and if IL-6 levels were associated with baseline depression severity and change in depression severity in response to exercise. Data from 116 adults (42.7±11.5y) with mild-to-moderate depression (Patient Health Questionnaire >9) who participated in the physical exercise arm of the Regassa RCT (www.regassa.se) were analyzed. Participants were requested to complete three 60-min exercise sessions weekly for 12 weeks. Blood samples were provided at baseline and post-intervention following an overnight fast and were analyzed for serum levels of IL-6 using ELISA. IL-6 values were logarithm-transformed. Higher baseline serum IL-6 levels were significantly associated with reduced depression severity after exercise. Reduced IL-6 levels following exercise were significantly associated with parallel reductions in depression severity. These findings are consistent with a previously reported association between reduced serum IL-1ß levels and reduced depression severity following 12 weeks of physical exercise in 105 depressed adults. Findings support associations between IL-6, depressive symptoms, and exercise response, and provide support for the plausible involvement of IL-6 in the antidepressive effect of exercise.

TERT rs2736100 genotypes are associated with differential risk of myeloproliferative neoplasms in Swedish and Chinese male patient populations.

The telomerase reverse transcriptase (TERT) gene rs2736100_C allele has recently been shown to be associated with an increased risk for myeloproliferative neoplasms (MPNs) among Caucasians. However, it is unknown if this association is present in other ethnical populations and whether rs2736100 allele frequencies mirror the incidence of MPNs in a population. Here we genotyped TERT rs2736100 variants in 126 Swedish and 101 Chinese MPN patients and their age-, sex-, and ethnically-matched healthy controls. Healthy Chinese adults had a higher frequency of the A allele and lower frequencies of the C allele compared to Swedish counterparts (57.4 vs 47.0 % for A, 42.6 vs 53.0 % for C, P = 0.006). Both Swedish and Chinese patients harbored significantly higher C allele frequency than their controls (62.7 vs 53.0 % and 57.4 vs 42.6 % for Swedish and Chinese, respectively, P = 0.004). Swedes and Chinese bearing the CC genotype had a significantly increased risk of MPN compared to AA carriers (OR = 2.47; 95 % CI: 1.33-4.57, P = 0.003, for Swedes, and OR = 3.45; 95 % CI: 1.52-7.85, P = 0.005, for Chinese). Further analyses showed that rs2736100_CC was associated with robustly enhanced risk in males only (CC vs AA, OR = 5.11; 95 % CI: 2.19-11.92, P < 0.0001). The CC-carrying MPN patients exhibited significantly higher TERT expression than patients with the AC genotype. Collectively, the rs2736100_C is a risk allele for MPNs in Swedish and Chinese males, and the lower incidence of MPNs in the Chinese population is correlated with a lower rs2736100_C risk allele frequency.

MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro.

BACKGROUND: MicroRNAs (miRNAs) are small regulatory molecules that cause translational repression by base pairing with target mRNAs. Cumulative evidence suggests that changes in miRNA expression may in part underlie the pathophysiology and treatment of neuropsychiatric disorders, including major depressive disorder (MDD). METHODS: A miRNA expression assay that can simultaneously detect 423 rat miRNAs (miRBase v.17) was used to profile the prefrontal cortex (PFC) of a genetic rat model of MDD (the Flinders Sensitive Line [FSL]) and the controls, the Flinders Resistant Line (FRL). Gene expression data from the PFC of FSL/FRL animals (GEO accession no. GSE20388) were used to guide mRNA target selection. Luciferase reporter assays were used to verify miRNA targets in vitro. RESULTS: We identified 23 miRNAs that were downregulated in the PFC of the FSL model compared with controls. Interestingly, one of the identified miRNAs (miR-101b) is highly conserved between rat and human and was recently found to be downregulated in the PFC of depressed suicide subjects. Using a combination of in silico and in vitro analyses, we found that miR-101b targets the neuronal glutamate transporter SLC1A1 (also known as EAAC1 or EAAT3). Accordingly, both mRNA and protein levels of SLC1A1 were found to be upregulated in the PFC of the FSL model. CONCLUSIONS: Besides providing a list of novel miRNAs associated with depression-like states, this preclinical study replicated the human association of miR-101 with depression. In addition, since one of the targets of miR-101b appears to be a glutamate transporter, our preclinical data support the hypothesis of a glutamatergic dysregulation being implicated in the etiology of depression.

hTERT genetic variation in depression.

BACKGROUND: Telomeres are protective DNA-protein complexes forming the chromosome ends. TL differs between tissues. Shorter telomere length (TL) in blood leukocytes (LTL) has been associated with major depression, and with previous exposure to childhood adversity. TL studies on non-invasively sampled salivary DNA are less common. Telomerase, with its catalytic subunit hTERT, counteracts telomere shortening. Reduced telomerase activity associates with depression-like behavior in mice. Recently, the minor allele of the hTERT polymorphism rs2736100 was associated with shorter LTL among primarily healthy individuals. We hypothesized that (i) TL in saliva DNA is shortened in adults with a history of depression, and that (ii) rs2736100 is implicated in depression and depressive episodes in bipolar disorder type 1 (BD1). METHODS: Individuals with a history of depression and those without (controls) were identified using self-reported questionnaires from a well-characterized population-based cohort. Clinical BD1 patients were diagnosed by specialized psychiatrists. Saliva TL was measured in age-matched depressed individuals and controls (n=662) using qRT-PCR. rs2736100 was genotyped in 436 depressed individuals, 1590 controls, and 368 BD1 patients. RESULTS: Saliva TL was shorter in depressed individuals compared to controls. The rs2736100 minor allele was associated with depression among those without experience of childhood adversity, and with number of depressive episodes in BD1 patients responding well to lithium. LIMITATION: Psychopathological symptoms were recorded at two time points only, 3 and 6 years prior to DNA sampling. CONCLUSIONS: This is the first report on hTERT genetic variation in mood disorder. It proposes that genetic variation in hTERT may influence the susceptibility to depression.

Telomerase dysregulation in the hippocampus of a rat model of depression: normalization by lithium.

BACKGROUND: Telomeres are protective DNA-protein complexes at the ends of each chromosome, maintained primarily by the enzyme telomerase. Shortening of the blood leukocyte telomeres is associated with aging, several chronic diseases, and stress, eg, major depression. Hippocampus is pivotal in the regulation of cognition and mood and the main brain region of telomerase activity. Whether there is telomere dysfunction in the hippocampus of depressed subjects is unknown. Lithium, used in the treatment and relapse prevention of mood disorders, was found to protect against leukocyte telomere shortening in humans, but the mechanism has not been elucidated. To answer the questions whether telomeres are shortened and the telomerase activity changed in the hippocampus and whether lithium could reverse the process, we used a genetic model of depression, the Flinders Sensitive Line rat, and treated the animals with lithium. METHODS: Telomere length, telomerase reverse transcriptase (Tert) expression, telomerase activity, and putative mediators of telomerase activity were investigated in the hippocampus of these animals. RESULTS: The naïve Flinders Sensitive Line had shorter telomere length, downregulated Tert expression, reduced brain-derived neurotrophic factor levels, and reduced telomerase activity compared with the Flinders Resistant Line controls. Lithium treatment normalized the Tert expression and telomerase activity in the Flinders Sensitive Line and upregulated ß-catenin. CONCLUSION: This is the first report showing telomere dysregulation in hippocampus of a well-defined depression model and restorative effects of lithium treatment. If replicated in other models of mood disorder, the findings will contribute to understanding both the telomere function and the mechanism of lithium action in hippocampus of depressed patients.

Mood Stabilizers and the Influence on Global Leukocyte DNA Methylation in Bipolar Disorder.

Little is known about the relationship between treatments for bipolar disorder (BD), their therapeutic responses and the DNA methylation status. We investigated whether global DNA methylation levels differ between healthy controls and bipolar patients under different treatments. Global DNA methylation was measured in leukocyte DNA from bipolar patients under lithium monotherapy (n = 29) or combination therapy (n = 32) and from healthy controls (n = 26). Lithium response was assessed using the Alda scale. Lithium in monotherapy was associated with hypomethylation (F = 4.63, p = 0.036). Lithium + valproate showed a hypermethylated pattern compared to lithium alone (F = 7.27, p = 0.011). Lithium response was not associated with DNA methylation levels. These data suggest that the choice of treatment in BD may lead to different levels of global DNA methylation. However, further research is needed to understand its clinical significance.