Table 1.
Leukocyte telomere length (LTL) studies in mood disorders: summary of main findings
| Study | Population studied | Subjects (n)* | Mean age (yr)* | Mean duration of ill-ness (yr) | Mean TL* | LTL assay technique | Chief findings | Additional notes |
|---|---|---|---|---|---|---|---|---|
| Major depressive disorder (MDD) | ||||||||
| Simon et al., 200623) | Chronic MDD & BD cases with or without comorbid ADs | 44/44 | 51/51 | 32 | 6.98/7.64 kb | Southern blot | Significantly shorter LTL in mood disorders | Active physical illnesses excluded in subjects. No data on the possible association between duration of illness and telomere shortening. |
| Hartmann et al., 201043) | Inpatients with MDD | 54/20 | 49/49 | 15 | 7.20/7.55 kb | Southern blot | Statistically significant shorter LTL in MDD | Psychiatric and physical comorbidity not excluded in MDD subjects. Association between chronicity/severity of MDD and telomere shortening was not shown. Potential confounding factors were not controlled for. |
| Hoen et al., 201128) | Outpatients with CHD with or without MDD | 206/746 | 62/68 | Not documented | 0.86/0.90 (T/S ratio) | Q-PCR | LTL significantly shorter in subjects with MDD | The association between LTL and MDD may have been confounded by greater cardiac disease severity in the depression group. When full covariates were analyzed, LTL difference just missed significance (p = 0.06). |
| Wolkowitz et al., 201134) | Un-medicated MDD outpatients and matched controls | 18/17 | 37/37 | 13 | 5,101/5,141 (bp) | Q-PCR | LTL not significantly different in cases versus controls. However, shorter LTL was noted in long-standing MDD cases. | Shorter LTL observed in those MDD cases who had more lifetime days of untreated depression. LTL inversely correlated with peripheral circulating levels of proinflammatory cytokines and oxidative stress markers. Study limited by small sample size. |
| Teyssier et al., 201233) | MDD subjects and matched controls | 17/16 All female sample |
40/38 | 12 of the MDD subjects were 1st episode | 13.42/13.60† | Q-PCR | LTL not significantly different in the two groups. Physical comorbidity was excluded, particularly, CVD. Psychiatric comorbidity also excluded. Anxiety symptoms may have been present. | MDD subjects had increased expression of certain genes involved in telomere maintenance. Also, in MDD subjects increased expression of an enzyme involved in repair of oxidative damage to the DNA. Limitations: All female, all Caucasian sample. Majority with short duration of MDD. Seventy percent receiving antidepressant medications. |
| Hoen et al., 201329) | Two population based samples of subjects with ASD and DD and controls | ASD: 108/970 DD: 97/980 |
ASD: 52/54 DD: 51/54 |
NA | NA | Q-PCR | The presence of ASD and not DD over the preceding year predicted significant LTL shortening 2.2 years later. | Strength of the study is its prospective design. Limitation: psychiatric patients were from a general population and may have been of mild severity. |
| Verhoeven et al., 201424) | Current and remitted MDD patients from the NESDA cohort | Current MDD subjects: 1,095 Remitted MDD subjects: 802 Controls: 510 |
41/41 | MDD duration in the current group: 21 mo Duration in the remitted group: 11 mo |
5,474/5,553 bp | Q-PCR | Statistically significant shorter LTL in current and remitted MDD compared to controls. | Within the current MDD subjects, both higher depression severity and longer symptom duration were associated with shorter LTL. Telomere shortening in the remitted group was not correlated to the number of years in remission and use of antidepressant medications. LTL shortening in both MDD groups remained significant even after adjusting for somatic comorbidity. |
| Shalev et al., 201426) | Sample consisted of subjects with internalizing disorders including MDD. It was derived from the birth cohort of the Dunedin Multidisciplinary Development Study. | Internalizing disorder from age 11 to 38 yr: 455 | Longitudinal study from 11–38 yr old | NA | NA | Q-PCR | The persistence of “internalizing disorder” diagnoses between ages 11–38 yr predicted shorter LTL at age 38 yr in a dose-response manner in men, but not in women. | High co-morbidity between different internalizing disorders such as GAD, PTSD. Approximately 75% of the study subjects had exceeded clinical cut-off for one or more of such physical health parameters as metabolic abnormalities, cardiorespiratory fitness, and systemic inflammation. |
| Needham et al., 201532) | MDD | 75/96 | 30.3/29.2 | NA | 1.12/1.14 (T/S ratio) | Q-PCR | LTL not significantly different in the two groups. However, in MDD subjects taking antidepressant medications LTL was significantly shorter than control. This may be because of greater severity of depression in the MDD subgroup. | Relatively young cohort Limitation: long duration between DNA extraction and LTL analysis may have confounded the results. |
| Schaakxs et al., 201530) | Late life depression | 355/128 | 70.6/70.1 | NA | 5,036/5,055 bp | Q-PCR | No significant difference in LTL. | Age and the number of chronic medical diseases were significantly inversely correlated with LTL. However, presence of major depression, severity and number of depressive episodes were not. Controlling for medication use, chronic medical illnesses and lifestyle factors did not change the results. |
| Bipolar disorder (BD) | ||||||||
| Simon et al., 200623) | BD subjects with/without ADs | Total patients 44/controls 44. Fifteen patients with MDD, 15 with BD and co-occurring AD and 14 with BD and no AD | 51.5/50.5 | 35 | 7,030/7,640 bp | Southern blot | Across all mood disorder subjects LTL was significantly shorter than control. | Patients had chronic MDD or BD. Somatic comorbidity was excluded but psychiatric conditions, particularly AD were not. Limitations: no data on potential confounders like lifetime stress exposure, medication use, substance abuse or BMI. |
| Elvsåshagen et al., 201137) | Outpatients with BD type II–16 patients were euthymic and 12 had depressive episode, mild or moderate. | 28/28 | 35/35 | 19 | 10,067/10,619 bp Percentage of short telomeres: BD type II, 15.04%; control, 13.48% |
Quantitative FISH technique | LTL shortening not statistically significant in BD versus control. However, load of short telomeres was significantly greater in BD. | The load of short telomeres and TL were not significantly correlated with illness duration. Limitations: small sample size, no control for early life stress. |
| Rizzo et al., 201338) | BD type I, all female samples. BD subjects had higher titers of IgG antibody against CMV. | 22/17 | 39.5/44.6 | 9.45 | 0.71/0.90 (T/S ratio) | Q-PCR | BD subjects had significantly shorter LTL as compared to controls. | Major psychiatric and physical comorbid conditions controlled for. Results were biased as CMV IgG levels were associated with expansion of senescent CD8 + CD28 T cells and with shorter LTL in BD subjects. |
| Martinsson et al., 201339) | BD patients along with age and sex matched controls. BD subjects were on lithium treatment. | 202/135 | NA | NA | NA | Q-PCR | LTL significantly longer in BD subjects compared to controls. | TL positively correlated with lithium treatment duration of >30 mo (p = 0.031). LTL negatively associated with number of depressive episodes (p < 0.007). Lithium responders had significantly longer TL than lithium non-responders (p = 0.047). Limitations: the study did not control for smoking, obesity, inflammation and somatic disorders. |
| Lima et al., 201540) | Patients with BD type I and II, matched controls. Patients had relatively high psychiatric comorbidity, especially AD. | 85/95 | 38/39 | NA | NA | PCR | Patients had significantly shorter TL than controls (p < 0.001). No significant difference between BD subtypes. Short LTL was associated with panic disorder co-morbidity. | No information regarding illness duration was given. Smoking, BMI, medication use and somatic illnesses were not controlled for. |
| Barbé-Tuana et al., 201641) | BD type I outpatients meeting remission criteria according to defined scores on HRSD and YMRS. | 26/34 BD cases consisted of early and late stage patients |
46.5/44 | 15.25 | 0.75/1.50 (T/S ratio, calculated from graph) | Real time Q-PCR | TLwas significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and 0.005) | Early stage patients had average disease duration of 8 yr. Late stage cases had mean disease duration of 22.50 yr. All BD subjects were on pharmacotherapy. Small sample size precluded the analysis of the effect of pharmacotherapy on TL. |
TL, telomere length; AD, anxiety disorder; kb, kilobase; CHD, chronic heart disease; T/S, telomere repeat (T) copy number to single (S) copy number; Q-PCR, quantitative polymerase chain reaction; bp, base pair; CVD, cardiovascular disease; ASD, anxiety spectrum disorders; DD, depressive disorders (MDD & dysthymia); NA, not available; NESDA, Netherlands Study of Depression and Anxiety; GAD, generalized anxiety disorder; PTSD, post-traumatic stress disorder; BMI, body mass index; FISH, florescence in situ hybridization; IgG, immunoglobulin G; CMV, cytomegalovirus; HRSD, Hamilton Rating Scale for Depression; YMRS, Young Mania Rating Scale.
*
Psychiatric/controls.
†
Mean Ct ratio: cycle threshold for telomeric signal relative to cycle threshold for single copy gene.