Long-Term Lithium Treatment in Bipolar Disorder Is Associated With Longer Leukocyte Telomeres.

Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres.

Transl Psychiatry. 2013; 3: e261
Martinsson L, Wei Y, Xu D, Melas PA, Mathé AA, Schalling M, Lavebratt C, Backlund L

Telomere shortening is a hallmark of aging and has been associated with oxidative stress, inflammation and chronic somatic, as well as psychiatric disorders, including schizophrenia and depression. Additionally, antidepressants have been found to protect against telomere shortening. However, pharmacological telomere studies are lacking in bipolar disorder (BD). Therefore, the objective of this study was to explore telomere length (TL) in patients with BD in the context of lithium treatment. We determined TL by quantitative real-time PCR using peripheral blood leukocytes. Participants were outpatients diagnosed with BD type 1 or 2 (n=256) and healthy controls (n=139). Retrospective case-control and case-case study designs were applied. Lithium response (LiR) was scored using the Alda-Scale. Lithium-treated BD patients overall, as well as those on lithium monotherapy, had 35% longer telomeres compared with controls (P<0.0005, partial ?(2)=0.13). TL correlated positively with lithium treatment duration of >30 months (P=0.031, R(2)=0.13) and was negatively associated with increasing number of depressive episodes (P<0.007). BD patients responding well to lithium treatment had longer telomeres than those not responding well. This is the first study to report a positive effect of long-term lithium treatment on TL. Importantly, longer TL was also associated with a better LiR in BD patients. These data suggest that lithium exerts a protective effect against telomere shortening especially when therapeutically efficacious. We hypothesize that induction of telomerase activity may be involved in LiR in BD. HubMed – depression


Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy.

Transl Psychiatry. 2013; 3: e258
Bakermans-Kranenburg MJ, van Ijzendoorn MH

The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups. We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the ‘out-group’), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15?IU to more than 7000?IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18-0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15-0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT. HubMed – depression


Negative beliefs and psychological disturbance in spine surgery patients: a cause or consequence of a poor treatment outcome?

Eur Spine J. 2013 May 23;
Havakeshian S, Mannion AF

PURPOSE: Chronic musculoskeletal pain is often associated with psychological distress and maladaptive beliefs and these are sometimes reported to have a negative impact on surgical outcome. The influence of a surgical intervention, and in particular its outcome, on the course of change in psychological status is poorly documented. In this prospective study, we sought to examine the dynamic interplay between psychological factors and outcome in patients undergoing decompression surgery for spinal stenosis/herniated disc. METHODS: Before and 12 months after surgery, 159 patients (100 men, 59 women; 65 ± 11 years) completed a questionnaire booklet containing questions on socio-demographics, medical history, pain characteristics (intensity, frequency, use of medication), psychological disturbance [ZUNG Depression Scale and Modified Somatic Perception Questionnaire (MSPQ)], catastrophising (sub-scale of the Coping Strategies Questionnaire) and disability (Roland and Morris questionnaire) and the Fear Avoidance Beliefs Questionnaire about physical activity (FABQ-PA). The global outcome of surgery was assessed at 12 months using a five-point Likert scale and dichotomised as “good” (operation helped/helped a lot; coded 1) and “poor” (operation helped only little/did not help/made things worse; coded 0). RESULTS: Valid questionnaire data were available for 148 patients at 12 months’ follow-up: 113 (76.4 %) reported a good outcome and 35 (23.6 %) a poor outcome. In univariate analyses, the following baseline variables each significantly (p < 0.05) predicted a good 12-month global outcome: no involvement in a disability claim, and lower LBP frequency, average LBP in the last week, average score on all pain scales, FABQ-PA and catastrophising. In multiple logistic regression, only lower FABQ-PA scores [OR 0.877 (95 %CI 0.809-0.949), p = 0.001] and lower LBP frequency at baseline [OR 0.340 (1.249-1.783), p < 0.0001] significantly predicted a good outcome at 12 months. A second "explanatory" logistic regression model revealed that a good outcome at 12 months was significantly associated with improvements (from baseline to 12 months) in average score on all the pain intensity scales [OR 1.6879 (1.187-2.398)], general health [OR 1.246 (1.004-1.545)], psychological disturbance [OR 1.073 (1.006-1.144)] and Roland Morris Disability [OR 1.243 (1.074-1.439)]. CONCLUSION: In a multivariable prospective (predictive) model, FABQ-PA was the only baseline psychological factor that significantly predicted outcome. Future studies should assess whether pre-operative cognitive-behavioural therapy in patients with maladaptive beliefs improves treatment outcome. Psychological disturbance did not significantly predict outcome, but it improved post-operatively in patients with a good outcome and worsened in those with a poor outcome. Rather than being a risk factor for poor outcome, in this group it appeared to be more a consequence of long-standing, unremitting pain that improved when symptoms resolved after successful surgery. HubMed – depression


[Schizophrenia – a disorder in its own right? : Results from 25 years of the ABC study.]

Nervenarzt. 2013 May 23;
Häfner H, Maurer K, An der Heiden W

BACKGROUND: The ABC schizophrenia study conducted by the same team over 25 years initially aimed at illuminating the onset, prodromal stage and sex differences in age at first hospitalization in schizophrenia. New hypotheses were systematically generated from the results achieved. METHODS: A population-based sample of 276 first admission cases (232 first episodes, age 12-59 years), including a subsample of 130 first admissions (115 first episodes), were assessed to study prodromal stage, first illness episode, medium and long-term course and symptom dimensions in schizophrenia. The samples were compared with age and sex-matched healthy controls and with patients first admitted for unipolar depression. A total of 1,109 consecutive first admissions for schizophrenia spectrum disorders independent from the other study samples were assessed to study changes in symptomatology across the age range. RESULTS: Before the onset of psychotic symptoms the prodromal stages of schizophrenia and severe and moderately severe depression are difficult to distinguish. The most frequent symptom in the course of schizophrenia, depressed mood, also represents the most frequent initial symptom in both disorders. Prodromal depression is a predictor of more depressive and positive symptoms in the first episode but not in the further course of the illness. Psychosis incidence for men, diagnosed according to ICD 9 (295, 297, 298.3/4), shows a pronounced peak at age 15-24 years, for women a lower peak at age 15-29 years and a second, still lower peak at the menopausal age of 45-49 years. The explanation, confirmed in animal experiments, lies in a protective effect of estrogen due to reduced D2 receptor sensitivity. The effect is antagonized by an elevated genetic risk. Functional and social impairment emerge even at the prodromal stage and the severity depends on sex and social status. Young men with schizophrenia show a less favorable social course because of the earlier age of onset and socially adverse illness behavior. Late onset is associated with a milder, primarily paranoid symptomatology and less severe social impairment. Schizophrenia is a disorder of all ages showing roughly equal life time incidence rates for men and women but considerable difference in certain periods of age. The symptom dimensions show a plateau-like course 2-5 years after the first episode. Hidden behind this picture are irregular symptom exacerbations which vary in duration. Schizophrenia conveys the picture of recurrent vulnerability to crisis and not of a stable residual state of disordered brain development or of a progressive neurodegenerative process. HubMed – depression