Chronic mood disorders have been associated with a shortened telomere, a marker of increased mortality rate and ageing, and impaired cellular immunity. However, treatment may confound these relationships. We examined the relationship of glucose tolerance, white blood cell count and telomere length to depression in newly diagnosed, antidepressant-naïve patients. Subjects with major depression (n=15), and matched healthy control subjects (n=70) underwent a two-hour oral glucose tolerance test and evaluation of blood cell count and telomere content. The depression group had significantly higher two-hour glucose concentrations and a lower lymphocyte count than control subjects (respective means [SD] for two-hour glucose were 125.0 mg/dL [67.9] vs 84.6 [25.6] (p<.001); for lymphocyte count 2.1 × 109/L [0.6] vs. 2.5 ×109/L [0.7] p=.028).Telomere content was significantly shortened in the depression group (87.9 [7.6]) compared to control subjects (101.0 [14.3]; p<0.01). Abnormal glucose tolerance, lymphopenia and a shortened telomere are present early in the course of depression independently of the confounding effect of antidepressant treatment, supporting the concept of major depression as an accelerated ageing disease.

OBJECTIVE Patients with serious mental illnesses exhibit a reduced lifespan compared with the general population, a finding that can not solely rely on high suicide risk, low access to medical care and unhealthy lifestyle. The main causes of death are medical related pathologies such as type 2 diabetes mellitus and cardiovascular disease; however pharmacological treatment might play a role. MATERIAL AND METHODS We compared a two hour glucose load in naïve patients at the onset of a serious mental illness (N=102) (84 patients with a first episode of schizophrenia and related disorders, 6 with a first episode of bipolar I disorder and 12 with a first episode of major depression disorder) with another psychiatric diagnose, adjustment disorder (N=17) and matched controls (N=98). RESULTS Young patients with serious mental illness showed an increased two hour glucose load compared with adjustment disorder and the control group. Mean two hour glucose values [±Standard Deviation] were: for schizophrenia and related disorders 106.51 mg/dL [±32.0], for bipolar disorder 118.33 mg/dL [±34.3], for major depressive disorder 107.42 mg/dL [±34.5], for adjustment disorder 79.06 mg/dL[±24.4] and for the control group 82.11 mg/dL [±23.3] (p<0.001). CONCLUSIONS Our results reflect an abnormal metabolic pathway at the onset of the disease before any pharmacological treatment or other confounding factors might have taken place. Our results suggest a similar glycemic pathway in serious mental illnesses and the subsequent need of primary and secondary prevention strategies.

Newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis appear to have increases in pro-inflammatory cytokines. Patients characterized by primary, enduring negative symptoms (deficit symptoms) differ from patients without such features with regard to course of illness, treatment response, risk factors and metabolic disturbances. We hypothesized that they would also differ on the inflammatory markers, interleukin-6 (IL6) and C-reactive protein (CRP) concentrations. Newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis were categorized into deficit (N=20) and nondeficit (N=42) groups, and were matched on age, gender, body mass index, smoking, cortisol level, socioeconomic status, and the severity of psychotic symptoms. Fasting concentrations of IL6 levels were significantly higher in deficit (mean [SD]) (8.0 pg/ml [12.7]) than nondeficit patients (0.3 pg/ml [1.3]) CRP levels were also significantly higher in the deficit patients (0.3 mg/dl [0.4]) vs. (0.2 mg/dl [0.4]), respectively. In contrast, 2-h glucose concentrations (2HG) in a glucose tolerance test were lower in the deficit than the nondeficit group. Our results show a double dissociation with regard to glucose intolerance and inflammation: the deficit group has greater inflammation, but less severe glucose intolerance. These results provide further evidence for the validity of the deficit/nondeficit categorization.

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These results suggest that abnormal immune response is present before the effects of medication and other confounders had taken place. Increased immune parameters might underlie the high ratio of medical co-morbidities described in schizophrenia.