Длительность нелеченного психоза и длительность нелеченного заболевания

An 8 year prospective study conducted in first episode patients found that DUP was an independent predictor of prognosis in the medium to long term and that outcomes for psychopathological domains were significantly worse when DUP exceeded 3 months.23 Subsequent studies confirmed the association between a longer DUP and a worse outcome of negative symptoms3 as well as a poor influence on cognitive symptoms.24 In addition, other studies with large samples indicating a worse outcome in schizophrenics with longer DUP in terms of more severe positive, negative, and cognitive symptoms have been recently reported.9,10,25-27 In two previous studies by our group, an association between a longer DUP and a greater number of suicide attempters and a higher number of recurrences were found.28,29

In relation to neurobiological mechanisms, it has been hypothesized that the adverse effects on outcome associated with untreated psychosis may be biologically mediated. One toxicity model suggests that N-methyl-d-aspartic (NMDA) acid receptor hypofunctioning may induce psychosis and produce glutamatergically-medicated excitotoxic damage in neurons at the same time.30,31 For the latter, NMDA receptor hypofunction would result in reduced activation of GABAergic inhibitory neurons, leading to an excitotoxic state.31 Alternatively, prolonged stress, including stress resulting from untreated psychosis, may activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to greater glucocorticoid secretion which may contribute to neuronal damage.32 However, the evidence for neurotoxicity stemming from untreated psychosis is still an object of debate and there is as yet little evidence of an effect of long DUP on brain morphology. Furthermore, the possibility of cognitive dysfunction being a neurotoxic consequence of delayed treatment with antipsychotic drugs has been advanced, but this is only a hypothesis given that cognitive impairment may begin prior to the onset of psychosis and is poorly affected by available antipsychotics.

The hypothesis that not only schizophrenia and psychotic spectrum disorders but also depressive disorders tend to show anatomical deficits with the progression of the illness has been recently supported by a large meta-analysis conducted on 64 studies which reported that compared to healthy controls, depressed patients showed large volume reductions in frontal regions, particularly in the anterior cingulate and orbitofrontal cortex with smaller reductions in the prefrontal cortex. In addition, the hippocampus, putamen, and caudate nucleus showed moderate volume reductions.35 As a consequence, the hypothesis that early effective antidepressant treatments may block and partially reverse the neurobiological modifications occurring with the progression of the untreated depressive episode may be advanced.

To date, studies specifically investigating the role of the DUI in anxiety disorders have been conducted in panic disorder, generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD). Indeed, a study examining the cause and length of delays in reaching primary care and specialist services amongst patients with anxiety disorders indicated that patients with social phobia reported longer delays in reaching specialist care (>9 years) compared with patients with GAD or panic disorder.70

Duration of Untreated Psychosis and Duration of Untreated Illness: New Vistas