May duration of untreated illness influence the long-term course of major depressive disorder?

The aim of this naturalistic study was to investigate the possible influence of the duration of untreated illness (DUI) on the long-term course of Major Depressive Disorder (MDD). One hundred and thirteen patients with recurrent MDD, according to DSM-IV-TR criteria, followed up for 5 years, were selected, interviewed and their clinical charts were reviewed. The DUI was defined as the interval between the onset of the first depressive episode and the first adequate antidepressant treatment. The sample was divided into two groups according to the DUI: one group with a DUI12 months (n=38). The main demographic and clinical course variables were compared between the two groups using Student's t-tests or chi-square tests. Patients with a longer DUI showed an earlier age at onset (t=2.82, p=0.006) and a longer duration of illness (t=3.20, p=0.002) compared to patients with a shorter DUI. In addition, the total number of depressive episodes occurring before the first antidepressant treatment was higher in the group with a longer DUI (t=-2.223, p<0.03). Even though limited by the retrospective nature of the study, these preliminary findings would suggest that a longer DUI may negatively influence the course of MDD. Larger prospective studies are warranted to further investigate the role of the DUI within MDD.

Some biological correlates of drug resistance in schizophrenia: a multidimensional approach.

Drug resistance in schizophrenic disorders treated with an antipsychotic medication is highly problematic, lacking sound criteria to define it, and to discriminate between drug response and clinical remission. This article reviews some neurochemical, psychoimmunological, pharmacogenetic and neuromorphological patterns which can affect drug response and determine drug-resistance phenomena in schizophrenia. Several neurochemical abnormalities have been reported to be relevant for the pathogenesis of schizophrenic disorders and have been related to clinical symptoms as well as to the quality of response to antipsychotics: most of the findings come from studies on DA and 5HT brain metabolism, but more recently other non-dopaminergic pathways have been implicated (e.g., glutamatergic ones). Literature data suggest that schizophrenia may be associated with significant alterations of T-cell functions, showing the activation of the inflammatory response system (IRS), particularly in treatment-resistant schizophrenia, and differential effects on IRS have been reported for conventional and atypical antipsychotics. Furthermore molecular genetic approaches provide a novel method of dissecting the heterogeneity of psychotropic drug response, providing the means of determining the molecular substrates of drug efficacy and drug-induced adverse events. On the other hand, functional neuroimaging techniques, including single photon emission computed tomography (SPECT), positron emission tomography (PET) and functional magnetic resonance imaging (FMRI), providing an in vivo assessment of the expression and function of neuroreceptors, transporters and enzymes, seem to be particularly promising for a better understanding of 'real' drug resistance. Finally, a multidimensional approach taking into account all these variables in the future would likely be the more valuable strategy to optimise response, reducing relapses or resistant clinical situations.

MCP-1 gene (SCYA2) and schizophrenia: a case-control association study.

Dysregulation of the inflammatory response system has been linked to the pathophysiology of schizophrenia. Abnormal levels of proinflammatory cytokines and their receptors have been found in peripheral blood and cerebrospinal fluid of schizophrenic patients, suggesting the presence of immune activation. Monocyte chemoattractant protein 1 (MCP-1) influences the expression of cytokines related to T helper responses. MCP-1 also exerts several effects on monocytes, including the expression of several proinflammatory genes. The A-2518G polymorphism of the MCP-1 gene (SCYA2) appears to affect the transcriptional activity and monocyte MCP-1 production. The aim of this case-control study was to investigate the potential role of SCYA2 (A-2518G polymorphism) in conferring susceptibility to schizophrenia and to the resistance to antipsychotic treatment. The sample studied consisted of 191 DSM-IV schizophrenia or schizoaffective disorder (depressive subtype) patients and 161 matched healthy controls. No significant genotypic (chi(2) = 0.278, df = 2, P = 0.986) or allelic (chi(2) = 0.021, df = 1, P = 0.884) association was found between the A-2518G variant of the SCYA2 and the diagnosis. No differences in the age at onset of schizophrenia were found between the three genotype groups identified. Significant genotypic association was found between the A-2518G variant of the SCYA2 and the resistance to antipsychotic treatment (chi(2) = 6.26, df = 2, P = 0.04), with resistant patients more frequently carrying the G allele. The odds ratio associated to the presence of the G allele was 2.39 (95% CI = 1.14-4.98). These data suggest that the A-2518G variant of the SCYA2 has not a major role in the pathogenesis of schizophrenia, while it could be implicated in the resistance to antipsychotic treatment.