The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.

Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.

There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness.

Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.

Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.

The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.

The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Neurological soft signs (NSS) are a group of minor non-localisable neurological abnormalities found more often in patients with schizophrenia. The aim of the current study was to test for the effect of gender, age, parental age, age at onset and clinical symptomatology on NSS.

The study sample included 133 patients suffering from schizophrenia according to DSM-IV-TR (77 males and 56 females; aged 33.55±11.22 years old) and 122 normal controls (66 males and 56 females; aged 32.89±9.91 years old). The assessment included the Neurological Evaluation Scale (NES), and a number of scales assessing the clinical symptoms and adverse effects especially extrapyramidal. The statistical analysis included exploratory t-test, simple linear regression analysis, analysis of covariance and the calculation of correlation coefficients.

The results of the current study confirm that NSS are more frequent in patients with schizophrenia in comparison with normal controls (Wilks=0.622, p<0.0001), but do not support an effect of gender, age, age at onset, paternal or maternal age, education, medication status or clinical subtype of schizophrenia on NES scores.

Overall these results suggest that NSS constitute an independent (from the rest of symptoms), core (present in the vast majority of patients) and trait (unrelated to age and probably to the stage of schizophrenia) symptom of schizophrenia which could be of value in the clinical assessment and research of schizophrenia. Overall these results are not in full accord with the literature, but they could serve to fill in gaps and inconsistencies observed so far.