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Treatment of major depressive disorder (MDD) including treatment-resistant depression (TRD) remains a major unmet need. Although there are several classes of dissimilar antidepressant drugs approved for MDD, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. The efficacy and side effects of antidepressant drugs are mainly attributed to their actions on different monoamine neurotransmitters (serotonin, norepinephrine, and dopamine). Development of new antidepressants with novel targets beyond the monoamine pathways may fill the unmet need in treatment of MDD and TRD. The recent approval of intranasal Esketamine (glutamatergic agent) in conjunction with an oral antidepressant for the treatment of adult TRD patients was the first step toward expanding beyond the monoamine targets. Several other glutamatergic (AXS-05, REL-1017, AV-101, SLS-002, AGN24175, and PCN-101) and GABAergic (brexanolone, zuranolone, and ganaxolone) drugs are currently in different stages of clinical development for MDD, TRD and other indications. The renaissance of psychedelic drugs and the emergence of preliminary positive clinical trial results with psilocybin, Ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD) may pave the way towards establishing this class of drugs as effective therapies for MDD, TRD and other neuropsychiatric disorders. Going beyond the monoamine targets appears to be an effective strategy to develop novel antidepressant drugs with superior efficacy, safety, and tolerability for the improved treatment of MDD and TRD.
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.
Material and methods
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.
We would like to draw attention to the fact that the recently published DSM-5 (and also its predecessor, DSM-IV) contains annoying errors that are mainly logical in nature. These mistakes are undoubtedly a result of inadvertence, rather than either conceptual (professional) disagreements between authors/editors or shortage of scientific data for appropriate circumscription of diagnostic categories. The good news is that since these errors are mainly logical ones, they can be recognised and repaired.
It is unclear whether there is a direct link between economic crises and changes in suicide rates.
The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates.
Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation.
There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged.
Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.
White matter hyperintensities (WMHs) are one the most common neuroimaging findings in patients with bipolar disorder (BD). It has been suggested that WMHs are associated with impaired insight in schizophrenia and schizoaffective patients; however, the relationship between insight and WMHs in BD type I has not been directly investigated.
Patients with BD-I (148) were recruited and underwent brain magnetic resonance imaging (MRI). Affective symptoms were assessed using Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS17); the presence of impaired insight was based on the corresponding items of YMRS and HDRS17.
Multiple punctate periventricular WMHs (PWMHs) and deep WMHs (DWMHs) were observed in 49.3% and 39.9% of the cases, respectively. Subjects with lower insight for mania had significantly more PWMHs (54.6% vs 22.2%; p < 0.05) when compared to BD-I patients with higher insight for mania. The presence of PWMHs was independently associated with lower insight for mania: patients who denied illness according to the YMRS were 4 times more likely to have PWMHs (95% CI: 1.21/13.42) than other patients.
Impaired insight in BD-I is associated with periventricular WMHs. The early identification of BD-I subjects with PWMHs and impaired insight may be crucial for clinicians.
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