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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
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.
Bipolar disorder (BD) may be connected with accelerated aging, the marker of this can be shorter telomere length (TL). Some data suggest that lithium may exert a protective effect against telomere shortening. The study aimed to compare the TL between patients with BD and control subjects. The effect of long-term lithium treatment was also assessed.
The study group comprised 41 patients with BD, including 29 patients treated longitudinally with lithium (mean 16.5 years) and 20 healthy people. TL was assessed by the quantitative polymerase chain reaction (qPCR).
In the control group, the TL was significantly longer in males than in females. Male bipolar patients had significantly shorter TL compared with the control male group. In bipolar patients, there was no correlation between TL and duration of treatment. The TL was negatively correlated with age in male bipolar patients.
The study did not confirm the lithium effect on TL in bipolar patients. TL showed gender differences, being shorter in BD males, compared to control males, and longer in healthy males, compared to control females.
A polymorphism of serotonin transporter was studied in 226 patients with affective disorders (n = 132 for bipolar, n = 94 for unipolar affective disorder) and in 213 healthy subjects. Consensus diagnosis by at least two psychiatrists, according to the ICD-10 and DSM-IV criteria was made for each patient using SCID (Structured Clinical Interview for DSM-IV Axis I Disorders). A functional polymorphism in the promoter region of serotonin transporter gene, where 44 bp are either inserted (long allele) or deleted (short allele) was analysed. Genotype s/s was significantly more frequent in patients comparing to the control group (P = 0.011 for bipolar and P = 0.003 for unipolar affective disorder) - the most marked association was found in males with bipolar and unipolar illness. The allele frequencies also differ significantly between patients and controls (P = 0.003 for bipolar and P = 0.001 for unipolar affective disorder). The frequency of the low activity (short) allele was higher in patients than in controls (51.1% in bipolar, and 54.3 in unipolar vs 39.4% in controls). We suggest that the presence of allele s may increase the susceptibility to occurrence of affective disorder.
The aim of the study was to compare a clinical course and treatment results of depression occurring as the first depressive episode, the second depressive episode or the third or further depressive episode. The study was 1-year, prospective, naturalistic observation made by Polish psychiatrists.
One-hundred and seventy-nine patients with the first depressive episode (group I), 170 patients with the second episode (group II) and 183 patients with the third or further episode of depression (group III) were compared. The main analysed variable was remission, defined as the score of ≤7 points on 17-item Hamilton depression rating scale (HDRS), after 6 and 12 months of observation.
The groups of patients studied did not initially differ as to age, proportion of gender and intensity of depression. The percentages of remission after 6 months of observation in groups I.III were: 49%, 41% and 32%, and after 12 months 69%, 60% and 50%, respectively.
The results obtained indicate that the course of subsequent depressive episodes is less favourable compared to the first depressive episode. The percentages of remission obtained in individual groups studied may have implications regarding duration of pharmacological treatment of depressive episode.
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.
We hypothesised that men and women who engage in extreme or high-risk sports would score higher on standardised measures of bipolarity and impulsivity compared to age and gender matched controls.
Four-hundred and eighty extreme or high-risk athletes (255 males and 225 females) and 235 age-matched control persons (107 males and 128 females) were enrolled into the web-based case-control study. The Mood Disorder Questionnaire (MDQ) and Barratt Impulsiveness Scale (BIS-11) were administered to screen for bipolarity and impulsive behaviours, respectively.
Results indicated that extreme or high-risk athletes had significantly higher scores of bipolarity and impulsivity, and lower scores on cognitive complexity of the BIS-11, compared to controls. Further, there were positive correlations between the MDQ and BIS-11 scores.
These results showed greater rates of bipolarity and impulsivity, in the extreme or high-risk athletes, suggesting these measures are sensitive to high-risk behaviours.
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.
A case of agomelatine-induced hepatotoxicity is described in a 47-year female patient who has received the drug, 25 mg/day, for 4 months, for the treatment of depression.
The patient was admitted to the Department of Gastroenterology because of fatigue and nausea, with concomitant elevation of alanine aminotransferase (ALT), 550 U/L, and asparagine aminotransferase (AST), 300 U/L.
Liver biopsy showed diffuse lymphocyte infiltration in the dilated portal spaces without lesion of hepatic lobules. Several weeks after stopping agomelatine, the liver enzymes returned to normal. Subsequently, small gallstones in common bile duct were detected and removed by the endoscopic sphincterotomy.
It is hypothesized that choledocholithiasis could theoretically increase a risk of developing agomelatine-induced hepatotoxicity in this patient. Any pre-existing liver disease should be a contraindication for treatment with agomelatine.
Evidence for a possible association between a low level of cholesterol and increased suicidal behaviour has accumulated in the recent 3 decades. The present study investigates whether lipid levels can make state-dependent markers of suicidal behaviour in Polish patients with mood disorder recently admitted to a psychiatric hospital owing to an acute depressive episode.
Materials and methods
The study was conducted on 223 patients (73 male and 150 female) with unipolar (n=171) and bipolar (n=52) depression. They were interviewed to assess any occurrence of suicidal thoughts, suicidal tendencies and/or suicidal attempts during the 3 months before admission. Laboratory measurements [total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides and total lipids] were obtained within 24–72 h after hospital admission.
Suicidal thoughts, tendencies, and attempts were associated with low total cholesterol, LDL cholesterol, and total lipids in both male and female patients, in both diagnostic categories. Triglycerides were significantly lower in male and female patients with suicidal thoughts compared with their non-suicidal counterparts. No association with suicidality was found with HDL cholesterol.
The results of our study support a majority of research showing the association in depressed patients between suicidal behaviour and low levels of total and LDL cholesterol. In addition, the data suggest a similar association with low total lipids, and in some instances, with low triglycerides.
In bipolar patients, neuropsychological and biochemical disturbances persist into the remission period. Excellent lithium responders (ELRs) comprise around one third of lithium-treated patients and have total remission of recurrences on lithium monotherapy. The objective of the study was to assess the performance on neuropsychological tests and to measure brain-derived neurotrophic factor (BDNF) plasma levels in ELRs compared to patients where the effect of lithium was not optimal, and with matched healthy control subjects. The study was performed with 60 patients on prophylactic lithium treatment, 13 of whom were ELRs, and with 60 matched healthy controls. Neuropsychological tests from the CANTAB battery measuring spatial working memory and sustained attention were used. ELRs performed better on all neuropsychological tests, and had higher plasma BDNF levels than the remaining lithium patients but not different from those of healthy controls. ELRs may constitute a specific subgroup of bipolar patients in which long-term lithium administration can produce complete normality.
Studies on the determinants of the quality of life (QOL) after stroke bring differing results depending on the applied concept of QOL. This may lead to confusion about the contribution of various factors to the post-stroke QOL.
The aim of the study was: (i) to investigate functional and psychological QOL in the individuals after the first ischemic stroke; (ii) to identify the most important correlates of QOL; and (iii) to examine the significance of depression among the other possible predictors of QOL.
A hospital-based sample of 72 stroke patients was followed up to 6 months after stroke onset. QOL was assessed using the Polish version of the Quality of Life Index and the Sickness Impact Profile. A multiple regression procedure was performed to examine relationships between QOL and the study variables.
In spite of good recovery, the psychological and functional QOL of the examined patients was impaired, although the negative impact of stroke was greater on the objective QOL than on the subjective QOL. Stroke-related impairment, depression, functional disability and marital status predicted 80% of the variance in the functional QOL. Emotional support, depression and functional disability explained 38% of the variance in psychological well-being.
Depression and physical disability were the most important predictors of QOL after stroke since their impact on QOL was more robust in comparison to the remaining variables. For improving QOL, a comprehensive care for patients aimed at reducing physical dependence and ameliorating depressive symptoms could be recommended.
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