The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is ...an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.
Paternal postpartum depression (PD) is considered an affective disorder that affects fathers during the months following childbirth. Interestingly, it has been observed that during these months the ...chances of a male parent suffering from depression are double that for a non-parent male counterpart. We present the case of a 34-year-old man with no relevant medical history in who, overlapping her daughter's birth, several depressive symptoms emerged, such as fatigue, lack of concentration, sleeping disturbances and abandonment of care of the newborn. Prior to consultation, patient refused to eat and open his eyes, and his speech became progressively more parsimonious until reaching mutism. The patient was diagnosed with a severe depressive disorder with catatonia. Given the lack of improvement with pharmacological treatment and due to the evidence of electroconvulsive therapy (ECT)'s effectiveness on patients with catatonia, acute ECT treatment was indicated and started. It should be noted that PD is an important entity to consider in our differential diagnosis of young parents who present a depressive episode. Few cases of relatively young patients presenting with such clinical presentation have been described and, although this case presents some of the characteristics described in the epidemiology of PD, other clinical aspects are not typical of this entity. Informed consent was obtained from the patient for the purpose of publication.
The age at onset of bipolar disorder (BD) has significant implications for severity, duration of affective episodes, response to treatment, and psychiatric comorbidities. It has been suggested that ...early-onset BD (EO-BD) could represent a clinically distinct subtype with probable genetic risk factors different from those of late-onset BD (LO-BD). To date, several genes have been associated with BD risk but few studies have investigated the genetic differences between EO-BD and LO-BD. The aim of this study was to evaluate if variants of the gene coding for myo-inositol monophosphatase (IMPA2) are linked to age at onset of BD.
235 bipolar patients were recruited and assessed. The final sample consisting of 192 euthymic individuals, was compared according to the age at onset. Polymorphisms were genotyped in the IMPA2 gene (rs669838, rs1020294, rs1250171, and rs630110). Early-onset was defined by the appearance of a first affective episode before the age of 18.
The analyses showed that in the genotype distribution rs1020294 (p = .01) and rs1250171 (p = .01) were associated with the age at onset. The significant effect remained only in the rs1020294 SNP in which G carriers were more likely to debut later compared to patients presenting the AA genotype (p = .002; OR = 9.57, CI95%2.37–38.64). The results also showed that EO-BD tended to experience more alcohol misuse (p = .003; OR = .197, CI95%.07–.58) compared to LO-BD.
Our results provide evidence for genetic differences between EO-BD and LO-BD at the IMPA2 gene as well as clinical differences between subgroups with therapeutic implications.
•The age at onset of bipolar disorder has relevant clinical implications.•IMPA2 genetic variations are seen in bipolar patients with early and late onset.•Defining subgroup of patients may increase diagnostic and therapeutical accuracy.
Alterations of the endocannabinoid system (ECS) may play an important role in the development of schizophrenia and other psychotic disorders. Cannabis use is one of the environmental factors more ...repeatedly related to an increase the risk of developing a psychotic episode, while its use modifies the ECS normal function. In the present study we purposed to examine the gene by environment (GxE) interaction between 15 selected single nucleotide polymorphisms (SNPs) related to the ECS and cannabis use in a cohort of 321 patients with a first episode of psychosis (FEP) and 241 matched healthy controls. We found the fatty-acid amide hydrolase (FAAH) rs2295633 SNP genetic polymorphism was associated with a greater risk of presenting a FEP in subjects with relevant cannabis use, but not in subjects without a history of cannabis use. The probability of presenting a FEP was tenfold higher (OR: 10.69) in cannabis users who were homozygote carriers of the T allele of the FAAH rs2295633 SNP, compared to users of cannabis without this genotype. We also found that a higher a proportion of TT carriers of the FAAH rs2295633 SNP with a positive history of cannabis use was treated with high potency antipsychotic. This study has identified a GxE-environment interaction between a genetic polymorphism from the ECS and cannabis use involved in the risk of presenting a FEP. Although this preliminary data should be replicated with independent samples, our results highlight the importance of the pro-psychotic effects of exogenous cannabis use over the ECS in certain subjects.
Aims
Here, we present a clustering strategy to identify phenotypes of antipsychotic (AP) response by using longitudinal data from patients presenting first‐episode psychosis (FEP).
Method
One hundred ...and ninety FEP with complete data were selected from the PEPs project. The efficacy was assessed using total PANSS, and adverse effects using total UKU, during one‐year follow‐up. We used the Klm3D method to cluster longitudinal data.
Results
We identified four clusters: cluster A, drug not toxic and beneficial; cluster B, drug beneficial but toxic; cluster C, drug neither toxic nor beneficial; and cluster D, drug toxic and not beneficial. These groups significantly differ in baseline demographics, clinical, and neuropsychological characteristics (PAS, total PANSS, DUP, insight, pIQ, age of onset, cocaine use and family history of mental illness).
Conclusions
The results presented here allow the identification of phenotypes of AP response that differ in well‐known simple and classic clinical variables opening the door to clinical prediction and application of personalized medicine.
•Metabolic syndrome, obesity and impaired glucose metabolism can be considered risk factors for worse outcomes of bipolar disorder.•Metabolic risk factors have been related to a chronic course of ...illness, worse global functioning and rapid cycling in bipolar disorder.•Hypertension has not shown to have a significant impact on the course of bipolar disorder.•Prevention strategies could lead to the improvement of both medical and psychiatric prognoses.
Metabolic syndrome (MetS) and its component factors, obesity, hypertension, dyslipidaemia and insulin resistance, have shown a bidirectional relationship with the prevalence and severity of bipolar disorder (BD).
A systematic search of electronic databases (Pubmed, PsycINFO, clinicaltrials.gov) was conducted to explore and integrate current evidence about the role of MetS and its component factors with clinical outcomes of BD.
Thirty-four articles met the inclusion criteria. Studies were grouped by the metabolic factors assessed, which included MetS, obesity and body mass index (BMI), dyslipidaemia, impaired glucose metabolism (IGM), diabetes mellitus and hypertension. They were then classified according to outcomes such as course of episodes, rapid cycling, suicidal behavior, treatment response, and global and cognitive functioning.
Although current evidence remains controversial in most aspects of clinical outcomes, metabolic risk factors could alter the course of BD, with worse global functioning, poorer treatment response and a chronic course of illness, as well as enhancing rapid cycling. Further research is needed to elucidate the role of each risk factor in the mentioned outcomes.
•Lithium is the gold standard treatment for bipolar disorder.•Weight change with lithium was not clinically or statistically significant.•Weight change with lithium did not differ from ...placebo.•Weight gain was greater with some active comparators than with lithium.
Lithium remains the gold standard maintenance treatment for Bipolar Disorder (BD). However, weight gain is a side effect of increasing relevance due to its metabolic implications. We conducted a systematic review and meta-analysis aimed at summarizing evidence on the use of lithium and weight change in BD. We followed the PRISMA methodology, searching Pubmed, Scopus and Web of Science. From 1003 screened references, 20 studies were included in the systematic review and 9 included in the meta-analysis. In line with the studies included in the systematic review, the meta-analysis revealed that weight gain with lithium was not significant, noting a weight increase of 0.462 Kg (p = 0158). A shorter duration of treatment was significantly associated with more weight gain. Compared to placebo, there were no significant differences in weight gain. Weight gain was significantly lower with lithium than with active comparators. This work reveals a low impact of lithium on weight change, especially compared to some of the most widely used active comparators. Our results could impact clinical decisions.
•Overall lifestyle worsened after several months of the COVID-19 pandemic.•Rates of depression and anxiety remained similar during the study period.•Previous mental disease was independently ...associated with an unhealthier lifestyle.•Depression, anxiety and alcohol abuse were associated with unhealthier lifestyles.
This study aimed to compare self-reported changes on lifestyle behaviors during two phases of the COVID-19 pandemic in Spain, and to evaluate clinical and sociodemographic factors associated with lifestyles.
Two cross-sectional web surveys were conducted during lockdown (April 15-May 15, 2020) and seven months later (November 16-December 16, 2020). Lifestyle behaviors were self-reported by a multidimensional scale (SMILE-C). Two separate samples of respondents were analyzed. A multivariate regression model was performed to evaluate the association of SMILE-C scores with demographic and clinical variables.
The sample comprised, 3412 participants from the first survey (S1) and in the S1 and 3635 from the second (S2). SMILE-C score decreased across surveys (p < 0.001). The rates of positive screenings for depression and anxiety were similar between the surveys, whereas those for alcohol abuse decreased (p < 0.001). Most participants in S2 reported that their lifestyle had not changed compared to those before the pandemic. Variables independently associated with an unhealthier lifestyle were working as an essential worker, lower educational level, previous mental disease, worse self-rated health, totally/moderate changes on diet, sleep or social support, as well as positive screenings for alcohol abuse, anxiety and depression.
The cross-sectional design and recruitment by non-probabilistic methods limit inferring causality and the external validity of the results.
Overall lifestyle worsened seven months after the lockdown in Spain. Several demographic and clinical factors were associated with lifestyle scores. The contribution of common mental disorders to unhealthier lifestyles should be considered in order to prevent the negative impact of the pandemic.
•We conducted a systematic review and a meta-analysis to explore the relationship between parental age and risk of BD in the offspring.•The systematic search of the literature identified 16 relevant ...publications of which 14 provided data that could be included in random effects meta-analyses.•Younger maternal and paternal (≤ 20 years) or advanced age (≥ 35 or ≥ 45 years, respectively) were associated with an increased risk of BD in offspring when the reference age group was 25–29 years and data were adjusted for confounding variables.•Mechanisms underlying this association are largely unknown and may involve a complex interplay between psychosocial factors, genetic, biological, and with different impacts according to sex and age range.
Parenthood age may affect the risk for the development of different psychiatric disorders in the offspring, including bipolar disorder (BD). The present systematic review and meta-analysis aimed to appraise the relationship between paternal age and risk for BD and to explore the eventual relationship between paternal age and age at onset of BD. We searched the MEDLINE, Scopus, Embase, PsycINFO online databases for original studies from inception, up to December 2021. Random-effects meta-analyses were conducted.
Sixteen studies participated in the qualitative synthesis, of which k = 14 fetched quantitative data encompassing a total of 13,424,760 participants and 217,089 individuals with BD. Both fathers adjusted for the age of other parent and socioeconomic status odd ratio – OR = 1.29(95%C.I. = 1.13–1.48) and mothers aged ≤ 20 years (OR = 1.23(95%C.I. = 1.14–1.33) had consistently increased odds of BD diagnosis in their offspring compared to parents aged 25–29 years. Fathers aged ≥ 45 years adjusted OR = 1.29 (95%C.I. = 1.15–1.46) and mothers aged 35–39 years OR = 1.10(95%C.I. = 1.01–1.19) and 40 years or older OR = 1.2(95% C.I. = 1.02–1.40) likewise had inflated odds of BD diagnosis in their offspring compared to parents aged 25–29 years.
Early and delayed parenthood are associated with an increased risk of BD in the offspring. Mechanisms underlying this association are largely unknown and may involve a complex interplay between psychosocial, genetic and biological factors, and with different impacts according to sex and age range. Evidence on the association between parental age and illness onset is still tentative but it points towards a possible specific effect of advanced paternal age on early BD-onset.
Suicide attempts represent a public health concern. The objective of this study is to describe the clinical characteristics of patients visiting an emergency room for a suicide attempt and included ...in a suicide prevention program, the Catalonia Suicide Risk Code (CSRC), particularly focusing on the follow-up evaluations.
The CSRC program is divided in 3 phases: (1) alert and activation, (2) proactive telephone and face-to-face follow-up and (3) comprehensive preventive health monitoring. This is the analysis of the sample of patients attempting or intending suicide who were seen at a tertiary hospital in Barcelona, and their 1-year follow-up outcome.
Three hundred and sixty-five patients were included. In 15% of the cases, there was no previous psychiatric history but in the majority of cases, a previous psychiatric diagnosis was present. The most common type of suicide attempt was by drug overdose (84%). Up to 66.6% of the patients attended the scheduled follow-up visit in the CSRC program. A significant reduction in the proportion of patients visiting the emergency room for any reason (but not specifically for a suicide attempt) and being hospitalized in the first semester in comparison with the second six months after the CSRC activation (30.1% versus 19.9%, p=0.006; 14.1% versus 5.8%, p=0.002) was observed.
The clinical risk factors and the findings of the CSRC helped in the characterization of suicide attempters. The CSRC may contribute to reduce hospitalizations and the use of mental health care resources, at least in the short-term.
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