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Journal of Psychiatric Research Jan 2024Since the introduction of the concept of narcolepsy, there has been a proliferation of discussions about its association with psychiatry. To elucidate the causal role of... (Meta-Analysis)
Meta-Analysis
Since the introduction of the concept of narcolepsy, there has been a proliferation of discussions about its association with psychiatry. To elucidate the causal role of narcolepsy in the three psychiatric disorders [i.e., schizophrenia (SCZ), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD)], we applied a bidirectional Mendelian randomization study using two stages (discovery stage and validation stage) and data from three different genome-wide association studies of narcolepsy. The estimates from different stages were combined using fixed-effects meta-analysis. Our findings suggest that narcolepsy is associated with an increased risk of SCZ. Conversely, MDD may be causally related to narcolepsy. A causal relationship between narcolepsy and ADHD was excluded.
Topics: Humans; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Narcolepsy; Attention Deficit Disorder with Hyperactivity
PubMed: 38000183
DOI: 10.1016/j.jpsychires.2023.11.034 -
International Clinical... Sep 2023Antidepressant (AD)- emergent mood switch (AEMS) is a common complication of bipolar depression. This study aimed to investigate the prevalence and clinical correlates...
Antidepressant (AD)- emergent mood switch (AEMS) is a common complication of bipolar depression. This study aimed to investigate the prevalence and clinical correlates of subthreshold AEMS (i.e. not fulfilling DSM criteria for hypomanic episodes) in major depressive disorder (MDD) and, prognostically, its impact on AD treatment outcome and suicidality. The study involved 425 outpatients with MDD followed during the acute phase (12 weeks) and continuation (weeks 13-28) AD treatment. AEMS was assessed through the Altman Self-Rating Mania scale (ASRM ≥ 6). Several clinical features differentiated individuals with or without subthreshold AEMS (n = 204 vs. 221): negative self-perception [odds ratio (OR) 1.017-1.565]; panic disorder (OR 1.000-1.091); subthreshold hypomanic episodes (OR 1.466-13.352); childhood emotional abuse (OR 1.053-2.447); lifetime suicidal behaviour (OR 1.027-1.236); AD-related remission (χ 2 = 22.903 P < 0.0001) and suicide ideation (χ 2 = 16.701 P < 0.0001). In AEMS earlier onset showed a strong correlation with bipolar spectrum disorder (overall score: P = 0.0053; mixed depression: P = 0.0154; subthreshold hypomania: P = 0.0150) whereas late-onset was associated with more severe suicidal behaviour ( P < 0.001). In conclusion, our results demonstrate that subthreshold mood switches occur frequently in unipolar depression during acute AD treatment as well as in continuation phase. Time of switch onset seems to have the greatest diagnostic and prognostic value.
Topics: Humans; Child; Depressive Disorder, Major; Suicidal Ideation; Mania; Suicide; Antidepressive Agents
PubMed: 37351585
DOI: 10.1097/YIC.0000000000000479 -
Psychiatry Research Oct 2023Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation... (Meta-Analysis)
Meta-Analysis
Our meta-analysis demonstrated that intermittent theta burst stimulation (iTBS)/bilateral-TBS (Bi-TBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)/bilateral-rTMS (Bi-rTMS) had similar efficacy, acceptability, and safety profiles for antidepressant treatment-resistant major depressive disorder (AD-TRD). In our sensitivity analysis that excluded a study that compared Bi-TBS with Bi-rTMS for older adults, all efficacy outcomes were also comparable between iTBS and HF-rTMS. Because iTBS does not require higher stimulation intensity and a longer stimulus time than conventional HF-rTMS protocols, we speculated that for those with AD-TRD, iTBS/Bi-TBS is a more helpful therapeutic modality in clinical practice than HF-rTMS/Bi-rTMS.
Topics: Humans; Aged; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Depressive Disorder, Treatment-Resistant; Antidepressive Agents; Treatment Outcome
PubMed: 37657200
DOI: 10.1016/j.psychres.2023.115452 -
Psychopharmacology Bulletin Aug 2023The first monoamine oxidase inhibitors (MAOIs) used for the treatment of depression in the 1950-60s were credited with treating severe melancholic depression (MeD)... (Review)
Review
The first monoamine oxidase inhibitors (MAOIs) used for the treatment of depression in the 1950-60s were credited with treating severe melancholic depression (MeD) successfully and greatly reducing the need for electroconvulsive therapy (ECT). Following the hiatus caused by the then ill-understood cheese reaction, MAOI use was relegated to atypical and treatment-resistant depressions only, based on data from insufficiently probing research studies suggesting their comparatively lesser effectiveness in MeD. The siren attraction of new 'better' drugs with different mechanisms amplified this trend. Following a re-evaluation of the data, we suggest that MAOIs are effective in MeD. Additionally, the broad unitary conceptualisation of major depressive disorder (MDD) in the DSM model diminished the chance of demonstrating distinctive responses to different antidepressant drugs (ADs) such as SSRIs, TCAs, and MAOIs, thereby further reducing the interest in MAOIs. More reliable categorical distinction of MeD, disentangling it from MDD, may be possible if more sensitive measuring instruments (CORE, SMPI) are used. We suggest these issues will benefit from re-appraisement via an inductive reasoning process within a binary (rather than a unitary) model for defining the different depressive disorders, allowing for the use of more reliable diagnostic criteria for MeD in particular. We conclude that MAOIs remain essential for, , TCA-resistant MeD, and should typically be used prior to ECT; additionally, they have a role in maintaining remission in cases treated with ECT (and ketamine/esketamine). We suggest that MAOIs should be utilized earlier in treatment algorithms and with greater regularity than is presently the case.
Topics: Humans; Monoamine Oxidase Inhibitors; Depressive Disorder, Major; Depression; Depressive Disorder, Treatment-Resistant; Electroconvulsive Therapy
PubMed: 37601082
DOI: No ID Found -
EBioMedicine Mar 2024Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology,...
BACKGROUND
Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention.
METHODS
We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder.
FINDINGS
We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively).
INTERPRETATION
While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare.
FUNDING
European Union Horizon 2020.
Topics: Humans; Pharmacogenetics; Prospective Studies; Depressive Disorder, Major; Quality of Life; Psychiatry; Drug-Related Side Effects and Adverse Reactions
PubMed: 38364700
DOI: 10.1016/j.ebiom.2024.105009 -
Epilepsy & Behavior : E&B Nov 2023Children with epilepsy (CWE) are at risk for a range of adverse emotional, behavioral, and social outcomes. Approximately one-third of CWE experience depressive...
OBJECTIVE
Children with epilepsy (CWE) are at risk for a range of adverse emotional, behavioral, and social outcomes. Approximately one-third of CWE experience depressive disorders, and up to 20% of children and adolescents with epilepsy may experience suicidality, suggesting that epilepsy increases the risk for suicidality among children and adolescents with depressive disorders. Consequently, the goal of the present study is to compare rates of suicidality in children and adolescents diagnosed with depressive disorders with or without co-morbid epilepsy.
PARTICIPANTS AND METHODS
A retrospective chart review was conducted for 100 pediatric patients with a history of both seizures and depressive disorders and 100 patients with a history of depressive disorders only. Cases were coded for depression diagnosis, suicidality, suicidal ideation, suicide attempts, psychiatric hospitalizations, and self-injury. The distributions of these variables for the two groups were compared.
RESULTS
The age and sex distributions of the two groups were comparable. Patients with co-morbid depressive disorders and epilepsy found a high rate of suicidal ideation (69%) but did not differ from those with depressive disorders without epilepsy on any of the suicidality variables (all p > 0.20), with the exception of self-injury, which was higher in those without epilepsy.
CONCLUSIONS
CWE and co-morbid depression are at significant risk for suicidality, including ideation, attempts, and hospitalizations, but at rates that are comparable to those with depressive disorders without seizures. However, patients with co-morbid epilepsy are less likely to engage in other self-injurious behaviors. These findings support the need for careful monitoring of the psychiatric status of children and adolescents with epilepsy.
Topics: Humans; Adolescent; Child; Suicidal Ideation; Retrospective Studies; Prevalence; Suicide; Epilepsy; Seizures; Depressive Disorder; Risk Factors
PubMed: 37844439
DOI: 10.1016/j.yebeh.2023.109467 -
Biomedical Papers of the Medical... Sep 2023This review covers recent data on the relationship between major depressive disorder (MDD) and faecal microbiome and examines the co-relations between the use of... (Review)
Review
This review covers recent data on the relationship between major depressive disorder (MDD) and faecal microbiome and examines the co-relations between the use of probiotics and changes in psychiatric state. We conducted a thorough search of academic databases for articles published between 2018 and 2022, using specific keywords and previously established inclusion/exclusion criteria regarding faecal microbiota, depressive disorder, and probiotics. Of 192 eligible articles (reviews, original papers, and clinical trials), we selected 10 that fully met our criteria and performed a careful review to determine any correlation between microbiome, probiotic treatment, and depression. All patients were adults (mean age, 36.8), with at least one MDD episode and onset of depression during adolescence (duration of 31.39 years of depressive episodes). We found mixed but mostly positive results regarding the influence of probiotic/prebiotic/postbiotic effects on depression. We could not identify the precise mechanism of action that led to their improvement. Antidepressants did not alter the microbiota, according to studies that evaluated this aspect. Probiotic/prebiotic/postbiotic treatments were proven to be safe, with few and mild side effects. Probiotics seemingly could be beneficial in patients with depression, as evidenced by well-established depression scales. Based on this finding and the high tolerability and safety of probiotics, no caveats against their routine use can be made. Some unmet needs in this field include determination of the dominant type of microbiota in specific patients with depression; study of microbiome-directed/driven treatment regarding dose and duration adjustments; and multiple versus single strain treatments.
Topics: Adult; Adolescent; Humans; Depression; Depressive Disorder, Major; Brain-Gut Axis; Probiotics; Microbiota
PubMed: 37325818
DOI: 10.5507/bp.2023.024 -
Journal of Affective Disorders Aug 2023Major depressive disorder (MDD) and insomnia have been linked to deficiencies in cognitive performance. However, the underlying mechanism of cognitive impairment in MDD...
BACKGROUND
Major depressive disorder (MDD) and insomnia have been linked to deficiencies in cognitive performance. However, the underlying mechanism of cognitive impairment in MDD patients with insomnia symptoms (IS) remains unclear. This study aimed to explore the effects of IS in patients with MDD by comparing cognitive function indices among those with IS, those without insomnia symptoms (NIS), and healthy controls (HCs). In addition, we assessed whether the dysfunction of central nervous system (CNS) is one of the important pathophysiologic mechanisms of IS in patients with MDD by comparing the biochemical metabolism ratios in the anterior cingulate cortex (ACC).
METHOD
Fifty-five MDD with IS, 39 MDD without IS, and 47 demographically matched HCs underwent the MATRICS Consensus Cognitive Battery (MCCB) assessment and proton magnetic resonance spectroscopy (H-MRS). MCCB cognitive scores and biochemical metabolism in ACC were assessed and compared between groups.
RESULTS
Compared to the HCs group, IS and NIS groups scored significantly lower in seven MCCB cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning problem solving and social cognition). IS group showed a lower speed of processing and lower Cho/Cr ratio in the left ACC vs. NIS group and HCs. Also, in IS group, the Cho/Cr ratio in the left ACC was positively correlated with the composite T-score.
CONCLUSION
Patients with comorbidity of MDD with IS may exhibit more common MCCB cognitive impairments than those without IS, particularly speed of processing. Also, dysfunction of ACC may underlie the neural substrate of cognitive impairment in MDD with IS.
Topics: Humans; Depressive Disorder, Major; Sleep Initiation and Maintenance Disorders; Gyrus Cinguli; Cognition; Cognitive Dysfunction
PubMed: 37164065
DOI: 10.1016/j.jad.2023.04.132 -
Challenges in the management of depressive disorders comorbid with tuberculosis and type 2 diabetes.Current Opinion in Psychiatry Sep 2023The aim of this study was to address the most relevant diagnostic and therapeutic challenges in the management of depressive disorders among patients with diabetes... (Review)
Review
PURPOSE OF REVIEW
The aim of this study was to address the most relevant diagnostic and therapeutic challenges in the management of depressive disorders among patients with diabetes mellitus and tuberculosis (TB).
RECENT FINDINGS
Depressive disorder, diabetes mellitus and TB are considered important contributors to the global burden of diseases with an emphasis on developing countries. Depressive disorder increases the chance of negative outcomes during the treatment of both diabetes mellitus and TB, while biological and adaptive changes due to diabetes mellitus and TB increase in turn the chance of depressive disorder.
SUMMARY
In this review, we present major challenges in the management of depressive disorder among patients with TB and diabetes mellitus, from detection and clinical diagnosis using appropriate diagnostic tools, to selecting the best psychotherapeutic and/or pharmacological intervention, considering the potential, adverse events and interactions due to potential polypharmacy.
Topics: Humans; Diabetes Mellitus, Type 2; Tuberculosis; Comorbidity; Depressive Disorder; Diabetes Mellitus
PubMed: 37439587
DOI: 10.1097/YCO.0000000000000885 -
Nutrients Dec 2023Observational studies have implied a potential correlation between allergic diseases and major depressive disorder (MDD). However, the relationship is still inconclusive...
BACKGROUND
Observational studies have implied a potential correlation between allergic diseases and major depressive disorder (MDD). However, the relationship is still inconclusive as it is likely to be interfered with by substantial confounding factors and potential reverse causality. The present study aimed to investigate causal correlation of the two diseases by a Mendelian randomization (MR) study and further elucidate the underlying molecular mechanisms.
METHODS
With the biggest summary datasets of a genome-wide association study (GWAS) in the East Asian population, we conducted a two-sample, bidirectional MR study to assess the causal correlation between shrimp allergy (SA) and MDD. Subsequently, we identified the pleiotropic genes' susceptibility to the two diseases at whole-genome and tissue-specific levels, respectively. Enriched GO sets and KEGG pathways were also discovered to elucidate the potential underlying mechanisms.
RESULTS
With the most suitable MR method, SA was identified as a causal risk factor for MDD based on three different groups of independent genetic instruments, respectively ( < 2.81 × 10). In contrast, we did not observe a significant causal effect of MDD on SA. The GWAS-pairwise program successfully identified seven pleiotropic genetic variants (PPA3 > 0.8), indicating that the two diseases indeed have a shared genetic basis. At a whole-genome level, the MAGMA program identified 44 pleiotropic genes, which were enriched in allergy-related pathways, such as antigen processing and presentation pathway ( = 1.46 × 10). In brain-specific tissue, the S-MultiXcan program found 17 pleiotropic genes that were significantly enriched in immune-related pathways and GO sets, including asthma-related pathway, T-cell activation-related, and major histocompatibility complex protein-related GO sets. Regarding whole-blood tissue, the program identified six pleiotropic genes that are significantly enriched in tolerance induction-related GO sets.
CONCLUSIONS
The present study for the first time indicated a significant causal effect of SA on the occurrence of MDD, but the reverse was not true. Enrichment analyses of pleiotropic genes at whole-genome and tissue-specific levels implied the involvement of allergy and immune-related pathways in the shared genetic mechanism of the two diseases. Elucidating the causal effect and the acting direction may be beneficial in reducing the incidence rate of MDD for the massive group of SA patients in the East Asian region.
Topics: Humans; Causality; Depressive Disorder, Major; East Asian People; Genome-Wide Association Study; Shellfish Hypersensitivity
PubMed: 38201909
DOI: 10.3390/nu16010079