Association of major depression, schizophrenia and bipolar disorder with thyroid cancer: a bidirectional two-sample mendelian randomized study.

BACKGROUND: Major depressive disease (MDD), schizophrenia (SCZ), and bipolar disorder (BD) are common psychiatric disorders, and their relationship with thyroid cancer has been of great interest. This study aimed to investigate the potential causal effects of MDD, SCZ, BD, and thyroid cancer. METHODS: We used publicly available summary statistics from large-scale genome-wide association studies to select genetic variant loci associated with MDD, SCZ, BD, and thyroid cancer as instrumental variables (IVs), which were quality controlled and clustered. Additionally, we used three Mendelian randomization (MR) methods, inverse variance weighted (IVW), MR-Egger regression and weighted median estimator (WME) methods, to estimate the bidirectional causal relationship between psychiatric disorders and thyroid cancer. In addition, we performed heterogeneity and multivariate tests to verify the validity of the IVs. RESULTS: We used two-sample bidirectional MR analysis to determine whether there was a positive causal association between MDD and thyroid cancer risk. The results of the IVW analysis (OR = 3.956 95% CI = 1.177-13.299; P = 0.026) and the WME method (OR = 5.563 95% CI = 0.998-31.008; P = 0.050) confirmed that MDD may increase the risk of thyroid cancer. Additionally, our study revealed a correlation between genetic susceptibility to SCZ and thyroid cancer (OR = 1.532 95% CI = 1.123-2.088; P = 0.007). The results of the WME method analysis based on the median estimate (OR = 1.599 95% CI = 1.014-2.521; P = 0.043) also suggested that SCZ may increase the risk of thyroid cancer. Furthermore, our study did not find a causal relationship between BD and thyroid cancer incidence. In addition, the results of reverse MR analysis showed no significant causal relationships between thyroid cancer and MDD, SCZ, or BD (P > 0.05), ruling out the possibility of reverse causality. CONCLUSIONS: This MR method analysis provides new evidence that MDD and SCZ may be positively associated with thyroid cancer risk while also revealing a correlation between BD and thyroid cancer. These results may have important implications for public health policy and clinical practice. Future studies will help elucidate the biological mechanisms of these associations and potential confounders.

Childhood neglect, the neglected trauma. A systematic review and meta-analysis of its prevalence in psychiatric disorders.

Traumatic events increase risk of mental illnesses, but childhood neglect prevalence in psychiatric disorders is understudied. This systematic review and meta-analysis assessed neglect prevalence, including emotional neglect (EN) and physical neglect (PN), among adults with psychiatric disorders. We conducted a systematic search and meta-analysis in 122 studies assessing different psychiatric disorders. Prevalence was 46.6% (95%CI[34.5-59.0]) for unspecified neglect (Ne), 43.1% (95%CI[39.0-47.4]) for EN, and 34.8% (95%CI[30.6-39.2]) for PN. Although a moderating effect of the psychiatric diagnostic category was not confirmed, some clinical diagnoses had significantly lower prevalence rates than others. Patients with bipolar disorder and major depressive disorder showed lower prevalence rates of EN and PN, whereas lower prevalence was found in psychotic disorders and eating disorders for PN only. Neglect assessment was a significant moderator for Ne and PN. No moderating effect of age and sex on neglect prevalence was found. Heterogeneity levels within and between psychiatric diagnostic categories remained high. This is the first meta-analysis examining diverse types of neglect prevalence considering different psychiatric diagnoses. Our results explore the prevalence of childhood neglect and its subtypes among adults with psychiatric disorders, contributing to understanding the nuanced interplay between neglect and specific psychiatric conditions, and guiding interventions for affected individuals.

Cluster analysis dissecting cognitive deficits in older adults with major depressive disorder and the association with neurofilament light chain.

BACKGROUND: Cognitive impairment is a growing problem with increasing burden in global aging. Older adults with major depressive disorder (MDD) have higher risk of dementia. Neurofilament light chain (NfL) has been proven as a potential biomarker in neurodegenerative disease, including dementia. We aimed to investigate the association between cognitive deficits and NfL levels in older adults with MDD. METHODS: In this cross-sectional study, we enrolled 39 MDD patients and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer's type, as controls, from a tertiary psychiatric hospital. Both groups were over age 65 and with matched Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and each cognitive domain. RESULTS: In the MDD group, participants had higher rate of family psychiatry history and current alcohol use habit compared with controls. Control group of neurocognitive disorders showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits clustered with that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster. CONCLUSIONS: We noted the negative correlation between NfL levels and cognition in MDD patients clustered with neurodegenerative disorder, Alzheimer's type. NfL could be a promising candidate as a biomarker to predict subtype of patients in MDD to develop cognitive decline. Further longitudinal studies and within MDD cluster analysis are required to validate our findings for clinical implications.

Digital Tools to Facilitate the Detection and Treatment of Bipolar Disorder: Key Developments and Future Directions.

Bipolar disorder (BD) impacts over 40 million people around the world, often manifesting in early adulthood and substantially impacting the quality of life and functioning of individuals. Although early interventions are associated with a better prognosis, the early detection of BD is challenging given the high degree of similarity with other psychiatric conditions, including major depressive disorder, which corroborates the high rates of misdiagnosis. Further, BD has a chronic, relapsing course, and the majority of patients will go on to experience mood relapses despite pharmacological treatment. Digital technologies present promising results to augment early detection of symptoms and enhance BD treatment. In this editorial, we will discuss current findings on the use of digital technologies in the field of BD, while debating the challenges associated with their implementation in clinical practice and the future directions.

Psychomotor retardation: What about the partial responders to magnetic transcranial stimulation in treatment resistant depression ?

OBJECTIVE: Psychomotor retardation is a core clinical component of Major Depressive Disorder responsible for disability and is known as a treatment response marker of biological treatments for depression. Our objective was to describe cognitive and motoric measures changes during a treatment by repetitive Transcranial Magnetic Stimulation (rTMS) within the THETAD-DEP trial for treatment-resistant depression (TRD), and compare those performances at the end of treatment and one month after between responders (>50% improvement on MADRS score), partial responders (25-50%) and non-reponders (no clinically relevant improvement). Our secondary aim was to investigate baseline psychomotor performances associated with non-response and response even partial. METHODS: Fifty-four patients with treatment-resistant unipolar depression and treated by either high frequency 10 Hz rTMS or iTBS for 4 weeks (20 sessions) underwent assessment including French Retardation Rating Scale for Depression (ERD), Verbal Fluency test, and Trail Making Test A. before, just after treatment and one month later. RESULTS: 20 patients were responders (R, 21 partial responders (PR) and 13 non-responders (NR). rTMS treatment improved psychomotor performances in the R and PR groups unlike NR patients whose psychomotor performance was not enhanced by treatment. At baseline, participants, later identified as partial responders, showed significantly higher performances than non-responders. CONCLUSION: Higher cognitivo-motor performances at baseline may be associated with clinical improvement after rTMS treatment. This work highlights the value of objective psychomotor testing for the identification of rTMS responders and partial responders, and thus may be useful for patient selection and protocol individualization such as treatment continuation for early partial responders.

Risk Factors for Psychiatric Disorders in Patients with Multiple Sclerosis-A Single-Center Study in the Polish Population.

Aim: The aim of this study was to determine the prevalence of mental disorders in a group of patients with multiple sclerosis (MS) during outpatient treatment. Additionally, an attempt was made to assess the influence of parameters related to patients and their clinical status on the prevalence of mental disorders. Materials and Methods: This study was conducted between 2017 and 2018 in a group of 103 patients with MS who underwent treatment at the Outpatient Clinic of Neurology at the Clinical Hospital No. 1 in Zabrze, Poland. Sociodemographic data were collected, and the course of the underlying disease and comorbidities underwent assessment. The Mini International Neuropsychiatric Interview (MINI) and psychiatric examination were used to assess the occurrence of mental disorders. Results: In this study, female subjects accounted for 67.96% of patients (mean age: 43 years). Of all patients, 67% of subjects were clinically diagnosed with mental disorders during their lifetime. The results of the MINI Questionnaire showed that 33% of MS patients had a history of a major depressive episode, while 8.7% of patients met the criteria for a depressive episode. The same number of patients were treated for recurrent depressive disorders. Generalized anxiety disorder was diagnosed in 10.7% of patients, agoraphobia in 8.7% and panic disorder in 7.8%. Most patients (94.2%) had a low risk of suicide, according to the MINI Questionnaire. This study did not show a significant influence of age, sex, duration of MS symptoms or severity of symptoms as expressed by the Expanded Disability Status Score (EDSS) on the prevalence of mental disorders (p = 0.05). However, a significantly higher median EDSS score was found in patients with a history of mental disorders (p = 0.03). Additionally, a significant negative correlation was found between having a family and a psychiatric diagnosis (p = 0.01). A statistically significant negative correlation was found between the level of education and the suicide risk as assessed by the MINI Questionnaire (p = 0.03). Conclusions: This study showed a high prevalence of mental disorders in patients with MS, of which depressive episodes and anxiety disorders were the most commonly reported. There may exist a relationship between the degree of disability of MS patients and a higher prevalence of mental disorders. Patients with MS who do not have a family may be more susceptible to mental disorders. In turn, patients with a lower level of education may show a higher risk of suicide. This suggests the need for psychological and psychiatric support for patients with MS, with particular consideration given to those who are alone, those with more severe disability and patients with a lower level of education.

Is there a relationship between the severity of disease in major depressive disorder patients and dry eye disease?

PURPOSE: To investigate dry eye disease (DED) in newly diagnosed patients with depressive disorder (MDD). METHOD: This observational study included 48 MDD patients in Group 1 and 20 healthy controls in Group 2. Psychiatric and ophthalmic examinations, Beck Depression Inventory (BDI), Ocular Surface Disease Index (OSDI), Schirmer's test, tear breakup time (TBUT), Meibomian gland dysfunction (MGD), and ocular staining were conducted. The results were statistically compared. RESULTS: The participants, comprising 32 men and 36 women, had a mean age of 31.08 ± 11.7 years (18-64 years). Group 1 had a mean BDI score of 30.87 ± 8.56, while Group 2 had a score of 1.3 ± 1.3 (p < 0.001). In Group 1, 28 patients were diagnosed with DED, whereas in Group 2, six subjects were diagnosed with DED. The mean Schirmer's results in Group 1 and Group 2 were (mm/5 min) 10.87 ± 2.44 and 12.70 ± 2.3, respectively, and were significantly lower in Group 1 (p < 0.001). The mean OSDI scores in Group 1 (34.95 ± 15.8) were significantly higher compared to Group 2 (3.2 ± 3.1) (p < 0.001). There was no significant difference in mean TBUT between Group 1 (9.41 ± 2.6 s) and Group 2 (9.8 ± 0.61 s) (p > 0.05). Significant correlations were found between BDI scores and Schirmer's results as well as OSDI scores (p < 0.05, p = 0.02, respectively). No statistically significant correlations were found between BDI scores and TBUT or MGD (p > 0.05). CONCLUSION: DED was found to be more prevalent in the MDD group. The severity of MDD and DED, as indicated by BDI, OSDI, and Schirmer's results, was found to be correlated. It was observed that patients with higher depression scores had more severe dry eye. As a result, we recommend performing ophthalmic examinations in newly diagnosed MDD patients.

Causal relationship between psychiatric disorders and sensorineural hearing loss: A bidirectional two-sample mendelian randomization analysis.

OBJECTIVE: This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the causal links between psychiatric disorders and sensorineural hearing loss (SNHL). METHODS: Instrumental variables were chosen from genome-wide association studies of schizophrenia (SCH, N = 127,906), bipolar disorder (BD, N = 51,710), major depressive disorder (MDD, N = 500,199), and SNHL (N = 212,544). In the univariable MR analysis, the inverse-variance weighted method (IVW) was conducted as the primary analysis, complemented by various sensitivity analyses to ensure result robustness. RESULTS: SCH exhibited a decreased the risk of SNHL (OR = 0.949, P = 0.005), whereas BD showed an increased incidence of SNHL (OR = 1.145, P = 0.005). No causal association was found for MDD on SNHL (OR = 1.088, P = 0.246). Multivariable MR validated these results. In the reverse direction, genetically predicted SNHL was linked to a decreased risk of SCH with suggestive significance (OR = 0.912, P = 0.023). No reverse causal relationships were observed for SNHL influencing BD or MDD. These findings remained consistent across various MR methods and sensitivity analyses. CONCLUSION: This study demonstrated that the causal relationships between diverse psychiatric disorders with SNHL were heterogeneous. Specifically, SCH was inversely associated with SNHL susceptibility, and similarly, a reduced risk of SNHL was observed in schizophrenia patients. In contrast, BD exhibited an increased incidence of SNHL, although SNHL did not influence the prevalence of BD. No causal association between MDD and SNHL was found.

Global prevalence of major depressive disorder, generalized anxiety, stress, and depression among infertile women: a systematic review and meta-analysis.

BACKGROUND: In recent years, the global prevalence of infertility has increased among women (Talmor and Dunphy, Best Pract Res Clin Obstet Gynaecol 29(4):498-506, 2015) and is considered as a public health concern. One of the impacts of infertility is mental health problems in the patients, which can lead to complications such as stress, anxiety, and depression. The aim of this study is to investigate the global prevalence of major depressive disorder, general anxiety, stress, and depression in infertile women through a systematic review and meta-analysis. METHODS: To identify studies that have reported the prevalence of major depressive disorder, generalized anxiety, stress, and depression in infertile women, the PubMed, Scopus, Web of Science, Embase, ScienceDirect, and Google Scholar repositories were systematically searched. Articles published up until February 2023 were included, while no lower time limit was imposed in the search strategy. Heterogeneity of studies was examined using the I2 test and, thus, random-effects model was used to perform the analysis. Data analysis was conducted within the Comprehensive Meta-Analysis (v.2) software. RESULTS: In the review of 44 studies with a sample size of 53,300 infertile female patients, the overall prevalence of major depressive disorder (clinical depression), generalized anxiety, stress, and depression was found to be 22.9%, 13.3%, 78.8%, and 31.6% respectively. It was also found that mental health complications are more prevalent among infertile women in Asia (continent). CONCLUSION: Considering the prevalence of mental disorders among infertile women, health policymakers can use the results of the present meta-analysis to pay more attention to the mental health of infertile women and devise suitable interventions and programs to reduce and prevent the spread of psychological disorders among infertile women.

Perspectives on the impact of vortioxetine on the treatment armamentarium of major depressive disorder.

INTRODUCTION: Major Depressive Disorder (MDD) is a mental health issue that significantly affects patients' quality of life and functioning. Despite available treatments, many patients continue to suffer due to incomplete symptom resolution and side effects. AREAS COVERED: This manuscript examines Vortioxetine's role in Major Depressive Disorder (MDD) treatment, highlighting its potential to reshape therapeutic strategies due to its unique Multimodal action and proven broad-spectrum efficacy in multiple depressive domains. A detailed examination of Vortioxetine's pharmacological aspects, including indications, dosage, pharmacodynamics, and pharmacokinetics, is provided, emphasizing its safety and effectiveness. The discussion extends to Vortioxetine's role in acute-phase treatment and maintenance of MDD and its profound impact on specialized depression domains. EXPERT OPINION: Vortioxetine is distinguished for its novel multimodal serotonin modulation mechanism, showcasing significant promise as an innovative treatment for MDD. Its efficacy, which is dose-dependent, along with a commendable tolerability profile, positions it as a potential leading option for initial treatment strategies. The discourse on dosage titration, particularly the strategy of initiating treatment at lower doses followed by gradual escalation, underscores the approach toward minimizing initial adverse effects while optimizing therapeutic outcomes, aligning with the principles of personalized medicine in psychiatric care.

Measuring interpersonal trauma: Development and validation of the German version of the victimization experience schedule (VES).

OBJECTIVE: Interpersonal victimization experiences (VEs) significantly affect mental and physical health, particularly in disorders associated with life-time adversities, like fibromyalgia syndrome (FMS) and major depressive disorder (MDD). However, assessing VEs comprehensively remains challenging due to limited tools that encompass sub-traumatic events, such as bullying or discrimination, and contextual dimensions. We aimed to address this gap by validating the Victimization Experience Schedule (VES) in German, examining its reliability, and assessing VEs in clinical populations with FMS and MDD. METHODS: We investigated the relationship between VEs and clinical symptoms in individuals with FMS, MDD and healthy controls (N = 105) in a case-control study. We also analyzed correlations between different types of VEs and categories of early childhood abuse and posttraumatic-stress-disorder instruments. Additionally, we validated our findings in an independent sample of individuals with FMS (N = 97) from a clinical study. RESULTS: We observed excellent inter-rater reliability (Kw = 0.90-0.99), and VEs assessed using the VES were in alignment with subcategories of early childhood abuse. The prevalence of VEs extended beyond the categories covered by traditional survey instruments and was higher in individuals with MDD (4.0 ± 2.6) and FMS (5.9 ± 3.1) compared to controls (1.5 ± 1.7). We consistently identified a significant association between the number of VEs, the associated subjective distress, and clinical scores. Furthermore, distinct correlation patterns between VEs and clinical outcomes emerged across different cohorts. CONCLUSION: Our study emphasizes the VES's value in understanding VEs within MDD and FMS. These experiences span from traumatic to sub-traumatic and correlate with posttraumatic-stress and clinical symptoms, underscoring the VES's importance as an assessment tool.

The effect of the Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with major depressive disorder in Iran: a randomized controlled trial.

BACKGROUND: Depression is one of the most common mental disorders that leads to anxiety, sleep disturbances, and suicidal thoughts. Due to the high cost of treatment and the reluctance of many patients to seek medical help, major depressive disorder (MDD) is becoming more prevalent. Therefore, alternative methods like smartphone applications can help prevent and improve depression symptoms. The present study aimed to determine the effect of the newly developed Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with MDD. METHODS: This randomized controlled trial with a pretest-posttest design was conducted on Iranian patients with MDD in 2022. Sixty-four patients were recruited using convenience sampling and randomly assigned to two control and intervention groups. The intervention was conducted using the Yara smartphone application for three months. Data were collected using the Spielberger State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), and Beck Scale for Suicidal Ideation (BSSI). Data were first entered into IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA) and then analyzed using descriptive and analytical statistics. RESULTS: There was no statistically significant difference in the mean score of anxiety and sleep quality between the intervention and control groups before the intervention (p ≥ .05). However, this difference in the mean score of anxiety and sleep quality was statistically significant in the two groups after the intervention (p < .05). The results showed no statistically significant difference in the mean score of suicidal thoughts between the two groups before and after the intervention (p ≥ .05). The use of the Yara smartphone application had a significant positive effect on anxiety and sleep quality in depressed patients (p < .001). At the same time, it had no significant effect on suicidal thoughts (p ≥ .05). CONCLUSION: Considering the positive effect of using the Yara smartphone application on reducing anxiety and improving sleep quality in depressed patients, this application can help alleviate the problems of depressed patients alongside existing treatment methods. Thus, this application is recommended for this group of patients in psychiatric clinics and departments. The Yara application's effectiveness was not approved on suicidal thoughts in this study so that further investigation would be necessary. TRIAL REGISTRATION: Iranian Registry of Clinical Trial approval code (IRCT# IRCT20131112015390N7).

Abnormal amplitude of low-frequency fluctuations associated with sleep efficiency in major depressive disorder.

BACKGROUND: Sleep disturbance is one of the most frequent somatic symptoms in major depressive disorder (MDD), but the neural mechanisms behind it are not well understood. Sleep efficiency (SE) is a good indicator of early awakening and difficulty falling asleep in MDD patients. Our study aimed to investigate the relationship between sleep efficiency and brain function in MDD patients. METHODS: We recruited 131 MDD patients from the Fourth People's Hospital in Hefei, and 71 well-matched healthy controls who were enrolled from the community. All subjects underwent resting-state functional MRI. Brain function was measured using the fractional amplitude of low-frequency fluctuation (fALFF), sleep efficiency was objectively measured by polysomnography (PSG), and clinical scales were used to evaluate depressive symptoms and sleep status. Multivariate regression analysis was performed to assess the relationship between the amplitude of the low frequency fluctuation fraction and sleep efficiency. RESULT: Three brain regions with relevance to sleep efficiency in MDD patients were found: inferior occipital gyrus (Number of voxels = 25, peak MNI coordinate x/y/z = -42/-81/-6, Peak intensity = 4.3148), middle occipital gyrus (Number of voxels = 55, peak MNI coordinate x/y/z = -30/-78/18, Peak intensity = 5.111), and postcentral gyrus (Number of voxels = 26, peak MNI coordinate x/y/z = -27/-33/60, Peak intensity = 4.1263). But there was no significant relationship between fALFF and SE in the healthy controls. CONCLUSION: The reduced sleep efficiency in MDD may be related to their lower neural activity in the inferior occipital gyrus, middle occipital gyrus, and postcentral gyrus. The findings may provide a potential neuroimaging basis for the clinical intervention in patients with major depressive disorder with sleep disturbances.

Enhanced polygenic risk score incorporating gene-environment interaction suggests the association of major depressive disorder with cardiac and lung function.

BACKGROUND: Depression has been linked to an increased risk of cardiovascular and respiratory diseases; however, its impact on cardiac and lung function remains unclear, especially when accounting for potential gene-environment interactions. METHODS: We developed a novel polygenic and gene-environment interaction risk score (PGIRS) integrating the major genetic effect and gene-environment interaction effect of depression-associated loci. The single nucleotide polymorphisms (SNPs) demonstrating major genetic effect or environmental interaction effect were obtained from genome-wide SNP association and SNP-environment interaction analyses of depression. We then calculated the depression PGIRS for non-depressed individuals, using smoking and alcohol consumption as environmental factors. Using linear regression analysis, we assessed the associations of PGIRS and conventional polygenic risk score (PRS) with lung function (N = 42 886) and cardiac function (N = 1791) in the subjects with or without exposing to smoking and alcohol drinking. RESULTS: We detected significant associations of depression PGIRS with cardiac and lung function, contrary to conventional depression PRS. Among smokers, forced vital capacity exhibited a negative association with PGIRS (ß = -0.037, FDR = 1.00 × 10-8), contrasting with no significant association with PRS (ß = -0.002, FDR = 0.943). In drinkers, we observed a positive association between cardiac index with PGIRS (ß = 0.088, FDR = 0.010), whereas no such association was found with PRS (ß = 0.040, FDR = 0.265). Notably, in individuals who both smoked and drank, forced expiratory volume in 1-second demonstrated a negative association with PGIRS (ß = -0.042, FDR = 6.30 × 10-9), but not with PRS (ß = -0.003, FDR = 0.857). CONCLUSIONS: Our findings underscore the profound impact of depression on cardiac and lung function, highlighting the enhanced efficacy of considering gene-environment interactions in PRS-based studies.

Dynamic reconfigurations of brain networks in depressive and anxiety disorders: The influence of antidepressants.

Major Depressive Disorder (MDD) and anxiety disorders are highly comorbid recurrent psychiatric disorders. Reduced dynamic reconfiguration of brain regions across subnetworks may play a critical role underlying these deficits, with indications of normalization after treatment with antidepressants. This study investigated dynamic reconfigurations in controls and individuals with a current MDD and/or anxiety disorder including antidepressant users and non-users in a large sample (N = 207) of adults. We quantified the number of subnetworks a region switched to (promiscuity) as well as the total number of switches (flexibility). Average whole-brain (i.e., global) values and subnetwork-specific values were compared between diagnosis and antidepressant groups. No differences in reconfiguration dynamics were found between individuals with a current MDD (N = 49), anxiety disorder (N = 46), comorbid MDD and anxiety disorder (N = 55), or controls (N = 57). Global and sensorimotor network (SMN) promiscuity and flexibility were higher in antidepressant users (N = 49, regardless of diagnosis) compared to non-users (N = 101) and controls. Dynamic reconfigurations were considerably higher in antidepressant users relative to non-users and controls, but not significantly altered in individuals with a MDD and/or anxiety disorder. The increase in antidepressant users was apparent across the whole brain and in the SMN when investigating subnetworks. These findings help disentangle how antidepressants improve symptoms.

Childhood Clinical Features Preceding the Onset of Bipolar Versus Major Depressive Disorders During Adolescence.

OBJECTIVE: To identify childhood psychopathological features that predict the onset of adolescent Bipolar (BD) versus Unipolar Major Depressive Disorder (UD) during adolescence. METHOD: We analyzed clinical data from 495 juveniles diagnosed with DSM-5 UD (n = 359), and BD (n = 136), using bivariate analysis and multivariate logistic regression model. RESULTS: BD subjects exhibited earlier onset of any psychiatric feature compared to UD. Antecedents associated with later BD were: oppositional defiant > specific phobias > ADHD > obsessive compulsive (OCD). Antecedents selectively associated with later UD were: social anxiety and separation anxiety. Factors significantly and independently associated with later BD diagnosis were: [a] emotional dysregulation at onset of the mood disorder; [b] first depressive episode with mixed features; [c] antecedent ADHD; [d] antecedent OCD, and [e] antecedent oppositional-defiance. CONCLUSION: Identifying developmental differences in BD and UD symptoms can aid clinicians in early identification and treatment planning for bipolar disorder in youth.

Gender differences in prevalence and clinical correlates of anxiety in first-episode and drug-naïve patients with major depressive disorder comorbid with metabolic syndrome.

BACKGROUND: Although gender differences in major depressive disorder (MDD) have been widely reported, there has not been much focus on gender differences in comorbidity. In patients with MDD and comorbid metabolic syndrome (Mets), the goal of this study was to investigate potential gender differences in the prevalence and clinical correlates of concomitant anxiety. METHODS: Seven hundred and ninety-four first-episode and drug-naïve patients (FEDN) patients with MDD and comorbid Mets were recruited. For each patient, sociodemographic data, thyroid function indicators, and Mets parameters were acquired. Each participant completed the 14-item Hamilton Assessment Scale for Anxiety (HAMA) and the 17-item Hamilton Assessment Scale for Depression (HAMD). RESULTS: There were no gender differences in the prevalence of anxiety in patients with MDD and comorbid Mets. Female patients with MDD had a shorter duration of illness. Correlation analysis showed that HAMD score, TSH, TgAb, and TPOAb were associated with anxiety prevalence in female patients, whereas anxiety onset in male patients was only associated with TSH, TgAb, and TPOAb levels. In addition, multiple logistic regression analysis showed that TSH and TgAb predicted anxiety in male patients, whereas HAMD score and age of onset significantly predicted anxiety in female patients. LIMITATIONS: Cross-sectional design and no control for anxiety-related factors. CONCLUSIONS: Our study showed no gender differences in the prevalence of anxiety in patients with MDD and comorbid Mets. HAMD score was associated with anxiety in female patients, whereas TSH, TgAb, and TPOAb were associated with anxiety in male patients.

Major depressive disorder with hypersomnolence complaint: A comparison study with non-depressed individuals examining objective biomarkers.

BACKGROUND: Hypersomnolence is common in major depressive disorder (MDD), associated with more severe episodes, suicide and antidepressant resistance. Nevertheless, few studies used polysomnography (PSG) and multiple sleep latency test (MSLT) to characterize these patients. In this context, we compared patients visiting a sleep center for hypersomnolence complaint with MDD (HSC/MDD+) and without MDD (HSC/MDD-). METHODS: HSC/MDD+ and HSC/MDD- groups were defined according to DSM-5 criteria and CES-D scale, and had a 30 h-PSG with ad libitum-sleep and PSG followed by MLST. RESULTS: HSC/MDD+ had an increased self-declared total sleep time (sTST) of about 10 h30 similar to HSC/MDD- (630.8 ± 17.3 min-vs-616.5 ± 18.1 min, respectively, p = 0.39). Nevertheless, their objective TST (oTST) on ad libitum PSG was significantly longer and about 10 h50 (648.6 ± 23.9 min-vs-587.4 ± 19.0 min, respectively, p = 0.038). HSC/MDD+ also significantly better estimated their sleep duration, with a lower difference between their sTST and oTST compared to HSC/MDD- (10.0 ± 1.7 %-vs-17.4 ± 2.1 %, respectively, p = 0.009) and confirmed significantly more frequently the hypersomnia diagnosis -i.e. oTST>10H- (82.6 ± 8.1 %-vs-54.6 ± 10.9 %, respectively, p = 0.046). Using the Kupfer index (KI), we confirmed a reduced REM sleep latency in patients MDD/HSC+ (15.2 ± 10.0 %-vs-2.3 ± 2.3 %, respectively, p = 0.039). Both groups had comparable increased diurnal sleepiness assessed with the Epworth scale (14.1 ± 1.1-vs-14.8 ± 1.1, respectively, p = 0.65). HSC/MDD+ had less MSLT sleep latency <8 min (9.1 ± 5.1 %-vs-27.3 ± 6.8 %, respectively, p = 0.048). LIMITATIONS: Retrospective cross-sectional study. CONCLUSIONS: HSC/MDD+ accurately estimated their sleep duration, objectively confirmed hypersomnia and may specifically had a decreased Kupfer index.

A narrative review on insomnia and hypersomnolence within Major Depressive Disorder and bipolar disorder: A proposal for a novel psychometric protocol.

Sleep disorders have become increasingly prevalent, with many adults worldwide reporting sleep dissatisfaction. Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are common conditions associated with disrupted sleep patterns such as insomnia and hypersomnolence. These sleep disorders significantly affect the progression, severity, treatment, and outcome of unipolar and bipolar depression. While there is evidence of a connection between sleep disorders and depression, it remains unclear if sleep features differ between MDD and BD. In light of this, this narrative review aims to: (1) summarize findings on common sleep disorders like insomnia and hypersomnolence, strongly linked to MDD and BD; (2) propose a novel psychometric approach to assess sleep in individuals with depressive disorders. Despite insomnia seems to be more influent in unipolar depression, while hypersomnolence in bipolar one, there is no common agreement. So, it is essential adopting a comprehensive psychometric protocol for try to fill this gap. Understanding the relationship between sleep and MDD and BD disorders are crucial for effective management and better quality of life for those affected.

Dysconnectivity of the brain functional network and abnormally expressed peripheral transcriptional profiles in patients with anxious depression.

BACKGROUND: Major depressive disorder (MDD) is a heterogeneous mental disorder, and accompanying anxiety symptoms, known as anxious depression (AD), are the most common subtype. However, the pathophysiology of AD may be distinct in depressed patients without anxiety (NAD) and remains unknown. This study aimed to investigate the relationship between functional connectivity and peripheral transcriptional profiles in patients with AD and NAD. METHODS: Functional imaging data were collected to identify differences in functional networks among patients with AD (n = 66), patients with NAD (n = 115), and healthy controls (HC, n = 200). The peripheral transcriptional data were clustered as co-expression modules, and their associations with AD, AND, and HC were analyzed. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of the genes in the significant module were performed. Correlation analysis was performed to identify functional network-associated gene co-expression modules. RESULTS: A network was identified which consisted of 23 nodes and 28 edges that were significantly different among three sample groups. The regions of the network were located in temporal and occipital lobe. Two gene co-expression modules were shown to be associated with NAD, and one of which was correlated with the disrupted network in the AD group. The biological function of this module was enriched in immune regulation pathways. CONCLUSION: The results suggested that immune-related mechanisms were associated with functional networks in AD.