Functional disorders (FDs) are characterized by persistent somatic symptoms and are highly comorbid with internalizing disorders (IDs). To provide much-needed insight into FD etiology, we evaluated FD and ID familial coaggregation and shared familiality.

Lifelines is a three-generation cohort study, which assessed three FDs (myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS], irritable bowel syndrome [IBS], and fibromyalgia [FM]) and six IDs (major depressive disorder [MDD], dysthymia [DYS], generalized anxiety disorder [GAD], agoraphobia [AGPH], social phobia [SPH], and panic disorder [PD]) according to diagnostic criteria. Based on 153,803 individuals, including 90,397 with a first-degree relative in Lifelines, we calculated recurrence risk ratios (λRs) and tetrachoric correlations to evaluate familial aggregation and coaggregation of these disorders in first-degree relatives. We then estimated their familiality and familial correlations.

Familial aggregation was observed across disorders, with λR ranging from 1.45 to 2.23 within disorders and from 1.17 to 1.94 across disorders. Familiality estimates ranged from 22% (95% confidence interval [CI]: 16–29) for IBS to 42% (95% CI: 33–50) for ME/CFS. Familial correlations ranged from +0.37 (95% CI: 0.24–0.51) between FM and AGPH to +0.97 (95% CI: 0.80–1) between ME/CFS and FM. The highest familial correlation between an ID and FD was +0.83 (95% CI: 0.66–0.99) for MDD and ME/CFS.

There is a clear familial component to FDs, which is partially shared with IDs. This suggests that IDs and FDs share both genetic and family-environmental risk factors. Of the FDs, ME/CFS is most closely related to IDs.

Military Servicemembers and Veterans are at elevated risk for suicide, but rarely self-identify to their leaders or clinicians regarding their experience of suicidal thoughts. We developed an algorithm to identify posts containing suicide-related content on a military-specific social media platform.

Publicly-shared social media posts (n = 8449) from a military-specific social media platform were reviewed and labeled by our team for the presence/absence of suicidal thoughts and behaviors and used to train several machine learning models to identify such posts.

The best performing model was a deep learning (RoBERTa) model that incorporated post text and metadata and detected the presence of suicidal posts with relatively high sensitivity (0.85), specificity (0.96), precision (0.64), F1 score (0.73), and an area under the precision-recall curve of 0.84. Compared to non-suicidal posts, suicidal posts were more likely to contain explicit mentions of suicide, descriptions of risk factors (e.g. depression, PTSD) and help-seeking, and first-person singular pronouns.

Our results demonstrate the feasibility and potential promise of using social media posts to identify at-risk Servicemembers and Veterans. Future work will use this approach to deliver targeted interventions to social media users at risk for suicide.

Machine learning (ML) approaches are a promising venue for identifying vocal markers of neuropsychiatric disorders, such as schizophrenia. While recent studies have shown that voice-based ML models can reliably predict diagnosis and clinical symptoms of schizophrenia, it is unclear to what extent such ML markers generalize to new speech samples collected using a different task or in a different language: the assessment of generalization performance is however crucial for testing their clinical applicability.

In this research, we systematically assessed the generalizability of ML models across contexts and languages relying on a large cross-linguistic dataset of audio recordings of patients with schizophrenia and controls.

We trained ML models of vocal markers of schizophrenia on a large cross-linguistic dataset of audio recordings of 231 patients with schizophrenia and 238 matched controls (>4.000 recordings in Danish, German, Mandarin and Japanese). We developed a rigorous pipeline to minimize overfitting, including cross-validated training set and Mixture of Experts (MoE) models. We tested the generalizability of the ML models on: (i) different participants, speaking the same language (hold-out test set); (ii) different participants, speaking a different language. Finally, we compared the predictive performance of: (i) models trained on a single language (e.g., Danish) (ii) MoE models, i.e., ensemble of models (experts) trained on a single language whose predictions are combined using a weighted sum (iii) multi-language models trained on multiple languages (e.g., Danish and German).

Model performance was comparable to state-of-the art findings (F1: 70%-80%) when trained and tested on participants speaking the same language (out-of-sample performance). Crucially, however, the ML models did not generalize well - showing a substantial decrease of performance (close to chance) - when trained in a language and tested on new languages (e.g., trained on Danish and tested on German). MoE and multi-language models showed a better increase of performance (F1: 55%-60%), but still far from those requested for achieving clinical applicability.

Our results show that the cross-linguistic generalizability of ML models of vocal markers of schizophrenia is very limited. This is an issue if our first goal is to translate these vocal markers into effective clinical applications. We argue that more emphasis needs to be placed on collecting large open datasets to test the generalizability of voice-based ML models, for example, across different speech tasks or across the heterogeneous clinical profiles that characterize schizophrenia spectrum disorder.

None Declared

This study aimed to compare the pre- and post-operative vestibular and equilibrium functions of patients with cholesteatoma-induced labyrinthine fistulas who underwent different management methods.

Data from 49 patients with cholesteatoma-induced labyrinthine fistulas who underwent one of three surgical procedures were retrospectively analysed. The three management options were fistula repair, obliteration and canal occlusion.

Patients underwent fistula repair (n = 8), canal occlusion (n = 18) or obliteration procedures (n = 23). Patients in the fistula repair and canal occlusion groups suffered from post-operative vertigo and imbalance, which persisted for longer than in those in the obliteration group. Despite receiving different management strategies, all patients achieved complete recovery of equilibrium functions through persistent efforts in rehabilitation exercises.

Complete removal of the cholesteatoma matrix overlying the fistula is reliable for preventing iatrogenic hearing deterioration due to unremitting labyrinthitis. Thus, among the three fistula treatments, obliteration is the optimal method for preserving post-operative vestibular functions.

There is evidence that child maltreatment is associated with shorter telomere length in early life.

This study aims to examine if child maltreatment is associated with telomere length in middle- and older-age adults.

This was a retrospective cohort study of 141 748 UK Biobank participants aged 37–73 years at recruitment. Leukocyte telomere length was measured with quantitative polymerase chain reaction, and log-transformed and scaled to have unit standard deviation. Child maltreatment was recalled by participants. Linear regression was used to analyse the association.

After adjusting for sociodemographic characteristics, participants with three or more types of maltreatment presented with the shortest telomere lengths (β = −0.05, 95% CI −0.07 to −0.03; P < 0.0001), followed by those with two types of maltreatment (β = −0.02, 95% CI −0.04 to 0.00; P = 0.02), referent to those who had none. When adjusted for depression and post-traumatic stress disorder, the telomere lengths of participants with three or more types of maltreatment were still shorter (β = −0.04, 95% CI −0.07 to −0.02; P = 0.0008). The telomere lengths of those with one type of maltreatment were not significantly different from those who had none. When mutually adjusted, physical abuse (β = −0.05, 95% CI −0.07 to −0.03; P < 0.0001) and sexual abuse (β = −0.02, 95% CI −0.04 to 0.00; P = 0.02) were independently associated with shorter telomere length.

Our findings showed that child maltreatment is associated with shorter telomere length in middle- and older-aged adults, independent of sociodemographic and mental health factors.

Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).

Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.

Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.

The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.

Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.

In this study, we aimed to identify protein molecules in the hypothalamus in the female rats injected exogenous androgen before sexual differentiation.

Neonatal female SD rats were randomly divided into two groups: experimental group and control female group. Four neonatal male SD rats were control male group. All animals were subjected to intraperitoneal injection of testosterone propionate as experimental group or aseptic oil as control. The rats were sacrificed 90 days after the injection and the brains were collected. 2-DE were performed in order to establish profiles of proteome from rat hypothalamus and followed by MALDITOF- TOF mass spectrometry was used to identify proteins differentially expressed in rat hypothalamus from experimental group as compared to normal control group.

11 differential spots were cut off from the Silver stained gel, and 9 of the spots were identified, which were Dihydropyrimidinase-like 3 (DPYSL3), heterogeneous nuclear ribonucleoprotein K(hnRNP K), Profilin2, Triosephosphate isomerase 1(Tpi 1), Carbonic anhydrase II(CA II), Annexin A3, Protein disulfide isomerase associated 3 (PDIA3), Creatine kinase-B and Secernin 1.

The results of the present study indicate that the development of sexual differentiation may be associated with the alteration in the expression of a large number of cytosolic proteins in the hypothalamus.

Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated.

Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms.

All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86–96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47–82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly ‘very good’ (κ = 0.86–0.96).

The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.