BackgroundAcupuncture has been increasingly applied as an adjunctive treatment for major depressive disorder (MDD), yet its central neurobiological mechanisms remain insufficiently understood. Cerebral blood flow (CBF) and functional connectivity strength (FCS) provide complementary perspectives on regional metabolic activity and large-scale functional integration, and their coupling may reflect neurovascular coordination relevant to depression.MethodsTwenty patients with MDD and twenty matched healthy controls (HC) underwent resting-state MRI. Patients received intradermal acupuncture (IA) and were scanned before and immediately after stimulation, while healthy controls were scanned once. Voxel-wise analyses of CBF, FCS, and their ratio (CBF/FCS) were performed to characterize acupuncture-related changes in neurovascular coupling. Group comparisons and pre–post acupuncture effects were assessed at the whole gray matter level.ResultsAcupuncture induced significant alterations in CBF/FCS coupling across widespread brain regions, including the bilateral precuneus, postcentral gyrus, superior temporal pole, superior frontal gyrus, occipital cortex, and cerebellum. These regions are primarily involved in sensorimotor processing, cognitive control, and emotional regulation. Overall, IA was associated with an immediate increase in CBF/FCS coupling, suggesting enhanced coordination between cerebral perfusion and functional network integration.ConclusionThis study provides evidence that intradermal acupuncture modulates neurovascular coupling in patients with MDD, offering neuroimaging-based insights into its antidepressant mechanisms. The findings support the notion that acupuncture may facilitate more efficient brain function by optimizing the balance between neural activity and metabolic supply.
Two faces of police stress: Spanish validation of operational and organizational PSQ scales
IntroductionPolice officers face multiple psychosocial risks stemming from operational and organizational aspects of their work. The Police Stress Questionnaire (PSQ) includes operational (PSQ-Op) and organizational (PSQ-Org) versions to assess these stressors. This study aimed to validate both versions in a sample of Mossos d’Esquadra, examining their factorial structure, reliability, and convergent and discriminant validity.MethodsExploratory and confirmatory factor analyses were conducted to examine the internal structure of the PSQ-Op and PSQ-Org. Internal consistency was evaluated using reliability indices. Convergent and discriminant validity were assessed through correlations with measures of anxiety, depression, and coping strategies.ResultsBoth PSQ-Op and PSQ-Org showed an essentially unidimensional structure, indicating that each scale measures a coherent latent construct. Operational and organizational stress remained distinct domains. Both scales exhibited high reliability and adequate psychometric properties. Subtle gender differences were noted in the perception of specific stressors.DiscussionThese findings support the validity and reliability of the PSQ-Op and PSQ-Org for assessing psychosocial risks among Spanish police officers. The scales can inform interventions targeting workplace stress prevention and the promotion of organizational well-being, emphasizing the need to address operational and organizational stressors separately.
Psychometric validation of the revised Chinese version of the Dimensional Anhedonia Rating Scale in psychiatric outpatients
ObjectiveTo refine the Chinese version of the Dimensional Anhedonia Rating Scale (DARS) and evaluate the psychometric properties of the Revised Chinese DARS (RC-DARS) in a large sample of first-visit psychiatric outpatients.MethodsThe study was conducted in two sequential phases at a specialized psychiatric hospital. In Phase I (n = 277), the existing Chinese DARS underwent semantic and cultural refinement in accordance with ISPOR and TRAPD guidelines, incorporating cognitive interviews and back-translation procedures. In Phase II (n = 788), the RC-DARS was administered alongside the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Index (PSQI), and the MMPI Suicide Ideation Subscale (MMPI-SI). Exploratory and confirmatory factor analyses were conducted using common-factor extraction and the WLSMV estimator for ordinal indicators. Internal consistency, gender-based measurement invariance, and convergent validity were evaluated.ResultsExploratory analyses supported a four-factor domain structure. Confirmatory factor analysis demonstrated good model fit for the domain-based model (χ²/df = 3.81, CFI = 0.98, TLI = 0.97, RMSEA = 0.08, SRMR = 0.05), with substantially superior fit relative to an alternative reward-processing model. Internal consistency was excellent (Cronbach’s α = 0.95; McDonald’s ω = 0.96). Multi-group analyses supported configural, metric, and scalar invariance across gender (ΔCFI < 0.01). RC-DARS total scores were significantly negatively correlated with depressive symptoms (r = −0.443), anxiety (r = −0.317), sleep disturbance (r = −0.494), and suicide risk (r = −0.312) (all p <.001). Individuals with severe depressive symptoms exhibited significantly lower RC-DARS scores than those below the clinical threshold.ConclusionsThe RC-DARS demonstrates robust psychometric properties in a first-visit outpatient sample. The revision primarily enhances semantic precision and structural differentiation without materially altering score distributions. The scale may serve as a refined instrument for dimensional assessment of anhedonia in similar clinical contexts, pending longitudinal and multi-site validation.
Role of TRPC1 in the pathogenesis of depression induced by traumatic brain injury
BackgroundTraumatic brain injury (TBI) is one of the leading causes of mortality and disability, with many patients developing long-term sequelae. Depression is among the most common psychiatric complications following TBI, yet its underlying mechanisms remain unclear. Transient receptor potential canonical 1 (TRPC1) has been implicated in neurological disorders, but its role in post-TBI depression is not well understood.MethodsA controlled cortical impact (CCI) model was used to induce moderate TBI in mice. At 4 weeks post-injury, depressive-like behaviors were assessed using the tail suspension test (TST), forced swim test (FST), and sucrose preference test (SPT). Subsequently, reactive astrocytes and microglia were quantified, along with the expression of inflammatory cytokines, in the ipsilateral hippocampus. Synaptic function was also evaluated.ResultsBehavioral tests revealed that TBI mice exhibited significant depressive- and anxiety-like behaviors at 4 weeks post-injury. Concurrently, TRPC1 expression was downregulated in the ipsilateral hippocampus, accompanied by reduced levels of synaptic-associated proteins, elevated pro-inflammatory cytokines, and increased reactive astrocytes and microglia. Further experiments demonstrated that TRPC1 overexpression attenuated neuroinflammation, restored synaptic function, and ameliorated depressive-like behaviors in TBI mice.ConclusionThis study suggests that TBI may trigger depression by downregulating TRPC1, thereby promoting neuroinflammation and synaptic dysfunction. Conversely, TRPC1 overexpression mitigates these effects, highlighting its potential as a therapeutic target for post-TBI depression.
Protocol for a randomized trial to predict the efficacy of cognitive and behavioral interventions for symptoms of depression
IntroductionCognitive behavioral therapy (CBT) is one of the most common interventions for depression and has two key components: Cognitive Restructuring (CR) and Behavioral Activation (BA). However, no evidence-based guidelines exist to help clients and clinicians decide whether CBT would be a good first-line treatment for a given individual based on their personal characteristics, and which CBT intervention would benefit them more. We propose that specific capacities to learn from new information and experiences are prerequisites for response to CBT and that BA and CR require different learning capacities. In this study, we aim to develop predictive models of symptom change based on computationally-derived variables from behavioral tasks, in addition to clinical and demographic self-report data, to identify parameters and variables that can determine which individuals with depressive symptoms would benefit from CBT-based interventions and, ideally, which specific interventions they would benefit from more.Methods and analysisWe plan to recruit at least 1,500 adult participants who report having symptoms of depression and reside in U.S. After completing a series of questionnaires and behavioral tasks to assess their learning propensities, participants will be randomly assigned to a BA or a CR group. Using an online self-help tool, participants will then engage with designated modules according to their assigned group for five weeks. We will assess symptoms 1 week post-intervention (main end point of study) and follow up at 6, 18, and 42 weeks post-intervention. Upon enrolling and consenting into the main study, participants will be randomly assigned to either the training dataset or the held-out test dataset at a ratio of 2:1. This enables a clean separation of training and test datasets and prevent data leakage. We plan to build cross-validated predictive algorithms on the training dataset, and preregister our analysis plan before we validate our models and hypotheses in the held-out, unseen, test dataset. Enrollment of the study started 23rd January, 2024.Study protocol registrationClinicalTrials.gov, identifier (NCT06631183). The protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Numbers in brackets follow subsection numbers in the guidelines.
Venous Tourniquet vs. Arterial Tourniquet for Seizure Monitoring in ECT
Conditions: Major Depressive Disorder; Bipolar Disorder; Schizophrenia
Interventions: Device: Device: Arterial Tourniquet; Device: Device: Venous Tourniquet
Sponsors: Medipol University
Not yet recruiting
Interventions: Device: Device: Arterial Tourniquet; Device: Device: Venous Tourniquet
Sponsors: Medipol University
Not yet recruiting
Baseline Mismatch Negativity Amplitude Predicts Direction and Magnitude of Ketamine Effect in Healthy Volunteers — A “Disordinal” Effect
Mismatch negativity (MMN) is a component of the auditory event-related potential (ERP) that is elicited during a passive oddball paradigm where task-irrelevant infrequent deviants are presented in a stream of more frequent standard stimuli. MMN is believed to index a pre-attentive stage of auditory information processing closely linked to N-methyl-D-aspartate receptors (NMDAR) function. Ketamine is thought to act primarily as an NMDAR antagonist, has been used in clinical trials to model the symptoms of schizophrenia and is increasingly used in the clinic to treat depression.
[Comment] Magnetic seizure therapy: balancing efficacy and cognition
Few treatments in psychiatry match the antidepressant efficacy of convulsive therapy. Yet despite this therapeutic potency, persistent stigma and concerns about cognitive adverse effects—particularly autobiographical memory disturbance associated with electroconvulsive therapy, ECT—continue to limit its wider adoption.1 This tension is especially consequential in treatment-resistant depression (TRD), where convulsive therapies remain among the most effective treatments.2
Pregnancy Sickness Study Identifies New Genetic Links
The University of Southern California (USC) research team that identified the hormone-encoding gene GDF15 as a key driver of pregnancy sickness has identified nine additional genes linked to its most severe form, hyperemesis gravidarum (HG). Six of the identified genes had not been previously linked to the condition.
The Keck School of Medicine of USC team and international collaborators conducted a genome-wide association study (GWAS), scanning the entire genome for differences between women who developed HG during pregnancy and those who did not. They analyzed data from more than 10,000 women with the condition and more than 450,000 controls across European, Asian, African, and Latino ancestries. Their findings offer new clues about the condition and new hope for those affected.
Marlena Fejzo, PhD, a clinical assistant professor of population and public health sciences in the Center for Genetic Epidemiology at the Keck School of Medicine, led the present study and earlier research linking GDF15 to HG. Fejzo told GEN, “The study is much larger than previous studies and on a more diverse population allowing for identification of new genes associated with HG … The new genes give us new directions to explore for prediction, diagnosis, treatment, and response to therapies.”
Fejzo is first author of the team’s published report in Nature Genetics (“Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting”), in which the team stated, “Potential roles for candidate genes in appetite, insulin signaling, and brain plasticity provide pathways to explore etiological mechanisms and therapeutic avenues.”
HG, which affects about 2% of women, causes nausea and vomiting so severe that eating can become extremely difficult. “Most pregnancies are affected by nausea and vomiting (NVP), but in 0.3–10.8% of pregnancies the symptoms can be severe enough to cause maternal weight loss and adverse maternal and fetal outcomes,” the authors wrote. HG in its most severe form can even be life threatening.
HG was long misunderstood and often dismissed as psychological, growing evidence shows that it has a strong biological and genetic basis and can lead to severe malnourishment, putting both mother and baby at risk. Current treatments for HG are frequently ineffective in improving patient symptoms, the authors further pointed out, and so increase the risk of pregnancy termination, postpartum depression, and suicidal ideation, along with other maternal and offspring comorbidities. “Therefore, understanding of HG etiology is critical to begin to address the negative impact severe NVP has on maternal and child health.”
While historical hypotheses have previously centered around human chorionic gonadotropin (hCG), recent large-scale genetic studies have implicated the GDF15 gene encoding growth differentiation factor-15—a hormone associated with nausea and vomiting, the authors further pointed out. Earlier research by Fejzo and an international team had shown that the link between HG and GDF15 lies in women’s sensitivity to the hormone. They found that women exposed to lower levels of the hormone before pregnancy because of a mutation in the gene experience more severe symptoms, while women exposed to higher levels of the hormone before pregnancy have less severe nausea and vomiting symptoms.
“GDF15 was identified as the greatest genetic risk factor for HG in both a genome-wide and an exome-wide association study, and a rare mutation in GDF15 was associated with a greater than tenfold increased risk for HG,” the scientists noted in their newly reported study. Fejzo explained to GEN, “The mutation in GDF15 is rare. People who carry the mutation have abnormally low levels of GDF15 when they are not pregnant and that increases their risk of being hypersensitive to it during pregnancy when it is produced in massive amounts by the placenta.”
Commenting on their prior work implicating a role for GDF15 and HG, Fejzo further explained to GEN, “In our first GWAS study we found the association between the GDF15 gene and HG. Next, we published a whole-exome sequencing study that identified a mutation in GDF15 associated with HG. Then we published our study in Nature which provided strong evidence that hypersensitivity to the rise of GDF15 in pregnancy (due to low pre-pregnancy GDF15 in circulation) is the main driver of the condition.”
For their newly reported study the researchers carried out a multi-ancestry genome-wide association study of 10,974 HG/excessive vomiting in pregnancy cases and 461,461 controls across European, Asian, African, and Latino ancestries from nine contributing studies.
The results identified 10 genes that were linked to HG, including four that had previously been identified, and six new genes. “Because this is the largest study of HG ever conducted, we’ve been able to tease out important new details that were previously unknown,” said Fejzo. “The fact that we’ve studied women from multiple ancestry groups suggests that these results may be generalizable across a broad population.”
The four genes previously identified were growth differentiation factor 15 (GDF15), GFRAL, which produces the receptor for the GDF15 hormone of the same name, and IGFBP7 and PGR, both of which are involved in development of the placenta. The strongest link by far was to GDF15, which rises sharply during pregnancy. “We know that GDF15 and it’s receptor GFRAL are the main drivers and are in a signaling pathway that causes aversions, nausea, and vomiting,” Fejzo told GEN. “More work needs to be done to explore the other associations, but since studies suggest manipulating progesterone and/or IGFBP7 may not be safe in pregnancy, current studies are focusing on the GDF15 pathway.”
The six newly identified genes offer further clues that might help explain the basis of HG or point to new ways of treating it. They include FSHB, TCFL72 SLITRK1, SYN3, IGSF11, and CDH9. “Now that we’ve more than doubled the genes associated with HG, we can dig deeper into the biology behind this condition, as well as new possible pathways for treating it,” Fejzo said. Speaking to GEN, the researchers noted, “Because the new associations are novel, we need to understand the roles they may play in normal pregnancy and then compare that to pregnancies affected by HG.”
Of the newly identified genes, TCF7L2 stands out because it is one of the strongest genetic risk factors for type 2 diabetes and is also associated with gestational diabetes. “This is a brand-new target, and it’s not yet clear what it’s doing in pregnancy,” Fejzo said. In further commentary to GEN, Fejzo added, “The TCF7L2 gene is a type 2 diabetes-associated gene and a transcription factor that may control glucagon-like peptide-1 (GLP-1) expression and has been associated with liraglutide effects resulting in greater weight loss in obesity. So understanding its role in that rapidly evolving therapeutic arena has potential.”
Several of the other genes identified are involved in appetite and nausea, as well as brain plasticity, or how the brain learns and adapts to new information. Fejzo suggests the brain may learn to associate certain foods with feeling sick, leading to strong, lasting aversions during pregnancy. More research is needed to explore this possibility. “Other genes are associated with learning flexibility so we hypothesize that they may play a role in conditioned taste aversion and may provide new targets to alter or dampen learned aversions,” Fejzo told GEN. Historically, people believed the pregnancy hormone hCG was the cause, but we found no evidence to support that and instead, fascinatingly, we found a link to the follicle stimulating hormone receptor.”
Of the ten candidate genes six—GDF15, GFRAL, IGFBP7, PGR, TCF7L2 and SYN3—have been linked with cachexia—a wasting condition with similar symptoms to HG, including loss of appetite, weight loss and muscle wasting, the scientists noted. “Manipulation of GDF15, GFRAL, IGFBP7, PGR and TCF7L2 in animal models has shown effectiveness in reducing symptoms of cachexia. Thus, assuming analogous functions for these factors in HG, there is both genetic and biological support for causal and potentially reversible contributions for these genes in NVP.”
The researchers also found that some genes linked to HG were associated with other pregnancy outcomes. “This study also identified individual associations between risk genes and adverse outcomes including shorter pregnancy duration, pre-eclampsia, and birth weight,” they noted.
Several medications are available for treating HG, but even the most effective, Zofran, only partly relieves symptoms for about half of patients. The new findings reveal new potential treatment targets and could possibly also help match existing medications to patients based on their genetic profiles. “The ten genetic associations provide intriguing avenues to advance our understanding and pursue therapeutic pathways for a common pregnancy condition that in its most severe form is associated with substantial morbidity and even mortality for mothers and exposed offspring,” the scientists concluded.
Fejzo and her team just received approval to launch a clinical trial of metformin, a widely used diabetes medicine that increases GDF15 levels. The study will test whether taking metformin before pregnancy can desensitize women to the hormone, potentially reducing nausea and vomiting or preventing HG in women who have had it before. GEN was told, “We will be initiating a clinical trial to increase GDF15 prior to pregnancy in patients with a history of HG and planning to conceive to desensitize them to the hormone’s rapid rise in early pregnancy. We and others have shown preliminary evidence that this approach may work as in our retrospective study pre-pregnancy metformin use was associated with a significant reduction in HG risk.”
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<![CDATA[Bupropion may cause dose-linked tinnitus; this case shows symptoms improve after dose reduction, helping manage depression without stopping treatment.]]>