J Psychiatr Res [JOURNAL]
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200 papers
Correlation between cognitive dysfunction and amygdala connectivity in first-episode, treatment-naïve patients with anxious major depressive disorder.
Chen B, Huang Y, Feng S … +6 more , Liu C, Li H, Zhang Z, Fong LM, Wu K, Wu F
J Psychiatr Res · 2026 Jun · PMID 41797253 · Publisher ↗
BACKGROUND: Anxiety symptoms often co-occur in major depressive disorder (MDD), defining a clinical subtype known as anxious MDD (aMDD). Cognitive dysfunction is prevalent in aMDD patients and may arise from aberrant bra...
BACKGROUND: Anxiety symptoms often co-occur in major depressive disorder (MDD), defining a clinical subtype known as anxious MDD (aMDD). Cognitive dysfunction is prevalent in aMDD patients and may arise from aberrant brain functional activity. This study explores amygdala-based functional connectivity (FC) alterations in aMDD patients and their correlation with cognitive function. METHODS: We recruited 62 first-episode MDD patients, including 34 aMDD and 28 non-anxious MDD (naMDD), along with 52 matched healthy controls (HCs). The 17-item Hamilton Depression Rating Scale was utilized to evaluate the severity of anxiety and depression symptoms in MDD patients. All participants underwent the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) for cognitive assessment and MRI scanning. FC analysis was conducted using bilateral amygdala as seed regions. Partial correlation analysis was employed to investigate the correlation between aberrant FC and cognitive function. RESULTS: Compared to naMDD patients, aMDD patients exhibited more severe depressive symptoms and speed of processing (SOP) deficits, plausibly driven by comorbid anxiety. We found for the first time that, aMDD patients showed increased FC between the left amygdala and left cerebellum lobule VIII. This hyperconnectivity was positively correlated with SOP scores. Furthermore, aMDD patients demonstrated decreased FC between the left amygdala and the left superior temporal pole, which exhibited a positive correlation with Visual Learning (VIS) scores. These findings indicate that anxiety-related pathophysiology may induce circuit-specific connectivity disturbances that influence cognitive performance in aMDD. CONCLUSION: These aberrant FC patterns may be attributable to comorbid anxiety symptoms and cognitive dysfunction in MDD patients. This research provides fresh neurobiological insights for developing targeted interventions aimed at improving cognitive dysfunction in aMDD patients.
Developmental and sex-specific expression of alpha-synuclein in blood and hippocampus of Cc2d1a mice: Implications for autism spectrum disorders.
Dana H, Kocum F, Yilmaz ON … +3 more , Avci V, Demi̇rci̇ E, Sener EF
J Psychiatr Res · 2026 Jun · PMID 41795327 · Publisher ↗
PURPOSE: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social interaction and the presence of restricted, repetitive behaviors. It involves alterations in brain str...
PURPOSE: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social interaction and the presence of restricted, repetitive behaviors. It involves alterations in brain structure and function due to a combination of genetic, epigenetic, and environmental factors. The Cc2d1a gene is a recently identified candidate gene implicated in ASD. Alpha-synuclein (Snca), a presynaptic neuronal protein classically linked to neurodegeneration, has recently been proposed as a potential player in neurodevelopmental disorders. This study investigated the expression of the Snca gene and protein in a Cc2d1a mouse model of autism, focusing on sex-based and developmental stage differences. METHODS: Blood and hippocampal tissues were collected from male and female mice with heterozygous (+/-) and wild-type (+/+) genotypes at postnatal days 14, 30, and 60. Gene and protein expression levels of Snca were analyzed using quantitative real-time PCR (qRT-PCR) and ELISA. Behavioral tests were used to assess locomotor activity and anxiety. RESULTS: Male mice displayed higher locomotor activity than females in the open field test across developmental stages. At postnatal day 60, Snca mRNA expression increased in heterozygous females but decreased in wild-type females, whereas the opposite pattern was observed in males. Similar genotype- and sex-dependent trends were detected in hippocampal tissue. At the protein level, α-synuclein expression was consistently lower in the female hippocampus compared to males, while blood α-synuclein levels did not differ significantly between sexes. CONCLUSION: These findings demonstrate developmental and sex-specific differences in Snca expression in an ASD mouse model. Alpha-synuclein may serve as a promising biomarker for further studies in ASD pathophysiology.
Cannabis use patterns in first episode psychosis and schizophrenia: A scoping review and case series.
Jin JW, Neu NJ, Satz IB … +3 more , Annor J, ElSayed M, Brunette MF
J Psychiatr Res · 2026 Jun · PMID 41795326 · Publisher ↗
BACKGROUND: Cannabis use is associated with psychosis development and symptom relapse in persons with schizophrenia spectrum disorders (SCZ). As U.S. states legalize cannabis and products increase in potency, it is cruci...
BACKGROUND: Cannabis use is associated with psychosis development and symptom relapse in persons with schizophrenia spectrum disorders (SCZ). As U.S. states legalize cannabis and products increase in potency, it is crucial to better understand recent cannabis use patterns in SCZ. METHODS: We conducted a scoping review of research on cannabis quantity, frequency, or type in SCZ after January 2016 and present a case series of cannabis use in inpatients with psychosis (2023-2024). RESULTS: Scoping review: Of 672 references, ten studies (2631 participants) were included; none were designed to characterize cannabis quantity, frequency, or type of use over time. Cannabis measurement methodology varied; most studies did not use standardized measures. Frequency and quantity of use at baseline were reported by most studies and these ranged widely. At least a minority of participants with SCZ in each study used cannabis very frequently; quantity of used ranged widely from 0.6 ± 0.6 to 3.4 ± 2.2 joints/day. One small study detailed cannabis product type used for THC by SCZ participants (93% used flower, 80% edibles, 60% concentrates). CASE SERIES: Participants were inpatients (32.0 ± 14.4 years; 83.3% diagnosed with SCZ) who used cannabis 2.7 ± 2.1 days/week. All used cannabis leaf (3.1 ± 2.3 joints/day); half (all heavy users) also used concentrates (33.3%) or edibles (16.7%). CONCLUSION: There is insufficient recent research to confidently characterize cannabis use patterns in clinical populations of persons with SCZ in the era of cannabis legalization. As cannabis legalization expands and product potency increases, further research should characterize cannabis use and its consequences in SCZ.
The association between major depressive disorder and cannabis use disorder: A meta-analysis and meta-regression analysis.
Pini Alemar J, Pozzolo Pedro MO, Leopoldo K … +6 more , Mandaji JVG, Gimenes GK, Blaas IK, Torales J, Ventriglio A, Castaldelli-Maia JM
J Psychiatr Res · 2026 Jun · PMID 41793962 · Publisher ↗
OBJECTIVE: Major Depressive Disorder (MDD) and Cannabis Use Disorder (CUD) frequently co-occur, yet prevalence estimates vary widely across settings. This meta-analysis updates the evidence on the bidirectional associati...
OBJECTIVE: Major Depressive Disorder (MDD) and Cannabis Use Disorder (CUD) frequently co-occur, yet prevalence estimates vary widely across settings. This meta-analysis updates the evidence on the bidirectional association between MDD and CUD, emphasizing current-diagnosis subgroups, which are the most clinically relevant. METHODS: Following PRISMA and MOOSE guidelines, we systematically searched PubMed, Google Scholar, and SciELO. Random-effects models estimated current-diagnosis prevalence of MDD among individuals with CUD and of CUD among individuals with MDD. Subgroup analyses differentiated psychiatric and community samples. Sensitivity analyses (leave-one-out) and Egger's tests assessed robustness and publication bias. Meta-regressions evaluated demographic, methodological, and geographic moderators. RESULTS: In total, 55 studies comprising 3,279,774 individuals were included (454,547 and 112,328 living with CUD and MDD, respectively). Current MDD prevalence among individuals with CUD was elevated in both psychiatric samples (19.24%) and community samples (21.65%), indicating consistent comorbidity across settings. Current CUD prevalence among individuals with MDD showed stronger contextual variation, being substantially higher in psychiatric populations (28.45%) compared with community samples (4.61%). Sensitivity analyses demonstrated stable estimates across model specifications, although psychiatric samples exhibited greater variance. Studies with older populations and using ICD-10 (compared to DSM) presented higher MDD prevalence among individuals living with CUD in meta-regression models. Egger's tests revealed no consistent evidence of publication bias. CONCLUSION: Current-diagnosis estimates highlight a strong and clinically meaningful bidirectional association between MDD and CUD. Differences between psychiatric and community samples-especially the markedly higher current CUD prevalence in patients with MDD-underscore the need for systematic screening across treatment settings. Future work should improve diagnostic differentiation, particularly regarding the overlap between depressive symptoms and cannabis withdrawal.
DLPFC rTMS is more effective than sham or orbitofrontal stimulation for smoking cessation and alters frontal brain activity: A double-blind, sham-controlled randomized clinical trial.
Li X, Caulfield KA, Carpenter MJ … +4 more , Ramakrishnan V, Herrmann ES, Dancy M, George MS
J Psychiatr Res · 2026 Jun · PMID 41793961 · Full text
OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) shows promise for smoking cessation, but its neural mechanisms remain unclear. It is unknown whether rTMS reduces smoking by enhancing executive control or s...
OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) shows promise for smoking cessation, but its neural mechanisms remain unclear. It is unknown whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity. This study aimed to address this gap by comparing excitatory and inhibitory rTMS targeting distinct cortical circuits implicated in tobacco use disorder (TUD). METHODS: In a double-blind, sham-controlled design, treatment-seeking individuals with TUD were randomized to 15 sessions of personalized, fMRI-guided, E-field-dosed rTMS: (1) sham rTMS, (2) excitatory 10 Hz rTMS over the left dorsolateral prefrontal cortex (L-DLPFC; 3000 pulses/session), or (3) inhibitory 1 Hz rTMS over the left medial orbitofrontal cortex (L-mOFC; 900 pulses/session). fMRI scans were conducted pre- and post- 15 sessions of rTMS. Primary outcomes were reductions in cigarettes per day (CPD) and changes in blood-oxygen-level-dependent (BOLD) activity. RESULTS: Thirty-five of 46 participants completed the study (sham = 9; 10 Hz L-DLPFC = 12; 1 Hz L-mOFC = 14). The 10 Hz L-DLPFC group showed a significantly greater CPD reduction than 1 Hz L-mOFC and sham (-11.14 vs. -4.92 and -6.43, respectively; p < 0.0001, partial η = 0.135). rTMS to the L-DLPFC also increased prefrontal activity and decreased orbitofrontal activity (p < 0.05), with the degrees of CPD reduction correlating with enhanced activation in L-DLPFC (p < 0.05). CONCLUSIONS: Enhancing executive control via 10 Hz rTMS over the L-DLPFC was more effective for smoking reduction than suppressing reward circuitry with 1 Hz rTMS over the L-mOFC. Findings suggest that strengthening prefrontal regulation of reward processing is a key mechanism by which rTMS promotes smoking cessation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT04903028.
Cathodal tDCS over right orbitofrontal cortex enhances the ability in subclinical obsessive-compulsive disorder to shift to model-based control.
Ruan Z, Li Z, Luo X … +3 more , Yang Q, Yuan H, Peng Z
J Psychiatr Res · 2026 Jun · PMID 41785792 · Publisher ↗
While transcranial direct current stimulation (tDCS) targeting the orbitofrontal cortex (OFC) demonstrates therapeutic potential for obsessive-compulsive disorder (OCD), its neurocognitive mechanisms leading to reduced c...
While transcranial direct current stimulation (tDCS) targeting the orbitofrontal cortex (OFC) demonstrates therapeutic potential for obsessive-compulsive disorder (OCD), its neurocognitive mechanisms leading to reduced compulsive behaviors remain poorly understood. This study investigates the effects of stimulating the OFC on impaired arbitration between model-based (MB) and model-free (MF) reinforcement learning systems in subclinical OCD. In a randomized, sham-controlled trial, participants with elevated Obsessive-Compulsive Inventory-Revised (OCI-R) scores received six sessions of anodal (excitatory; n = 30), cathodal (inhibitory; n = 31), and sham (n = 32) tDCS over the right OFC, respectively. Arbitration control was quantified pre-/post-stimulation using a two-step decision-making task with computational modeling of MB-MF dynamics. Cathodal tDCS significantly enhanced inhibition of MB-to-MF transitions during MB-optimal complex task condition, promoting stable MB control (p < 0.001). Anodal stimulation showed no significant effects relative to sham. Right OFC cathodal tDCS improves arbitration control in subclinical OCD by facilitating context-appropriate MB strategy implementation, revealing a novel therapeutic mechanism for compulsivity remediation.
Normalization of elevated heart rate in patients with borderline personality disorder over the course of inpatient treatment (Dialectical Behavior Therapy): A case control study with psychiatric controls.
Nickel S, Macchia A, Mikusky D … +2 more , Spohrs J, Abler B
J Psychiatr Res · 2026 Jun · PMID 41780444 · Publisher ↗
BACKGROUND: Borderline Personality Disorder (BPD) is characterized by emotional dysregulation and autonomic nervous system (ANS) dysfunction, including elevated heart rate (HR) and reduced heart rate variability. Psychop...
BACKGROUND: Borderline Personality Disorder (BPD) is characterized by emotional dysregulation and autonomic nervous system (ANS) dysfunction, including elevated heart rate (HR) and reduced heart rate variability. Psychophysiological markers such as HR offer insight into underlying regulatory deficits and treatment response. Dialectical Behaviour Therapy (DBT) has shown efficacy in improving emotional regulation in BPD, but its impact on physiological markers such as HR are insufficiently characterized. OBJECTIVE: This study examines changes in HR in BPD patients during an inpatient DBT program and compares these outcomes to psychiatric controls. Additionally, it explores the relationship between HR reduction and changes in psychological symptomatology. METHODS: In a case-control design, data from N = 63 BPD (M = 26.7, SD = 10.2) patients and N = 55 psychiatric controls (M = 26.5, SD = 7.0) without BPD were collected. The psychiatric controls were hospitalized concurrently with the BPD patients and primarily had depression or anxiety disorders. HR was measured via electrocardiogram (ECG) at admission and discharge. Psychological symptomatology was assessed using standardized questionnaires (BDI-II; SCL-90-R, BSL-23, CTQ). RESULTS: At admission, HR was significantly higher in BPD patients compared to psychiatric controls. Furthermore, BPD patients showed a significant reduction in HR from admission to discharge, with a greater decrease than psychiatric controls. No significant correlation was found between HR reduction and changes in psychological symptom scores. However, baseline symptom severity predicted the extent of HR reduction. CONCLUSION: Inpatient psychotherapy may contribute to the normalization of autonomic dysregulation in BPD, reflected in decreased HR. HR may serve as a psychophysiological marker for treatment-associated physiological changes, with baseline severity moderating autonomic outcomes.
The role of change in peripartum heart rate variability in the prediction of depressive symptoms 18 months after childbirth: a follow-up study.
Singh Solorzano C, Spinoni M, Faraglia S … +1 more , Grano C
J Psychiatr Res · 2026 Jun · PMID 41780443 · Publisher ↗
Low vagally-mediated HRV (vmHRV) during peripartum predicts higher depressive symptoms (DS). No previous studies have investigated whether vmHRV recovery following delivery increases women's vulnerability to postpartum d...
Low vagally-mediated HRV (vmHRV) during peripartum predicts higher depressive symptoms (DS). No previous studies have investigated whether vmHRV recovery following delivery increases women's vulnerability to postpartum depressive symptomatology. The present study longitudinally explores the interaction between DS during pregnancy and changes in vagally-mediated HRV from pregnancy to 1-month postpartum as predictors of 18-month postpartum depressive symptoms. Nineteen women were evaluated during pregnancy (T1), and 1-month (T2) and 18-month (T3) postpartum. Sociodemographic information, depressive symptomatology (i.e., Edinburgh Postnatal Depression Scale), and a time-domain HRV index (i.e., the root mean square of successive difference between NN intervals, rMSSD) measured through a smartphone application were evaluated. rMSSD changes between 1-month postpartum and prepartum values were computed. Regression-based moderation analyses were conducted, adjusting for relevant sociodemographic and obstetric covariates. Higher prepartum depressive symptoms were associated with higher depressive symptoms at 18 months postpartum (b = 0.58, SE = 0.15, p < 0.001). Greater vmHRV recovery showed a trend-level inverse association with long-term depressive symptoms (b = -2.19, SE = 1.11, p = 0.053). Importantly, vmHRV recovery significantly moderated the longitudinal association between antenatal and postpartum depressive symptoms (b = -0.41, SE = 0.20, p = 0.039). Johnson-Neyman analyses indicated that the antenatal-postpartum association progressively weakened as vmHRV recovery increased and became non-significant only at high levels of recovery (Δ ln rMSSD >0.61; approximately the upper 10% of the observed distribution). Study limitation include potential artefacts in the physiological signal (e.g., due to hand movements). Women experiencing lower adaptive restoration of parasympathetic activity following childbirth may be at risk of persistent or exacerbated long-term depressive symptomatology. Findings raise the potential for improved identification of at-risk women and exploration of preventive interventions (e.g., HRV-biofeedback, vagus nerve stimulation) to facilitate the recovery of vmHRV and, consequently, mitigate postpartum depressive symptoms.
Social context in motion: The effects of personality traits on the dynamic links between interpersonal processes and suicidal ideation.
Tsypes A, Scott LN
J Psychiatr Res · 2026 Jun · PMID 41780442 · Full text
BACKGROUND: Suicidal ideation (SI) is dynamic and closely tied to social context, yet most work treats these links as static or unidirectional. We tested a transactional account whereby SI and interpersonal appraisals co...
BACKGROUND: Suicidal ideation (SI) is dynamic and closely tied to social context, yet most work treats these links as static or unidirectional. We tested a transactional account whereby SI and interpersonal appraisals co-evolve over hours and examined personality trait moderators. METHOD: Young adults receiving behavioral treatment who endorsed SI and/or suicidal behavior in the past four months (N = 140) completed 21 days of ecological momentary assessment (7 prompts/day). At each prompt, participants reported current SI and rated interpersonal strain (rejection/criticism/exclusion/stress) and enrichment (enjoyment/connection/meaning/support) from interpersonal interactions. Dynamic structural equation models estimated five features of SI: reactivity, generation, inertia, instability, and intensity. Negative Affectivity, Detachment, and Disinhibition trait domains were tested as moderators. RESULTS: Interpersonal strain was associated with higher subsequent SI (reactivity), and higher SI was associated with higher subsequent strain (generation). Likewise, interpersonal enrichment was associated with lower subsequent SI, and higher SI was associated with lower subsequent enrichment. Detachment uniquely moderated these dynamic processes: higher Detachment was associated with larger SI increases after strain and larger SI decreases after enrichment, as well as higher SI intensity and instability, higher strain, and lower enrichment. Facet models indicated that Anhedonia concentrated Detachment-related risk (higher mean SI, higher strain intensity and instability, lower enrichment, higher SI inertia and instability, and stronger reactivity to strain/enrichment). In contrast, Intimacy Avoidance was associated with lower strain instability and lower enrichment intensity. Negative Affectivity and Disinhibition did not moderate dynamic paths. CONCLUSIONS: SI was linked to interpersonal appraisals through short-cycle, bidirectional associations that were moderated by Detachment, especially its Anhedonia facet.
Tai Chi and wellness for Gulf War Illness: Combined analysis of in-person and remote randomized controlled trials.
Polizzi CP, Crow TM, Ting M … +5 more , Busser C, Kaiser AP, Wang C, Mori DL, Niles BL
J Psychiatr Res · 2026 Jun · PMID 41774973 · Full text
BACKGROUND: Veterans with Gulf War Illness (GWI) experience a wide range of physical, neurological, cognitive, and mood complications that can lead to distressing psychological symptoms. Despite its debilitating impact o...
BACKGROUND: Veterans with Gulf War Illness (GWI) experience a wide range of physical, neurological, cognitive, and mood complications that can lead to distressing psychological symptoms. Despite its debilitating impact on physical and psychological functioning, effective treatment options for GWI remain limited. Tai Chi, an ancient Chinese mind-body practice, may be efficacious in reducing GWI symptoms and associated mental health challenges. The present study combined data from two randomized controlled trials (RCTs) examining a Tai Chi group intervention relative to a Wellness comparison group intervention. Primary outcomes were GWI symptoms (health symptoms, pain interference, fatigue, and depressed mood), with secondary outcomes including anxiety, stress, sleep disturbances, mindfulness, health-related quality of life, and PTSD symptoms. We also evaluated whether treatment delivery modality (in-person versus remote) influenced outcomes. METHODS: Participants were 114 veterans with GWI and chronic pain. They completed self-report measures at baseline, posttreatment, 3-month follow-up, and 9-month follow-up. RESULTS: Preliminary multilevel modeling indicated that treatment modality (in-person versus remote) did not significantly influence outcomes. Both Tai Chi and Wellness interventions were associated with improvements in health symptoms, pain interference, depression, anxiety, mindfulness, mental and physical health-related quality of life, and PTSD symptoms. CONCLUSIONS: Tai Chi and Wellness group interventions may demonstrate similar efficacy in improving GWI symptoms and mental health outcomes among veterans with GWI and chronic pain. These interventions can be delivered in-person and remotely with comparable therapeutic benefits, offering flexible and accessible treatment options for this underserved population.
Likely neurodivergence and variant connective tissue in patients with chronic pain/chronic fatigue: a case-control study.
Quadt L, Savage G, Bond R … +3 more , Davies KA, Critchley HD, Eccles JA
J Psychiatr Res · 2026 Jun · PMID 41774972 · Publisher ↗
Neurodivergent traits are frequently observed in individuals with chronic pain and/or chronic fatigue (CP/CF), yet the underlying mechanisms remain unclear. This study investigated the proportion of likely autism and att...
Neurodivergent traits are frequently observed in individuals with chronic pain and/or chronic fatigue (CP/CF), yet the underlying mechanisms remain unclear. This study investigated the proportion of likely autism and attention deficit hyperactivity disorder (ADHD) in patients with CP/CF and examined whether joint hypermobility-a marker of variant connective tissue-mediated this relationship. We conducted a case-control study using an online survey. Eighty-three adults with CP/CF and 91 adults from a non-clinical comparison group completed validated screening measures for autism, ADHD, and joint hypermobility. Odds ratios (ORs) and 95% confidence intervals (CIs) for likely neurodivergence were calculated using binary logistic regression. Mediation analysis tested whether joint hypermobility explained the association between likely neurodivergence and CP/CF. Participants with CP/CF had markedly higher odds of likely autism (adjusted OR 14.3 95% CI [6.5, 31.5]) and likely ADHD (adjusted OR 12.9 95% CI [5.0, 26.7]) than the comparison group. The presence of joint hypermobility significantly mediated the relationship between neurodivergent traits and CP/CF (indirect effect: b = 1.6 95% CI [1.2, 2.1]). Our findings reveal a trans-diagnostic pattern of major clinical importance. In patients with CP/CF, routine screening for neurodivergence should be considered to optimise fair access to appropriate support for improved quality of life.
Neuroprotective, cognitive, and immunomodulatory effects of Valproic acid combined with dextromethorphan in bipolar disorder.
Huang CC, Tzeng NS, Chang YH … +2 more , Hong JS, Lu RB
J Psychiatr Res · 2026 Jun · PMID 41774971 · Publisher ↗
Valproic acid (VPA) is recognized for its neurotrophic properties and is widely used in psychiatric and peripheral disorders, while dextromethorphan (DM) has demonstrated anti-inflammatory and neuroprotective effects. Th...
Valproic acid (VPA) is recognized for its neurotrophic properties and is widely used in psychiatric and peripheral disorders, while dextromethorphan (DM) has demonstrated anti-inflammatory and neuroprotective effects. This study examined whether adjunctive DM provides additional benefits on cognitive or immunomodulatory beyond standard VPA treatment in bipolar disorder (BD). BD aged 20-65 received open-label VPA (500-2500 mg/day; target blood level 50-100 μg/dl) for one week and were then randomized to VPA plus placebo (BDVPA) or VPA plus extended-release DM (BDVPA + DM; 30 or 60 mg/day) for twelve weeks. Neuropsychological measures (Continuous Performance Test, CPT; Wechsler Memory Scale-Revised, WMS-R), symptom severity, cytokines, and BDNF were assessed at baseline and post-treatment. A total of 109 participants (mean age 31.04 years, SD = 10.04) were enrolled; 96 completed cognitive testing and blood sampling (66 BD, 30 BD). Two groups showed no significant differences at baseline in cognition, cytokines, or BDNF. MANOVA showed significant time effects across groups in memory, attention, TNF-α, CRP, IL-8, and BDNF (p < .05), with no group-by-time interactions. Within-group analyses showed modest improvements in several WMS-R and CPT indices in both groups, and small-to-moderate cognitive effect sizes. Both groups showed reductions in selected inflammatory markers and increases in BDNF. Although exploratory within-group patterns suggested slightly larger numerical changes in the BDVPA + DM group, the absence of differential treatment effects limits interpretation. A fully blinded, placebo-controlled trial with long-term follow-up is needed to further clarify whether low-dose DM as an adjunct confers additive neuropsychological or immunomodulatory benefits in BD.
Evaluation of the Zurich social competence training for adolescents and young adults with autism spectrum disorder (KOMPASS).
Schneebeli M, Krinitski D, Staib M … +5 more , Seeger-Schneider G, Pauli D, Gundelfinger R, Walitza S, Jenny B
J Psychiatr Res · 2026 Jun · PMID 41774970 · Publisher ↗
PURPOSE: Increased social demands during adolescence and early adulthood pose specific challenges for individuals with autism spectrum disorder (ASD) without accompanying intellectual impairment. Targeted group-based soc...
PURPOSE: Increased social demands during adolescence and early adulthood pose specific challenges for individuals with autism spectrum disorder (ASD) without accompanying intellectual impairment. Targeted group-based social competence trainings are effective interventions. This work evaluates the Zurich social competence training (KOMPASS), a manualized program for adolescents and young adults (12-25 years) with ASD. METHODS: In this quasi-experimental longitudinal study with a naturalistic waiting period and follow-up, we assessed participants of the KOMPASS intervention (N = 108) at our clinic through parent-, teacher- and self-reports along with a computerized task. A subset of participants (N = 65) was additionally assessed during a waiting period prior to intervention, allowing within-subject comparison of change before and during treatment. One-year follow-up data for the KOMPASS intervention group were collected (N = 62). Furthermore, we analyzed pre- and post-data from 35 individuals who completed KOMPASS at external clinics using the KOMPASS- manual without prior introduction to the method. Critically, we used Bayesian statistics to show evidence for stability of effects and comparable outcomes across settings. RESULTS: Compared to the waitlist period, the KOMPASS training period showed a significant decrease in social and behavioral difficulties associated with ASD and improvements in social competences, which were sustained one year after training. General psychiatric symptoms also improved post-intervention in the KOMPASS training period. Participants from external clinics demonstrated similar significant improvements, affirming the manual's effectiveness in external settings. No significant gender or age moderation effects were observed for the primary outcomes. Participants and caregivers expressed satisfaction with the training. CONCLUSION: KOMPASS demonstrates significant effects in improving social functioning and reducing ASD-related difficulties in adolescents and young adults. The study benefits from a large sample, a naturalistic waiting-period comparison, a one-year follow-up, multi-informant assessment, and external validation. Limitations include the quasi-experimental design, the lack of formal fidelity monitoring, and reliance on some older assessment measures.
Static and dynamic functional connectivity alterations in mice with LPS-induced depression: A 9.4T fMRI study using independent component and graph theory analyses.
Liu Y, Rao B, Zhou F
J Psychiatr Res · 2026 Jun · PMID 41771236 · Publisher ↗
BACKGROUND: Systemic inflammation has emerged as a significant contributor to the pathophysiology of neuropsychiatric disorders, particularly depression. The lipopolysaccharide (LPS)-induced inflammation model in rodents...
BACKGROUND: Systemic inflammation has emerged as a significant contributor to the pathophysiology of neuropsychiatric disorders, particularly depression. The lipopolysaccharide (LPS)-induced inflammation model in rodents is widely used to study inflammation-related behavioral and neural changes, with a strong emphasis on understanding the mechanisms of LPS-induced depression. However, the effects of systemic inflammation on the dynamic architecture of brain functional networks in the context of depression are not well understood. METHODS: Using high-field (9.4 T) resting-state functional magnetic resonance imaging (rs-fMRI), we investigated the impact of LPS-induced systemic inflammation on brain functional network organization in mice. Independent component analysis (ICA) was used to extract 15 functional brain networks. Static and dynamic functional network connectivity (sFNC and dFNC) were analyzed, and graph theory-based metrics were applied to evaluate global, local, and nodal efficiency. Behavioral tests (open field, elevated plus maze, tail suspension) and biochemical assays (serum IL-6, CXCL1, and brain regional ATP levels) were performed to assess emotional state, inflammation, and brain metabolism. RESULTS: LPS administration significantly increased anxiety- and depression-like behaviors, elevated peripheral inflammatory markers, and reduced ATP levels in multiple brain regions. ICA-based analysis revealed significant alterations in both static and dynamic connectivity across cortical, limbic, cerebellar, and basal ganglia networks. Graph theory analysis showed preserved global and local efficiency but a significant reduction in nodal efficiency within the basal ganglia. Moreover, dynamic metrics revealed reduced temporal variability of global and local efficiency following LPS treatment. Several brain network metrics were significantly correlated with behavioral outcomes, serum cytokine levels, and regional ATP concentrations. CONCLUSIONS: Our findings demonstrate that acute systemic inflammation disrupts both the static structure and dynamic regulation of brain functional networks in mice. These alterations are linked to emotional and metabolic disturbances and highlight the basal ganglia and cortical networks as key nodes of inflammation-related vulnerability. This study provides novel systems-level insights into the neural mechanisms underlying inflammation-associated neuropsychiatric symptoms.
The effect of glutamatergic modulators on sleep behavior and architecture in depressive disorders: A systematic review.
Valentino K, Ballum H, Cheung W … +11 more , Dri C, Teopiz KM, Kwan ATH, Wong S, Shen B, Cheng MCH, Le GH, Rosenblat JD, Mansur RB, Lo HKY, McIntyre RS
J Psychiatr Res · 2026 Jun · PMID 41763189 · Publisher ↗
BACKGROUND: Approximately 80% of individuals diagnosed with major depressive disorder (MDD) report symptoms of insomnia. Glutamatergic modulators, such as ketamine, are reported to be effective for the treatment of depre...
BACKGROUND: Approximately 80% of individuals diagnosed with major depressive disorder (MDD) report symptoms of insomnia. Glutamatergic modulators, such as ketamine, are reported to be effective for the treatment of depressive symptomatology in adults with MDD. Disrupted glutamate homeostasis is linked to poor sleep quality and sleep disorders. Herein, we sought to systematically determine the effect of glutamatergic modulators on sleep mechanisms in preclinical and clinical studies. METHODS: In accordance with the PRISMA guidelines, a systematic search was performed using the following electronic databases: PubMed, Medline, Cochrane Library, PsycInfo, Embase, Scopus, and Web of Science. Databases were searched from inception to November 27, 2024. Study screening and selection was performed by three reviewers (K.V., B.S., and W.C.). Included studies reported on the effects of glutamatergic modulators on sleep behaviors, architecture, and mechanisms. RESULTS: Preclinical studies reported that glutamatergic modulators, notably ketamine impact mechanistic pathways known to subserve sleep. Including serotonergic, dopaminergic, and GABAergic systems. It was reported that ketamine effects on electroencephalogram (EEG) delta power during non-rapid eye movement (NREM) sleep, and normalizes clock suppressor gene expression. Furthermore, while esketamine enhances delta power during NREM sleep, arketamine does not exhibit a similar effect. Separately, mGlu2/3 activators are suggested to reduce rapid eye movement (REM) sleep. Clinical studies indicate that improved sleep in patients with MDD can mediate ketamine's antidepressant effects. CONCLUSION: Our findings indicate that glutamatergic modulators, primarily ketamine, are associated with improvement across several sleep behaviors commensurate in MDD, suggesting that mechanisms subserving sleep are potential targets for depression treatment.
Could peripheral immunological markers discriminate schizophrenia and schizoaffective disorders from bipolar disorder?
Jeannin J, Romeo B, Lestra V … +4 more , Martelli C, Amirouche A, Benyamina A, Hamdani N
J Psychiatr Res · 2026 Jun · PMID 41763188 · Publisher ↗
INTRODUCTION: Schizoaffective disorder (SZ-AFF) is a controversial diagnostic at the interface between bipolar disorder (BD) and schizophrenia (SZ). Immunological profiles should discriminate these disorders notably duri...
INTRODUCTION: Schizoaffective disorder (SZ-AFF) is a controversial diagnostic at the interface between bipolar disorder (BD) and schizophrenia (SZ). Immunological profiles should discriminate these disorders notably during an acute phase. The objective of this study is to characterize the immunological profile of SZ-AFF as compared to SZ and BD and to assess wether the manic phase differs between SZ-AFF and BD. METHODS: White blood cells and ratio were compared across diagnosis SZ-AFF; SZ and BD in this retrospective study. These same markers were also compared in patients during mania between SZ-AFF and BD. Correlations between psychometric scales and these markers were performed. RESULTS: Neutrophil-lymphocytes ratio was lower in SZ-AFF as compared to SZ (p = .04) and to BD (p = .03). Leukocytes (p = .02), neutrophils (p < .01), monocytes (p = .01) levels were lower in SZ-AFF as compared to BD but not SZ. We found that patients with SZ-AFF had lowest leukocyte (p = .03) and neutrophil (p = .01) levels than patients with BD during mania. We found a negative correlations between PANSS total score and lymphocyte (p = .03) and monocyte (p = .01) levels in SZ-AFF. CONCLUSION: In our study, we found that the immunological profiles could specifically discriminate patients with SZ-AFF, SZ or BD patients and that the immunological profile of SZ-AFF is closer to SZ than to BD. Further mania may involve different immunological mechanisms according to the diagnosis. Thus, we may consider SZ-AFF as a clinical/immunological spectrum of SZ.
Effects of MBSR and escitalopram on self-compassion in anxiety disorders.
Baker AW, Philip SR, Armstrong CH … +6 more , Szuhany KL, Mete M, Dutton MA, Simon NM, Bui E, Hoge EA
J Psychiatr Res · 2026 Jun · PMID 41759355 · Publisher ↗
BACKGROUND: Self-compassion is recognized as important for psychological well-being and has been linked to reduced anxiety levels. Mindfulness-based interventions, such as the 8-week Mindfulness-Based Stress Reduction pr...
BACKGROUND: Self-compassion is recognized as important for psychological well-being and has been linked to reduced anxiety levels. Mindfulness-based interventions, such as the 8-week Mindfulness-Based Stress Reduction program (MBSR), have shown promise in treating anxiety disorders, but no studies to date have compared the effects of MBSR to the gold-standard medication treatment (escitalopram) on self-compassion or its subscales. The primary aim of this study was to examine the effects of MBSR versus escitalopram on self-compassion (total score and subscales) in adults with anxiety disorders. METHODS: We conducted a comparative effectiveness trial, delivering escitalopram versus MBSR virtually over 8 weeks for anxiety disorders in 198 adults. We assessed the impact of each treatment on self-compassion and its subscales using the Self-Compassion Scale. Baseline group differences were tested using chi-square tests for categorical variables and t-tests for continuous variables. We used longitudinal mixed-effects models to test whether MBSR produced greater improvements in self-compassion than escitalopram at each assessment point. RESULTS: Contrary to our hypothesis, MBSR did not demonstrate greater improvement in self-compassion compared to escitalopram at each assessment point. All domains of self-compassion improved over time when across treatment groups. Additionally, both treatment groups showed improvements in most subscales. Two of the subscales showed differences in response by treatment group. In the mixed model predicting the Common Humanity subscale, participants in the MBSR group evidenced an improvement in Common Humanity over time whereas the escitalopram group remained relatively unchanged in Common Humanity over time (Estimate = -0.34, t = -2.44, 95% CI = [-0.61, -0.06], p = 0.016). In the mixed effects model predicting Mindfulness, the MBSR group evidenced greater improvement in Mindfulness between baseline and post-treatment than the escitalopram group (Estimate = -0.26, t = -2.05, 95% CI = [-0.51, -0.01], p = 0.042). DISCUSSION: Although meditation was not generally superior to medication for improving self-compassion among individuals with anxiety disorders, several significant improvements were found across both interventions, and meditation may be more effective for promoting two self-compassion subscales-mindfulness and common humanity. MBSR's facet-specific benefits support its use where enhancing self-relational capacities is a treatment priority.
Effectiveness of transcranial direct current stimulation (tDCS) on attention and memory biases in individuals with post-traumatic stress disorder (PTSD): a randomized, single-blind, parallel-group study.
Estaji R, Ahmadizadeh MJ
J Psychiatr Res · 2026 Jun · PMID 41759354 · Publisher ↗
Based on neurocognitive models, the development and maintenance of post-traumatic stress disorder (PTSD) are correlated with cognitive biases, including attention and memory biases, which are associated with imbalanced a...
Based on neurocognitive models, the development and maintenance of post-traumatic stress disorder (PTSD) are correlated with cognitive biases, including attention and memory biases, which are associated with imbalanced activation of prefrontal regions, particularly the dorsolateral prefrontal cortex (dlPFC). The present study investigated how modulation of the dlPFC could lead to cognitive bias modification in war veterans with PTSD. We explored the effectiveness of 10 sessions of anodal tDCS over the left dlPFC concurrent with cathodal tDCS over the right dlPFC on attention and memory biases in 30 male war veterans with PTSD. The participants were randomly assigned to "real" and "sham" groups in a randomized, single-blind, parallel-group design. They underwent 10 sessions of real (2 mA, 20 min) or sham tDCS over five consecutive days. We measured participants' performance on attention bias (emotional Dot-probe and emotional Stroop tasks) and memory bias (autobiographical memory test) at pre-test, post-test, and 1-month follow-up stages. The results showed significant improvement in autobiographical memory bias in the tDCS group at both the post-test and follow-up stages compared to sham group. However, no significant effect of tDCS was observed on attention bias. Furthermore, within the tDCS group, the degree of improvement in memory specificity was correlated with a reduction in intrusion symptoms, providing preliminary evidence that modifying this cognitive bias may directly impact a core clinical feature of PTSD. Given the sample size and high variability of attentional measures, these null findings should be interpreted with caution and do not definitively rule out an effect of tDCS on attentional processes. In conclusion, tDCS over the dlPFC could improve imbalance between neural networks and cortical regions involved in autobiographical memory bias in PTSD; however, further studies are required to confirm these findings.
Inflammatory markers associated with dementia: a systematic review and meta-analysis.
Kuring JK, Mathias JL, Ward L … +1 more , Tachas G
J Psychiatr Res · 2026 Jun · PMID 41759353 · Publisher ↗
BACKGROUND: Dementia has been linked to several modifiable risk factors, including mental illness. The inflammatory-mediated neurodegeneration hypothesis posits a causal relationship between the two whereby mental illnes...
BACKGROUND: Dementia has been linked to several modifiable risk factors, including mental illness. The inflammatory-mediated neurodegeneration hypothesis posits a causal relationship between the two whereby mental illness triggers an inflammatory response, which in turn acts as a catalyst for the neurodegenerative changes that lead to dementia. Existing meta-analyses have yet to investigate inflammatory markers in Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), or fronto-temporal dementia (FTD) in the context of the inflammatory-mediated neurodegeneration hypothesis. This meta-analysis therefore explored whether a) AD, VaD, DLB, and FTD are each associated with greater inflammation than healthy controls, independent of comorbid mental or physical health problems with a known inflammatory response, and b) there are any similarities in the inflammatory profiles associated with these dementia subtypes. METHODS: PubMed, EMBASE, PsycINFO and CINAHL searches identified 41 eligible studies. RESULTS: AD is associated with an inflammatory response, with tentative evidence to indicate that VaD, DLB, and FTD are also associated with inflammation. However, the inflammatory response appears to differ across these conditions. LIMITATIONS: The data for VaD, DLB, FTD and a number of inflammatory markers were limited. CONCLUSIONS: Although tentative, AD, VaD, DLB, and FTD appear to be associated with discrete inflammatory processes that are not attributable to other common comorbid mental or physical health problems that cause inflammation. Whether this inflammatory response plays a causal role in the development of dementia and/or is triggered by prior mental illness remains to be determined.
Potential effects of cannabidiol on formalin-induced inflammatory pain in morphine-dependent rats.
Aalidaeijavadi Z, Khodagholi F, Haghparast A
J Psychiatr Res · 2026 Jun · PMID 41747636 · Publisher ↗
Chronic morphine exposure leads to tolerance and dependence, complicating pain management and reducing the efficacy of opioid analgesics. Cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has been rec...
Chronic morphine exposure leads to tolerance and dependence, complicating pain management and reducing the efficacy of opioid analgesics. Cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, has been recognized for its anti-inflammatory and analgesic potential. This study examined the effects of CBD on acute and inflammatory phases of formalin-induced nociception in morphine-dependent and non-dependent rats. Eighty-four male Wistar rats were divided into the control (non-dependent) and dependent groups. Morphine dependence was induced through an oral escalating-dose regimen in drinking water containing 3% sucrose (to mask bitterness) for 14 days, while controls received only sucrose. CBD (25-200μg/5 μL, ICV) was administered prior to the formalin test. Formalin injection produced a clear biphasic nociceptive response (P < 0.001 in both phases), confirming the model's validity. Morphine dependence alone did not significantly affect baseline pain responses (P > 0.05). However, CBD produced a significant, dose-dependent reduction in pain behaviors during both the early (0-5 min) and the late (20-50 min) phases (P<0.001 vs. vehicle). The 100 μg/5 μL and 200 μg/5 μL doses showed the most robust and consistent antinociceptive effect. CBD produced robust antinociceptive effects in both morphine-treated and non-treated rats, with no statistically significant difference between groups. Open-field results indicated no significant differences in locomotor activity, confirming that the observed analgesia was not related to motor impairment. These findings demonstrate that CBD effectively attenuates both acute and inflammatory pain. Moreover, it maintains its effectiveness in animals treated with morphine. This highlights its potential as a non-opioid supplementary therapy for managing pain in individuals with opioid dependence.
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