Major Depressive Disorder (MDD) is a complex mental health condition characterized by a wide spectrum of symptoms. According to the Diagnostic Statistical Manual 5 (DSM-5) criteria, patients can present with up to 1,497 different symptom combinations, yet all receive the same MDD diagnosis. This diversity in symptom presentation poses a significant challenge to understanding the disorder in the wider population. Subtyping offers a way to unpick this phenotypic diversity and enable improved characterization of the disorder. According to reviews, MDD subtyping work to date has lacked consistency in results due to inadequate statistics, non-transparent reporting, or inappropriate sample choice. By addressing these limitations, the current study aims to extend past phenotypic subtyping studies in MDD.

(1) To investigate phenotypic subtypes at baseline in a sample of people with MDD;

(2) To determine if subtypes are consistent between baseline 6- and 12-month follow-ups; and

(3) To examine how participants move between subtypes over time.

This was a secondary analysis of a one-year longitudinal observational cohort study. We collected data from individuals with a history of recurrent MDD in the United Kingdom, the Netherlands and Spain (N=619). The presence or absence of symptoms was tracked at three-month intervals through the Inventory of Depressive Symptomatology: Self-Report (IDS-SR) assessment. We used latent class and three-step latent transition analysis to identify subtypes at baseline, determined their consistency at 6- and 12-month follow-ups, and examined participants’ transitions over time.

We identified a 4-class solution based on model fit and interpretability, including (Class 1) severe with appetite increase, (Class 2), severe with appetite decrease, (Class 3) moderate, and (Class 4) low severity. The classes mainly differed in terms of severity (the varying likelihood of symptom endorsement) and, for the two more severe classes, the type of neurovegetative symptoms reported (Figure 1). The four classes were stable over time (measurement invariant) and participants tended to remain in the same class over baseline and follow-up (Figure 2).

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We identified four stable subtypes of depression, with individuals most likely to remain in their same class over 1-year follow-up. This suggests a chronic nature of depression, with (for example) individuals in severe classes more likely to remain in the same class throughout follow-up. Despite the vast heterogeneous symptom combinations possible in MDD, our results emphasize differences across severity rather than symptom type. This raises questions about the meaningfulness of these subtypes beyond established measures of depression severity. Implications of these findings and recommendations for future research are made.

C. Oetzmann Grant / Research support from: C.O. is supported by the UK Medical Research Council (MR/N013700/1) and King’s College London member of the MRC Doctoral Training Partnership in Biomedical Sciences., N. Cummins: None Declared, F. Lamers: None Declared, F. Matcham: None Declared, K. White: None Declared, J. Haro: None Declared, S. Siddi: None Declared, S. Vairavan Employee of: S.V is an employee of Janssen Research & Development, LLC and hold company stocks/stock options., B. Penninx : None Declared, V. Narayan: None Declared, M. Hotopf Grant / Research support from: M.H. is the principal investigator of the RADAR-CNS programme, a precompetitive public–private partnership funded by the Innovative Medicines Initiative and the European Federation of Pharmaceutical Industries and Associations. The programme received support from Janssen, Biogen, MSD, UCB and Lundbeck., E. Carr: None Declared

Significant advances in the research of sport-related concussion (SRC) and repetitive head impacts (RHI) over the previous decade have translated to improved injury identification, diagnosis, and management. However, an objective gold standard for SRC/RHI treatment has remained elusive. SRC often result in heterogenous clinical outcomes, and the accumulation of RHI over time is associated with long-term declines in neurocognitive functioning. Medical management typically entails an amalgamation of outpatient medical treatment and psychiatric and/or behavioral interventions for specific symptoms rather than treatment of the underlying functional and/or structural brain injury. Transcranial photobiomodulation (tPBM), a form of light therapy, has been proposed as a non-invasive treatment for individuals with traumatic brain injuries (TBI), possibly including SRC/RHI. With the present proof-of-concept pilot study, we sought to address important gaps in the neurorehabilitation of former athletes with a history of SRC and RHI by examining the effects of tPBM on neurocognitive functioning.

The current study included 49 participants (45 male) with a history of SRC and/or RHI. Study inclusion criteria included: age 18-65 years and a self-reported history of SRC and/or RHI. Exclusion criteria included: a history of neurologic disease a history of psychiatric disorder, and MRI contraindication. We utilized a non-randomized proof-of-concept design of active treatment over the course of 8-10 weeks, and neurocognitive functioning was assessed at pre- and post-treatment. A Vielight Neuro Gamma at-home brain tPBM device was distributed to each participant following baseline assessment.

Participants completed standardized measures of neurocognitive functioning, including the California Verbal Learning Test (CVLT-3), Delis Kaplan Executive Function System (D-KEFS), Continuous Performance Test (CPT-3), and The NIH Toolbox Cognition Battery. Neurocognitive assessments were collected prior to and following tPBM treatment. Paired t-tests and Wilcoxon’s signed-rank tests were used to evaluate change in performance on measures of neurocognitive functioning for normal and nonnormal variables, respectively, and estimates of effect size were obtained.

Study participants’ ability for adapting to novel stimuli and task requirements (i.e., fluid cognition; t=5.96; p<.001; d=.90), verbal learning/encoding (t=3.20; p=.003; d=.48) and delayed recall (z=3.32; p=.002; d=.50), processing speed (t=3.13; p=.003; d=.47), sustained attention (t=-4.39; p<.001; d=-.71), working memory (t=3.61; p=.001; d=.54), and aspects of executive functioning improved significantly following tPBM treatment. No significant improvements in phonemic and semantic verbal fluencies, reading ability, and vocabulary were shown following tPBM treatment.

The results of this pilot study demonstrate that following 8-10 weeks of active tPBM treatment, retired athletes with a history of SRC and/or RHI experienced significant improvements in fluid cognition, learning and memory, processing speed, attention, working memory, and aspects of executive functioning. Importantly, the majority of effect sizes ranged from moderate to large, suggesting that tPBM has clinically meaningful improvements on neurocognitive functioning across various cognitive domains. These results offer support for future research employing more rigorous study designs on the potential neurorehabilitative effects of tPBM in athletes with SRC/RHI.

We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.

The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.

We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.

Persons discharged from inpatient psychiatric services are at greatly elevated risk of harming themselves or inflicting violence on others, but no studies have reported gender-specific absolute risks for these two outcomes across the spectrum of psychiatric diagnoses. We aimed to estimate absolute risks for self-harm and interpersonal violence post-discharge according to gender and diagnostic category.

Danish national registry data were utilized to investigate 62,922 discharged inpatients, born 1967–2000. An age and gender matched cohort study was conducted to examine risks for self-harm and interpersonal violence at 1 year and at 10 years post-discharge. Absolute risks were estimated as cumulative incidence percentage values.

Patients diagnosed with substance misuse disorders were at especially elevated risk, with the absolute risks for either self-harm or interpersonal violence being 15.6% (95% CI 14.9, 16.3%) of males and 16.8% (15.6, 18.1%) of females at 1 year post-discharge, rising to 45.7% (44.5, 46.8%) and 39.0% (37.1, 40.8%), respectively, within 10 years. Diagnoses of personality disorders and early onset behavioral and emotional disorders were also associated with particularly high absolute risks, whilst risks linked with schizophrenia and related disorders, mood disorders, and anxiety/somatoform disorders, were considerably lower.

Patients diagnosed with substance misuse disorders, personality disorders and early onset behavioral and emotional disorders are at especially high risk for internally and externally directed violence. It is crucial, however, that these already marginalized individuals are not further stigmatized. Enhanced care at discharge and during the challenging transition back to life in the community is needed.

We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C.

We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C.

Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields.

To report two cases of transmastoid clipping of a sigmoid sinus diverticulum.

Two patients with pulsatile tinnitus resulting from a sigmoid sinus diverticulum underwent clipping at the diverticulum neck using intra-operative Doppler ultrasonography.

At six months’ follow up, both patients reported complete resolution of pulsatile tinnitus with no complications.

Transmastoid clipping of a sigmoid sinus diverticulum can be a safe and effective method of managing pulsatile tinnitus resulting from a sigmoid sinus diverticulum.

Carotid artery aneurysm is a potentially fatal complication of skull base osteomyelitis. It is important to know the warning signs for this complication, as early diagnosis is of great importance. This report aimed to determine whether the pattern of cranial nerve involvement may predict the occurrence of aneurysm involving the internal carotid artery in skull base osteomyelitis.

Two diabetic patients with skull base osteomyelitis were incidentally diagnosed with pseudo-aneurysm of the petrous internal carotid artery on follow-up magnetic resonance imaging. They presented with lower cranial nerve palsy; however, facial nerve function was almost preserved in both cases. Computed tomography angiography confirmed aneurysms at the junction of the horizontal and vertical segments of the petrous carotid artery.

Internal carotid artery trapping was conducted using coil embolisation. Post-coiling magnetic resonance imaging demonstrated no procedure-related complications. Regular follow up has demonstrated that patients’ symptoms are improving.

One should be mindful of this potentially fatal complication in skull base osteomyelitis patients with lower cranial nerve palsies, with or without facial nerve involvement, especially in the presence of intracranial thromboembolic events or Horner's syndrome.

Parental criminal offending is an established risk factor for offending among offspring, but little evidence is available indicating the impact of offending on early childhood functioning. We used data from a large Australian population cohort to determine associations between exposure to parental offending and a range of developmental outcomes at age 5 years.

Multi-generation data in 66 477 children and their parents from the New South Wales Child Development Study were combined using data linkage. Logistic and multinomial regressions tested associations between any and violent offending histories of parents (fathers, mothers, or both parents) obtained from official records, and multiple measures of early childhood developmental functioning (social, emotional–behavioural, cognitive, communication and physical domains) obtained from the teacher-reported 2009 Australian Early Development Census.

Parental offending conferred significantly increased risk of vulnerability on all domains, particularly the cognitive domain. Greater risk magnitudes were observed for offending by both parents and by mothers than by fathers, and for violent than for any offending. For all parental offending exposures, vulnerability on multiple domains (where medium to large effects were observed) was more likely than on a single domain (small to medium effects). Relationships remained significant and of comparable magnitude following adjustment for sociodemographic covariates.

The effect of parental offending on early childhood developmental outcomes is pervasive, with the strongest effects on functioning apparent when both parents engage in violent offending. Supporting affected families in early childhood might mitigate both early developmental vulnerability and the propensity for later delinquency among these offspring.

Childhood maltreatment and a family history of a schizophrenia spectrum disorder (SSD) are each associated with social-emotional dysfunction in childhood. Both are also strong risk factors for adult SSDs, and social-emotional dysfunction in childhood may be an antecedent of these disorders. We used data from a large Australian population cohort to determine the independent and moderating effects of maltreatment and parental SSDs on early childhood social-emotional functioning.

The New South Wales Child Development Study combines intergenerational multi-agency data using record linkage methods. Multiple measures of social-emotional functioning (social competency, prosocial/helping behaviour, anxious/fearful behaviour; aggressive behaviour, and hyperactivity/inattention) on 69 116 kindergarten children (age ~5 years) were linked with government records of child maltreatment and parental presentations to health services for SSD. Multivariable analyses investigated the association between maltreatment and social-emotional functioning, adjusting for demographic variables and parental SSD history, in the population sample and in sub-cohorts exposed and not exposed to parental SSD history. We also examined the association of parental SSD history and social-emotional functioning, adjusting for demographic variables and maltreatment.

Medium-sized associations were identified between maltreatment and poor social competency, aggressive behaviour and hyperactivity/inattention; small associations were revealed between maltreatment and poor prosocial/helping and anxious/fearful behaviours. These associations did not differ greatly when adjusted for parental SSD, and were greater in magnitude among children with no history of parental SSD. Small associations between parental SSD and poor social-emotional functioning remained after adjusting for demographic variables and maltreatment.

Childhood maltreatment and history of parental SSD are associated independently with poor early childhood social-emotional functioning, with the impact of exposure to maltreatment on social-emotional functioning in early childhood of greater magnitude than that observed for parental SSDs. The impact of maltreatment was reduced in the context of parental SSDs. The influence of parental SSDs on later outcomes of maltreated children may become more apparent during adolescence and young adulthood when overt symptoms of SSD are likely to emerge. Early intervention to strengthen childhood social-emotional functioning might mitigate the impact of maltreatment, and potentially also avert future psychopathology.