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Early adverse life events are thought to have lasting effects on mental health, yet evidence in humans remains largely correlative. This study investigated whether the timing of maternal separation in rats differentially affects anxiety-related behaviour and neuropeptide levels in adulthood.
Methods:
Male Wistar rats were subjected to short-term (ST, 15 min) or long-term (LT, 180 min) maternal separation during one of three postnatal windows: PND 2–6, PND 8–9, or PND 10–14. In adulthood, anxiety-like behaviour was assessed using the elevated plus maze (EPM). Brains were subsequently analysed for neuropeptide Y (NPY) and neurokinin A (NKA) levels across discrete brain regions.
Results:
LT separation produced markedly time-dependent and opposing effects on both behaviour and neurochemistry. Separation during PND 8–9 reduced time spent on the open arms of the EPM and decreased hippocampal NPY levels, whereas separation during PND 10–14 produced the opposite pattern in both measures. LT separation at PND 8–9 also induced more widespread alterations in neuropeptide levels compared to the other time windows. ST separation produced no significant behavioural or neurochemical effects.
Conclusion:
The LT consequences of early maternal separation are critically dependent on the precise timing of the stressor, with a narrow postnatal window around PND 8–9 appearing particularly sensitive. These findings underscore the importance of considering developmental timing when studying the impact of early life adversity, with potential translational relevance for understanding stress-related psychopathology in humans.
Test anxiety affects up to 40% of university students and is associated with academic failure, depression and suicidal ideation, yet clinical screening and high-frequency research designs remain hampered by the burden of 20-item instruments such as the Test Anxiety Inventory (TAI). Although brief measures exist (e.g. the ten-item Westside Test Anxiety Scale and the five-item TAI), a validated, gender-invariant hierarchy of ultra-short forms tailored to contemporary undergraduates is lacking.
Aims
To develop and validate a hierarchy of brief TAI versions (ten-item Short Form, five-item Ultra-Short Form and three-item Micro Form) suitable for systematic screening and ecological monitoring in student mental health contexts.
Method
A large sample of Israeli undergraduates (N = 1803) completed the Hebrew TAI. Items were selected based on exploratory factor analysis loadings. Structural validity and gender measurement invariance were confirmed via confirmatory factor analysis.
Results
The five-item Ultra-Short Form showed excellent fit (comparative fit index (CFI) = 0.995, root mean square error of approximation (RMSEA) = 0.05) and the three-item Micro Form exhibited strong standardised factor loadings (≥0.79). Strict scalar invariance was established across genders for all versions. All versions maintained high internal consistency (α ≥ 0.85) and strong correlations with the full scale (r ≥ 0.88). Selected items prioritised somatic over cognitive distress, suggesting contemporary students experience test anxiety as a visceral, physiological ‘survival threat’ rather than cognitive rumination.
Conclusions
These validated brief measures offer a promising toolkit for ‘agile assessment’ in student mental health settings, enabling early identification of at-risk students, pending external criterion validation and independent replication.
Placebos have historically been used as comparative tools in randomised controlled trials (RCTs), but their therapeutic effect, particularly in psychiatric conditions, warrant a more detailed exploration to improve research design and clinical practice.
Aims
This systematic review and meta-analysis examines the factors influencing placebo treatment effects across major psychiatric disorders, including depression, anxiety disorders, obsessive–compulsive disorder (OCD) and post-traumatic stress disorder (PTSD).
Method
This PROSPERO registered systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify RCTs with at least one placebo and one medication arm (citalopram or escitalopram), across four major groups of psychiatric conditions. Data extraction focused on study characteristics, methodology, target condition, participant demographics and outcome measurements. Cohen’s d effect sizes for placebo and medication groups were calculated, with random-effects model meta-analyses performed to assess heterogeneity and their correlates.
Results
The review included 80 studies with 312 outcome measures, involving 19 776 participants (7 to 91 years old). A large placebo response was observed (effect size: 1.01; 95% CI: 0.93–1.10) with significant heterogeneity (I2: 99.61%). Significant differences in placebo responses were noted across clinical conditions, independent of the medication type. PTSD and depressive disorders exhibited the highest placebo effect size (1.14 and 1.02, respectively), whereas OCD showed the lowest (effect size: 0.62, P < 0.01). Anxiety disorders displayed a moderately large placebo effect size (0.86), with significant variability among anxiety disorder subclasses, specifically noting the lowest placebo effect size in specific phobia (0.23, P < 0.01). The medication effect size (1.43) also demonstrated considerable heterogeneity (I2: 99.76%) but was not significantly different across psychiatric conditions (P = 0.61). Placebo response magnitude was larger in studies with more study arms (b: 0.181, P < 0.01) and younger mean age of the participant (b: −0.010, P < 0.01). Moreover, clinician-rated outcomes versus patient self-reports (effect size: 1.07 v. 0.76, P < 0.01), multicentre studies (p < 0.01) and using intention-to-treat data (effect size: 1.08 v. 0.86, P = 0.01) were associated with larger placebo effect size.
Conclusions
This study used a unique approach to examine placebo responses from the same interventions across multiple major psychiatric disorders. We found substantial placebo responses across psychiatric conditions and significant heterogeneity, influenced by a range of study-related and demographic factors. The findings underscore the complexity of placebo responses and highlight the importance of considering these variances in both research design and clinical translation.
Anxiety disorders are often associated with impairments in memory, attention, decision-making, and psychomotor function, leading to a reduced quality of life (QoL). Alprazolam, commonly prescribed for acute anxiety disorders, has generated interest regarding its potential impact on anxiety-associated cognitive and psychomotor impairment, especially since effects of short-term use have not been well studied. This review summarizes clinical evidence on the short-term (up to 8 weeks) effects of alprazolam on cognitive performance, psychomotor function, and QoL outcomes in individuals with anxiety disorders. A comprehensive search guided by the participants, intervention, comparisons, and outcomes (PICO) framework identified relevant studies in humans that compared alprazolam with placebo or active comparators. From 1210 articles screened, 10 studies met the inclusion criteria and assessed the short-term impact of alprazolam use on cognition (4), psychomotor function (3), and/or QoL (5). Three of the four studies evaluating cognitive function showed that alprazolam use in adults with panic disorder did not result in any major cognitive impairment. Two of the three studies assessing psychomotor performance demonstrated that short-term alprazolam use either improved or preserved performance. One study recommended gradual upward dose titration to minimize potential negative effects. All five studies found alprazolam enhanced patients’ QoL. In conclusion, short-term alprazolam use in anxiety disorders appears to conserve cognitive function and psychomotor performance, with a positive impact on QoL. Elucidating alprazolam’s effects on cognitive and psychomotor symptoms, beyond its established anxiolytic action, could support more precise identification of patient groups most likely to derive therapeutic benefit.
Anxiety disorders are highly prevalent mental health conditions and are closely associated with early-life adversity. Although research on childhood adversity and anxiety disorders has expanded rapidly, the overall knowledge structure and emerging trends remain unclear. This bibliometric study systematically searched English-language publications from Web of Science Core Collection, Scopus and PubMed. Bibliometrix was used to analyze annual publication trends, countries, institutions, authors and journals. VOSviewer was applied to construct keyword co-occurrence and institutional collaboration networks, and CiteSpace was used to visualize thematic evolution and keyword bursts. A total of 4,481 eligible publications were included. The annual number of publications increased steadily since 2000, with marked acceleration after 2010. Research output and influence were mainly concentrated in the United States and Western Europe. High-frequency keywords included anxiety disorders, depression, childhood abuse, adverse childhood experiences and post-traumatic stress responses. Keyword analyses indicated a thematic shift from specific trauma types and diagnostic categories toward cumulative adversity, cross-diagnostic risk factors, emotional regulation, psychological resilience and symptom networks. This field has evolved from descriptive correlational studies to an interdisciplinary area integrating multilayered and mechanistic perspectives. Future studies should strengthen longitudinal designs, cross-cultural samples and multimodal data integration.
Cognitive behavioural therapy (CBT) is the first-line treatment for anxiety and related disorders. Limited research has explored long-term outcomes following CBT for anxiety-related disorders in naturalistic settings, particularly for generalized anxiety disorder (GAD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD).
Aims:
This study examined long-term outcomes and attrition after group CBT for GAD, SAD, and PTSD in a naturalistic sample. Across disorders, it was hypothesized that gains would be maintained long-term, with a gradual return of clinically relevant symptoms observed at later follow-up points.
Method:
Data were collected from individuals completing CBT at a tertiary anxiety treatment clinic. Symptom changes pre- to post-treatment and over a 2-year follow-up were examined, as well as the influence of baseline depressive symptoms on change over time. Worry, social anxiety, and post-traumatic stress symptoms were assessed at pre- and post-treatment and 3, 6, 9, 12, and 24 months.
Results:
On average, symptom improvements were maintained over the 2-year follow-up for all disorders. Higher pre-treatment depression was associated with greater symptom severity throughout the study but generally did not affect the magnitude of symptom change. The exception was PTSD, where baseline depression was also associated with changes in symptom severity across the whole study period. This effect was not observed for those with SAD and GAD. Attrition was high across the follow-up period.
Conclusion:
This study provides preliminary evidence for the long-term efficacy of CBT in a naturalistic setting. It also highlights challenges with retaining clients in long-term follow-up in naturalistic settings.
Duration of untreated illness (DUI) in anxiety disorders profoundly shapes clinical outcomes, yet systematic assessment remains neglected. This editorial synthesises current evidence, underscores the consequences of prolonged treatment delay and proposes disorder-specific and system-level interventions to reduce DUI in anxiety disorders: a priority for clinical progress and health policy reform.
Anxiety disorders are common and disabling. Current drugs have limited efficacy, notable side-effects and little innovation. This editorial briefly reviews past, current and emerging anxiolytic treatments, including psychedelic-assisted therapies, and highlights key themes. There remains a major need for improved medications to reduce disability and improve quality of life.
Anxiety disorders are distressing and impairing and may be becoming more prevalent. There remains much uncertainty about key factors in the development and maintenance of anxiety disorders, which may underpin some of the limitations of existing psychological, pharmacological and other treatments.
Anxiety disorders are highly prevalent yet lack objective biomarkers. Whereas threat-related attentional biases are well documented, less is known about broader eye movement alterations that may characterise anxiety.
Aims
To characterise multi-paradigm eye movement profiles in anxiety disorders and evaluate their potential as behavioural markers for disorder differentiation.
Method
Eye movements were recorded in 91 patients with anxiety disorders, 118 with depressive disorders and 98 healthy controls during free viewing of neutral-stimuli, smooth-pursuit and fixation-stability tasks. Principal component analysis was applied to derive latent eye movement dimensions, which were then tested for group differences, associations with symptom severity and classification performance.
Results
Compared with both patients with depression and healthy controls, patients with anxiety disorders exhibited hyper-scanning during free viewing, characterised by increased saccade frequency and path length, and hyper-pursuit during smooth pursuit, reflected in increased velocity gain, fewer intrusive saccades and more catch-up saccades. Principal component analysis identified six latent components, among which active visual exploration, pupillary arousal and smooth-pursuit control demonstrated robust group differences. Machine learning models trained on 6 components yielded areas under the receiver operating characteristic curve of 0.82 for anxiety versus healthy controls, 0.83 for depression versus healthy controls and 0.61 for anxiety versus depression.
Conclusions
Hyper-scanning and hyper-pursuit emerge as defining eye movement signatures of anxiety, linking core mechanisms of vigilance and prediction with measurable behavioural markers. These insights position eye-tracking as a promising behavioural modality for mechanism-informed differentiation across affective disorders.
Edited by
Liz McDonald, East London NHS Foundation Trust,Roch Cantwell, Perinatal Mental Health Service and West of Scotland Mother & Baby Unit,Ian Jones, Cardiff University
Perinatal anxiety is characterised by intense symptoms of anxiety and fear and includes affective, cognitive and behavioural components. Anxiety disorders include generalised anxiety disorder, panic disorder, specific phobias and social anxiety disorder. Obsessive compulsive disorder and post-traumatic stress disorder are also included here to remain in line with the majority of published evidence, and because of agreement that anxiety is a central characteristic of these disorders. Some level of antenatal anxiety is common but when it becomes extreme or persistent it can be associated with maternal, fetal and infant morbidity, as well as emotional and cognitive problems in children and teenagers and risk of the child developing an anxiety disorder.
This chapter provides an overview of the different anxiety and associated disorders. It focuses on issues to consider in perinatal anxiety, namely the consideration of symptoms versus disorders, normal versus pathological anxiety and pregnancy-specific versus general anxiety. The subsequent sections of the chapter focus on each of the anxiety and associated disorders in turn: their epidemiology, aetiology, presentation, course and outcomes including for the infant and family; and, finally, their management.
Mental health conditions, including anxiety disorders, are a major cause of morbidity across Sub-Saharan Africa. There are scarce mental health resources and providers in Madagascar, which substantiates a need for clear and accessible assessment tools for assessing mental health conditions. Yet, before this study, there were no validated scales to measure anxiety disorder symptoms in Madagascar. We assessed the psychometric properties of the culturally adapted 10-item Hopkins Symptom Checklist (HSCL-10-SW) anxiety subscale in the Bay of Ranobe region, in southwestern Madagascar. The study participants were part of the ongoing HIARA cohort study. The HSCL-10-SW includes the original HSCL-10 anxiety subscale in addition to three culturally relevant items that were derived through qualitative research: irritability, lost in thoughts/overthinking and forgetfulness. We administered the HSCL-10-SW to 809 participants (41.2% males) aged 16 years (mean age 36.9) and above in October 2023. Our exploratory factor analysis supported a two-factor structure: Fear Anxiety and Cognitive-Somatic Anxiety. We found discriminant validity between Fear anxiety and Depression factors. Although the HSCL-10-SW demonstrated acceptable psychometric validity, we suggest that additional qualitative studies should be conducted to explore the local conceptualization of anxiety disorders in southwestern Madagascar.
To examine the impact the COVID-19 pandemic in Ireland on symptoms and functioning in individuals across a range of mental health disorders.
Methods:
A systematic bibliographic search of case reports, cross-sectional and longitudinal studies was conducted between March 12th, 2020, and December 20th, 2024, among studies evaluating the impact of the COVID-19 pandemic on symptoms and functioning for individuals with pre-existing mental health disorders and for those who presented with self-harm or died by probable suicide in the Republic of Ireland. Studies were independently screened by two reviewers according to inclusion and exclusion criteria, with selected variables extracted and summarised. Risk of bias assessments and narrative synthesis of included studies were conducted.
Results:
Twenty-eight studies met inclusion criteria. Findings were heterogeneous and disorder specific. An increase in presentations of self-harm, anxiety disorders, and eating disorders to child and adolescent mental health services and emergency departments was noted, with relative stability of symptoms in other cohorts including bipolar disorder and treatment-resistant schizophrenia. Significant symptom deterioration, with poor quality of life and functioning was demonstrated in individuals with emotionally unstable personality disorder both cross-sectionally and longitudinally.
Conclusions:
Most people with pre-existing mental disorders did not experience significant exacerbation associated with the pandemic, with exception of those with eating disorders and EUPD.
Journalists covering war are exposed to grave risk which can cause mental health difficulties.
Aims
To determine the long-term psychiatric health of journalists who covered wars in Afghanistan and the Middle East between September 2001 (following 9/11) and 2013 (waning of the Arab Spring uprisings).
Method
Observational, qualitative study involving journalists from CNN, The New York Times, the Washington Post, the Associated Press and National Public Radio. Data collected via study website and Zoom interviews. Of 324 journalists identified, 202 (62.3%) were traceable. Of these, 16 (4.9%) were deceased, 156/186 (83.9%) consented and 30/186 (16.1%) declined participation. Of 156 journalists who provided psychometric data, 99 (63.4%) agreed to interview. Duration of exposure to and severity of risk were recorded. Psychometric data included the General Anxiety Disorder seven-item scale, the nine-item Patient Health Questionnaire, the PTSD Checklist for DSM-5 and the Structured Clinical Interview Schedule for DSM-5 to elicit 12-month and lifetime prevalence of psychiatric diagnoses.
Results
One hundred and twelve (71.8%) were male, mean age was 57.0 (s.d. = 9.75) years and 77/156 (49.4%) spent more than 3 years in war zones. Time in a war zone correlated with risk severity (r = 0.476, p < 0.001). Lifetime and 12-month prevalence of post-traumatic stress disorder (PTSD) 27%/6%; major depression 34%/8%; any anxiety disorder 28%/11%; alcohol use disorder 34%/4%; acute stress disorder 6%/0%; dissociative disorder 2%/0%. Severity of risk predicted lifetime PTSD only (odds ratio 2.55, 95% CI: 1.27–5.14, p = 0.009). Counselling was available to 63/156 (40.4%) journalists while covering conflict.
Conclusions
Journalists who covered wars in Afghanistan, Iraq and elsewhere that began after 9/11 have a high lifetime prevalence of PTSD, major depression, any anxiety disorder and alcohol use disorder; 12-month prevalence for PTSD and any anxiety disorder remains elevated, albeit less so. War journalism is hazardous, and risk severity predicts PTSD, highlighting the importance of therapy availability.
Parental prenatal mood and anxiety disorders (PMADs) are linked to child neurodevelopmental disorders (NDDs), but evaluations of the magnitude and mechanisms of this association are limited. This study estimates the strength of the association and whether it is impacted by genetic and environmental factors.
Methods
A systematic search of PubMed, CENTRAL, PsycINFO, OVID, and Google Scholar was performed for articles published from January 1988 to September 2025. Of 2,420 articles screened, 74 met the inclusion criteria. Meta-analyses were conducted on 21 studies, and 53 were included in the narrative synthesis. We conducted random-effects meta-analyses, along with tests for heterogeneity (I2) and publication bias (Egger’s test). The review followed PRISMA and MOOSE guidelines.
Results
Maternal PMADs were associated with a significantly increased risk of attention-deficit/hyperactivity disorder (ADHD; odds ratio [OR] 1.91, 95% confidence interval [CI] 1.45–2.52) and autism spectrum disorder (ASD; OR 1.75, 95% CI 1.43–2.14) in children. Paternal PMADs were also associated with the risk of NDDs, with combined odds for ASD and ADHD (OR = 1.23, 95% CI 1.14–1.33). Several studies suggested that the link between parental PMADs and offspring NDDs might be impacted by both genetic and environmental factors, including the impact of ongoing parental depression on child behavior.
Conclusions
Parental PMADs are associated with increased risk of NDDs in children. These findings likely reflect a combination of inherited liability and environmental processes; clarifying mechanisms will require genetically informed designs. Regardless of mechanism, offering optional, family-centered developmental support may help promote child well-being in families where a parent is experiencing PMADs.
Children displaced by armed conflict are at high risk of experiencing psychological distress. The ongoing war in Gaza has resulted in widespread trauma among Palestinian youth, yet limited data exist on their mental health following displacement. This study assessed the prevalence and correlates of anxiety and depressive symptoms among war-displaced Palestinian refugee children and adolescents resettled in Qatar.
Aims
To estimate the prevalence of clinically significant anxiety and depressive symptoms and to identify psychosocial and trauma-related factors associated with symptom severity in this population.
Method
A cross-sectional study was conducted among 350 Palestinian children (aged 8–17 years) residing in a residential compound in Qatar. Symptoms of anxiety and depression were measured using the Screen for Child Anxiety Related Emotional Disorders-Child Version and the Short Mood and Feelings Questionnaire-Child Version, respectively. A Resilience and Demographic Questionnaire was devised to assess trauma exposure and psychosocial variables. Multiple linear regression identified factors associated with symptom severity.
Results
Clinically significant anxiety and depressive symptoms were found in 70.9 and 46.0% of participants, respectively. Separation anxiety was the most common subtype. Female gender, witnessing death, physical injury and disrupted caregiving were significantly associated with worse outcomes.
Conclusions
This study highlights the urgent need for trauma-informed, culturally sensitive mental health services for displaced Palestinian children and young people. While clinical interventions are vital, a sustainable resolution to the conflict is essential to mitigate further psychological harm.
An increase in mental disorders has been suggested, but the interpretation of such trends remains unclear. This study examines changes in the 12-month prevalence of anxiety and mood disorders over 12 years and evaluates whether clinical characteristics or sociodemographic, vulnerability and health-lifestyle risk factors contributed to these trends.
Aims
To assess trends in the 12-month prevalence of anxiety disorders (i.e. panic disorder, agoraphobia, social anxiety disorder or generalised anxiety disorder) and mood disorders (major depressive disorder, dysthymia or bipolar disorder) and explore whether changes in clinical profiles or risk factors influenced these trends.
Method
Data from 11 615 respondents (mean age 43.5 years, 53.5% female) in the Netherlands Mental Health Survey and Incidence Studies (NEMESIS) were analysed, covering 2007–2009 (NEMESIS-2, n = 6646) and 2019–2022 (NEMESIS-3, n = 4969). Diagnoses were determined using the Composite International Diagnostic Interview 3.0.
Results
The 12-month prevalence of all anxiety and mood disorders was significantly higher in 2019–2022 compared to 2007–2009, with relative increases across disorders ranging from approximately a half to more than double their previous rates. Any anxiety or mood disorder increased from 10.2 to 16.7%. Clinical profiles were equally severe in 2019–2022; rather, there was increased mental health care use, a higher number of comorbid disorders and earlier onset. Examination of 14 risk factors showed no consistent evidence of greater prevalence or increased relative impact over time.
Conclusions
There was a consistent rise in the 12-month prevalence of anxiety and mood disorders over 12 years. This increase was not explained by changes in risk factors or less severe disorder reporting. Instead, these findings suggest a concerning decline in public mental health, highlighting the need for effective prevention strategies, timely interventions and better mental health resource allocation to address growing clinical demands.
People with severe COVID anxiety have significant fears of contagion, physiological symptoms of anxiety in response to a COVID stimulus and employ often disproportionate safety behaviours at the expense of other life priorities.
Aims
To characterise the long-term trajectory of severe COVID anxiety, and the factors that influence recovery.
Method
This prospective cohort study followed 285 people with severe COVID anxiety in the UK over 18 months. A nested randomised feasibility trial tested an online cognitive–behavioural therapy (CBT)-based intervention (no. ISRCTN14973494). Descriptive statistics and linear regression models identified factors associated with change in COVID anxiety over 18 months.
Results
Most participants experienced major reductions in COVID anxiety over time (69.8% relative cohort mean decrease, P < 0.001), but a quarter of people (23.7%, 95% CI: 17.8–30.1) continued to worry about COVID every day, and for 13% symptoms remained severe even after the ending of all public health restrictions. Increasing age, being from a minority ethnic background that confers greater risk from COVID-19, and the persistence of high levels of health anxiety and depressive symptoms, predicted slower improvements in severe COVID anxiety after adjusting for other clinical and demographic factors. Neither a trial CBT-based intervention, nor contextual factors including daily case rates, vaccination status or having contracted COVID-19, appeared to affect the trajectory of severe COVID anxiety.
Conclusions
For most people severe COVID anxiety improves significantly with time. However, interventions treating depression and health anxiety, and targeting older people and those from greater-risk minority backgrounds, warrant further investigation in future pandemics.
This chapter reviews a broad spectrum in Child and Adolescent Mental Health; that of the anxiety disorders. The chapter briefly introduces the concept of attachment and touches on how attachment disorders, and attachment styles evolve. It focuses in on PTSD and C-PTSD, with a particular spotlight on C-PTSD as a new diagnostic concept, and considers its importance in understanding presentations of trauma and emotional dysregulation in children and young people. The chapter also investigates the epidemiology and course of anxiety disorders; and considers the differentiating features of the different presentations. We finish with an overview of interventions, including the rise of computerised approaches in treating the anxiety disorders in young people.