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The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review.Journal of Psychopharmacology (Oxford,... Dec 2023Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this... (Review)
Review
BACKGROUND
Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this systematic review, we aimed to review the relationship between the 5-HT7 receptor system and mood and anxiety disorders, and to explore the pharmacology and therapeutic potential of medications that target the 5-HT7 receptor for their treatment.
METHODS
Medline, Cochrane Library, EMBASE, PsycINFO databases, the National Institute of Health website Clinicaltrials.gov, controlled-trials.com, and relevant grey literature were used to search for original research articles, and reference lists of included articles were then hand searched.
RESULTS
Sixty-four studies were included in the review: 52 animal studies and 12 human studies. Studies used a variety of preclinical paradigms and questionnaires to assess change in mood, and few studies examined sleep or cognition. Forty-four out of 47 (44/47) preclinical 5-HT7 modulation studies identified potential antidepressant effects and 20/23 studies identified potential anxiolytic effects. In clinical studies, 5/7 identified potential antidepressant effects in major depressive disorder, 1/2 identified potential anxiolytic effects in generalized anxiety disorder, and 3/3 identified potential antidepressant effects in bipolar disorders.
CONCLUSION
While there is some evidence that the 5-HT7 receptor system may be a potential target for treating mood and anxiety disorders, many agents included in the review also bind to other receptors. Further research is needed using drugs that bind specifically to 5-HT7 receptors to examine treatment proof of concept further.
Topics: Animals; Humans; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major
PubMed: 37994803
DOI: 10.1177/02698811231211228 -
BMJ Open Jul 2023To systematically review 1-year recovery rates for young people experiencing depression and/or anxiety who are not receiving any specific mental health treatment. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically review 1-year recovery rates for young people experiencing depression and/or anxiety who are not receiving any specific mental health treatment.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE, Embase, PsycINFO, Web of Science and Global Health were searched for articles published from 1980 through to August 2022.
ELIGIBILITY CRITERIA
Articles were peer-reviewed, published in English and had baseline and 1-year follow-up depression and/or anxiety outcomes for young people aged 10-24 years without specific treatment.
DATA EXTRACTION AND SYNTHESIS
Three reviewers extracted relevant data. Meta-analysis was conducted to calculate the proportion of individuals classified as recovered after 1 year. The quality of evidence was assessed by the Newcastle-Ottawa Scale.
RESULTS
Of the 17 250 references screened for inclusion, five articles with 1011 participants in total were included. Studies reported a 1-year recovery rate of between 47% and 64%. In the meta-analysis, the overall pooled proportion of recovered young people is 0.54 (0.45 to 0.63).
CONCLUSIONS
The findings suggest that after 1 year about 54% of young people with symptoms of anxiety and/or depression recover without any specific mental health treatment. Future research should identify individual characteristics predicting recovery and explore resources and activities which may help young people recover from depression and/or anxiety.
PROSPERO REGISTRATION NUMBER
CRD42021251556.
Topics: Humans; Adolescent; Depression; Anxiety; Anxiety Disorders; MEDLINE; Peer Review
PubMed: 37479525
DOI: 10.1136/bmjopen-2023-072093 -
Journal of Affective Disorders Oct 2023Considerable comorbidity exists between insomnia and anxiety, and evidence shows that the benefits of CBT for insomnia extend to anxiety. Using data from two large...
Does treating insomnia with digital cognitive behavioural therapy (Sleepio) mediate improvements in anxiety for those with insomnia and comorbid anxiety? An analysis using individual participant data from two large randomised controlled trials.
BACKGROUND
Considerable comorbidity exists between insomnia and anxiety, and evidence shows that the benefits of CBT for insomnia extend to anxiety. Using data from two large trials of digital CBT (dCBT) for insomnia, we evaluated whether improving sleep is an effective treatment target to reduce both insomnia and anxiety symptoms in individuals with insomnia and clinically significant anxiety.
METHODS
This was a controlled sub-analysis combining individual participant data from two previous randomised controlled trials of dCBT for insomnia (Sleepio). Participants (N = 2172) with insomnia disorder and clinically significant anxiety symptoms were included in this sub-analysis and received either dCBT or control (usual care or sleep hygiene education). Assessments were evaluated at baseline, post-intervention (week 8 or 10), and follow-up (week 22 or 24). Mediation was evaluated using structural equation models.
RESULTS
dCBT for insomnia was superior to control at reducing both insomnia (Hedges' g range = 0.77-0.81; both p < 0.001) and anxiety symptoms (Hedges' g range = 0.39-0.44; both p < 0.001) at all time points. Baseline insomnia symptoms moderated the effects of dCBT on insomnia, however no variables moderated treatment effects on anxiety. Reductions in anxiety symptoms at follow-up were mediated by improvements in sleep at post-intervention (% mediated = 84 %), suggesting a causal pathway.
LIMITATIONS
Participants did not have a formal anxiety disorder diagnosis and so the effects of dCBT for insomnia on anxiety may differ by anxiety disorder.
CONCLUSIONS
Addressing sleep using dCBT for insomnia may serve as a treatment target from which to improve anxiety in individuals with insomnia and clinically significant comorbid anxiety.
CLINICAL TRIAL REGISTRATIONS
Digital Insomnia therapy to Assist your Life as well as your Sleep (DIALS) - ISRCTN60530898 http://www.isrctn.com/ISRCTN60530898. Oxford Access for Students Improving Sleep (OASIS) - ISRCTN61272251 http://www.isrctn.com/ISRCTN61272251.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Anxiety; Anxiety Disorders; Treatment Outcome; Comorbidity; Cognitive Behavioral Therapy; Randomized Controlled Trials as Topic
PubMed: 37390923
DOI: 10.1016/j.jad.2023.06.053 -
Psychopharmacology Nov 2023Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. Fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well known.
OBJECTIVE
We aimed to systematically review the effect of six clinically effective SSRIs on acquisition, expression, and extinction of cued and contextual conditioned fear.
METHODS
We searched the Medline and Embase databases, which yielded 128 articles that met the inclusion criteria and reported on 9 human and 275 animal experiments.
RESULTS
Meta-analysis showed that SSRIs significantly reduced contextual fear expression and facilitated extinction learning to cue. Bayesian-regularized meta-regression further suggested that chronic treatment exerts a stronger anxiolytic effect on cued fear expression than acute treatment. Type of SSRI, species, disease-induction model, and type of anxiety test used did not seem to moderate the effect of SSRIs. The number of studies was relatively small, the level of heterogeneity was high, and publication bias has likely occurred which may have resulted in an overestimation of the overall effect sizes.
CONCLUSIONS
This review suggests that the efficacy of SSRIs may be related to their effects on contextual fear expression and extinction to cue, rather than fear acquisition. However, these effects of SSRIs may be due to a more general inhibition of fear-related emotions. Therefore, additional meta-analyses on the effects of SSRIs on unconditioned fear responses may provide further insight into the actions of SSRIs.
Topics: Animals; Humans; Selective Serotonin Reuptake Inhibitors; Bayes Theorem; Fear; Anxiety Disorders; Stress Disorders, Post-Traumatic
PubMed: 36847831
DOI: 10.1007/s00213-023-06333-7 -
Nutrients Dec 2023It is unclear whether diet-associated inflammation is related to the development of anxiety disorders. We aimed to investigate the association between energy-adjusted...
It is unclear whether diet-associated inflammation is related to the development of anxiety disorders. We aimed to investigate the association between energy-adjusted dietary inflammatory index (E-DII) scores and the incidence of anxiety disorders, and explore the joint effects of E-DII scores with other inflammatory lifestyles in enhancing anxiety risk. In the UK Biobank Study of 96,679 participants, baseline E-DII scores were calculated from the average intake of at least two 24 h dietary recalls. Multivariable-adjusted Cox models were used to evaluate the associations between E-DII scores and the incidence of total anxiety disorders, and primary types and subtypes; additive and multiplicative interactions of a pro-inflammatory diet and seven inflammatory lifestyles were examined. After a median follow-up of 9.4 years, 2785 incident cases of anxiety disorders occurred. Consuming a pro-inflammatory diet was significantly associated with a higher risk of total anxiety disorders (HR = 1.12, 95% CI = 1.00-1.25), and positive associations were consistently identified for primary types and subtypes of anxiety disorders, with HRs ranging from 1.08 to 1.52, and were present in women only. Both additive and multiplicative interactions of current smoking and a proinflammatory diet on total anxiety risk were identified. A proinflammatory diet was associated with a higher incidence of anxiety disorders, and current smoking may synergize with a proinflammatory diet to promote anxiety risk, particularly among women.
Topics: Humans; Female; Prospective Studies; Diet; Anxiety Disorders; Inflammation; Life Style
PubMed: 38201952
DOI: 10.3390/nu16010121 -
Psychological Medicine Nov 2023Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While... (Review)
Review
Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use is quite prevalent in many individuals afflicted with psychiatric illnesses, there is considerable controversy as to whether cannabis may worsen these conditions or provide some form of therapeutic benefit. The development of pharmacological agents which interact with components of the endocannabinoid system in more localized and discrete ways then via phytocannabinoids found in cannabis, has allowed the investigation if direct targeting of the endocannabinoid system itself may represent a novel approach to treat psychiatric illness without the potential untoward side effects associated with cannabis. Herein we review the current body of literature regarding the various pharmacological tools that have been developed to target the endocannabinoid system, their impact in preclinical models of psychiatric illness and the recent data emerging of their utilization in clinical trials for psychiatric illnesses, with a specific focus on substance use disorders, trauma-related disorders, and autism. We highlight several candidate drugs which target endocannabinoid function, particularly inhibitors of endocannabinoid metabolism or modulators of cannabinoid receptor signaling, which have emerged as potential candidates for the treatment of psychiatric conditions, particularly substance use disorder, anxiety and trauma-related disorders and autism spectrum disorders. Although there needs to be ongoing clinical work to establish the potential utility of endocannabinoid-based drugs for the treatment of psychiatric illnesses, the current data available is quite promising and shows indications of several potential candidate diseases which may benefit from this approach.
Topics: Humans; Endocannabinoids; Mental Disorders; Anxiety; Anxiety Disorders; Cannabis; Cannabinoid Receptor Agonists; Hallucinogens
PubMed: 37671673
DOI: 10.1017/S0033291723002465 -
Brain Imaging and Behavior Dec 2023Major depressive and social anxiety disorders have a high comorbidity rate and similar cognitive patterns. However, their unique and shared neuroanatomical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major depressive and social anxiety disorders have a high comorbidity rate and similar cognitive patterns. However, their unique and shared neuroanatomical characteristics have not been fully identified.
METHODS
Voxel-based morphometric studies comparing gray matter volume between patients with major depressive disorder/social anxiety disorder and healthy controls were searched using 4 electronic databases from the inception to March 2022. Stereotactic data were extracted and subsequently tested for convergence and differences using activation likelihood estimation. In addition, based on the result of the meta-analysis, behavioral analysis was performed to assess the functional roles of the regions affected by major depressive disorder and/or social anxiety disorder.
RESULTS
In total, 34 studies on major depressive disorder with 2873 participants, and 10 studies on social anxiety disorder with 1004 subjects were included. Gray matter volume conjunction analysis showed that the right parahippocampal gyrus region, especially the amygdala, was smaller in patients compared to healthy controls. The contrast analysis of major depressive disorder and social anxiety disorder revealed lower gray matter volume in the right lentiform nucleus and medial frontal gyrus in social anxiety disorder and lower gray matter volume in the left parahippocampal gyrus in major depressive disorder. Behavioral analysis showed that regions with lower gray matter volume in social anxiety disorder are strongly associated with negative emotional processes.
CONCLUSIONS
The shared and unique patterns of gray matter volume abnormalities in patients with major depressive and social anxiety disorder may be linked to the underlying neuropathogenesis of these mental illnesses and provide potential biomarkers. PROSPERO registration number: CRD42021277546.
Topics: Humans; Gray Matter; Depressive Disorder, Major; Phobia, Social; Magnetic Resonance Imaging; Cerebral Cortex; Brain
PubMed: 37725323
DOI: 10.1007/s11682-023-00797-z -
Journal of Neural Transmission (Vienna,... Sep 2023Neuropsychiatric disorders, such as major depression, anxiety disorders, and post-traumatic stress disorder, tend to be long-term conditions in whose development and... (Review)
Review
Neuropsychiatric disorders, such as major depression, anxiety disorders, and post-traumatic stress disorder, tend to be long-term conditions in whose development and maintenance stress are central pathogenic factors. Translational mouse models are widely used in neuropsychiatric research, exploiting social and non-social stressors to investigate the mechanisms underlying their detrimental effects. However, most studies focus on the short-term consequences of chronic stress, whereas only a few are interested in the long-term course. This is counterintuitive given the human conditions that preclinical models are designed to mimic. In this review, we have summarized the limited work to date on long-term effects of chronic stress in mice models. First, the different models are presented and a definition of short- vs. long-term sequelae is proposed. On this basis, behavioral, endocrine, and vegetative effects are addressed before examining data on cellular and molecular alterations in the brain. Finally, future directions for research on the long-term effects of stress are discussed.
Topics: Mice; Animals; Adult; Humans; Anxiety Disorders; Brain; Stress Disorders, Post-Traumatic; Depressive Disorder, Major; Stress, Psychological; Anxiety
PubMed: 36786896
DOI: 10.1007/s00702-023-02598-6 -
Frontiers in Public Health 2023This study examined the prevalence of anxiety and depression-along with the potential risk and protective factors-among Chinese prison officers during the prolonged...
OBJECTIVE
This study examined the prevalence of anxiety and depression-along with the potential risk and protective factors-among Chinese prison officers during the prolonged COVID-19 pandemic.
METHOD
A cross-sectional survey of 1,268 officers from five prisons in western and southern China was administered between June and July 2022. The questionnaires comprised two sections. In the first section, the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to evaluate the prevalence of anxiety and depression, respectively, among prison officers. In the second section, the potential influencing factors were examined. Categorical data were compared using χ tests and -tests; binary logistic regression analysis was performed to identify factors associated with anxiety and depression.
RESULTS
The prevalence rates of anxiety and depression among the prison officers were 72.6% and 69.8%, respectively. Risk factors for anxiety were older age, being unmarried, work-family conflicts, job demands, and COVID-19 burnout; protective factors were exercise, positive family relationships, and group cohesion. Work-family conflicts, job demands, intolerance of uncertainty regarding COVID-19, and COVID-19 burnout were risk factors for depression, whereas annual income >150,000 RMB, exercise, positive family relationships, group cohesion, and job autonomy were protective factors against depression.
CONCLUSION
The prevalence of anxiety and depression among Chinese prison officers was relatively high during the prolonged COVID-19 pandemic, and more targeted measures should be implemented to improve their mental health. This study offers a reference for improving prison officers' mental health in response to similar public health emergencies in the future.
Topics: Humans; Anxiety; Anxiety Disorders; COVID-19; Cross-Sectional Studies; Depression; East Asian People; Pandemics; Prevalence; Prisons; Correctional Facilities Personnel
PubMed: 37601183
DOI: 10.3389/fpubh.2023.1218825 -
Frontiers in Immunology 2023Previous epidemiological investigations and related research efforts consistently have outlined an observable association between anxiety disorders and adhesive...
BACKGROUND
Previous epidemiological investigations and related research efforts consistently have outlined an observable association between anxiety disorders and adhesive capsulitis (AC). However, the intricate nature of the causal connection between these entities has yet to be fully clarified. Therefore, this investigative study aims to thoroughly examine and delineate the causal interrelationship between anxiety disorders and AC using a bidirectional, two-sample Mendelian randomization (MR) approach.
METHODS
To pursue this inquiry, datasets related to anxiety disorders and AC were meticulously obtained from a publicly accessible genomewide association study. Instrumental variables, in the form of single nucleotide polymorphisms, were subsequently identified, undergoing a rigorous screening process that included intensity adjustment and the amelioration of linkage disequilibrium. The primary analytical tool for scrutinizing causal ramifications was the inverse variance weighting (IVW) methodology, complemented by supplementary analytical techniques such as weighted median, MR-Egger, simple mode, and weighted mode. Additionally, evaluations of heterogeneity and pleiotropy were meticulously conducted. Heterogeneity was assessed using Cochran's Q-test in conjunction with the IVW and MR-Egger methods, while pleiotropy was appraised through the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was undertaken to enhance the reliability of our findings. Finally, AC was utilized to infer reverse causality concerning the risk of anxiety disorders.
RESULTS
The random effects IVW analysis results yielded statistical significance ( = 9.362 × 10), demonstrating a causal link between anxiety disorders and elevated susceptibility to AC, reflected in an odds ratio of 1.267 (95% confidence interval: 1.141-1.407). Conversely, the inverse MR analysis predominantly produced null findings. Furthermore, sensitivity analyses underscored the robustness of our conclusions.
CONCLUSION
In summary, our meticulously conducted study unequivocally supports the presence of a causal connection between anxiety disorders and an increased propensity for AC. Unfortunately, the reverse MR analysis failed to provide compelling evidence indicative of a reciprocal genetic causative relationship between AC and anxiety disorders.
Topics: Humans; Mendelian Randomization Analysis; Reproducibility of Results; Bursitis; Analysis of Variance; Anxiety Disorders
PubMed: 38259492
DOI: 10.3389/fimmu.2023.1297477