Correlation of preoperative inflammatory factors and emotional disorders with postoperative delirium in patients with craniocerebral trauma

BACKGROUND Traumatic brain injury(TBI)imposes a substantial societal and familial burden due to its high disability and fatality rates,rendering it a serious public health problem.Some patients with TBI have poor treatment outcomes and are prone to postoperative delirium(POD),which affects their quality of life.Anxiety has been linked to increased POD incidence in some studies,while others have found no correlation.AIM To investigate the correlation of POD risk factors,preoperative inflammatory factors,and mood disorders in patients with TBI.METHODS We retrospectively collected data on the treatment of 80 patients with TBI from November 2021 to September 2023.Patients were grouped as POD and non-POD,according to their POD status,and the general data of the two groups were compared.Inflammatory factor levels were detected preoperatively,and the Hamilton Depression Scale(HAMD)and Hamilton Anxiety Scale(HAMA)were used to investigate the risk factors associated with POD in these patients.Logistic regression was used to identify the independent risk factors.RESULTS Twenty-one patients(26.25%)developed POD,including 7,10,and 4 cases of the excitatory,inhibitory,and mixed types,respectively.There were 59 cases(73.75%)in the non-POD group.Compared with the non-POD group,the POD group had a significantly higher proportion of patients with low Glasgow Coma Scale(GCS)scores before admission,unilateral mydriasis,preoperative hemorrhagic shock,intraventricular hemorrhage(IVH),and postoperative hyperglycemic hyperosmolar disease(P<0.05).In the POD group,interleukin-6(IL-6),human tumor necrosis factor-α(TNF-α),myeloperoxidase levels,HAMA,and HAMD scores were higher than those in the non-POD group(all P<0.05).Logistic multivariate analysis showed that GCS score at admission,IVH,IL-6,TNF-α,HAMA,and HAMD were independent risk factors for POD in patients with TBI(P<0.05).CONCLUSION Low GCS score at admission,IVH,elevated IL-6 and TNF-α,other inflammatory indicators,anxiety,and depression,can increase the risk of POD in patients with TBI after surgery.

Astrocytic Kir4.1 potassium channels as a novel therapeutic target for epilepsy and mood disorders

Astrocytic Kir4.1 channels and spatial potassium buffering：Astrocytes play a crucial role in maintaining the structural and functional integrity of the brain,which includes formation of the blood-brain barrier,maintenance of water and ion homeostasis,metabolism of neurotransmitters and secretion of various neuroactive molecules.

Neuroimmune crosstalk through brain-derived neurotrophic factor and its precursor pro-BDNF: New insights into mood disorders

Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic factor (BDNF)and its precursor pro-BDNF, are involved in the neuroimmune crosstalk duringthe development of mood disorders. BDNF is implicated in the pathophysiologyof psychiatric and neurological disorders especially in antidepressant pharmacotherapy.In this review, we describe the functions of BDNF/pro-BDNF signalingin the central nervous system in the context of mood disorders. In addition, wesummarize the developments for BDNF and pro-BDNF functions in mooddisorders. This review aims to provide new insights into the impact ofneuroimmune interaction on mood disorders and reveal a new basis for furtherdevelopment of diagnostic targets and mood disorders.

Relationship between uncertainty in illness,mood state and coping style in patients with temporomandibular disorders

Objective:To investigate the relationship between uncertainty in illness,mood state and coping style in patients with temporomandibular disorders(TMD)in the hospital,in order to identify nursing measures.Methods:Chinese versions of the Mishel Uncertainty In Illness Scale(MUIS),Brief Profile Of Mood States(BPOMS)and Medical Coping Modes Questionnaire(MCMQ)were used to assess uncertainty in illness,mood state and coping style,respectively,in 126 patients with TMD.Results:The total score of uncertainty in illness of the patients was 91.33±16.38,which was at middle level.The total score of mood state was 37.93±17.0.The order of coping style rated from high to low was confrontation(18.81±3.65),avoidance(15.44±4.26)and acceptance(10.41±5.04).Acceptance was positively correlated with uncertainty in illness(r=0.463,p<0.001),and mood state(r=0.187,p<0.05).Avoidance and confrontation were negatively correlated with uncertainty in illness and mood state(r=0.286,p<0.01),(r=0.175,p<0.05),(r=0.171,p<0.05),(r=0.221,p<0.01).Conclusions:Both uncertainty in illness and mood state were related to coping style.These data suggest that nurses should be trained to offer appropriate guidance to help decrease patients'uncertainty in illness and relieve their negative emotions.

Dimensional Characteristics of Children and Adolescents with Mood Disorders and Autism Spectrum Disorders

Objective: We sought to identify clinical discriminators between predominantly mood disordered and predominantly autism spectrum disordered research subjects that may reflect phenotypic state and treatment response characteristics. Method: Participants were 26 boys and 4 girls aged 2 to 18 years (Mean Age = 7.70). Subjects with DSM-IV diagnoses of Major depression (N = 2), Bipolar Disorder (N = 4) and Mood Disorder not otherwise specified (NOS) (N = 11) represented the mood disorder group (MD) (N = 17, Mean Age = 8.2) and those with diagnoses of Autistic Disorder (N = 1), Asperger’s Disorder (7) or Pervasive Developmental Disorder (NOS) (N = 3) comprised the autism spectrum disorder (ASD) group (N = 9, Mean Age = 6.8). Primary outcome measurements were continuous actigraphic measurements collected over one to three week periods. Secondary outcomes included personality and observational measurements. Personality characteristics reflected significant cross-group impairments related to self-control and self-discipline and differed relative to intellectual measures. Observational measurements reflected greater general impairments among the ASD group. Results: Predominantly mood disordered children demonstrated greater impairments related to sleep (P = 0.000) and sleep onset latency (P = 0.000) and were more active than ASD children during evening periods (P = 0.000). ASD children had lower verbal functioning and greater deviations from the norm on measures of cognitive development (P = 0.003) and psychosis (P = 0.047). Conclusions: Sleep disturbances, evening activity levels and phase delayed sleep appear to differentiate predominant mood and autism spectrum disordered children suggesting future areas for further exploration of neurological and phenotypic treatment response characteristics.

False dogmas in mood disorders research:Towards a nomothetic network approach

The current understanding of major depressive disorder(MDD)and bipolar disorder(BD)is plagued by a cacophony of controversies as evidenced by competing schools to understand MDD/BD.The DSM/ICD taxonomies have cemented their status as the gold standard for diagnosing MDD/BD.The aim of this review is to discuss the false dogmas that reign in current MDD/BD research with respect to the new,data-driven,machine learning method to model psychiatric illness,namely nomothetic network psychiatry(NNP).This review discusses many false dogmas including:MDD/BD are mind-brain disorders that are best conceptualized using a bio-psycho-social model or mind-brain interactions;mood disorders due to medical disease are attributable to psychosocial stress or chemical imbalances;DSM/ICD are the gold standards to make the MDD/BD diagnosis;severity of illness should be measured using rating scales;clinical remission should be defined using threshold values on rating scale scores;existing diagnostic BD boundaries are too restrictive;and mood disorder spectra are the rule.In contrast,our NNP models show that MDD/BD are not mind-brain or psycho-social but systemic medical disorders;the DSM/ICD taxonomies are counterproductive;a shared core,namely the reoccurrence of illness(ROI),underpins the intertwined recurrence of depressive and manic episodes and suicidal behaviors;mood disorders should be ROI-defined;ROI mediates the effects of nitro-oxidative stress pathways and early lifetime trauma on the phenome of mood disorders;severity of illness and treatment response should be delineated using the NNP-derived causome,pathway,ROI and integrated phenome scores;and MDD and BD are the same illness.

Gut microbiota in autism and mood disorders

The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal(GI)system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases.In the last few years,the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism,dementia and mood disorder,has been raised.The evidence of the inflammatory state alteration,highlighted in disorders such as schizophrenia,major depressive disorder and bipolar disorder,strongly recalls the microbiota alteration,highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders.Up to now,available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders.The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date,with few but promising results.A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder(ASD),as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.

Mood disorders: A potential link between ghrelin and leptin on human body?

Leptin and ghrelin are two hormones associated with multiple physiological functions, especially energy balance. Leptin is an adipocyte-secreted hormone discovered in 1950 and ghrelin which was found in 1999, is a peptide hormone produced and secreted in the stomach. A number of previous studies showed that these hormones could be associated with different types of mood disorders. The results of previous studies, nevertheless, are confounded by diverse sample selection and different methodologies. A search for related articles in the Pub Med database was attempted. The search covered studies, reports, reviews and editorials published in the last ten years. Older references served as auxiliary sources for comparison purposes. However, due to the different results of the studies, there is a need for more investigation in order to establish the exact biochemical mechanisms that are responsible for these diseases and ghrelin's and leptin's effects on mood.

Psychological and Physiological Health Benefits of a Structured Forest Therapy Program for Children and Adolescents with Mental Health Disorders

Mental health conditions in children and adolescents can be improved by slow mindful nature connection known as forest therapyor bathing.Forest therapy has recently received growing attention as an enabler of relaxation and preventive health care withdemonstrated clinical efficacy.However,it is not well-known that forest therapy also decreases mental health issues amongindividuals with mental health disorders.This study explored the psychological and physiological health benefits of structuredforest therapy programs for children and adolescents with mental health disorders.A one-group pre-test-posttest design wasemployed for our study participants.Twelve participants(aged 9–14 years)engaged in two one-hour guided standard sequenceforest therapy experiences.A Mindful Attention Awareness Scale(MAAS),Connectedness to Nature Scale(CNS),Profile ofMood States(POMS),place meanings(e.g.,functional,emotional,and cognitive attachment to the forest)questionnaire,andphysiological health assessment were administered to the participants.Our results showed that negative mood states weresignificantly reduced and that a positive mood state was significantly improved after the structured forest therapy programs.Also,mindfulness,nature connection,place meanings,and physiological health were significantly boosted after theinterventions.The results demonstrate substantial psychological and physiological health and well-being outcomes ofstructured forest therapy for similar individuals.

Evaluating the emotion regulation of positive mood states among people with bipolar disorder using hierarchical clustering

BACKGROUND People with bipolar disorder(BD)frequently struggle with the recurrence of affective symptoms.However,the interplay between coping mechanism and positive mood state remains under-researched.AIM To explore the associations among behavioral approach system(BAS)sensitivity level,coping,and positive mood states among people with BD.METHODS Using a cross-sectional study design,90 participants with BD were presented with four BAS-activating life event scenarios and assessed with regard to their BAS trait sensitivity,coping flexibility,and mood states.A hierarchical clustering method was used to identify different groups with different styles of coping.Multiple hierarchical regression analyses were conducted to examine the mediating and moderating roles of different components of coping on mood states.RESULTS A three-cluster solution was found to best fit the present data set.The findings showed that a low mass of coping combined with low BAS sensitivity level protects people with BD from detrimentally accentuating mood states when they encounter BAS-activating life events.Moreover,coping flexibility is demonstrated to mediate and moderate the relationships between BAS sensitivity level and mood states.Specifically,subduing the perceived controllability and reducing the use of behavioral-activation/emotion-amplifying coping strategies could help buffer the effect of positive affect.CONCLUSION The judicious use of coping in emotion regulation for people with BD when encountering BAS-activating life events was indicated.Practical applications and theoretical implications are highlighted.

Hypomanic/manic switch after transcranial magnetic stimulation in mood disorders:A systematic review and meta-analysis

BACKGROUND Nowadays there is an increasing use of transcranial magnetic stimulation(TMS)both in neurological and psychiatric fields.After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression,TMS has been widely used in the context of mood disorders(MD).However,growing reports regarding the possibility of developing hypomanic/manic switch(HMS)have generated concern regarding its use in MDs.AIM To investigate the actual risk of developing HMS due to TMS in the treatment of MD.METHODS We led our research on PubMed,Scopus and Web of Science on March 22,2020,in accordance to the PRISMA guidelines for systematic review.Only double blind/single blind studies,written in English and focused on the TMS treatment of MD,were included.A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software.The assessment of Risk of Bias was done using Cochrane risk of bias tool.This protocol was registered on PROSPERO with the CRD42020175811 code.RESULTS Twenty-five studies were included in our meta-analysis:Twenty-one double blind randomized controlled trials(RCT)and four single blind-RCT(no.of subjects involved in active stimulation=576;no.of subjects involved in sham protocol=487).The most frequently treated pathology was major depressive episode/major depressive disorder,followed by resistant depression,bipolar depression and other MD.The majority of the studies used a repetitive TMS protocol,and the left dorsolateral prefrontal cortex was the main target area.Side effects were reported in eight studies and HMS(described as greater energy,insomnia,irritability,anxiety,suicidal attempt)in four studies.When comparing active TMS vs sham treatment,the risk of developing HMS was not significantly different between conditions.CONCLUSION Applying the most usual protocols and the appropriate precautionary measures,TMS seems not to be related to HMS development.

Effects of music and music therapy on mood in neurological patients

Mood disorder and depressive syndromes represent a common comorbid condition in neurological disorders witha prevalence rate that ranges between 20% and 50% of patients with stroke, epilepsy, multiple sclerosis, and Parkinson's disease. Notwithstanding, these conditions are often under-diagnosed and under-treated in the clinical practice and negatively affect the functional recovery, the adherence to treatment, the quality of life, and even the mortality risk. In addition, a bidirectional association between depression and neurological disorders may be possible being that depressive syndromes may be considered as a risk factor for certain neurological diseases. Despite the large amount of evidence regarding the effects of music therapy(MT) and other musical interventions on different aspects of neurological disorders, no updated article reviewing outcomes such as mood, emotions, depression, activity of daily living and so on is actually available; for this reason, little is known about the effectiveness of music and MT on these important outcomes in neurological patients. The aim of this article is to provide a narrative review of the current literature on musical interventions and their effects on mood and depression in patients with neurological disorders. Searching on Pub Med and Psyc Info databases, 25 studies corresponding to the inclusion criteria have been selected; 11 of them assess the effects of music or MT in Dementia, 9 explore the efficacy on patients with Stroke, and 5 regard other neurological diseases like Multiple Sclerosis, Amyotrophic Lateral Sclerosis/motor neuron disease, Chronic quadriplegia, Parkinson's Disease, and Acquired Brain dysfunctions. Selected studies are based on relational and rehabilitative music therapy approaches or concern music listening interventions. Most of the studies support the efficacy of MT and other musical interventions on mood, depressive syndromes, and quality of life on neurological patients.

Who says this is a modern disorder? The early history of attention deficit hyperactivity disorder

Attention-deficit hyperactivity disorder(ADHD) is a complex, heterogeneous and multifactorial neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity and impulsivity. Although the first clinical description of a constellation of symptoms highly resembling to what currently could be diagnosed as ADHD is generally attributed to George F Still in 1902, there are scattered but significant published historical medical, scientific and non-scientific reports, much prior to Still's lectures, of what is currently conceptualized as ADHD. The present report aimed at exploring the early history of ADHD, prior to the 20^(th) century in the medical literature and in other historical sources, to provide clinicians, researchers and other professionals with a better understanding of the roots and current conceptualization of this disorder. It is possible to find clues and highly suggestive descriptions of individuals presenting symptoms resembling what is currently defined as ADHD in the literature, in paintings or in the Bible. However, the earliest medical reports of individuals with abnormal degrees of inattention, distractibility and overactivity date from the last quarter of the 18^(th) century, included in two of the first textbooks specifically on the subject of mental diseases, published by the German Melchior Adam Weikard and the Scottish Sir Alexander Crichton. During the 19^(th) century some eminent physicians from Germany, France or Great Britain, such as Charles West, Thomas C Albutt, Thomas S Clouston, William W, Ireland, John Haslam, Heinrich Neumann, or Désiré-Magloire Bourneville, among others provided clinical depictions of patients that most likely presently would be diagnosed as having ADHD. Whilst some of the children described by Still and his predecessors may have suffered from a variety of neurological and psychiatric disorders, many of these patients showed clear symptoms of ADHD and may present with comorbid disorders, as it is commonly the case in clinical practice.

Agomelatine:a potential novel approach for the treatment of memory disorder in neurodegenerative disease

Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B(MT/MT)and antagonist of 5-hydroxytryptamine 2C receptors.It is used clinically to treat major depressive episodes in adults.The pro-chronobiological activity of agomelatine reconstructs sleep-wake rhythms and normalizes circadian disturbances via its agonistic effect of melatonin receptor 1A/melatonin receptor 1B,which work simultaneously to counteract depression and anxiety disorder.Moreover,by antagonizing neocortical postsynaptic 5-hydroxytryptamine 2C receptors,agomelatine enhances the release of dopamine and noradrenaline in the prefrontal cortex,increases the activity of dopamine and noradrenaline,and thereby reduces depression and anxiety disorder.The combination of these two effects means that agomelatine exhibits a unique pharmacological role in the treatment of depression,anxiety,and disturbance of the circadian rhythm.Emotion and sleep are closely related to memory and cognitive function.Memory disorder is defined as any forms of memory abnormality,which is typically evident in a broad range of neurodegenerative diseases,including Alzheimer’s disease.Memory impairment and cognitive impairment are common symptoms of neurodegenerative and psychiatric diseases.Therefore,whether agomelatine can improve memory and cognitive behaviors if used for alleviating depression and circadian-rhythm sleep disorders has become a research“hotspot”.This review presents the latest findings on the effects of agomelatine in the treatment of psychologic and circadian-rhythm sleep disorders in clinical trials and animal experiments.Our review evaluates recent studies on treatment of memory impairment and cognitive impairment in neurodegenerative and psychiatric diseases.

Neurochemical metabolites in the medial prefrontal cortex in bipolar disorder A proton magnetic resonance spectroscopy study

The aim of this study was to investigate proton magnetic resonance spectroscopy metabolite values in the medial prefrontal cortex of individuals with euthymic bipolar disorder. The subjects consisted of 15 patients with euthymic bipolar disorder type I and 15 healthy controls. We performed proton magnetic resonance spectroscopy of the bilateral medial prefrontal cortex and measured levels of N-acetyl aspartate, choline and creatine. Levels of these three metabolites in the medial prefrontal cortex were found to be lower in patients with bipolar disorder compared with healthy controls. A positive correlation was found between illness duration and choline levels in the right medial prefrontal cortex. Our study suggests that during the euthymic period, there are abnormalities in cellular energy and membrane phospholipid metabolism in the medial prefrontal cortex, and that this may impair neuronal activity and integrity.

Mood Spectrum Model:Evidence reconsidered in the light of DSM-5

AIM: to investigate studies conducted with the Mood Spectrum Structured Interviews and Self-Report versions(SCI-MOODS and MOODS-SR).METHODS: We conducted a review of studies published between 1997 and August 2014. The search was performed using Pubmed and Psyc INFO databases. Analysis of the papers followed the inclusion and exclusion criteria recommended by the PRISMA Guidelines, namely:(1) articles that presented a combination of at least two terms, "SCI-MOODS" [all fields] or "MOODS-SR" [all fields] or "mood spectrum" [all fields];(2) manuscript in English;(3) original articles; and(4) prospective or retrospective original studies(analytical or descriptive), experimental or quasi-experimental studies. Exclusion criteria were:(1) other study designs(case reports, case series, and reviews);(2) non-original studies including editorials, book reviews and letters to the editor; and(3) studies not specifically designed and focused on SCI-MOODS or MOODS-SR.RESULTS: The search retrieved 43 papers, including 5 reviews of literature or methodological papers, and 1 case report. After analyzing their titles and abstracts, according to the eligibility criteria, 6 were excluded and 37 were chosen and included. The SCI-MOODS and the MOODS-SR have been tested in published studies involving 52 different samples across 4 countries(Italy, United States, Spain and Japan). The proposed mood spectrum approach has demonstrated its usefulness mainly in 3 different areas:(1) Patients with the socalled "pure" unipolar depression that might manifest hypomanic atypical and/or sub-threshold aspects systematically detectable with the mood questionnaire;(2) Spectrum features not detected by other instruments are clinically relevant, because they might manifest in waves during the lifespan, sometimes together, sometimes alone, sometimes reaching the severity for a full-blown disorder, sometimes interfering withother mental disorders or complicating the course of somatic diseases; and(3) Higher scores on the MOODSSR factors assessing "psychomotor disturbances","mixed instability" and "suicidality" delineate subtypes of patients characterized by the more severe forms of mood disorders, the higher risk for psychotic symptoms,and the lower quality of life after the remission of the full-blown-episode.CONCLUSION: The mood spectrum model help researchers and clinicians in the systematic assessment of those areas of psychopathology that are still neglected by the Diagnostic and Statistical Manual of Mental Disorders 5classification.

Review of double mood stabilizer treatments for bipolar disorder in China

Background: Although treatment guidelines for bipolar disorder in many countries commonly include lithium carbonate joint with sodium valproate, this combination is not effective for all patients. Moreover, some adverse reactions related to this treatment, neurotoxicity and interaction with other drugs justify and call for a new reviewing of the issue. Methods: Evidence base for the interactions of combined drugs, the metabolic features, action mechanism, efficacy and side effects of these treatment combinations were reviewed. Considerable attention was given to the relationship of the mutual action of these drugs with their clinical efficacy but also their side effects. Results: The efficacy of combination therapy of lithium with valproate for treatment and prevention of mania were superior to monotherapy of lithium or valproate. Conclusion: Double mood stabilizer therapy is the best relative treatment for patients with bipolar disorder, especially mania and related episodes.

Contingent negative variation of mood disorder patients

Studies on brain-evoked potential and contingent negative variation （CNV） in mood disorder remain controversial. To date, no CNV difference between unipolar and bipolar depression has been reported. Brain-evoked potentials were measured in the present study to analyze CNV in three subtypes of mood disorder （mania, unipolar depression, and bipolar depression）, and these results were compared with normal controls. In the mania group, CNV amplitude B was greater than in controls, and the depression group exhibited lower CNV amplitude B and smaller A-S＇2 area, and prolonged post-imperative negative variation latency. The CNV comparison between unipolar and bipolar depression found that the prolonged post-imperative negative variation latency was only in unipolar depression. These results suggest that prolonged post-imperative negative variation latency is a characteristic of unipolar depression, and CNV amplitude change is a state characteristic of mood disorder patients.

Metabolic syndrome and childhood trauma: Also comorbidity and complication in mood disorder

Studies for prevalence and causal relationship established that addressing comorbidities of mental illnesses with medical disease will be another revolution in psychiatry. Increasing number of evidence shows that there is a bidirectional connection between mood disorders and some medical diseases. Glucocorticoid/insulin signal mechanisms and immunoenflammatory effector systems are junction points that show pathophysiology between bipolar disorder and general medical situations susceptible to stress. A subgroup of mood disorder patients are under risk of developing obesity and diabetes. Their habits and life styles, genetic predisposition and treatment options are parameters that define this subgroup. Medical disease in adults had a significant relationship to adverse life experiences in childhood. This illustrates that adverse experiences in childhood are related to adult disease by two basic etiologic mechanisms:(1) conventional risk factors that actually are compensatory behaviors, attempts at selfhelp through the use of agents and foods; and(2) the effects of chronic stress.

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.