BACKGROUND:The present study aimed to examine clinical differences between subjects with early-onset (<21 years) and adult-onset (>30 years) bipolar I disorder, in particular, in relation to anxiety comorbidity. METHOD:Subjects were selected from a cohort of 161 consecutive patients with bipolar disorder type I as diagnosed by the Structured Clinical Interview for DSM Disorder (SCID-I). Clinical characteristics and axis I comorbidity were compared between those whose illness first emerged before the age of 21 years (n=58) and those whose first episode occurred after the age of 30 years (n=27). Psychopathology was assessed using the 18-item version of the Brief Psychiatric Rating Scale (BPRS). The frequency of delusions, hallucinations, and formal thought disorders was evaluated with the SCID-I. Overall, social and occupational functioning was assessed by the Global Assessment of Functioning (GAF). RESULTS:Most subjects with early-onset bipolar disorder were males, had panic disorder and substance abuse comorbidity, longer duration of illness, exhibited mood-incongruent delusions, and presented with a mixed episode at onset more frequently than the later adult-onset subjects. Mixed mania at the first episode of illness and lifetime panic disorder comorbidity predicted mixed polarity at the first hospitalization episode in the early-onset subjects. CONCLUSIONS:Overall, early age at onset seems to delineate a distinct bipolar I disorder subtype characterized by a greater likelihood of mixed episodes, lifetime panic disorder comorbidity, and schizophrenia-like delusions.

AIM:This study aimed to investigate whether separation anxiety (SA) constitutes a dimension related to age at onset of panic disorder (PD), in homogeneous subgroups of outpatients with PD, based on their age of onset and symptom severity. METHODS:A sample of 232 outpatients with PD was assessed with the Panic Disorder Severity Scale (PDSS) and the Sheehan Disability Scale (SDS) for functional impairments. Separation anxiety was evaluated using structured interviews and questionnaires. We applied a K-Means Cluster Analysis based on the standardized "PD age of onset" and "the PDSS total score" to identify distinct but homogeneous groups. RESULTS:We identified three groups of patients: group 1 ("PD early onset/severe", N = 97, 42%, onset 23.2 ± 6.7 years), group 2 ("PD early onset/not severe", N = 76, 33%, onset 23.4 ± 6.0 years) and group 3 ("PD adult onset/not severe", N = 59, 25%, onset 42.8 ± 7.0 years). Patients with early onset/severe PD had significantly higher scores on all SA measures than PD late-onset/not severe. Regression analyses showed that SA scores, but not PDSS scores, were predictive of impairment in SDS work/school, social life, and family functioning domains. CONCLUSIONS:Our data indicate a significant relationship between SA and PD with an earlier age of onset and an impact on individual functioning. This may have important implications for implementing preventive interventions targeting early risk factors for the subsequent onset of PD.

AIMS:Candidates for bariatric surgery are routinely screened for psychiatric disorders because abnormal eating behaviors are considered common among these patients. This study aimed to evaluate the frequency and persistence, in terms of one month-to-lifetime prevalence ratio, of binge eating disorder (BED) and the potential association with impulsivity features and bipolar spectrum comorbidity in a sample of obese patients undergoing a psychiatric evaluation for bariatric intervention. METHODS:Overall, 80 candidates to bariatric surgery were assessed consecutively over 12 months within the framework of a collaboration between the University of Pisa Psychiatry and Internal Medicine Departments. Patients were evaluated through structured clinical interviews and self-report questionnaires. RESULTS:The lifetime and last-month frequencies of BED according to DSM-5 criteria were 46.3% and 17.5%, respectively, with a prevalence ratio of 37.8%. Rates of formal bipolar disorder diagnoses were extremely low in patients with or without BED. However, patients with BED showed more severe dyscontrol, attentional impulsivity and bipolar spectrum features than patients with no BED. CONCLUSIONS:The relationship of BED, impulsivity, and mood disorders in bariatric patients is more complex than usually reported in the literature. In particular, the presence of bipolar spectrum features should be systematically investigated in these patients because of their essential clinical and therapeutical implications.

Behavioral Inhibition (BI) is an early temperamental trait characterized by shyness, withdrawal, avoidance, uneasiness, and fear of unfamiliar situations, people, objects, and events. The DSM-5 refers to behavioral inhibition as a temperamental factor related to neurodevelopmental conditions in childhood, including attention deficit hyperactivity disorder, selective mutism and specific phobias; and to its influence in adult anxiety disorders including social anxiety disorder, agoraphobia, and generalized anxiety disorder, but, interestingly, not separation anxiety disorder (SAD). However, there are phenomenological overlaps between BI and SAD. We aimed to explore whether there is a correlation between BI as an early temperamental trait and childhood or adult separation anxiety disorder.The study was conducted in 377 consecutive adult (mean age 40.2±12.4 years) outpatients with anxiety and mood disorders as principal diagnosis, grouped on the presence/absence of a DSM-5 diagnosis of childhood or adult separation anxiety disorder. Separation anxiety was assessed by the Structured Clinical Interview for Separation Anxiety (SCI-SAS) and the Adult Separation Anxiety Checklist (ASA-27). Behavioral inhibition was assessed by the Retrospective Self-Report of Inhibition (RSRI).The four comparison groups included: 1) 168 patients without childhood or adult SAD, 2) 81 with adult SAD, 3) 97 with both adult SAD and childhood SAD, and 4) 31 with childhood SAD only. The group with both adult and childhood SAD had the highest scores on RSRI total and sub-scale scores. Both groups with adult SAD had significantly higher RSRI scores than the group with only childhood SAD or without SAD. Significant bivariate correlations were found between ASA-27 scores and RSRI scores. Correlations between RSRI scores and measures of anxiety and depressive symptoms were significantly weaker than those on the ASA-27. Regression analyses showed a significant predictive value of RSRI scores on ASA-27 total score, but not of age of onset of SAD.BI has an onset in the very first years of life and may represent a potential developmental endophenotype for later anxiety disorders. Our findings indicate that BI and SAD are connected, especially in individuals with adult SAD. This may have important clinical and therapeutic implications for preventive interventions.

Background The effect of psychopathology on swallowing ability tends to be an overlooked issue in the assessment of dysphagic patients, possibly overshadowed by the given prominence to organic pathologies and the difficulties on the management of these patients. In addition, it should also be kept in mind that a great number of psychotropic drugs can affect swallowing adding problematic clinical issues in this area. Despite this, assessment of dysphagia should be considered as an extremely important issue, due to its impact on basic symptomatology, course of illness and quality of life. Objective This review aims to be an overview of relevant data on psychopathology associated with dysphagia and impairment of swallowing function. Materials and methods An extensive bibliographic search was carried out in different medical databases (PubMed and Psycharticles) to comprehensively identify the most relevant publications available on dysphagia in eating disorders published until December 2020, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) method. Research articles, either theoretical or empirical-based, published in peer-reviewed journals and in English language, were included. Case reports were also considered in the analysis when it was appropriate for completeness purposes. Titles and abstracts were reviewed according to the eligibility criteria. Results In total, 260 published studies were identified and 40 were finally selected after removal of duplicates and relevance. Primarily we investigated the correlation between dysphagia and eating disorders, analysing the complex relationship between the two conditions. Then we provided an overview of the assessment of dysphagic symptoms in other psychiatric syndromes. Limits No exclusion criteria or statistical methods were applied nor was an assessment of study-level or outcome-level bias applicable for our purpose. The topic is vast and research bias could not be excluded; moreover, data available are heterogeneous and lacking systematic approach. Conclusions With this review, the authors want to provide an overview of the most considerable and clinically useful information about the topic, focusing on some key points to disentangle psychiatric components from the complexity of patient with dysphagia. It should be a relevant concern for all clinicians and should be always thoroughly assessed, considered its frequency in clinical practice and its implications in every kind of patients' morbidity, mortality and quality of life. Special attention should be paid to mentally ill patients, who might display complex and multiple comorbidities, as well as consequences of abnormal eating behaviours, occasionally exacerbated by psychotropic medications. More systematic studies are needed, while it seems clear that a multidisciplinary approach is pivotal in the assessment and management of dysphagic patients.

Objectives: The aim of this study was to identify, by using K-Means Cluster Analysis, homogeneous sub-groups of individuals with panic disorder (PD) based on their age of onset and symptom severity to investigate whether separation anxiety constitutes a dimension related to age at onset of PD, hypothesizing a connection with an earlier and more severe form of PD. Methods: A sample of 232 outpatients with a SCID-I diagnosis of primary PD was included in the analyses. Each patient was assessed with the Panic Disorder Severity Scale (PDSS) and the Sheehan Disability Scale (SDS) for functional impairments. Separation anxiety was evaluated using the Childhood and Adult sections of the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), the Separation Anxiety Symptom Inventory (SASI), the Adult Separation Anxiety Questionnaire (ASA-27), and a subscale of the Panic-Agoraphobic Spectrum Scale (PAS-SR). We applied a K-Means Cluster Analysis based on the standardized 'PD age of onset' and 'the PDSS total score' to identify distinct but homogeneous groups. To that end, groups were compared with ANOVA and Chi-square test where appropriate, according to the type of variables. Linear regressions were used to study the association of separation anxiety to functional disability. Results: We defined three groups of patients determined by the second K-means Cluster Analysis: group 1 ('PD early onset/severe' , N=97, 42%), group 2 ('PD early onset/not severe', N=76, 33%) and group 3 ('PD adult onset/not severe', N=59, 25%). The mean PD age of onset was 23.2 ± 6.7 years in Group 1, 23.4 ± 6.0 years in Group 2 and 42.8 ± 7.0 years in Group 3.Subjects with PD early onset/severe had significantly higher scores on all measures of separation anxiety compared to PD late-onset/not severe. Regression analyses showed that separation anxiety scores, but not PDSS scores were predictive of impairment in SDS work/school, social life, and family functioning domains.Conclusions: Our data indicate a significant relationship between separation anxiety and PD with an earlier age of onset and more severe symptomatology, with an impact on individual functioning. This may have important implications for implementing preventive interventions that can target early risk factors for the subsequent onset of PD.

BACKGROUND:Behavioral Inhibition (BI) is an early temperamental trait characterized by shyness, withdrawal, avoidance, uneasiness, and fear of unfamiliar situations, people, objects, and events. The DSM-5 refers to behavioral inhibition as a temperamental factor related to neurodevelopmental conditions in childhood, including attention deficit hyperactivity disorder, selective mutism, and specific phobias; and to its influence on adult anxiety disorders including social anxiety disorder, agoraphobia, and generalized anxiety disorder, but, interestingly, not separation anxiety disorder (SAD). However, there are phenomenological overlaps between BI and SAD. We aimed to explore whether there is a correlation between BI as an early temperamental trait and childhood or adult separation anxiety disorder.METHODS:The study was conducted in 377 consecutive adults (mean age 40.2±12.4 years) outpatients with anxiety and mood disorders as the principal diagnosis, grouped on the presence/absence of a DSM-5 diagnosis of childhood or adult separation anxiety disorder. Separation anxiety was assessed by the Structured Clinical Interview for Separation Anxiety (SCI-SAS) and the Adult Separation Anxiety Checklist (ASA27). Behavioral inhibition was assessed by the Retrospective Self-Report of Inhibition (RSRI).RESULTS:The four comparison groups included: 1) 168 patients without childhood or adult SAD, 2) 81 with adult SAD, 3) 97 with both adult SAD and childhood SAD, and 4) 31 with childhood SAD only. The group with both adult and childhood SAD had the highest scores on RSRI total and sub-scale scores. Both groups with adult SAD had significantly higher RSRI scores than the group with only childhood SAD or without SAD. Significant bivariate correlations were found between ASA-27 scores and RSRI scores. Correlations between RSRI scores and measures of anxiety and depressive symptoms were significantly weaker than those on the ASA-27. Regression analyses showed a significant predictive value of RSRI scores on ASA-27 total score, but not of age of onset of SAD.CONCLUSIONS:BI has an onset in the very first years of life and may represent a potential developmental endophenotype for later anxiety disorders. Our findings indicate that BI and separation anxiety are connected in individuals with affective and anxiety disorders. This may have important clinical and therapeutic implications for preventive interventions.

This study aims to evaluate clinical correlates of psychiatric comorbidity and length of hospitalization in patients admitted in a general hospital emergency medicine setting. Overall, 160 patients hospitalized for different acute medical pathologies were selected consecutively over 12 months. All subjects were evaluated with proper forms to collect data on medical and psychiatric diagnoses. Levels of C-reactive protein were also measured in all patients. Statistical analyses were conducted with univariate, logistic, and multiple linear regressions. Patients with psychiatric comorbidity had significantly longer hospitalization than did patients with no psychiatric diagnoses (days 10.9±9.5 vs. 6.9±4.5, p<0.005). Agitation and delirium were more frequent in the psychiatry comorbidity study group (p<0.05), as was cognitive impairment (p=0.001). These variables predicted longer hospitalisation (respectively: t=-3.27, p=0.002; t=-2.64, p=0.009; t=-2.85, p=0.006). Psychiatric comorbidity acts as an adjunct factor in determining clinical severity and predicting a more difficult recovery in patients hospitalized in an emergency medicine setting.

BACKGROUNDSeparation anxiety disorder may be important when considering risk of suicide. The aim of this study was to examine the association between both childhood and adult separation anxiety (disorder) and measures of suicide risk in a large cohort of outpatients with anxiety and mood disorders.METHODSThe sample included 509 consecutive adult psychiatric outpatients with DSM-IV mood disorders or anxiety disorders as a principal diagnosis recruited at the Department of Psychiatry, University of Pisa, Italy, between 2015 and 2018. Suicide risk was evaluated by the Hamilton Depression Rating Scale (HDRS) item 3. Patients were classified in 2 groups: those with a score ≥ 1 and those with a score of 0 on HDRS item 3. Suicide risk was also evaluated by specific items within the Mood Spectrum, Self-Report (MOODS-SR), a questionnaire evaluating lifetime suicidal symptoms. Separation anxiety (disorder) was assessed based on the Structured Interview for Separation Anxiety Symptoms in Adulthood/Childhood (SCI-SAS-A/C), the Separation Anxiety Symptom Inventory (SASI), and the Adult Separation Anxiety Scale (ASA-27).RESULTSOf the 509 patients, 97 had an HDRS item 3 score ≥ 1, and 412 had a score of 0. Adult separation anxiety disorder was more frequent among individuals who had suicidal thoughts (53.6%) than those who did not (39.6%) (P = .01). Dimensional separation anxiety symptoms on all scales were elevated in patients with suicidality when compared to patients without (SASI: P = .02; SCI-SAS-C: P < .001; SCI-SAS-A: P < .001; ASA-27: P = .002). Logistic regression found that adult separation anxiety disorder (odds ratio [OR] = 1.86, 95% CI = 1.16-2.97), major depression (OR = 7.13, 95% CI = 3.18-15.97), bipolar I disorder (8.15, 95% CI = 3.34-19.90), and bipolar II disorder (OR = 8.16, 95% CI = 3.50-19.05) predicted suicidal thoughts. Linear regression found that depression (P = .001) and ASA-27 separation anxiety (P = .001) significantly predicted lifetime suicide risk. Mediation analysis found that separation anxiety significantly mediated the association between depression and suicide risk.CONCLUSIONSThis study indicates a substantial role of separation anxiety in predicting suicidal thoughts, both as state-related symptoms (evaluated by HDRS item 3) and as longitudinal dimensional symptoms (as evaluated by MOODS-SR). Greater understanding of the influence of separation anxiety in patients with affective disorders may encourage personalized interventions for reducing suicide risk.

The mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow is well known to be present in several clinical settings, including acute coronary syndrome, heart failure, diabetes and peripheral vascular disease. The aim of this review was to explore the current literature focusing on the great opportunity that EPCs can have in terms of regenerative medicine.

Lo scopo di questa rassegna critica sul delirium è discutere alcune modifiche nell’inquadramento del disturbo che si sono verificate con il passaggio dal DSM-IV al DSM-5 e le relative prospettive di trattamento. Il delirium consiste in una disfunzione del metabolismo cerebrale transitoria, essenzialmente reversibile, che ha un esordio acuto o subacuto e si manifesta clinicamente mediante una vasta gamma di anormalità neuropsichiatriche. Il delirium rappresenta un predittore di declino cognitivo ed è associato con un maggior rischio di morte. Il trattamento di prima linea del delirium è l’aloperidolo anche se vi sono sempre maggiori evidenze cliniche relative all’efficacia e alla tollerabilità degli antipsicotici atipici.

The 1990–1991 Gulf War employed more women servicemembers than any prior conflict. Gender-based differences among veterans of this era have yet to be explored. This study is among the first and most recent to stratify Gulf War veteran demographics, lifestyle factors, and self-reported diagnoses by gender.Data from the cross-sectional Gulf War Era Cohort and Biorepository pilot study (n = 1,318; collected between 2014 and 2016), including users and nonusers of the Veterans Health Administration, were used to calculate demographics and adjusted odds ratios.Women veterans were oversampled and comprised approximately 23% of the sample. Women reported similar rates of Veterans Health Administration use (44%) and deployment (67%) as men (46% and 72%, respectively). Women were less likely than men to report frequent alcohol use (adjusted odds ratio [aOR], 0.59; 95% confidence interval [CI], 0.43–0.81; p = .0009) or have a history of smoking (aOR, 0.65; 95% CI, 0.49–0.84; p = .0014). Among common health conditions, women were more likely than men to report a diagnosis of osteoporosis (aOR, 4.24; 95% CI, 2.39–7.51; p < .0001), bipolar disorder (aOR, 2.15; 95% CI, 1.15–4.04; p = .0167), depression (aOR, 2.39; 95% CI, 1.81–3.16; p < .0001), irritable bowel syndrome (aOR, 2.10; 95% CI, 1.43–3.09; p = .0002), migraines (aOR, 2.96; 95% CI, 2.18–4.01; p < .0001), asthma (aOR, 1.86; 95% CI, 1.29–2.67; p = .0008), and thyroid problems (aOR, 4.60; 95% CI, 3.14–6.73; p < .0001). Women were less likely than men to report hypertension (aOR, 0.55; 95% CI, 0.41–0.72; p < .0001), tinnitus (aOR, 0.46; 95% CI, 0.33–0.63; p < .0001), and diabetes (aOR, 0.44; 95% CI, 0.28–0.69; p = .0003).Health differences exist between female and male veterans from the 1990–1991 Gulf War. Gender-specific analyses are needed to better understand the unique health care needs of Gulf War Era veterans and direct future research.

The aim of this commentary is to discuss some clinical characteristics and treatment perspectives of delirium in the light of transition from the DSM-IV to the DSM-5. Such a transient dysfunction of cerebral metabolism, essentially reversible, presents an acute or subacute onset, and manifests itself clinically through a wide range of neuropsychiatric abnormalities. Delirium is a predictor of cognitive decline and is associated with a greater mortality. First line treatment of delirium is represented by haloperidol though atypical antipsychotics effectiveness and tolerability are increasingly evident.

Complicated grief (CG) refers to the severe and prolonged (≥ 6 months) grief reaction following the loss of a beloved person that occurs in approximately 10 – 20% of bereaved individuals and is associated with an increased risk for the development of depression and anxiety disorders [1]. So far, the underlying processes contributing to the vulnerability to CG are not yet well understood but likely comprise the complex interplay of genetic, temperamental and psychological factors that interactively influence the severity and persistence of grief reactions. In light of its central role in social behavior, stress regulation and attachment, the oxytocin receptor (OXTR) gene may play a key role in the conferral of CG. Additionally, temperamental traits such as behavioral inhibition (BI) or psychological characteristics such as symptoms of separation anxiety (SA) may predispose to the development of CG. For instance, adult SA has been linked to higher symptom severity and impairment in individuals with CG [2]. Therefore, the present study for the first time aimed to address the involvement of OXTR gene variation in the emergence of CG and the potential moderating effects of BI and SA. To this end, 96 adult outpatients (70 female, 26 male; mean age ± SD = 39.96 ± 12.71 years) with DSM-IV mood and anxiety disorders were assessed for CG using the Inventory of Complicated Grief (ICG). All patients were genotyped for OXTR rs2254298 and characterized for BI using the Retrospective Self-Report of Inhibition (RSRI) and SA symptoms using the Adult Separation Anxiety Scale (ASA-27). Patients were grouped according to genotype (GG vs. AG/AA carriers). The influence of grouped OXTR genotype, RSRI and ASA-27 scores, respectively, on ICG score was investigated via hierarchical multiple regression analyses. No differences were observed with regard to age, sex, or questionnaire scores (all p ≥ 0.05). No main effects of OXTR genotype, RSRI or ASA-27 scores on CG were observed, however ICG scores differed as a function of OXTR genotype and RSRI score (OXTR x BI, p=0.031), and, on a trend-level, ASA-27 score (OXTR x ASA, p=0.064). Specifically, in patients homozygous for the OXTR G allele, increased levels of both BI and ASA were related to higher ICG scores. Of note, this pattern appears to be reversed under conditions of low BI or low ASA. In line with the ‘differential susceptibility hypothesis’ [3], the present findings suggest that while OXTR GG genotype carriers are more vulnerable to the development of CG in the presence of risk-increasing factors, they at the same time are the least likely to develop CG in the absence of these risk factors. Taken together, the present results for the first time provide evidence for an interaction of OXTR gene variation with BI and potentially also symptoms of adult SA in the moderation of clinically relevant grief reactions and may therefore inspire new insights into the development and improvement of therapeutic options in the prevention and treatment of CG.

Objectives: Complicated grief (CG) following bereavement significantly increases the risk for mood and anxiety disorders. The severity of grief reactions may be interactively influenced by temperamental and psychological factors such as behavioural inhibition (BI) and separation anxiety (SA) as well as biological factors. Given its central role in attachment and stress processing, a genetic variant in the oxytocin receptor (OXTR) gene was thus investigated in order to elucidate the direction of association as well as its interaction with BI and SA in the moderation of CG severity.Methods: Ninety-three patients with mood and anxiety disorders were evaluated for CG by means of the Inventory of Complicated Grief (ICG), for BI using the Retrospective Self-Report of Inhibition (RSRI), and for symptoms of SA during adulthood using the Adult Separation Anxiety Scale (ASA-27). All patients were genotyped for OXTR rs2254298.Results:OXTR genotype interacted with BI and, on a trend-level, with adult SA, to increase CG. Specifically, higher levels on the RSRI and ASA-27 scales, respectively, were related to higher ICG scores in GG genotype carriers.Conclusions: The present study for the first time suggests a gene-environment interaction effect of an OXTR gene variant with BI and possibly also symptoms of adult SA in the moderation of vulnerability for CG.

Background: The impact of combined variants of Oxytocin Receptor (OXTR) and G protein beta 3 subunit genes was investigated in relation to retrospective reports of childhood as well as contemporary adult separation anxiety (SA), based on evidence of a beta/gamma dimer-mediated signaling for OXTR.Methods: A case-control association study (225 healthy adults and 188 outpatients with depression) was performed to establish Risk-Combined Genotype (RCG) of the studied variants (OXTR rs53576 and the functional G(33 subunit rs5443). Current SA was evaluated by the ASA-27 and retrospective childhood symptoms by the SASI. GG genotype of OXTR rs53576 combined with T-carrier genotype of GP3 rs5443 represented the RCG.Results: Compared to non-RCG, those with RCG had significantly higher levels of childhood and adult SA. The RCG was significantly associated with childhood SA threshold score (OR=2.85, 90%CI: 1.08-7.50). Childhood SA was, in turn, strongly associated with a threshold SA score in adulthood (OR=15.58; 95% CI: 4.62-52.59).Limitations: Although the overall sample size is sizable, comparisons among subgroups with specific combination of alleles are based on relatively small numbers.Conclusions:: Our study indicates that variations in OXTR and GP3 genes are specifically associated with presence and severity of SA in childhood and adulthood, but not with depression or anxiety in general. Because there is increasing interest in oxytocin in social behavior, the gene-SA associations identified have potential translational and clinical relevance.

Objective: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD).Methods: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network.Results: The present article (Part II) summarises findings on potential biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine, dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF and BDNF, immunology and CO2 hypersensitivity), neurophysiology (EEG, heart rate variability) and neurocognition. The accompanying paper (Part I) focuses on neuroimaging and genetics.Conclusions: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high quality research has accumulated that should improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorization of mental disorders places “separation anxiety disorder” within the broad group of anxiety disorders, and its diagnosis no longer rests on establishing an onset during childhood or adolescence. In previous editions of DSM, it was included within the disorders usually first diagnosed in infancy, childhood, or adolescence, with the requirement for an onset of symptoms before the age of 18 years: symptomatic adults could only receive a retrospective diagnosis, based on establishing this early onset. The new position of separation anxiety disorder is based upon the findings of epidemiological studies that revealed the unexpectedly high prevalence of the condition in adults, often in individuals with an onset of symptoms after the teenage years; its prominent place within the DSM-5 group of anxiety disorders should encourage further research into its epidemiology, etiology, and treatment. This review examines the clinical features and boundaries of the condition, and offers guidance on how it can be distinguished from other anxiety disorders and other mental disorders in which “separation anxiety” may be apparent.