Hypothalamus-pituitary-adrenal axis imbalance and inflammation contribute to sex differences in separation- and restraint-induced depression.

Whether social contact contributes to the underlying mechanisms of depression and the observed sex differences is unclear. In this study, we subjected young male and female mice to separation- and restraint-induced stress for 4 weeks and assessed behaviors, neurotransmitter levels, hormones, and inflammatory cytokines. Results showed that, compared with controls, male mice exposed to stress displayed significant decreases in body weight and sucrose preference after 1 week. In the fourth week, they exhibited a higher degree of anxiety (open field test) and depressive-like behavior (forced swim test). Moreover, the males showed significant decreases in monoamine neurotransmitters, including norepinephrine and dopamine in striatum, and an increase in pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1ß in serum. In contrast, females showed persistent loss of weight during stress and displayed significant decreases in sucrose preference after stress. Importantly, the females but not males showed activation of the hypothalamus-pituitary-adrenal (HPA) axis, with significantly higher levels adrenocorticotropic hormone. Additionally, mRNA level of c-fos and AVP showed there was significant interaction between stress and sex. Finally, we conclude that an imbalance of the HPA axis and inflammation might be important contributors to sex differences in separation/restraint-induced depressive behavior and that changes might be mediated by c-fos and AVP.

Phenomenological contribution to understanding of vocally disruptive behaviour: A clinical case study in a patient with dementia.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) cause great suffering in patients and their families. Phenomenology can help clarify the diagnosis and propose some new therapeutic responses using Daseinsanalyse. Separation issues understood using the phenomenological description of the melancholic type (MT) by Tellenbach may further shed light on our understanding of depression in dementia. SUBJECT AND METHODS: In a 90-year-old woman presenting with advanced (Clinical Dementia Rating 3) mixed dementia and BPSD in the form of vocally disruptive behaviour (VDB), we discuss separation anxiety as the aetiopathogenic hypothesis. Depression and BPSD were assessed using the Neuropsychiatric Inventory, Cornell scale, and Montgomery-Åsberg Depression Rating Scale to confirm our second phenomenological diagnostic hypothesis, ie, melancholy. The Big Five Inventory scale filled in by a proxy was also used to evaluate the patient's premorbid personality. We then propose an explanatory frame of VDB and depression through the standard phenomenological assessment of its relation to time, space, self, and other. RESULTS: Confirming MT, we found an inhibited temperament and low openness to experience in the patient, as well as a symbiotic relationship with a close relative (the other). CONCLUSION: Separation anxiety may well explain the patient's MT expressed by VDB. Melancholic type and her symbiotic relationship led to a situation unbearable to the patient and her close relative unable to delegate care to a specialized team. RUNNING HEAD: Phenomenology in vocally disruptive behaviour in dementia. We have found new explanations in similar clinical cases in dementia as follows. A patient presenting with vocally disruptive behaviour has a melancholic type, a behavioural-inhibited temperament, and marital violence in the past. Phenomenology may help explain this profile with neurobiological disorders. The life trajectory, from childhood into older age, must be taken into account to understand behavioural and psychological symptoms of dementia.

Persistent complex bereavement symptoms explain impairments above depression, posttraumatic stress, and separation anxiety: an incremental validity study.

The present study examined the incremental validity of persistent complex bereavement disorder (PCBD) symptoms using an on-line survey of 255 bereaved college students. A series of hierarchical multiple regression analyses examined the extent to which PCBD symptoms explained unique variance in different domains of life impairment, beyond symptoms of depression, posttraumatic stress, and separation anxiety. The results supported the incremental validity of PCBD symptoms for fear of future losses, sleep impairment, and work/social impairment. However, PCBD symptoms did not account for loneliness scores. These findings collectively support the validity and clinical utility of the DSM-5's PCBD construct.

The characteristics of the comorbidity between social anxiety and separation anxiety disorders in adult patients.

Objective: In the present study, we compared social anxiety disorder (SAD) patients with (n = 31) and without childhood and adulthood separation anxiety disorder (SeAD) (n = 50) with respect to suicidal behavior, avoidant personality disorder (AvPD), other anxiety disorders (ADs), and major depression as well as some sociodemographic variables. Methods: In assessment of patients, we used Structured Clinical Interview for Separation Anxiety Symptoms, childhood and adulthood Separation Anxiety Symptom Inventories, Liebowitz Social Anxiety Scale, The SCID-II Avoidant Personality Disorder Module, Beck Depression Inventory, and Beck Scale for Suicidal Ideation. Results: SAD patients with SeAD had higher comorbidity rates of AvPD, other lifetime ADs and panic disorder, and current major depression than those without SeAD. The current scores of SAD, depression, and suicide ideation and the mean number of AvPD symptoms were significantly higher in comorbid group compared to pure SAD subjects. The SAD and SeAD scores had significant associations with current depression, suicide ideations, and AvPD. The mean number of AvPD criteria and the current severity of depression were significantly associated with the comorbidity between SAD and SeAD. Conclusion: Our findings might indicate that the comorbidity of SeAD with SAD may increase the risk of the severity of AvPD and current depression.

Early life voiding dysfunction leads to lower urinary tract dysfunction through alteration of muscarinic and purinergic signaling in the bladder.

Lower urinary tract dysfunction (LUTD) is a common problem in children and constitutes up to 40% of pediatric urology clinic visits. Improved diagnosis and interventions have been leading to better outcomes in many patients, whereas some children are left untreated or do not respond to the treatment successfully. In addition, many of these patients are lost by the pediatric urologists during their teenage years, and the outcome in later life largely remains unidentified. Studies suggest childhood LUTD is associated with subsequent adult urinary tract symptoms. However, whether and how early life LUTD attributes to urinary symptoms in those patients later in life remains to be elucidated. In the current study, we investigated the effects of early life voiding perturbation on bladder function using a neonatal maternal separation (NMS) protocol in mice. The NMS group displayed a delayed development of voluntary voiding behavior, a significant reduction of functional bladder capacity, and bladder overactivity compared with control mice later in life. In vitro evaluation of detrusor smooth muscle and molecular study showed a decrease in muscarinic contribution alongside an increase in purinergic contribution in detrusor contractility in NMS mice compared with control group. These results suggest that early life bladder dysfunction interfered with the normal maturation of the voluntary micturition control and facilitated LUTD in a later stage, which is at least partly attributed to an alteration of muscarinic and purinergic signaling in the urinary bladder.

Paneth Cell Defects Induce Microbiota Dysbiosis in Mice and Promote Visceral Hypersensitivity.

BACKGROUND & AIMS: Separation of newborn rats from their mothers induces visceral hypersensitivity and impaired epithelial secretory cell lineages when they are adults. Little is known about the mechanisms by which maternal separation causes visceral hypersensitivity or its relationship with defects in epithelial secretory cell lineages. METHODS: We performed studies with C3H/HeN mice separated from their mothers as newborns and mice genetically engineered (Sox9flox/flox-vil-cre on C57BL/6 background) to have deficiencies in Paneth cells. Paneth cell deficiency was assessed by lysozyme staining of ileum tissues and lysozyme activity in fecal samples. When mice were 50 days old, their abdominal response to colorectal distension was assessed by electromyography. Fecal samples were collected and microbiota were analyzed using Gut Low-Density Array quantitative polymerase chain reaction. RESULTS: Mice with maternal separation developed visceral hypersensitivity and defects in Paneth cells, as reported from rats, compared with mice without maternal separation. Sox9flox/flox-vil-Cre mice also had increased visceral hypersensitivity compared with control littermate Sox9flox/flox mice. Fecal samples from mice with maternal separation and from Sox9flox/flox-vil-cre mice had evidence for intestinal dysbiosis of the microbiota, characterized by expansion of Escherichia coli. Daily gavage of conventional C3H/HeN adult mice with 109 commensal E coli induced visceral hypersensitivity. Conversely, daily oral administration of lysozyme prevented expansion of E coli during maternal separation and visceral hypersensitivity. CONCLUSIONS: Mice with defects in Paneth cells (induced by maternal separation or genetically engineered) have intestinal expansion of E coli leading to visceral hypersensitivity. These findings provide evidence that Paneth cell function and intestinal dysbiosis are involved in visceral sensitivity.

Please Don't Leave Me-Separation Anxiety and Related Traits in Borderline Personality Disorder.

PURPOSE OF REVIEW: In light of the apparent symptomatic resemblance of separation anxiety disorder (SAD) symptoms on the one hand and abandonment fears, anxiousness, and separation insecurity central to borderline personality disorder (BPD) on the other hand, a comprehensive overview of separation anxiety and related traits in BPD is provided. RECENT FINDINGS: Epidemiological, environmental, psychological, and neurobiological data connecting BPD to separation events, feelings of loneliness, insecure attachment styles, dimensional separation anxiety as well as SAD per se suggest a partly shared etiological pathway model underlying BPD and SAD. Differential diagnostic aspects and implications for treatment are discussed, highlighting separation anxiety as a promising transdiagnostic target for specific psychotherapeutic and pharmacological treatment approaches in BPD. This innovative angle on cross-disorder symptomatology might carry potential for novel preventive and therapeutic avenues in clinical practice by guiding the development of interventions specifically targeting separation anxiety and attachment-related issues in BPD.

Sex, Sexual Orientation, Gender Atypicality, and Indicators of Depression and Anxiety in Childhood and Adulthood.

The current study evaluated the possibility that greater negative mental health outcomes reported among gay, lesbian, and gender-atypical individuals, compared to gender-typical individuals, are present in childhood and persist into adulthood. Sex and sexual orientation differences in self-reported adulthood and recalled childhood indicators of depression and anxiety and their association with current and retrospectively reported gender (a)typicality were examined in a non-clinically recruited community sample of Canadian heterosexual men (n = 98), heterosexual women (n = 142), gay men (n = 289), and lesbian women (n = 69). Indicators of depression and anxiety were constructed based on diagnostic criteria for generalized anxiety disorder, major depression, agoraphobia, social anxiety disorder, panic disorder, obsessive-compulsive disorder, and specific phobias. Factor reduction analyses yielded three factors: (1) indicators of childhood separation anxiety, (2) indicators of childhood depression and anxiety, and (3) indicators of adulthood depression and anxiety. Lesbian women scored higher on childhood separation anxiety than all other groups. Heterosexual men scored lower on indicators of childhood separation anxiety than gay men and lower on indicators of childhood and adulthood depression and anxiety than all other groups. No other significant group differences were observed. Correlational analysis suggested that for men, but not for women, gender-atypical behavior was associated with negative mental health. The current study indicated that childhood should be considered a critical time period during which the noted sexual orientation-related mental health discrepancies manifest and that childhood gender atypicality is a key factor for understanding the emergence of such discrepancies.

Hard is Normal: Military Families' Transitions Within the Process of Deployment.

US military deployments have become more frequent and lengthier in duration since 2003. Over half of US military members are married, and many also have children. The authors sought to understand the process of deployment from the perspective of the military family. After a thorough search of the literature, 21 primary research reports of 19 studies with an aggregate sample of 874 were analyzed using qualitative metasynthesis. The deployment process was experienced in four temporal domains. The military family as a whole shared the pre-deployment transition: all family members felt uncertain about the future, needed to complete tasks to "get ready" for deployment, and experienced a sense of distancing in preparation for the upcoming separation. The AD member went through the deployment transition independently, needing to "stay engaged" with the military mission, building a surrogate family and simultaneously trying to maintain connection with the family at home. In parallel, the home front family was going through a transposement transition, moving forward as an altered family unit, taking on new roles and responsibilities, and trying to simultaneously connect with the deployed member and find support from other military families. In post-deployment, the family went through the "reintegration" transition together, managing expectations, and readjusting family roles, all needing understanding and appreciation for their sacrifices during the recent separation. Effective family communication was important for military family well-being after deployment but unexpectedly challenging for many. Clinical, research, and policy recommendations are discussed.

Perinatal Brain Injury is Accompanied by Disturbances in Expression of SLC Protein Superfamily in Endotheliocytes of Hippocampal Microvessels.

The peculiarities in expression of transport proteins and the proteins implicated in the control of glycolysis by the cellular components of neurovascular units were examined in animals of different age under normal conditions and after modeled perinatal stress or hypoxic brain injury. In both cases, the specialties in expression of transport proteins in ontogenesis were revealed. The perinatal hypoxic brain injury resulted in up-regulation of MCT1, MCT4, and GLUT4 expression in endotheliocytes of hippocampal microvessels accompanied by transient elevation of HIF-1α and GSK3 expression.

Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia.

Adult separation anxiety differentiates patients with complicated grief and/or major depression and is related to lifetime mood spectrum symptoms.

BACKGROUND: Increasing literature has been focused on complicated grief (CG) and its distinctiveness from other potentially loss related mental disorders such as major depression (MD). In this regard, symptoms of separation distress seem to play a key role. The aim of this study was to compare the clinical features of CG to those of MD and of CG+MD, with particular attention to separation anxiety. METHODS: Fifty patients with CG (26 with and 24 without MD) and 40 with MD were consecutively recruited. Assessments included: SCID-I/P, Inventory of Complicated Grief (ICG), Adult Separation Anxiety Symptom Questionnaire (ASA-27), Work and Social Adjustment Scale (WSAS), Mood Spectrum-Self Report (MOODS-SR)-lifetime version. RESULTS: Patients with MD reported significantly higher ASA-27 scores than patients with CG either alone or with MD. In all groups, ASA-27 total scores were significantly correlated with the MOODS-SR total scores and with those of its depressive component and rhythmicity domain. No significant differences were reported in the WSAS scores. LIMITATIONS: Major limitations are the small sample size and the use of lifetime instruments. CONCLUSIONS: Our results suggest a correlation between adult separation anxiety symptoms and lifetime mood spectrum symptoms both in patients with CG and MD. Further studies are needed to better understand the role of adult separation anxiety in the development of these disorders and for their nosographic autonomy as well.

Early life stress induces renal dysfunction in adult male rats but not female rats.

Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats.

The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

Aberrant serotonin (5-HT) signalling and exposure to early life stress have both been suggested to play a role in anxiety- and impulsivity-related behaviours. However, whether congenital 5-HT deficiency × early life stress interactions influence the development of anxiety- or impulsivity-like behaviour has not been established. Here, we examined the effects of early life maternal separation (MS) stress on anxiety-like behaviour and behavioural disinhibition, a type of impulsivity-like behaviour, in wild-type (WT) and tryptophan hydroxylase 2 (Tph2) knock-in (Tph2KI) mice, which exhibit ~60-80% reductions in the levels of brain 5-HT due to a R439H mutation in Tph2. We also investigated the effects of 5-HT deficiency and early life stress on adult hippocampal neurogenesis, plasma corticosterone levels and several signal transduction pathways in the amygdala. We demonstrate that MS slightly increases anxiety-like behaviour in WT mice and induces behavioural disinhibition in Tph2KI animals. We also demonstrate that MS leads to a slight decrease in cell proliferation within the hippocampus and potentiates corticosterone responses to acute stress, but these effects are not affected by brain 5-HT deficiency. However, we show that 5-HT deficiency leads to significant alterations in SGK-1 and GSK3ß signalling and NMDA receptor expression in the amygdala in response to MS. Together, these findings support a potential role for 5-HT-dependent signalling in the amygdala in regulating the long-term effects of early life stress on anxiety-like behaviour and behavioural disinhibition.

Adult separation anxiety during pregnancy and its relationship to depression and anxiety.

AIMS: The current study, the first of its kind, investigated the overlap between adult separation anxiety (ASA) and the symptoms of depression and anxiety in the context of pregnancy. METHODS: Women attending an antenatal clinic were screened using the Adult Separation Anxiety Scale (ASA-27). As most perinatal clinics use the Edinburgh Depression Scale (EDS), this study explored the relationship between ASA and the anxiety and depression symptoms by comparing the ASA-27 scores with the scores on the EDS. A subsample including both screen positives and screen negatives on ASA-27 was clinically interviewed using the Mini International Neuropsychiatric Interview (MINI). RESULTS: Women with ASA were significantly more likely to be screened positive for depression (EDS total score) and anxiety (EDS-3A anxiety subscale) than those without ASA. The diagnosis of ASA disorder in this population had only a moderate but significant association with the diagnoses of generalized anxiety disorder [χ2 (1) = 25.9, P = 0.000, Φ = 0.443] and major depression [χ2 (1) = 16, P = 0.000, Φ = 0.348] made using the MINI. CONCLUSION: Adult separation anxiety warrants independent assessment in order to tailor appropriate interventions for the individual subtypes of anxiety in the perinatal period.

The relationship of separation anxiety with the age of onset of panic disorder.

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.

[Separation anxiety disorder: evidence of literature and clinical implications]. / Disturbo d'ansia di separazione dell'adulto: evidenze di letteratura e implicazioni cliniche.

Since the mid-90s several studies have proven the existence of an Adult form of the Separation Anxiety Disorder (ASAD) not yet nosologically recognized by the international psychiatric classification systems (DSM and ICD). An increasing amount of evidence showed that the separation anxiety disorder may arise at any age, not always in continuation with the correspondent childhood disorder. So, a revision of the diagnostic criteria for this disorder is brought into question, as the onset is currently limited before 18 years of age. Different tools have been developed for the assessment of ASAD: 1) the Adult Separation Anxiety Structured Interview (ASA-SI), a semi-structured interview with items derived and adapted from the DSM-IV-TR childhood disorder; 2) the Adult Separation Anxiety-27 (ASA-27), a self-administered rating scale containing the same items of ASA-SI; 3) the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), a structured interview including two specific forms for childhood and adulthood. However, according to available evidence, the separation anxiety may be a dimension with cross-nosographical presentation in nearly all the commonest mood and anxiety disorders; moreover, it is connected to greater personal dysfunction and lower responsiveness to treatment. Furthermore, a deeper comprehension of the psychobiological nature of separation anxiety should lead to newer and more effective therapeutic intervention. Literature is reviewed awaiting the publication of DSM-V.

[Mamadou or anxiety resulting from a departure for the European Eldorado]. / Mamadou ou l'angoisse d'un départ vers l'Eldorado européen.

Candidates for emigration are susceptible to a psychotic breakdown accompanied by feelings of guilt arising from abandoning their community of origin. The elimination of this guilt involves, essentially, a denial of identity with a touch of megalomania which makes treatment difficult.

Separation Anxiety and Measures of Suicide Risk Among Patients With Mood and Anxiety Disorders.

BACKGROUND: Separation 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. METHODS: The 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). RESULTS: Of 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. CONCLUSIONS: This 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.

Reductions in platelet 18-kDa translocator protein density are associated with adult separation anxiety in patients with bipolar disorder.

BACKGROUND: Recent studies indicate that adult separation anxiety disorder is a discrete diagnostic entity and worthy of attention. Previously, we found a significant association between platelet expression of the 18-kDa translocator protein (TSPO) and adult separation anxiety in patients with panic disorder or major depression. The aim of this study was to explore whether adult separation anxiety might be a factor differentiating TSPO expression in a sample of patients with bipolar disorder. METHODS: The equilibrium binding parameters of the specific TSPO ligand [(3)H]PK 11195 were estimated on the platelet membranes of 24 adult outpatients with a DSM-IV diagnosis of bipolar disorder (with or without separation anxiety disorder) and 14 healthy controls. Patients were assessed by SCID-I, HAM-D, YMRS, the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS-A) and the Adult Separation Anxiety Self-Report Checklist (ASA-27). RESULTS: A significant reduction in mean platelet TSPO density was found in bipolar patients with respect to controls. However, the lower density was only evident in the subgroup of bipolar patients who also fulfilled DSM-IV criteria for adult separation anxiety disorder. Individual TSPO density values correlated significantly and negatively with both SCI-SAS-A and ASA-27 total scores. CONCLUSIONS: TSPO expression may be a useful biological marker of adult separation anxiety co-occurring with other anxiety and mood disorders, including bipolar disorder.