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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.
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Ansiedade de Separação , Transtornos Fóbicos , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Ansiedade de Separação/diagnóstico , Ansiedade de Separação/psicologia , Humanos , Inibição Psicológica , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
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. LEVEL OF EVIDENCE: Level I (evidence obtained from at least one properly designed randomized controlled trials; systematic reviews and meta-analyses; experimental studies).
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Transtornos de Deglutição , Transtornos da Alimentação e da Ingestão de Alimentos , Deglutição , Transtornos de Deglutição/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Serviços de Saúde , Humanos , Qualidade de VidaRESUMO
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.
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Células Progenitoras Endoteliais/fisiologia , Animais , Doenças Cardiovasculares/fisiopatologia , Separação Celular , HumanosRESUMO
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.
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Ansiedade de Separação/psicologia , Apego ao Objeto , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Ansiedade de Separação/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , HumanosRESUMO
OBJECTIVE/INTRODUCTION: High levels of comorbidity between separation anxiety disorder (SEPAD) and panic disorder (PD) have been found in clinical settings. In addition, there is some evidence for a relationship involving bipolar disorder (BD) and combined PD and SEPAD. We aim to investigate the prevalence and correlates of SEPAD among patients with PD and whether the presence of SEPAD is associated with frank diagnoses of mood disorders or with mood spectrum symptoms. METHODS: Adult outpatients (235) with PD were assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Panic Disorder Severity Scale (PDSS), the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), and the Mood Spectrum Self-Report Instrument (MOODS-SR, lifetime version). RESULTS: Of ther 235 subjects, 125 (53.2%) were categorized as having SEPAD and 110 (46.8%) as not. Groups did not differ regarding onset of PD, lifetime prevalence of obsessive compulsive disorder (OCD), social phobia, simple phobia, BD I and II, or major depressive disorder (MDD). SEPAD subjects were more likely to be female and younger; they showed higher rates of childhood SEPAD, higher PDSS scores, and higher MOODS-SR total and manic component scores than subjects without SEPAD. Discussion SEPAD is highly prevalent among PD subjects. Patients with both PD and SEPAD show higher lifetime mood spectrum symptoms than patients with PD alone. Specifically, SEPAD is correlated with the manic/hypomanic spectrum component. CONCLUSION: Our data confirm the high prevalence of SEPAD in clinical settings. Moreover, our findings corroborate a relationship between mood disorders and SEPAD, highlighting a relationship between lifetime mood spectrum symptoms and SEPAD.
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Ansiedade de Separação/epidemiologia , Transtorno Bipolar/epidemiologia , Transtorno de Pânico/epidemiologia , Adulto , Comorbidade , Transtorno Depressivo Maior/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtornos Fóbicos/epidemiologia , PrevalênciaRESUMO
Social anxiety disorder (SAD) is a condition characterized by pervasiveness and impairment in social functioning, with a prevalence in the general population between 1.9% and 12.1%. The most consistent findings on its neurobiological underpinnings involve a wide range of neurotransmitters (serotonin, norepinephrine, glutamate, and GABA) and neuropeptides (oxytocin), but no comprehensive hypothesis is yet available. In particular, oxytocin is becoming increasingly established as a "prosocial neuropeptide" and, as such, is a major focus of current research, with a great range of therapeutic applications including SAD treatment. Specifically, the amygdala plays a pivotal role in conditioning and processing of fear, and exaggerated amygdala responses in SAD patients have been observed during various social-emotional stimuli. In addition to the amygdala, other brain areas of interest in SAD-related circuitry are represented by the medial prefrontal cortex, dorsal raphe, striatum, locus coeruleus, prefrontal cortex, insular cortex, and anterior cingulate cortex. The aim of this review is to provide an update on neurobiological correlates of SAD, with a special focus on neurotransmitters and brain areas possibly involved, and suggestions for future research that could lead to more specific therapeutic interventions.
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Transtornos de Ansiedade/fisiopatologia , Neurotransmissores/fisiologia , Transtornos de Ansiedade/metabolismo , Encéfalo/fisiopatologia , Humanos , Rede Nervosa/fisiopatologia , Neurotransmissores/metabolismoRESUMO
OBJECTIVES: Circulating endothelial progenitor cells (EPCs) are related to endothelial function and progression of coronary artery disease. There is evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression. We investigated the relationships between the level of circulating EPCs and depression and anxiety in patients with acute coronary syndrome (ACS). METHODS: Patients with ACS admitted to three Cardiology Intensive Care Units were evaluated by the SCID-I to determine the presence of lifetime and/or current mood and anxiety disorders according to DSM-IV criteria. The EPCs were defined as CD133(+) CD34(+) KDR(+) and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed where appropriate. RESULTS: Out of 111 ACS patients, 57 were found to have a DSM-IV lifetime or current mood or anxiety disorder at the time of the inclusion in the study. The ACS group with mood or anxiety disorders showed a significant decrease in circulating EPC number compared with ACS patients without affective disorders. In addition, EPC levels correlated negatively with severity of depression and anxiety at index ACS episode. CONCLUSIONS: The current study indicates that EPCs circulate in decreased numbers in ACS patients with depression or anxiety and, therefore, contribute to explore new perspectives in the pathophysiology of the association between cardiovascular disorders and affective disorders.
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Síndrome Coronariana Aguda/sangue , Transtornos de Ansiedade/sangue , Transtorno Depressivo/sangue , Células Progenitoras Endoteliais/metabolismo , Síndrome Coronariana Aguda/psicologia , Idoso , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/fisiopatologia , Transtorno Depressivo/complicações , Transtorno Depressivo/fisiopatologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
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.
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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.
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Cirurgia Bariátrica , Transtorno da Compulsão Alimentar , Transtorno Bipolar , Obesidade Mórbida , Humanos , Transtorno da Compulsão Alimentar/complicações , Transtorno da Compulsão Alimentar/epidemiologia , Transtorno Bipolar/complicações , Transtorno Bipolar/epidemiologia , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/cirurgia , Cirurgia Bariátrica/psicologia , Comorbidade , Comportamento ImpulsivoRESUMO
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.
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Transtorno de Pânico , Adulto , Humanos , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/diagnóstico , Ansiedade de Separação/complicações , Ansiedade de Separação/epidemiologia , Ansiedade de Separação/diagnóstico , Idade de Início , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Gamma aminobutyric acid (GABA) and glutamate (Glu) are the major neurotransmitters of the human central nervous system, and their actions are determined by specific transporters. Several studies suggest that GABA- and Glu-uptake mechanisms are modified in patients with bipolar disorder (BD). We explored the functionality of the GABA and Glu transporters in three groups of patients with BD, each with a different polarity of index episode (manic, depressive, or euthymic) at the time of blood draw. METHODS: Forty patients with a diagnosis of BD, according to DSM-IV-TR criteria, and 15 healthy subjects were enrolled in the study. GABA and Glu uptake were evaluated in freshly prepared platelets using [(3) H]GABA or [(3) H]glutamate. RESULTS: Compared to controls, GABA uptake was significantly increased in patients with depressive episodes and significantly decreased in subjects with manic episodes. Glu uptake was significantly increased in patients with index manic episodes and in euthymic patients compared to healthy controls. Moreover, a positive correlation was found between GABA platelet uptake and Hamilton Depression Rating Scale scores and between Glu platelet uptake and Young Mania Rating Scale scores in patients with manic episodes. CONCLUSIONS: We found a relationship between GABA- and Glu-uptake levels and the polarity of episodes in patients with BD. Our data suggest that the functionality of both GABA and Glu transporters could represent a useful neurobiological marker to characterize the real polarity of an index episode of illness in patients with BD.
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Transtorno Bipolar/sangue , Ácido Glutâmico/sangue , Ácido gama-Aminobutírico/sangue , Adulto , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicometria , Análise de Regressão , Trítio/sangue , Adulto JovemRESUMO
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.
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Transtornos de Ansiedade/psicologia , Ansiedade de Separação/diagnóstico , Transtornos do Humor/psicologia , Suicídio/psicologia , Adulto , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/diagnóstico , Ansiedade de Separação/complicações , Ansiedade de Separação/psicologia , Feminino , Humanos , Entrevista Psicológica , Masculino , Transtornos do Humor/complicações , Transtornos do Humor/diagnóstico , Escalas de Graduação Psiquiátrica , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
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.
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Ansiedade de Separação/sangue , Ansiedade de Separação/complicações , Transtorno Bipolar/complicações , Plaquetas/metabolismo , Regulação da Expressão Gênica/fisiologia , Receptores de GABA/sangue , Adulto , Feminino , Humanos , Isoquinolinas/metabolismo , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Ligação Proteica/fisiologia , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas , Trítio/metabolismoRESUMO
This article explores accruing evidence supporting the occurrence of an adult form of separation anxiety disorder (ASAD), a category yet to be recognized by international classification systems. ASAD can have its first onset in adulthood, although in a portion of cases, it represents a persistence or recurrence of the childhood-onset type. Recent large-scale clinic studies have suggested that ASAD is associated with high levels of disability. In addition, the presence of ASAD in individuals with anxiety disorders seems to signal a poor outcome to cognitive-behavioral therapy. The existing evidence suggests possible grounds for removing the childhood-onset requirement for the category of separation anxiety disorder, thereby allowing for first onset in adulthood. There is a pressing need to design and test appropriate treatments for ASAD and to educate clinicians to identify and manage the condition.
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Ansiedade de Separação/classificação , Ansiedade de Separação/diagnóstico , Adulto , Manual Diagnóstico e Estatístico de Transtornos Mentais , HumanosRESUMO
Individuals with a diagnosis of adult separation anxiety (ASAD) have extreme anxiety about separations, actual or imagined, from major attachment figures. ASAD might represent a psychological/behavioral model for research probably involving a dysregulation of those neurobiological mechanisms of attachment, in particular central oxytocin (OT), described in numerous animal studies. As experimental strategy, we chose the nucleotidic sequencing of the human OT gene of patients with ASAD to evaluate whether OT mutations were related to potential alteration of its production. With this aim, mutation scanning of proximal promoter and untranslated and coding regions of the OT gene was carried out in 36 patients with ASAD, 14 patients without ASAD, and 26 controls. No mutations were found in promoter and coding regions of the OT gene in our population. One rare 3'UTR single nucleotide variant (rs17339677) and one intron 2 molecular variant (rs34097556), which showed a high frequency, were evidenced. There was no significant difference in the genotype distribution of this intron 2 polymorphism between patients and healthy individuals. Further research is needed to investigate the association between ASAD and OT peptide and receptor polymorphisms.
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Ansiedade de Separação/genética , Mutação/genética , Ocitócicos , Ocitocina/genética , Regiões 3' não Traduzidas , Adulto , Fatores Etários , Idade de Início , Análise Mutacional de DNA , Feminino , Frequência do Gene , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Íntrons , Masculino , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Sequências Reguladoras de Ácido NucleicoRESUMO
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.
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Delírio/diagnóstico , Delírio/tratamento farmacológico , Manual Diagnóstico e Estatístico de Transtornos Mentais , HumanosRESUMO
RATIONALE: Recent studies indicate that Adult Separation Anxiety Disorder (ASAD) may represent a discrete diagnostic entity worthy of attention. Adults with separation anxiety report extreme anxiety and fear about separations from major attachment figures (partner, children or parents). These symptoms affect individual's behavior, lead to severe impairment in social relationships and are not better accounted for by the presence of agoraphobia. In a previous study we found platelet expression reduction of the 18 kDa Translocator Protein (TSPO) (the new nomenclature for the peripheral-type benzodiazepine receptor) in patients with panic disorder who also fulfilled the diagnostic criteria for ASAD. OBJECTIVES: To explore whether separation anxiety might be a factor differentiating TSPO expression in a sample of patients with major depression. METHODS: The equilibrium binding parameters of the specific TSPO ligand [3H]PK 11195 were estimated on platelet membranes from 40 adult outpatients with DSM-IV diagnosis of MDD, with or without separation anxiety symptoms, and 20 healthy controls. Patients were assessed by SCID-I, HAM-D, 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 of platelet TSPO density mean value was found in depressed patients with associated ASAD symptoms, while no significant differences were found between depressed patients without ASAD and the control group. Individual TSPO density values were significantly and negatively correlated with both SCI-SAS-A and ASA-27 total scores, but not with HAM-D total score or HAM-D anxiety/somatization factor score. CONCLUSIONS: The reduction of platelet TSPO density in our sample of patients with depression was specifically related to the presence of ASAD. These data suggest that TSPO expression evaluation is a useful biological marker of ASAD.
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Ansiedade de Separação/metabolismo , Transtorno Depressivo Maior/metabolismo , Receptores de GABA/sangue , Receptores de GABA/genética , Adulto , Idoso , Antineoplásicos , Ansiedade de Separação/genética , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Transtorno Depressivo Maior/genética , Feminino , Humanos , Isoquinolinas , Masculino , Pessoa de Meia-Idade , Glicoproteínas da Membrana de Plaquetas/química , Glicoproteínas da Membrana de Plaquetas/metabolismo , Escalas de Graduação PsiquiátricaRESUMO
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.
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Ansiedade de Separação/genética , Interação Gene-Ambiente , Pesar , Inibição Psicológica , Transtornos do Humor/genética , Receptores de Ocitocina/genética , Temperamento/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The impact of combined variants of Oxytocin Receptor (OXTR) and G protein ß3 subunit genes was investigated in relation to retrospective reports of childhood as well as contemporary adult separation anxiety (SA), based on evidence of a ß/γ 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 Gß3 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 Gß3 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 Gß3 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.
Assuntos
Ansiedade de Separação/genética , Depressão/genética , Subunidades beta da Proteína de Ligação ao GTP/genética , Polimorfismo de Nucleotídeo Único , Receptores de Ocitocina/genética , Adulto , Ansiedade/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
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.