Anxiety Spectrum Research Articles

Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis

Direct comparisons of brain function between obsessive compulsive disorder (OCD) and other anxiety or OCD spectrum disorders are rare. This study aimed to investigate the specificity of altered frontal-striatal and limbic activations during planning in OCD, a prototypical anxiety disorder (panic disorder) and a putative OCD spectrum disorder (hypochondriasis). The Tower of London task, a 'frontal-striatal' task, was used during functional magnetic resonance imaging measurements in 50 unmedicated patients, diagnosed with OCD (n=22), panic disorder (n=14) or hypochondriasis (n=14), and in 22 healthy subjects. Blood oxygen level-dependent (BOLD) signal changes were calculated for contrasts of interest (planning versus baseline and task load effects). Moreover, correlations between BOLD responses and both task performance and state anxiety were analysed. Overall, patients showed a decreased recruitment of the precuneus, caudate nucleus, globus pallidus and thalamus, compared with healthy controls. There were no statistically significant differences in brain activation between the three patient groups. State anxiety was negatively correlated with dorsal frontal-striatal activation. Task performance was positively correlated with dorsal frontal-striatal recruitment and negatively correlated with limbic and ventral frontal-striatal recruitment. Multiple regression models showed that adequate task performance was best explained by independent contributions from dorsolateral prefrontal cortex (positive correlation) and amygdala (negative correlation), even after controlling for state anxiety. Patients with OCD, panic disorder and hypochondriasis share similar alterations in frontal-striatal brain regions during a planning task, presumably partly related to increased limbic activation.

P01-142 - Adult separation anxiety in patients with complicated grief: relationship with post traumatic stress versus mood spectrum symptomatology

IntroductionAround 9–20% of bereaved individuals experience symptoms of complicated grief (CG) associated with significant distress and impairment. Increasing research has been focused on identifying the distinctive set of psychiatric symptoms that characterize this condition with respect to major depression, corroborating the need to include this syndrome in the forthcoming DSM-V as a distinctive diagnosis. Vulnerability to CG has been rooted in attachment disturbances and authors reported that symptoms of separation anxiety in childhood should be considered as predictors of CG onset in adulthood.ObjectivesTo date no study explored symptoms of adult separation anxiety among patients with CG with respect to healthy control subjects (HC).AimsTo explore adult separation anxiety and mood spectrum symptoms in patients with CG with respect to HC.Methods53 patients with CG and 50 control subjects were recruited, Department of Psychiatry, University of Pisa. Assessments: SCID-I/P, the Inventory of Complicated Grief (ICG), the Adult Separation Anxiety Questionnaire (ASA-27), the Work and Social Adjustment Scale (WSAS), the Impact of Event Scale (IES) and the Mood Spectrum-Self Report (MOODS-SR) lifetime version.ResultsPatients with CG reported significantly higher scores on the MOODS-SR, ASA_27, IES and WSAS with respect to controls. The scores on the ASA_27 were more strongly associated with IES scores with respect to other scales.ConclusionsOur results suggest a correlation between adult separation anxiety and CG onset after the loss of a loved one in adulthood, with a possible correlation to a post-traumatic stress symptomatology. Further studies are needed.

Association Between Traumatic Injury and Psychiatric Disorders and Medication Prescription to Youths Aged 10–19

Objective: Few clinical epidemiologic investigations have assessed whether youths exposed to a traumatic injury demonstrate elevations in the full spectrum of provider-recognized psychiatric disorders compared with unexposed, noninjured youths. Methods: In a population-based prospective cohort study, data for children and adolescents aged ten to 19 who were enrolled in the Group Health Cooperative health plan were screened for injury visits in the index year of 2001 (N=20,507). Psychiatric diagnoses, including anxiety and acute stress, depressive, substance use, and disruptive behavior disorders, given to these youths over the next three years (2002–2004) were documented, as were psychotropic medication prescriptions. Regression analyses assessed for an independent association between injury and psychiatric disorders and prescription of psychotropic medication. Results: In adjusted regression analyses, injury in the index year was independently associated with significantly increased odds of receiving a diagnosis of anxiety or acute stress (odds ratio [OR]=1.21, 95% confidence interval [CI]=1.02–1.44), depression (OR=1.30, CI=1.10–1.53), and a substance use disorder (OR=1.56, CI=1.21–2.00) and of receiving a psychotropic medication prescription (OR=1.37, CI=1.20–1.57). Youths with traumatic brain injuries also were significantly more likely to receive psychotropic medication prescriptions. Conclusions: Traumatic injury was independently associated with an increased risk of receiving a full spectrum of anxiety, depressive, and substance use diagnoses among youths aged ten to 19. Population-based surveillance procedures that incorporate screening and stepped-care interventions targeting the spectrum of postinjury emotional disturbances have the potential to improve the quality of mental health care for youths treated in general medical settings. (Psychiatric Services 62:264–271, 2011)

Association Between Traumatic Injury and Psychiatric Disorders and Medication Prescription to Youths Aged 10–19

Few clinical epidemiologic investigations have assessed whether youths exposed to a traumatic injury demonstrate elevations in the full spectrum of provider-recognized psychiatric disorders compared with unexposed, noninjured youths. In a population-based prospective cohort study, data for children and adolescents aged ten to 19 who were enrolled in the Group Health Cooperative health plan were screened for injury visits in the index year of 2001 (N=20,507). Psychiatric diagnoses, including anxiety and acute stress, depressive, substance use, and disruptive behavior disorders, given to these youths over the next three years (2002-2004) were documented, as were psychotropic medication prescriptions. Regression analyses assessed for an independent association between injury and psychiatric disorders and prescription of psychotropic medication. In adjusted regression analyses, injury in the index year was independently associated with significantly increased odds of receiving a diagnosis of anxiety or acute stress (odds ratio [OR]=1.21, 95% confidence interval [CI]=1.02-1.44), depression (OR=1.30, CI=1.10-1.53), and a substance use disorder (OR=1.56, CI=1.21-2.00) and of receiving a psychotropic medication prescription (OR=1.37, CI=1.20-1.57). Youths with traumatic brain injuries also were significantly more likely to receive psychotropic medication prescriptions. Traumatic injury was independently associated with an increased risk of receiving a full spectrum of anxiety, depressive, and substance use diagnoses among youths aged ten to 19. Population-based surveillance procedures that incorporate screening and stepped-care interventions targeting the spectrum of postinjury emotional disturbances have the potential to improve the quality of mental health care for youths treated in general medical settings.

P01-562 - Cross sectional study of psychiatric comorbidities among adolescents with obsessive compulsive symptoms

BackgroundObsessive symptoms among children and adolescent age groups are increasing, an observation made by mental health professions working with this age group. Our epidemiological study is targeting secondary school students to estimate the prevalence of obsessive symptoms, obsessive compulsive disorder and to evaluate psychiatric comorbidities among students with obsessive compulsive symptoms.Materials and methodsThe study is a cross sectional carried on 1299 secondary school students, the sample size was chosen based on an estimated OCD prevalence of 2% in literature. Equal samples were recruited from the 3 educative zones in Alexandria Governorate. Obsessive compulsive symptoms were assessed by the Arabic version of Lyeton obsessive inventory child version LOI-CV. Students scoring above 35 were subjected to the Mini International Neuropsychiatric Interview for children MINI-KID Arabic version to assess psychiatric comorbidities. OCD patient students detected by MINI-KID were assessed by psychiatric interview to confirm fulfilling criteria of OCD according to DSM IV - TR criteria.ResultsThe sample was equally distributed according to gender with 51.7% and 48.3% of males and females respectively. The prevalence of obsessive compulsive symptoms was 15.5%, while that of obsessive compulsive disorder was 2.2%. Comorbidity with other psychiatric disorders was high for substance abuse 18.9%, Dysthymia 16.4%, social phobia 15.9%, Major depression 13.9%, Generalized anxiety disorder 12.9%.ConclusionThe prevalence of obsessive compulsive symptoms is high among adolescent age group, there is high Comorbidity between obsessive symptoms and psychiatric disorders particularly substance abuse, mood disorders and non OCD Anxiety spectrum disorders.

Neurogenetic Syndromes: Behavioral Issues and Their Treatmentedited by ShapiroBruce K., M.D., and AccardoPasquale J., M.D. Baltimore, Md., Brookes Publishing 2010, 328 pp., $59.95.

Neurogenetic Syndromes: Behavioral Issues and Their Treatmentedited by ShapiroBruce K., M.D., and AccardoPasquale J., M.D. Baltimore, Md., Brookes Publishing 2010, 328 pp., $59.95.

The effects of catechol-O-methyl-transferase polymorphism Val158Met on functional connectivity in healthy young females: A resting EEG study

The catechol-O-methyl-transferase (COMT) gene has been linked to a wide spectrum of human phenotypes, including cognition, affective response, pain sensitivity, anxiety and psychosis. This study examined the modulatory effects of COMT Val158Met on neural interactions, indicated by connectivity strengths. Blood samples and resting state eyes-closed EEG signals were collected in 254 healthy young females. The COMT Val158Met polymorphism was decoded into 3 groups: Val/Val, Val/Met and Met/Met. The values of mutual information of 20 frontal-related channel pairs across delta, theta, alpha and beta frequencies were analyzed based on the time–frequency mutual information method. Our one-way ANOVA analyses revealed that the significant connection–frequency pairs were relatively left lateralized ( P < 0.01) and included F7–T3 and F7–C3 at delta frequency, and F3–F4, F7–T3, F7–C3, F7–P3, F3–C3, F3–F7 and F4–F8 at theta frequency. The F-test at F7–T3 and F7–C3 theta surpassed the statistical threshold of P < 0.003 (after Bonferroni correction). For all the above connection–frequency pairs, there was a dose-dependent trend in the connectivity strengths of the alleles as follows: Val/Val > Val/Met > Met/Met. Our analyses complemented previous literature regarding neural modulation by the COMT Val158Met polymorphism. The implication to the pathogenesis in schizophrenia was also discussed. Further studies are needed to clarify whether there is gender difference on this gene–brain interaction.

S-norfluoxetine microinfused into the basolateral amygdala increases allopregnanolone levels and reduces aggression in socially isolated mice

A decrease of brain allopregnanolone biosynthesis may play a role in emotion, impulsive behavior, and anxiety spectrum disorders by decreasing GABAergic neurotransmission. In male mice, four weeks of social isolation induces behavioral dysfunctions such as aggression, fear, and anxiety-like behavior associated with a decrease in allopregnanolone biosynthesis in selected corticolimbic structures comprising the basolateral amygdala (BLA), olfactory bulb, hippocampus, and medial prefrontal cortex. Importantly, no decrease in allopregnanolone biosynthesis has been found in the striatum and cerebellum. Given the importance of the amygdaloid complex in emotional behavior, we hypothesized that this brain area may play a pivotal role in decreasing social isolation-induced aggression. Thus, socially isolated mice were directly infused with S-norfluoxetine (S-NFLX) or pregnanolone (an analog of allopregnanolone) into the BLA and striatum. When S-NFLX (2.5, 3.75, and 5 nmol/0.2 μl) or pregnanolone (1.25, 2.5, 3.75, and 5.0 nmol/0.2 μl) is directly infused into the BLA, these agents dose-dependently reduced aggression (S-NFLX up to 93% and pregnanolone up to 96%) of a socially isolated mouse to a same-sex intruder. However, S-NFLX (3.75 and 5 nmol) infused directly into the striatum failed to alter aggression. Allopregnanolone content in the BLA after S-NFLX (3.75 nmol) infusion was increased by 3-fold and in the hippocampus, by 80%. Allopregnanolone levels did not change in the olfactory bulb or in the frontal cortex of the same mice. S-NFLX (3.75 nmol) infused into the striatum failed to increase the levels of allopregnanolone. These results suggest that S-NFLX, acting as a selective brain steroidogenic stimulant (SBSS), increases corticolimbic allopregnanolone levels and regulates aggression, which underscores the pivotal role of the BLA and hippocampus in the regulation of aggressiveness in socially isolated mice. This article is part of a Special Issue entitled ‘Trends in Neuropharmacology: In Memory of Erminio Costa’.

Activity-Dependent Expression of Lmx1b Regulates Specification of Serotonergic Neurons Modulating Swimming Behavior

Genetic programs, environmental factors, and electrical activity interact to drive the maturation of the brain. Although the cascade of transcription factors that leads to specification of the serotonergic phenotype has been well characterized, its interactions with electrical activity are not known. Here we show that spontaneous calcium spike activity in the hindbrain of developing Xenopus laevis larvae modulates the specification of serotonergic neurons via regulation of expression of the Lmx1b transcription factor. Activity acts downstream of Nkx2.2 but upstream of Lmx1b, leading to regulation of the serotonergic phenotype. Using global manipulation of activity and targeted alteration of Lmx1b expression, we also demonstrate that changes in the number of serotonergic neurons change larval swimming behavior. The results link activity-dependent regulation of a transcription factor to transmitter specification and altered behavior.

Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V?

The obsessive-compulsive (OC) spectrum has been discussed in the literature for two decades. Proponents of this concept propose that certain disorders characterized by repetitive thoughts and/or behaviors are related to obsessive-compulsive disorder (OCD), and suggest that such disorders be grouped together in the same category (i.e. grouping, or "chapter") in DSM. This article addresses this topic and presents options and preliminary recommendations to be considered for DSM-V. The article builds upon and extends prior reviews of this topic that were prepared for and discussed at a DSM-V Research Planning Conference on Obsessive-Compulsive Spectrum Disorders held in 2006. Our preliminary recommendation is that an OC-spectrum grouping of disorders be included in DSM-V. Furthermore, we preliminarily recommend that consideration be given to including this group of disorders within a larger supraordinate category of "Anxiety and Obsessive-Compulsive Spectrum Disorders." These preliminary recommendations must be evaluated in light of recommendations for, and constraints upon, the overall structure of DSM-V.

Intranasal/intravenous sedation for the dental care of adults with severe disabilities: a multicentre prospective audit

This study was designed to provide an evaluation of the combined intranasal/intravenous midazolam sedation technique. It involved adults with severe disabilities which prevented them from being able to co-operate with dental treatment and intravenous cannulation for sedation. Following a previous retrospective audit, additional treatment centres were enrolled and a standardised form used to collect prospective data about the effectiveness of the technique in facilitating cannulation, dental examination and treatment. Data was also collected on safety and patient acceptability. In a total of 316 sedation episodes in primary and secondary care settings, cannulation was achieved in 96.2% (304). Dental examination and treatment was able to be carried out without major interference from the patient in 78.8% (241) episodes. Adverse sedation events occurred in 6.0% (19), the most frequent being desaturation which was easily managed. There were no incidents with serious sequelae. Favourable acceptability ratings were given by carers regarding advantages of ease of administration and speed of onset of the intranasal dose, plus reduction in the stress associated with cannulation and treatment. This study provides further evidence to support the effectiveness, safety and acceptability of this technique. The authors suggest this provides sufficient basis to justify its use by suitably trained dental practitioners in primary care as part of the spectrum of anxiety and behaviour management for this group.

General Factor of Personality Questionnaire (GFPQ): Only one Factor to Understand Personality?

This study proposes a psychometric approach to assess the General Factor of Personality (GFP) to explain the whole personality. This approach defends the existence of one basic factor that represents the overall personality. The General Factor of Personality Questionnaire (GFPQ) is presented to measure the basic, combined trait of the complete personality. The questionnaire includes 20 items and is constituted by two scales with 10 items each one: the Extraversion Scale (ES) and the Introversion Scale (IS). The GFPQ shows adequate internal consistency and construct validity, while the relationships with the personality factors of other models and with psychopathology are as expected. It correlates positively and significantly with Extraversion (E) and Psychoticism (P), and negatively with Neuroticism (N) of Eysenck's EPQ (Eysenck Personality Questionnaire); it correlates positively and significantly with the Sensation Seeking Scaled (SSS) of Zuckerman, and is inside the expected direction with Sensitivity to Reward (SR) and Sensitivity to Punishment (SP) of the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), which represent the approach and avoidance trends of behavior, respectively. It not only relates negatively with the personality disorders of the anxiety spectrum, but also with the emotional disorders in relation to anxiety and depression, and it relates positively with the antisocial personality disorder.

Social anxiety disorder: what are we losing with the current diagnostic criteria?

To assess the rate of comorbidities and the functional impairment associated with the social anxiety disorder (SAD), with an emphasis on the so-called subthreshold clinical signs and symptoms. Psychiatric comorbidities and psychosocial functioning were evaluated in 355 volunteers (college students) who had been diagnosed as SAD (n = 141), Subthreshold SAD (n = 92) or Controls (n = 122). The rate of comorbidities was 71.6% in the SAD group and 50% in subjects with Subthreshold SAD, both significantly greater than Controls (28.7%). Concerning psychosocial functioning, the SAD group had higher impairment than the other two groups in all domains evaluated, and subjects with Subthreshold SAD presented intermediate values. The rates of psychiatric comorbidities and the impairment of psychosocial functioning increase progressively along the spectrum of social anxiety. The fact that Subthreshold SAD causes considerable disability and suffering in comparison with control subjects justifies a review of the validity of the diagnostic criteria.

Association study between GABA receptor genes and anxiety spectrum disorders

Human anxiety disorders are complex diseases with relatively unknown etiology. Dysfunction of the Gamma-aminobutyric acid (GABA) system has been implicated in many neuropsychiatric conditions, including anxiety and depressive disorders. In this investigation, we explored four GABA receptor genes for their possible associations with genetic risk for anxiety disorders and depression. Our study sample consisted of 589 cases and 539 controls selected from a large population-based twin registry based upon a latent genetic risk factor shared by several anxiety disorders, major depression, and neuroticism. We subjected these to a two-stage protocol, in which all candidate genetic markers were screened for association in stage 1 (N=376), the positive results of which were tested for replication in stage 2 (N=752). We analyzed data from 26 single nucleotide polymorphisms (SNPs) from four GABA receptor genes: GABRA2, GABRA3, GABRA6, and GABRG2. Of the 26 SNPs genotyped in stage 1, we identified two markers in GABRA3 that met the threshold (P < or = .1) to be tested in stage 2. Phenotypic associations of these two markers failed to replicate in stage 2. These findings suggest that common variation in the GABRA2, GABRA3, GABRA6, and GABRG2 genes does not play a major role in liability to anxiety spectrum disorders.

Editorial: From measured behavior to etiology

Editorial: From measured behavior to etiology

Off-Label Use of Antipsychotic Medications in the Department of Veterans Affairs Health Care System

This study aimed to determine the prevalence of prescribing antipsychotics to adults without schizophrenia or bipolar disorder and to identify factors associated with such off-label use. Patients with at least one prescription for an antipsychotic medication from the Department of Veterans Affairs (VA) during fiscal year (FY) 2007 were identified in national VA administrative databases. Rates of off-label antipsychotic use were determined along with average doses. Multivariate logistic regression models identified sociodemographic and clinical characteristics associated with off-label use. Of the 279,778 individuals in FY 2007 who received an antipsychotic medication, 168,442 (60.2%) had no record of a diagnosis for which these drugs are approved. The most common mental illness diagnoses among patients given prescriptions for antipsychotics off label were posttraumatic stress disorder (PTSD, 41.8%), minor depression (39.5%), major depression (23.4%), and anxiety disorder (20.0%). Among VA patients with mental illness other than schizophrenia or bipolar disorder, the proportion who received prescriptions for antipsychotic medications ranged from a low of 9.1% among patients with adjustment reaction; to about 20% for those with depression, dementia, or PTSD; and to a high of 40.7% among patients with other psychoses. Doses were low, with over half of patients who received off-label quetiapine, risperidone, or first-generation antipsychotics receiving doses below those recommended for schizophrenia. In logistic regression models, patients diagnosed as having other psychosis or dementia had the highest odds of receiving an antipsychotic medication off label. Off-label use of antipsychotic medications was common. Given that these drugs are expensive, have potentially severe side effects, and have limited evidence supporting their effectiveness for off-label usage, they should be used with greater caution.

Anxiety and prepulse inhibition of acoustic startle in a normative sample: The importance of signal-to-noise ratio

Previous studies have used prepulse inhibition of the startle response (PPI) to investigate the anxiety spectrum, primarily in patient samples, with mixed results. The inconsistency in findings may be due, in part, to the use of non-optimal signal-to-noise ratios (SnRs: the difference between background noise intensity and prepulse intensity) in some studies. We proposed that, as SnR approaches +15 dB, anxiety spectrum variables will be negatively correlated with PPI, even in a normative sample. Thus, we used the MCMI-III to measure levels of trait anxiety, posttraumatic stress disorder (PTSD), and the three Cluster C personality disorders in a sample of 53 undergraduate females, and then correlated their scores with their PPI levels at SnRs of +5, +10, and +15 dB. All of the anxiety constructs except obsessive-compulsive personality disorder (OCPD) were correlated with PPI, but only in the +15 dB condition. Although OCPD symptomatology was not correlated with PPI, it was negatively correlated with PTSD and may have been indicative of adaptive functioning in this normative sample. The present study demonstrates that PPI is a sensitive index of anxiety symptomatology even in the normative range, and that a SnR near +15 dB may be necessary to reliably detect associations between PPI and these psychological variables.

Assessing Content Domains of Repetitive Thought in the Anxiety Spectrum: Rumination and Worry in Nonclinical and Clinically Anxious Samples

It has been hypothesized that anxious rumination may focus on ruminative content themes pertaining to gaining control and coping with future uncertainty (Nolen-Hoeksema, 2000), although it is unclear to what extent this content of repetitive thought is distinct from dimensions of depressive rumination, worry, and anxiety sensitivity. Two studies were conducted to test the role of rumination in the anxiety spectrum. Nonclinical (N = 491) and clinical participants with DSM-IV anxiety disorders (N = 282) completed a newly constructed measure of anxious rumination, as well as measures of depressive rumination, worry, anxiety sensitivity, and other symptoms. Support was found for a two-factor model of anxious rumination in both nonclinical and clinical samples. Anxious rumination factors showed convergence with depressive rumination and worry, but provided unique predictive validity in relation to anxiety, depressive, and composite symptom constellations. There was partial support for mood-state ruminative spe...

Restoring GABAergic Signaling and Neuronal Synchrony in Schizophrenia

Restoring GABAergic Signaling and Neuronal Synchrony in Schizophrenia

Prevalence and characteristics of significant social anxiety in children aged 8–13 years

Social anxiety has been frequently studied in both population- and clinical-based adult and adolescent samples. Corresponding research in children is scarce and is dominated by clinical studies. The aim of the present population-based study was to examine the prevalence of significant social anxiety (SSA) in preadolescent children and compare their characteristics with those of children without SSA. The spectrum of social anxiety is explored by comparing children with different levels of social anxiety, as defined by 1-2 versus 3-5 social situations feared. The sample consisted of 14,497 parents and their 3rd-7th grade children (8-13 years old) who participated in a health profile study, including questions covering DSM-IV criteria A-D for social anxiety disorder (SAD). Socio-demographic data, social and school functioning, somatic complaints, parent-child relationships, and use of health services were added to a logistic regression model to explore characteristics associated with children with, and without SSA. Associated emotional and behavioural problems were measured by the Strengths and Difficulties Questionnaire (SDQ) using parent and self-report. Parents described 2.3% of all children as significantly socially anxious and 0.9% feared at least three social situations. The majority of children with SSA managed their everyday life well. However, compared with children without SSA, children with SSA struggled more often in different areas of life and showed a significantly higher prevalence of associated emotional and behavioural symptoms. Our findings also support the notion of social anxiety as a spectrum concept. Social anxiety problems start in childhood and can be impairing, even in non-clinical populations and in reasonably young age groups. Increased awareness of different aspects of social anxiety is needed to identify children who are at risk and to devise appropriate interventions to improve the immediate and long-term outcome.