Childhood abuse, adult health, and health care utilization: results from a representative community sample.

The long-term consequences of childhood abuse on adult mental health have been a major focus of research. Much less attention has been directed to its effects on physical health outcomes. By use of data from the Ontario Health Survey (n = 9,953), the association between retrospective reports of childhood physical and sexual abuse and adult health and health care utilization was examined in men and women. The population health survey was conducted from November 1990 to March 1991 in the Canadian province of Ontario. An association of moderate strength was found between childhood abuse and multiple health problems, poor or fair self-rated health, pain that interferes with activities, disability due to physical health problems, and frequent emergency room and health professional visits but not frequent general practitioner visits. These effects were more pronounced in females and younger respondents. The strength of the associations reported here with odds ratios of 1.3-2.2 was lower than that found between childhood abuse and adult mental health, with odds ratios of 1.9-3.4. Given the growing evidence of the long-term effects of childhood abuse, greater efforts are clearly needed in developing more effective strategies for the prevention and treatment of child abuse.

Familial aggregation of anxiety-related quantitative traits in generalized social phobia: clues to understanding "disorder" heritability?

Social phobia, particularly the generalized form, is strongly familial. Given the probable continuity from extremes of normative personality (e.g., shyness) to social phobia to personality disorder (e.g., avoidant personality disorder), it is unlikely that social phobia itself, at the level of an Axis I disorder, is transmitted. Rather, it seems more parsimonious, and in keeping with current notions about the structure and heritability of mental disorders, that one or more temperamental risk factors for social phobia is transmitted. The goal of this study was to explore this possibility by examining relevant quantitative traits in a family study of generalized social phobia (GSP). First-degree (n = 103) relatives of patients with DSM-IV GSP and 65 first-degree relatives of not socially phobic comparison subjects (NC) completed a panel of self-report questionnaires that included measures of trait anxiety, social anxiety, and personality. Regression analysis was used to examine associations between group membership (i.e., whether that family member was a first-degree relative of a GSP proband) and these measures. First-degree relatives of GSP probands scored significantly higher than first-degree relatives of not socially phobic probands on measures of trait anxiety and social anxiety and on the Harm Avoidance subscale of the TPQ. One large factor, accounting for 84% of the variance, was strongly associated with being a first-degree relative of a GSP proband. Quantitative traits elevated in probands with generalized social phobia are also elevated in their first-degree relatives. Future family and genetic studies of social phobia should consider the possibility that one or more traits (or some aggregation thereof) may better approximate the phenotype of interest. More extensive efforts at phenotype refinement should be undertaken before such studies proceed.

Social phobia and potential childhood risk factors in a community sample.

BACKGROUND: This study examined the relationship between potential childhood risk factors and social phobia in an epidemiological sample. Identifying risk factors such as childhood adversities can often uncover important clues as to the aetiology of a disorder. This information also enables health care providers to predict which individuals are most likely to develop the disorder. METHODS: Data came from the Mental Health Supplement to the Ontario Health Survey of a survey of 8116 Canadian respondents, aged 15-64. Social phobia was diagnosed using the Composite International Diagnostic Interview (CIDI). Childhood risk factors were assessed by a series of standardized questions. RESULTS: A positive relationship was observed between social phobia and lack of close relationship with an adult, not being first born (in males only), marital conflict in the family of origin, parental history of mental disorder, moving more than three times as a child, juvenile justice and child welfare involvement, running away from home, childhood physical and sexual abuse, failing a grade, requirement of special education before age 9 and dropping out of high school. Many of these variables remained significant after controlling for phobias, major depressive disorder and alcohol abuse. The data also suggest that some childhood risk factors may interact with gender to influence the development of social phobia. CONCLUSIONS: Although an association was detected between social phobia and childhood risk factors, naturalistic prospective studies are needed to clarify the aetiological importance of these and other potential risk factors for the disorder.

Dopamine system genes not linked to social phobia.

Social phobia, particularly in its generalized form, has a genetic component in its etiology as suggested by positive twin studies and child temperament studies of social anxiety. Observations from functional imaging research suggest that dopamine function may be abnormal in the brains of patients with social phobia. Our investigation examined polymorphisms in the dopamine D2, D3 and D4 receptor genes, plus the dopamine transporter gene in a sample consisting of 17 multiplex social phobia families. We employed both parametric and non-parametric methods to test for linkage. Linkage was excluded for all loci under the broad diagnostic category. In the medium diagnostic category, the D3 receptor gene showed non-significant positive LOD scores (LOD = 0.62). We are able to clearly exclude a major effect for each of the four dopamine gene markers under the broad diagnosis of social phobia. Additional studies of dopamine system genes will be necessary to define clearly their role in social phobia.

Do selective serotonin re-uptake inhibitors enhance the efficacy of very brief cognitive behavioral therapy for panic disorder? A pilot study.

Selective serotonin re-uptake inhibitors (SSRIs) and cognitive behavioral therapies (CBTs) are both considered as first-line treatments for panic disorder, but the advantages of a combined therapy have yet to be definitively demonstrated. We evaluated in this pilot study the effects of combining SSRIs (vs. a placebo) with a very brief form of cognitive-behavioral therapy provided to all participants. Thirty-three subjects with DSM-IV panic disorder, with or without agoraphobia, were randomized to receive either paroxetine or a placebo with flexible dosing (10-50 mg/day). Medication visits were brief (15 min), infrequent (6 in total) and non-directive. An expert cognitive-behavior therapist administered one initial 45-min session and one subsequent 30-min session of very brief CBT (vbCBT) at weeks 5 and 7, respectively. Sessions were supplemented with educational and directive reading materials. Patients in both groups (i.e. vbCBT+paroxetine; vbCBT+placebo) improved similarly and substantially on most measures during the 10 weeks of acute treatment. At week 10, the proportion of panic-free patients was significantly higher in the paroxetine-treated group than in the placebo group (80 vs. 25%; P<0.007), as was the proportion of subjects who rated themselves as 'very much improved' at week 10 (60 vs. 13%; P<0.017). These findings point to the need for additional studies to confirm the effectiveness of very brief forms of CBT, and to document the circumstances in which combined treatment with an SSRI would be warranted.

Lifetime patterns of social phobia: a retrospective study of the course of social phobia in a nonclinical population.

This study describes the natural course of social phobia as recalled by a sample of nonclinical subjects and explores, using qualitative research methods, perceived risk factors and factors that may cause changes in its course. Thirty-nine respondents with a lifetime diagnosis of social phobia were interviewed using a semistructured interview schedule based on DSM-IV criteria. Four main lifetime patterns emerged: a slight worsening of social phobic symptoms over time, no change, slight improvement and complete remission. Thirty-eight percent of the sample was in remission at the time of interview. The mean age of onset was 12.8 +/- 4.1 years. The average duration of illness was 29.0 +/- 12.7 years. Factors perceived by respondents to precipitate social phobia, using contract analysis, were family and school environment, onset of adolescence, low self-esteem, temperament and poverty. Factors perceived to improve symptoms were building self-esteem, exposure, determination, maturity and counseling. Factors perceived to worsen symptoms were avoidance, exposure to negative attention and comorbid disorders.

A direct-interview family study of generalized social phobia.

OBJECTIVE: The goal of this direct-interview family study was to replicate and extend an earlier finding of a familial liability for social phobia. The authors hypothesized that there would be higher rates of the generalized type of social phobia--but not the nongeneralized (or "discrete") type--among relatives of probands with generalized social phobia. They also hypothesized that rates of avoidant personality disorder, a frequent comorbid condition, would be higher in relatives of probands with generalized social phobia. METHOD: The authors examined rates of three social phobia subtypes defined a priori--discrete, nongeneralized, and generalized--as well as rates of avoidant personality disorder by direct interview of 106 first-degree relatives of 23 patients with generalized social phobia and 74 first-degree relatives of 24 comparison subjects without social phobia. RESULTS: Relative risks for generalized social phobia and avoidant personality disorder were markedly higher (approximately 10-fold) among first-degree relatives of probands with generalized social phobia than among first-degree relatives of comparison probands. In contrast, relative risks for discrete social phobia and nongeneralized social phobia were not significantly different between the two groups of first-degree relatives. CONCLUSIONS: These results confirm earlier findings of a higher rate of social phobia among relatives of probands with generalized social phobia and extend these findings by specifically indicating that it is only the generalized type (and its probable axis II counterpart, avoidant personality disorder) that occurs more often among the families of probands with generalized social phobia. Implications for subsequent genetic studies are discussed.

Genetic linkage to the serotonin transporter protein and 5HT2A receptor genes excluded in generalized social phobia.

Social phobia, particularly the generalized form, is strongly familial and frequently comorbid with major depression, panic disorder, and obsessive-compulsive disorder. It has also recently been shown to be responsive to selective serotonin reuptake inhibitors. We conducted a study to determine if generalized social phobia is genetically linked to either of two candidate genes: the serotonin transporter protein (5HTT) gene, or the 5HT2A receptor (5HT2AR) gene. Rates of social phobia (using several phenotype definitions) were ascertained and blood samples obtained from consenting first-degree family members of generalized social phobic probands. 5HT2AR and 5HTT genotyping was performed using the polymerase chain reaction (PCR). Linkage was tested using LINKAGE and GENEHUNTER software. No evidence of linkage was found; power analysis indicated that failure to find linkage was unlikely due to inadequate statistical power. These findings reasonably exclude linkage between generalized social phobia and the 5HTT or 5HT2AR genes in these samples, although modifier effects cannot be ruled out. Other 5HT receptor subtypes or indirect modulatory effects of 5HT on other neurotransmitter systems may be involved.

Hypochondriacal concerns and somatization in panic disorder.

To clarify the relationship between panic disorder and the symptoms of hypochondriasis and somatization, we evaluated these symptoms and diagnoses in patients attending an Anxiety Disorders Clinic. Structured clinical interviews, self-report measures, and symptom diaries were used to assess 21 patients with panic disorder, 23 patients with social phobia, and 22 control subjects with no psychiatric disorders. Ten of the patients with panic disorder (48%) also met DSM-IV criteria for hypochondriasis, whereas only one of the patients with social phobia and none of the healthy control subjects met the criteria for this diagnosis. None of the participants met DSM-IV criteria for somatization disorder, even though both anxiety groups reported high levels of somatic symptoms. The panic disorder group reported higher levels of fear about illness and disease conviction and endorsed more somatic symptoms than did the other groups. A higher proportion of panic disorder patients reported previously diagnosed medical conditions (48%) as compared with patients with social phobia (17%) or healthy control subjects (14%). The panic disorder patients with DSM-IV hypochondriasis obtained higher scores on measures of hypochondriacal concerns, somatization, blood-injury phobia, and general anxiety and distress than did the panic disorder patients without hypochondriasis. The results suggest a strong association between panic disorder and hypochondriasis.

Paroxetine in the treatment of generalized social phobia: open-label treatment and double-blind placebo-controlled discontinuation.

We conducted an 11-week forced-escalation open-label study of paroxetine in the treatment of 36 patients with generalized social phobia. At the mean dosage of 47.9 +/- 6.2 mg/day, 23 of 30 completers (77%) were deemed responders on the basis of a clinician rating of either "very much improved" or "much improved" on the Clinical Global Impressions scale. Duke Social Phobia Scale ratings declined from 35.5 +/- 13.1 at baseline to 19.7 +/- 17.4 at week 11 (p < 0.0005), and Liebowitz Social Anxiety Scale ratings declined from 75.1 +/- 25.4 at baseline to 37.2 +/- 32.5 at week 11 (p < 0.0005). Sixteen responders were randomized to an additional 12 weeks of either paroxetine (with no dosage change) or placebo (after a taper period) on a double-blind basis. To the best of our knowledge, this is the first controlled medication-discontinuation study in social phobia. One of eight patients randomized to continue paroxetine relapsed versus five of eight patients randomized to placebo. These findings call for a double-blind, placebo-controlled treatment study of paroxetine in generalized social phobia. They also suggest that relapse rates are high if medication is discontinued early and that further study is needed to determine (1) the optimal duration of maintenance pharmacotherapy for social phobia and (2) if specific psychotherapeutic interventions before medication discontinuation may prevent relapse.

Plasma neuropeptide Y in anxiety disorders: findings in panic disorder and social phobia.

The demonstration in preclinical studies that centrally administered neuropeptide Y (NPY) has anxiolytic effects had led to speculation that NPY may play a role in human anxiety disorders. We therefore decided to study plasma NPY levels in 22 patients with DSM-III-R anxiety disorders (11 with panic disorder and 11 with social phobia, generalized type) and 12 never psychiatrically ill comparison subjects. Under resting conditions, plasma NPY levels did not differ among the three diagnostic groups. Following hand immersion in ice water, plasma NE levels--but not NPY levels--increased immediately, but there were no significant differential diagnostic effects. These results are convergent with prior reports of normal sympathetic nerve activity in patients with anxiety disorders.

[3H]paroxetine binding to platelets of patients with social phobia: comparison to patients with panic disorder and healthy volunteers.

Recent studies suggest that serotonergic functioning may be aberrant in patients with social phobia. Capacity of the serotonin (5-HT) transporter, as determined by 3H-paroxetine binding, was measured in 18 drug-free patients with generalized social phobia and compared to 15 drug-free patients with panic disorder and 23 healthy control subjects. The density (Bmax) and affinity (1/Kd) of 3H-paroxetine binding sites was similar in all three groups. To the extent that the serotonin transporter in platelets and neurons is comparable, these findings suggest that this aspect of serotonergic function is normal in patients with social phobia.

Nucleotide sequence of the gene for the immunity protein to colicin A. Analysis of codon usage of immunity proteins as compared to colicins.

The nucleotide sequence of the structural gene for the immunity protein to colicin A (cai) has been established. This sequence consists of 534 base pairs. According to the predicted amino acid sequence, the polypeptide chain of this immunity protein comprises 178 amino acids and has a relative molecular mass of 20462. As expected from its localization in the inner membrane, large hydrophobic fragments are found along the polypeptide chain that also contains clusters of mostly positively charged residues. The cai like the ceiA genes encode proteins that are weakly expressed as compared to the corresponding colicins (A and E1). Codon usage reflects this difference. In contrast, the four genes for immunity to cloacin DF13 and to colicin E3 and for these bacteriocins, all of which are highly expressed and are organized in operon, display similar codon usage. These results are discussed with regards to the possible relationship between expressivity and codon usage.