Effects of psychological interventions on systemic levels of inflammatory biomarkers in humans: A systematic review and meta-analysis.

The purpose of the present investigation was to systematically review randomized controlled trials examining the effects of psychological interventions on inflammatory biomarkers in adult populations and to quantitatively analyze those effects by meta-analysis. Two researchers independently searched key electronic databases, selected eligible publications, extracted data, and evaluated methodological quality. Nineteen randomized controlled trials examining a total of 1510 participants were included. The overall combined effect size from pre to post psychological intervention on pro-inflammatory biomarker levels was statistically significant, showing an attenuating effect, although of a small magnitude (s' g = 0.15, p = .008, CI [0.04-0.26]). However, this effect was not maintained into the follow-up period (g < -0.01, p = .964, CI [-0.19-0.18]). Looking at the individual biomarkers assessed across studies, only C-reactive protein (CRP) was found to significantly decrease following psychological intervention. A number of moderation analyses were conducted, none of which reached statistical significance. However, the numerically largest - and significant - within-group effect size was obtained for the group of studies that had preselected participants based on elevated psychological distress (g = 0.29, p = .047). In conclusion, psychological interventions appear efficacious in reducing pro-inflammatory biomarker levels. Future studies are recommended to carefully select individuals based on inflammatory (e.g., the presence of low-grade inflammation) and/or psychological (e.g., psychological distress) criteria.

When worry may be good for you: Worry severity and limbic-prefrontal functional connectivity in late-life generalized anxiety disorder.

BACKGROUND: Late-life generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older adults. However, its neural markers have received relatively little attention. In this study, we explored the association between worry severity and limbic-prefrontal connectivity during emotional reactivity in late-life GAD. METHODS: We recruited 16 anxious (GAD) and 20 non-anxious (HC) older adults to perform the faces/shapes emotional reactivity task during functional magnetic resonance imaging (fMRI). We investigated the functional connectivity of both the amygdala and the bed nucleus of stria terminalis (BNST) with the prefrontal cortex (PFC) using generalized psychophysiological interaction (gPPI) analysis. We tested for (1) group differences in connectivity, (2) association between worry severity and connectivity, and (3) interaction between group and worry severity and its association with connectivity. RESULTS: Amygdala-PFC and BNST-PFC functional connectivity were associated with worry severity in an inverse U-shape, and was independent of depression severity, global anxiety, neuroticism, and general cognitive function. LIMITATIONS: Our limitations include slightly skewed PSWQ distributions, lack of non-anxious individuals with high worry, small sample size, and low depression comorbidity in a sample of late-life GAD that may not generalize to GAD in younger populations. CONCLUSIONS: This suggests that moderate worry is associated with maximum engagement of the limbic-PFC connectivity, while severe worry is associated with failure of the limbic-PFC emotional regulation circuit. This may explain the aberrant and exaggerated responses to negative stimuli observed in participants with pathological worry.

A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders.

BACKGROUND: Previous cross-sectional data showed that children and adolescents with attention-deficit hyperactivity disorder (ADHD) are at increased risk of comorbid conduct, mood, and anxiety disorders as well as impairments in cognitive, social, family, and school functioning. However, longitudinal data were needed to confirm these initial impressions. METHODS: Using DSM-III-R structured diagnostic interviews and raters blinded as to diagnosis, we reexamined psychiatric diagnoses at 1- and 4-year follow-ups in children with ADHD and controls. In addition, subjects were evaluated for cognitive, achievement, social, school and family functioning. RESULTS: Analyses of follow-up findings revealed significant differences between children with ADHD and controls in rates of behavioral, mood, and anxiety disorders, with these disorders increasing markedly from baseline to follow-up assessments. In addition, children with ADHD had significantly more impaired cognitive, family, school, and psychosocial functioning than did controls. Baseline diagnosis of conduct disorder predicted major depression and bipolar disorder at follow-up, and anxiety disorders at baseline predicted anxiety disorders at follow-up. CONCLUSION: These results confirm and extend previous retrospective results indicating that children with ADHD are at high risk of developing a wide range of impairments affecting multiple domains of psychopathology such as cognition, interpersonal, school, and family functioning. These findings provide further support for the value of considering psychiatric comorbidity in both clinical assessment and research protocols involving children with ADHD.

Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness.

Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is highly comorbid with conduct disorder and sometimes co-occurs with bipolar disorder. This pattern of comorbidity is also seen among relatives of ADHD probands. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. A similar pattern has been observed for ADHD and bipolar disorder. Given these results, along with the observed comorbidity between conduct and bipolar disorders, we used data from our study of 140 ADHD and 120 control families to determine if conduct and bipolar disorders in ADHD boys should be considered alternative manifestations of the same familial disorder. The probands and their relatives were examined with DSM-III-R structured diagnostic interviews and were assessed for cognitive, achievement, social, school, and family functioning. Our results provide fairly consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes are different manifestations of the same familial condition. As predicted by this hypothesis, there was a significant three-way association between variables assessing the family history of each disorder. Moreover, when families were stratified into bipolar, antisocial, and other types, few differences emerged between the bipolar and antisocial families.

Attention-deficit hyperactivity disorder with bipolar disorder: a familial subtype?

OBJECTIVE: To clarify the nosological status of children with attention-deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHOD: Blind raters and structured psychiatric interviews were used to examine 140 children with ADHD, a sample of 120 non-ADHD comparisons, and their 822 first-degree relatives. Data analyses tested specific hypotheses about the familial relationship between ADHD and BPD. RESULTS: After stratifying the ADHD sample into those with and without BPD, the authors found that (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls; (2) the two subgroups did not differ significantly from one another in their relatives' risk for ADHD; (3) a fivefold elevated risk for BPD was observed among relatives when the proband child had BPD but not when the proband had ADHD alone; (4) an elevated risk for major depression with severe impairment was found for relatives of ADHD + BPD probands; (5) both ADHD and BPD occurred in the same relatives more often than expected by chance alone; and (6) there was a trend for random mating between ADHD parents and those with mania. CONCLUSIONS: The data suggest that comorbid ADHD with BPD is familially distinct from other forms of ADHD and may be related to what others have termed childhood-onset BPD.

A pilot family study of childhood-onset mania.

OBJECTIVE: To investigate the familial association of attention-deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) among the first-degree relatives of children with comorbid ADHD and BPD. BACKGROUND: In contrast to a growing body of literature on childhood non-bipolar depression, little is known about childhood BPD. Among the explanations accounting for the lack of recognition and identification of these children is the symptomatic overlap of BPD with ADHD. Family-genetic studies provide information external to the clinical picture and thus are uniquely suited to clarify such issues of diagnostic comorbidity. METHOD: Structured diagnostic interviews were used to obtain DSM-III-R psychiatric diagnoses on first-degree relatives (n = 46) of referred children (aged < or = 12 years) satisfying diagnostic criteria for mania using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version (n = 16). For comparison, diagnostic information on the first-degree relatives of non-bipolar ADHD children and control children was examined. RESULTS: The results show high rates of comorbidity between BPD and ADHD in children and high rates of both BPD and ADHD in the first-degree relatives of these children. Moreover, ADHD and BPD cosegregated among the relatives of children with BPD. CONCLUSIONS: These findings, which are consistent with the authors' prior study of children with ADHD, provide family-genetic evidence for the validity of BPD and ADHD when they exist comorbidly in children. Moreover, they suggest that the comorbid condition of ADHD+BPD may be a distinct nosological entity.

Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children.

OBJECTIVE: To examine the prevalence, characteristics, and correlates of mania among referred children aged 12 or younger. Many case reports challenge the widely accepted belief that childhood-onset mania is rare. Sources of diagnostic confusion include the variable developmental expression of mania and its symptomatic overlap with attention-deficit hyperactivity disorder (ADHD). METHOD: The authors compared 43 children aged 12 years or younger who satisfied criteria for mania, 164 ADHD children without mania, and 84 non-ADHD control children. RESULTS: The clinical picture was fully compatible with the DSM-III-R diagnosis of mania in 16% (n = 43) of referred children. All but one of the children meeting criteria for mania also met criteria for ADHD. Compared with ADHD children without mania, manic children had significantly higher rates of major depression, psychosis, multiple anxiety disorders, conduct disorder, and oppositional defiant disorder as well as evidence of significantly more impaired psychosocial functioning. In addition, 21% (n = 9) of manic children had had at least one previous psychiatric hospitalization. CONCLUSIONS: Mania may be relatively common among psychiatrically referred children. The clinical picture of childhood-onset mania is very severe and frequently comorbid with ADHD and other psychiatric disorders. Because of the high comorbidity with ADHD, more work is needed to clarify whether these children have ADHD, bipolar disorder, or both.

A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a familial disorder that places the siblings of ADHD children at high risk for ADHD, conduct, mood, and anxiety disorders. Although the pattern of psychiatric risk has been well documented by prior family studies, neither the short- nor long-term outcome of these high-risk siblings has been prospectively examined. OBJECTIVE: To document the 4-year psychiatric, psychosocial, and neuropsychological outcome of the siblings of children with ADHD. METHOD: DSM-III-R structured diagnostic interviews and blind raters were used to conduct a 4-year follow-up of siblings from ADHD and control families. The siblings were also evaluated for cognitive, achievement, social, school, and family functioning. RESULTS: At follow-up, significant elevations of behavioral, mood, and anxiety disorders were found among the siblings of ADHD children. The high-risk siblings had high rates of school failure and showed evidence of neuropsychological and psychosocial dysfunction. These impairments aggregated among the siblings who had ADHD. CONCLUSIONS: The siblings of ADHD children are at high risk for clinically meaningful levels of psychopathology and functional impairment. In addition to supporting hypotheses about the familial transmission of ADHD, the results suggest that the high-risk siblings might be appropriate targets for primary preventive interventions.

A pilot study of neuropsychological function in girls with ADHD.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is known to have neuropsychological consequences that are evident from psychological tests and from measures of school failure. However, most available data are based on studies of boys. Our goal was to assess, in this pilot study, whether ADHD in girls expressed neuropsychological features similar to those found in boys. METHOD: Subjects were 43 girls, aged 6 to 17 years, with DSM-III-R ADHD and 36 comparison girls without ADHD. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. RESULTS: Girls with ADHD were significantly more impaired on estimated IQ than comparison girls despite being matched on other demographic variables. Relative to comparison girls, the girls with ADHD were also significantly more impaired on the Freedom From Distractibility subtests of the WISC-R and on arithmetic and reading achievement scores. Although their mean performance on executive function tests was generally poorer than that of control girls, there were no statistically significant differences on these measures. CONCLUSIONS: Girls with ADHD have impairments in some tests of attention and achievement. However, neuropsychological performance on tests of executive function was less impaired than that previously documented in boys with ADHD. If confirmed in a larger sample, these findings suggest that girls with ADHD may be less vulnerable to executive function deficits than boys.

Is comorbidity with ADHD a marker for juvenile-onset mania?

OBJECTIVE: To compare the characteristics and correlates of mania in referred adolescents and to determine whether attention-deficit hyperactivity disorder (ADHD) is a marker of very early onset mania. METHOD: From 637 consecutive admissions, 68 children (< or = 12 years) and 42 adolescents (> 13 years) who satisfied criteria for mania were recruited. These were compared with the 527 nonmanic referrals and 100 normal controls. RESULTS: With the exception of comorbidity with ADHD, there were more similarities than differences between the children and adolescents with mania in course and correlates. There was an inverse relationship between the rates of comorbid ADHD and age of onset of mania: higher in manic children intermediate in adolescents with childhood-onset mania, and lower in adolescents with adolescent-onset mania. CONCLUSIONS: ADHD is more common in childhood-onset compared with adolescent-onset cases of bipolar disorder, suggesting that in some cases, ADHD may signal a very early onset of bipolar disorder. Clinical similarities between the child- and adolescent-onset cases provide evidence for the clinical validity of childhood-onset mania.

Attention-deficit hyperactivity disorder and juvenile mania: an overlooked comorbidity?

OBJECTIVE: To evaluate the psychiatric, cognitive, and functional correlates of attention-deficit hyperactivity disorder (ADHD) children with and without comorbid bipolar disorder (BPD). METHOD: DSM-III-R structured diagnostic interviews and blind raters were used to examine psychiatric diagnoses at baseline and 4-year follow-up in ADHD and control children. In addition, subjects were evaluated for cognitive, academic, social, school, and family functioning. RESULTS: BPD was diagnosed in 11% of ADHD children at baseline and in an additional 12% at 4-year follow-up. These rates were significantly higher than those of controls at each assessment. ADHD children with comorbid BPD at either baseline or follow-up assessment had significantly higher rates of additional psychopathology, psychiatric hospitalization, and severely impaired psychosocial functioning than other ADHD children. The clinical picture of bipolarity was mostly irritable and mixed. ADHD children with comorbid BPD also had a very severe symptomatic picture of ADHD as well as prototypical correlates of the disorder. Comorbidity between ADHD and BPD was not due to symptom overlap. ADHD children who developed BPD at the 4-year follow-up had higher initial rates of comorbidity, more symptoms of ADHD, worse scores on the CBCL, and a greater family history of mood disorder compared with non-BPD, ADHD children. CONCLUSIONS: The results extend previous results documenting that children with ADHD are at increased risk of developing BPD with its associated severe morbidity, dysfunction, and incapacitation.

The impact of comorbid mood and personality disorders in the cognitive-behavioral treatment of panic disorder.

The present review examined the effect of comorbid major depressive disorder and personality disorder on the outcome of cognitive-behavioral interventions for panic disorder. Panic disorder patients often present with these comorbid conditions, but for the most part, treatment studies have paid little attention to them. Most studies on the effects of comorbidity on treatment outcome address pharmacological treatment. However, there is a growing literature on the effect of additional disorders on the outcome of cognitive-behavioral interventions for panic disorder. Findings from the studies of comorbidity with depression are equivocal, possibly reflecting inconsistencies in measurement methodology across studies. However, personality psychopathology was found to exert a detrimental effect on the outcome of cognitive-behavioral treatment for panic disorder. Further research is necessary to elucidate the impact of these concurrent conditions on cognitive-behavioral treatment for panic disorder. It is suggested that studies utilizing cognitive-behavioral treatment routinely examine the influence of comorbid conditions on treatment outcome.

Conduct disorder with and without mania in a referred sample of ADHD children.

OBJECTIVE: To test the hypothesis that dysphoric and non-dysphoric types of CD could be distinguished from one another in their patterns of familiality, adversity, and comorbidity. METHODS: We examined 140 ADHD and 120 normal controls at baseline and 4 years later using assessments from multiple domains. We compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders on psychiatric outcomes at a 4-year follow-up, familial psychopathology and psychosocial functioning. RESULTS: We found that ADHD children with both disorders had higher familial and personal risk for mood disorders than those with CD only, who had a higher personal risk for antisocial personality disorder. Among ADHD probands, having both CD and BPD was associated with poorer functioning and an increased risk for psychiatric hospitalization. DISCUSSION: Although preliminary, our findings suggest that the distinction between dysphoric and non-dysphoric CD may be clinically meaningful. If confirmed, our findings could have important diagnostic and therapeutic implications for the management of antisocial youth.

Distinguishing obsessive features and worries: the role of thought-action fusion.

Obsessions are a key feature of obsessive-compulsive disorder (OCD), and chronic worry is the cardinal feature of generalized anxiety disorder (GAD). However, these two cognitive processes are conceptually very similar, and there is a need to determine how they differ. Recent studies have attempted to identify cognitive processes that may be differentially related to obsessive features and worry. In the current study we proposed that (1) obsessive features and worry could be differentiated and that (2) a measure of the cognitive process thought-action fusion would distinguish between obsessive features and worry, being strongly related to obsessive features after controlling for the effects of worry. These hypotheses were supported in a sample of 173 undergraduate students. Thought-action fusion may be a valuable construct in differentiating between obsessive features and worry.

Comorbid generalized anxiety disorder in primary social phobia: symptom severity, functional impairment, and treatment response.

As many as 50% of patients with a primary anxiety disorder may meet criteria for an additional anxiety disorder. However, there is insufficient research on the cooccurrence of the anxiety disorders, although investigations of this nature may facilitate our understanding of their cause, phenomenology, and treatment. The present study examined the occurrence of generalized anxiety disorder (GAD) among patients with social phobia (SP) compared with SP patients without GAD. Of 122 treatment-seeking patients meeting DSM-III-R criteria for SP, 29 (23.8%) also met criteria for an additional diagnosis of GAD. SP patients with comorbid GAD demonstrated greater severity on measures of social anxiety and avoidance, general anxiety, cognitive (but not somatic) symptoms of anxiety, depressed mood, functional impairment, and overall psychopathology. Group differences remained significant when comorbidity with other anxiety and mood disorders was controlled. The content of worry among the SP patients with GAD was not specific to social concerns and appeared similar to the reported content of worry in samples of patients with primary GAD. Nevertheless, SP patients with and without GAD responded similarly to cognitive-behavioral group therapy for social phobia. Implications for the understanding and treatment of comorbid SP and GAD are discussed.

Social anxiety and emotion knowledge: a meta-analysis.

It has been proposed that social anxiety is associated with poor emotion knowledge (EK), although studies have revealed mixed results. The aim of the present paper was to systematically investigate the association between EK and both non-clinical and clinical social anxiety by means of meta-analyses. Systematic, electronic database literature searches were performed, and meta-analyses were conducted on 43 included studies. Results showed that social anxiety was negatively associated with EK. The strongest association was found between clinical levels of social anxiety and the ability to understand one's own emotions (intrapersonal EK). Regarding interpersonal EK, a subgroup analysis showed that social anxiety was more strongly associated with a decreased ability to understand complex emotions than to recognize basic emotions. No differences were found between patients with social anxiety disorder (SAD) and patients with other anxiety disorders. Although a large between study heterogeneity and differing methodologies may prevent any firm conclusions from being reached, the results indicate that poor EK may play an important role in SAD, and that it could be beneficial to target EK in the treatment of SAD.

Differential patterns of physical symptoms and subjective processes in generalized anxiety disorder and unipolar depression.

Given the substantial comorbidity between generalized anxiety disorder (GAD) and unipolar depressive disorders (UDDs), some have suggested that these disorders be combined in future editions of the DSM. However, decisions regarding nosology should not only account for current manifestations of symptom profiles, but also the potential diagnostic utility of associated characteristics, which, given past research, may suggest greater distinctiveness between these disorder classes. In the present investigation, we examined the role of one-item indices of physical, emotional/motivational, and cognitive symptoms in differentiating GAD from UDDs. We assessed these symptoms with one-item measures in order to provide an initial examination of the viability of these constructs as diagnostic criteria. In Study 1, in an unselected college sample, muscle pains and aches, gastrointestinal symptoms, emotion intensity, and intolerance of uncertainty were associated with GAD symptoms; conversely, low positive affect was associated with UDDs symptoms. In Study 2, we extended these findings to a clinical population and found that muscle pains and aches, positive affect, goal motivation, emotion intensity, and intolerance of uncertainty were higher in GAD than in UDDs.

Anxiety and cognitive efficiency: differential modulation of transient and sustained neural activity during a working memory task.

According to the processing-efficiency hypothesis (Eysenck, Derakshan, Santos, & Calvo, 2007), anxious individuals are thought to require greater activation of brain systems supporting cognitive control (e.g.,dorsolateral prefrontal cortex; DLPFC) in order to maintain equivalent performance to nonanxious subjects. A recent theory of cognitive control (Braver, Gray, & Burgess, 2007) has proposed that reduced cognitive efficiency might occur as a result of changes in the temporal dynamics of DLPFC recruitment. In this study, we used a mixed blocked/ event-related fMRI design to track transient and sustained activity in DLPFC while high- and low-anxious participants performed a working memory task. The task was performed after the participants viewed videos designed to induce neutral or anxiety-related moods. After the neutral video, the high-anxious participants had reduced sustained but increased transient activation in working memory areas, in comparison with low-anxious participants. The high-anxious group also showed extensive reductions in sustained activation of "default-network" areas (possible deactivation). After the negative video,the low-anxiety group shifted their activation dynamics in cognitive control regions to resemble those of the high-anxious group. These results suggest that reduced cognitive control in anxiety might be due to a transient, rather than sustained, pattern of working memory recruitment. Supplementary information for this study may be found at www.psychonomic.org/archive.

Situational panic attacks: impact on distress and impairment among patients with social phobia.

To investigate the impact of situational panic attacks in social phobia, this study examined symptoms of social anxiety and avoidance, dysfunction, and associated psychopathology among individuals with social phobia who experience situational panic attacks, individuals meeting criteria for both social phobia and panic disorder, and individuals with social phobia but no report of panic attacks. One hundred thirty-three persons with a principal diagnosis of social phobia were evaluated. Fifty-seven individuals, who experienced panic attacks exclusively in the context of feared social situations, were compared to 15 individuals with social phobia who also experienced spontaneous panic attacks and met criteria for panic disorder and 61 social phobics who did not experience panic attacks. Compared to social phobics without panic, social phobics with situational panic attacks demonstrated greater fear and avoidance of social situations and higher ratings of somatic anxiety, were more distressed and impaired by their social phobias, and reported higher levels of anxiety sensitivity and hopelessness than social phobics without panic. Additionally, social phobia patients with situational panic but without panic disorder reported greater hopelessness than participants with comorbid panic disorder. In regression analyses, situational panic attacks accounted for significant unique variance beyond that contributed by the presence of comorbid panic disorder. Situational panic attacks are common in social phobia. They are associated with significant and unique disturbances compared either to the absence of panic attacks or to panic attacks in the context of comorbid panic disorder and deserve attention in both research and treatment of social phobia.

Familial subtypes of attention deficit hyperactivity disorder: a 4-year follow-up study of children from antisocial-ADHD families.

ADHD is a familial disorder with high rates of comorbidity with conduct disorder in childhood and antisocial personality and substance use disorders in adulthood. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. Previously, we proposed a family-based stratification that defined Antisocial families as those with either conduct disorder or antisocial personality disorder in the probands or relatives. To provide predictive validity for that stratification, we assessed psychopathology in these families 4 years after their initial assessment. Results show that the probands and siblings from Antisocial families had higher rates of psychopathology during the 4-year follow-up period compared with siblings from Non-antisocial and control families. They also had more deviant ratings on the Child Behavior Checklist (especially for anxious/depressed, delinquent, and aggressive behavior). We found fewer group differences in the academic, psychosocial, and intellectual correlates of ADHD. These results confirm and extend previous work indicating that Antisocial ADHD may be a nosologically and clinically meaningful subform of ADHD.