Background. Studies measuring the effects of psychotherapy on brain function are under-represented relative to analogous studies of medications, possibly reflecting historical biases. However, psychological constructs relevant to several modalities of psychotherapy have demonstrable neurobiological correlates, as indicated by functional neuroimaging studies in healthy subjects. This review examines initial attempts to measure directly the effects of psychotherapy on brain function in patients with depression or anxiety disorders.

Method. Fourteen published, peer-reviewed functional neuroimaging investigations of psychotherapy were identified through a MEDLINE search and critically reviewed. Studies were compared for consistency of findings both within specific diagnostic categories, and between specific modalities of psychotherapy. Results were also compared to predicted neural models of psychotherapeutic interventions.

Results. Behavioral therapy for anxiety disorders was consistently associated with attenuation of brain-imaging abnormalities in regions linked to the pathophysiology of anxiety, and with activation in regions related to positive reappraisal of anxiogenic stimuli. In studies of major depressive disorder, cognitive behavioral therapy and interpersonal therapy were associated with markedly similar changes in cortical–subcortical circuitry, but in unexpected directions. For any given psychiatric disorder, there was only partial overlap between the brain-imaging changes associated with pharmacotherapy and those associated with psychotherapy.

Conclusions. Despite methodological limitations, initial neuroimaging studies have revealed convergent and mechanistically sensible effects of psychotherapy on brain function across a range of psychiatric disorders. Further research in this area may take advantage of emerging neuroimaging techniques to explore a broader range of psychotherapies, with the ultimate goal of improving clinical decision-making and treatment.

Background. Co-morbidity within anxiety disorders, and between anxiety disorders and depression, is common. According to the theory of Gray and McNaughton, this co-morbidity is caused by recursive interconnections linking the brain regions involved in fear, anxiety and panic and by heritable personality traits such as neuroticism. In other words, co-morbidity can be explained by one disorder being an epiphenomenon of the other and by a partly shared genetic etiology. The aim of this paper is to evaluate the theory of Gray and McNaughton using the results of genetic epidemiological studies.

Method. Twenty-three twin studies and 12 family studies on co-morbidity are reviewed. To compare the outcomes systematically, genetic and environmental correlations between disorders are calculated for the twin studies and the results from the family studies are summarized according to the method of Klein and Riso.

Results. Twin studies show that co-morbidity within anxiety disorders and between anxiety disorders and depression is explained by a shared genetic vulnerability for both disorders. Some family studies support this conclusion, but others suggest that co-morbidity is due to one disorder being an epiphenomenon of the other.

Conclusions. Discrepancies between the twin and family studies seem partly due to differences in used methodology. The theory of Gray and McNaughton that neuroticism is a shared risk factor for anxiety and depression is supported. Further research should reveal the role of recursive interconnections linking brain regions. A model is proposed to simultaneously investigate the influence of neuroticism and recursive interconnections on co-morbidity.

Background. Many changes in social behavior take place during adolescence. Sexuality and romantic interests emerge during this time, and adolescents spend more time with peers and less time with parents and family. While such changes in social behavior have been well documented in the literature, relatively few neurophysiological explanations for these behavioral changes have been presented.

Method. In this article we selectively review studies documenting (a) the neuronal circuits that are dedicated to the processing of social information; (b) the changes in social behavior that take place during adolescence; (c) developmental alterations in the adolescent brain; and (d) links between the emergence of mood and anxiety disorders in adolescence and changes in brain physiology occurring at that time.

Results. The convergence of evidence from this review indicates a relationship between development of brain physiology and developmental changes in social behavior. Specifically, the surge of gonadal steroids at puberty induces changes within the limbic system that alters the emotional attributions applied to social stimuli while the gradual maturation of the prefrontal cortex enables increasingly complex and controlled responses to social information.

Conclusions. Observed alterations in adolescent social behavior reflect developmental changes in the brain social information processing network. We further speculate that dysregulation of the social information processing network in this critical period may contribute to the onset of mood and anxiety disorders during adolescence.

This issue particularly features papers on treatment, including randomized controlled trials, studies derived from them, and follow-up studies.

Background. In bulimic syndromes, binge episodes are thought to be caused by dietary restraint and negative moods. However, as central serotonin (5-hydroxytryptamine: 5-HT) mechanisms regulate appetite and mood, the 5-HT system could be implicated in diet- and mood-based binge antecedents.

Method. We used hand-held computers to obtain repeated ‘online’ measurements of eating behaviors, moods, and self-concepts in 21 women with bulimic syndromes, and modeled 5-HT system activity with a measure of platelet [3H]paroxetine-binding density.

Results. Mood and self-concept ratings were found to be worse before binge episodes (than at other moments), and cognitive restraint was increased. After binges, mood and self-concept deteriorated further, and thoughts of dieting became more intense. Intriguingly, lower paroxetine-binding density predicted poorer mood and self-concept before a binge, larger post-binge decrements in mood and self-concept, and larger post-binge increases in dietary restraint.

Conclusions. Paroxetine binding thus seemed to reflect processes that impacted upon mood-related antecedents to binge episodes, and consequences implicating mood and dietary restraint.

Background. There is continuing controversy about how age affects depression and anxiety, with a lack of consistent results across studies. Two reasons for this inconsistency are age bias in measures and different patterns of exposure to risk factors across age groups in various studies.

Method. Data on anxiety and depression symptoms were collected in a community survey of 7485 persons aged 20–24, 40–44 or 60–64 years. These measures were investigated for factorial invariance across age groups. Data were also collected on a wide range of potential risk factors, including social, physical health and personal factors, with the aim of determining whether these factors might partly or wholly account for age group differences.

Results. The invariance of correlated latent factors representing anxiety and depression was examined across age groups, and a generalized measure of psychological distress was computed. Depression, anxiety and psychological distress showed a decline across age groups for females and a decline from 40–44 to 60–64 years for males. Some of these age differences were accounted for by other risk factors, with the most important being recent crises at work and negative social relationships with family and friends.

Conclusion. Psychological distress generally declined across the age range 20–64 years and this was not attributable to measurement bias. Differential exposure to risk factors explained some, but not all, of the age group difference. Therefore other mechanisms that explain the lower level of distress in older age groups remain to be identified.

Background. Recent research in the United States has demonstrated striking health disparities across ethnic groups. Despite a longstanding interest in ethnic disadvantage in psychiatric epidemiology, patterns of psychiatric morbidity across ethnic groups have never been examined in a nationally representative sample.

Method. Ethnic differences in psychiatric morbidity are analyzed using data from the National Comorbidity Survey (NCS). The three largest ethnic groups in the United States – Hispanics, Non-Hispanic Blacks and Non-Hispanic Whites – were compared with respect to lifetime risk and persistence of three categories of psychiatric disorder: mood disorder, anxiety disorder, and substance use disorder.

Results. Where differences across ethnic groups were found in lifetime risk, socially disadvantaged groups had lower risk. Relative to Non-Hispanic Whites, Hispanics had lower lifetime risk of substance use disorder and Non-Hispanic Blacks had lower lifetime risk of mood, anxiety and substance use disorders. Where differences were found in persistence of disorders, disadvantaged groups had higher risk. Hispanics with mood disorders were more likely to be persistently ill as were Non-Hispanic Blacks with respect to both mood disorders and anxiety disorders. Closer examination found these differences to be generally consistent across population subgroups.

Conclusions. Members of disadvantaged ethnic groups in the United States do not have an increased risk for psychiatric disorders. Members of these groups, however, do tend to have more persistent disorders. Future research should focus on explanations for these findings, including the possibility that these comparisons are biased, and on potential means of reducing the disparity in persistence of disorders across ethnic groups.

Background. Despite increasing adoption of clinical practice guidelines in psychiatry, there is little measurement of provider implementation of these recommendations, and the resulting impact on clinical outcomes. The current study describes one effort to measure these relationships in a cohort of public sector out-patients with bipolar disorder.

Method. Participants were enrolled in the algorithm intervention of the Texas Medication Algorithm Project (TMAP). Study methods and the adherence scoring algorithm have been described elsewhere. The current paper addresses the relationships between patient characteristics, provider experience with the algorithm, provider adherence, and clinical outcomes. Measurement of provider adherence includes evaluation of visit frequency, medication choice and dosing, and response to patient symptoms. An exploratory composite ‘adherence by visit’ score was developed for these analyses.

Results. A total of 1948 visits from 141 subjects were evaluated, and utilized a two-stage declining effects model. Providers with more experience using the algorithm tended to adhere less to treatment recommendations. Few patient factors significantly impacted provider adherence. Increased adherence to algorithm recommendations was associated with larger decreases in overall psychiatric symptoms and depressive symptoms over time, but did not impact either immediate or long-term reductions in manic symptoms.

Conclusions. Greater provider adherence to treatment guideline recommendations was associated with greater reductions in depressive symptoms and overall psychiatric symptoms over time. Additional research is needed to refine measurement and to further clarify these relationships.

Background. Structural brain volume abnormalities are among the most extensively studied endophenotypes in schizophrenia. Bivariate genetic model fitting (adjusted to account for selection) was used to quantify the genetic relationship between schizophrenia and brain volumes and to estimate the heritability of these volumes.

Method. We demonstrated by simulation that the adjusted genetic model produced unbiased estimates for endophenotype heritability and the genetic and environmental correlations. The model was applied to brain volumes (whole brain, hippocampus, third and lateral ventricles) in a sample of 14 monozygotic (MZ) twin pairs concordant for schizophrenia, 10 MZ discordant pairs, 17 MZ control pairs, 22 discordant sibling pairs, three concordant sibling pairs, and 114 healthy control subjects.

Results. Whole brain showed a substantial heritability (88%) and lateral ventricles substantial common environmental effects (67%). Whole brain showed a significant genetic correlation with schizophrenia, whereas lateral ventricles showed a significant individual specific correlation with schizophrenia. There were significant familial effects for hippocampus and third ventricle, but the analyses could not resolve whether these were genetic or environmental in origin (around 30% each).

Conclusions. Using genetic model fitting on twin and sibling data we have demonstrated differential sources of covariation between schizophrenia and brain volumes, genetic in the case of whole brain volume and individual specific environment in the case of lateral ventricles.

Background. In patients with schizophrenia, passivity delusions are characterized by a difficulty in determining the agency of purposive actions. Neuropsychological and functional neuroimaging data suggest that passivity delusions are associated with dysfunction of the parietal lobe association cortex.

Method. Cortical volume calculated from magnetic resonance imaging data in a group of 12 patients with schizophrenia characterized by motor passivity delusions was compared statistically with the cortical volume of 11 patients without passivity delusions.

Results. Reduced cortical volume was observed in parietal and frontal association cortices in the passivity group.

Conclusions. These data provide direct evidence for the involvement of the parietal lobe in the pathophysiology of passivity delusions in schizophrenia.

The Committee on Chronotherapeutics was recently formed by the International Society for Affective Disorders (ISAD), which has asked us to provide a consensus review of chronotherapeutics (light and wake therapy) in affective disorders. We consider these non-pharmaceutical, biologically based therapies to be potentially powerful adjuvants ready for clinical application. We also stress the need for additional studies, both in-patient and out-patient, to broaden the evidence base for indications and efficacy.

Background. Expert committees of clinicians have chosen diagnostic criteria for psychiatric disorders with little guidance from measurement theory or modern psychometric methods. The DSM-III-R criteria for major depression (MD) are examined to determine the degree to which latent trait item response models can extract additional useful information.

Method. The dimensionality and measurement properties of the 9 DSM-III-R criteria plus duration are evaluated using dichotomous factor analysis and the Rasch and 2 parameter logistic item response models. Quantitative liability scales are compared with a binary DSM-III-R diagnostic algorithm variable to determine the ramifications of using each approach.

Results. Factor and item response model results indicated the 10 MD criteria defined a reasonably coherent unidimensional scale of liability. However, person risk measurement was not optimal. Criteria thresholds were unevenly spaced leaving scale regions poorly measured. Criteria varied in discriminating levels of risk. Compared to a binary MD diagnosis, item response model (IRM) liability scales performed far better in (i) elucidating the relationship between MD symptoms and liability, (ii) predicting the personality trait of neuroticism and future depressive episodes and (iii) more precisely estimating heritability parameters.

Conclusions. Criteria for MD largely defined a single dimension of disease liability although the quality of person risk measurement was less clear. The quantitative item response scales were statistically superior in predicting relevant outcomes and estimating twin model parameters. Item response models that treat symptoms as ordered indicators of risk rather than as counts towards a diagnostic threshold more fully exploit the information available in symptom endorsement data patterns.

Background. Dissociation, defined as a disruption in usually integrated mental functions, is found not only in DSM-IV dissociative disorders, but also in post-traumatic stress disorder and eating disorders. Dissociative phenomena are also common in the general population, and may reflect a constitutionally determined cognitive style rather than a pathological trait acquired through experiencing adverse life events. In pathological dissociation, evidence has been presented for episodic memory dysfunction. In contrast, in high-dissociative subjects increased performance has been found for episodic memory and dual task performance. These findings have been linked to changes in working memory capacity.

Method. In the present study, the authors sought to extend these findings by using functional magnetic resonance imaging during performance of two parametric working memory tasks. We tested 21 healthy low- and high-dissociative participants.

Results. High-dissociative participants performed slightly better during both tasks. Imaging data showed that both groups activated similar networks for both tasks, i.e. (bilateral) dorsolateral (DL) and ventrolateral prefrontal cortex (PFC), parietal cortex, and supplementary motor area. Group×task interactions were found in the high-dissociative group in L DLPFC and L parietal cortex; in the low-dissociative group in R fusiform gyrus. The differences in the high-dissociative group were independent from performance differences, implying that high-dissociative subjects generally recruit this network to a greater extent.

Conclusions. These results confirm earlier findings using a verbal WM task in high-dissociative participants, and are compatible with the conceptualization of non-pathological dissociation as an information-processing style, characterized by distinct attentional and mnemonic abilities.

Background. Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously.

Method. Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975–1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk.

Results. ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences.

Conclusions. Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.

Background. The nature of delusions remains unclear despite their interest to researchers and importance in psychopathology. Here we present a review of the contributions from various disciplines, principally cognitive neuroscience, towards a new understanding.

Method. Narrative review of published research.

Results. The main areas of activity revolve around reasoning biases, attributional and attentional biases, theory of mind, and the role of emotion, with each area beginning to be explored using functional neuroimaging techniques. Of heuristic interest are neurological models, which include confabulation and delusional misidentification and the one- versus two-stage (perceptual versus reasoning plus perceptual) accounts of the latter.

Conclusions. These different approaches are shown to each highlight mechanisms which are suggested to cause, contribute to, or modulate the genesis and form of delusions. Such contributions coupled with traditional phenomenological methods should provide the foundations for a cognitive neuropsychiatry of delusions.

Background. Although children with hyperkinetic disorder and/or attention deficit hyperactivity disorder (ADHD) show disordered executive neuropsychological functioning, the nature of these changes remains controversial. Additionally, impairments in non-executive neuropsychological functioning have been relatively unexplored. Here, the authors describe the neuropsychological functioning of a sample of stimulant drug-naive boys with hyperkinetic disorder on a battery of neuropsychological tasks sensitive to impairments of both executive and non-executive functions.

Method. Seventy-five stimulant drug-naive boys meeting diagnostic criteria for ICD-10 hyperkinetic disorder were compared with 70 healthy developing controls matched for age but not IQ on computerized tests of neuropsychological functioning from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a Go/No-Go inhibition task.

Results. Boys with hyperkinetic disorder exhibited impairments on tasks with a prominent executive component – working memory, planning, strategy formation, attentional set-shifting and on a reaction time task. However, they were also impaired on tasks without prominent executive components – pattern and spatial recognition, spatial span, delayed matching to sample and paired associates learning. Contrary to predictions, no impairment was observed on the Go/No-Go inhibition task.

Conclusions. Medication-naive boys with hyperkinetic disorder displayed a broad range of neuropsychological impairments. Deficits were demonstrated on tasks with and without prominent executive components. Impairments were not confined to tasks dependent upon frontostriatal functioning, cannot wholly be explained by deficits in inhibitory control, nor can they be attributed to intelligence or previous exposure to stimulant medication.

Background. In the conditioned fear paradigm, repeated pairing of an aversive unconditioned stimulus (US) (e.g. electric shock) with a neutral conditioned stimulus (CS) (e.g. bright light) results in a conditioned fear response to the light alone. Animal studies have shown that the amygdala plays a critical role in acquisition of conditioned fear responses, while the medial prefrontal cortex (including anterior cingulate), through inhibition of amygdala responsiveness, has been hypothesized to play a role in extinction of fear responses. No studies have examined neural correlates of fear conditioning and extinction in patients with post-traumatic stress disorder (PTSD).

Method. Women with early childhood sexual-abuse-related PTSD (n=8) and women without abuse or PTSD (n=11) underwent measurement of psychophysiological (skin conductance) responding as well as positron emission tomographic (PET) measurement of cerebral blood flow during habituation, acquisition and extinction conditions. During habituation subjects were repeatedly exposed to a blue square on a screen. During acquisition, exposure to the blue square (CS) was paired with an electric shock to the forearm (US). With extinction, subjects were again exposed to the blue squares without shock. On a different day subjects went through the same procedure with electric shocks administered randomly in the absence of the blue square.

Results. Skin conductance responding to the CS was consistent with the development of conditioned responses with this paradigm. PTSD patients had increased left amygdala activation with fear acquisition, and decreased anterior cingulate function during extinction, relative to controls.

Conclusions. These findings implicate amygdala and anterior cingulate in the acquisition and extinction of fear responses, respectively, in PTSD.

Background. This randomized controlled trial investigates the efficacy of two non-pharmacologic treatments, bright light and high-density negative air ions for non-seasonal chronic depression. Both methods have shown clinical success for seasonal affective disorder (SAD).

Method. Patients were 24 (75%) women and 8 (25%) men, ages 22–65 years (mean age±S.D., 43·7±12·4 years), with Major Depressive Disorder, Single Episode (DSM-IV code, 296.2), Chronic (episode duration [ges ]2 years). Patients were entered throughout the year and randomly assigned to exposure to bright light (10000 lux, n=10), or high-density (4·5×1014 ions/s flow rate, n=12) or low-density (1·7×1011 ions/s, n=10, placebo control) negative air ions. Home treatment sessions occurred for 1 h upon awakening for 5 weeks. Blinded raters assessed symptom severity weekly with the Structured Interview Guide for the Hamilton Depression Rating Scale – Seasonal Affective Disorder (SIGH-SAD) version. Evening saliva samples were obtained before and after treatment for ascertainment of circadian melatonin rhythm phase.

Results. SIGH-SAD score improvement was 53·7% for bright light and 51·1% for high-density ions v. 17·0% for low-density ions. Remission rates were 50%, 50% and 0% respectively. The presence or severity of atypical symptoms did not predict response to either treatment modality, nor were phase advances to light associated with positive response.

Conclusions. Both bright light and negative air ions are effective for treatment of chronic depression. Remission rates are similar to those for SAD, but without a seasonal dependency or apparent mediation by circadian rhythm phase shifts. Combination treatment with antidepressant drugs may further enhance clinical response.

Background. In a recent longitudinal study of first-episode schizophrenia patients, we found that while dysfunction of the right dorsolateral prefrontal cortex (DLPFC), right thalamus, left cerebellum and cingulate gyrus normalized with antipsychotic treatment and significant reduction in symptomatology, the left DLPFC, left thalamus, and right cerebellum remained disturbed. In the present study we investigated whether these abnormalities are also present in clinically stable, relatively well-functioning schizophrenia patients in comparison to control subjects during performance of the N-back working-memory task.

Method. Twelve schizophrenia and 12 control subjects completed the study. The functional images collected during scanning were analyzed using a random-effects model in a restricted set of six regions of interest (ROIs). In addition, the exploratory search in the entire brain volume was performed.

Results. The ROI analyses revealed relative underactivation in the region of the left DLPFC and the right cerebellum, as well as overactivation in the left cerebellum. The exploratory whole-brain search exposed additional overactivation in the medial frontal, anterior cingulate, and left parietal cortices.

Conclusions. The present study provides evidence of significant underactivations in stable schizophrenia patients in regions that we have previously observed to be dysfunctional in acutely psychotic and partially remitted patients, together with extensive overactivations in several regions that potentially reflect some compensatory mechanism or increased effort on the working-memory task.

Background. Despite the availability of efficacious medications and psychotherapies, care of bipolar disorder in everyday practice is often deficient. This trial evaluated the effectiveness of a multi-component care management program in a population-based sample of people with bipolar disorder.

Method. Four hundred and forty-one patients treated for bipolar disorder during the prior year were randomly assigned to continued usual care or usual care plus a systematic care management program including: initial assessment and care planning, monthly telephone monitoring including brief symptom assessment and medication monitoring, feedback to and coordination with the mental health treatment team, and a structured group psychoeducational program – all provided by a nurse care manager. Blinded quarterly assessments generated week-by-week ratings of severity of depression and mania symptoms using the Longitudinal Interval Follow-Up Evaluation.

Results. Participants assigned to the intervention group had significantly lower mean mania ratings averaged across the 12-month follow-up period (Z=2·44, p=0·015) and approximately one-third less time in hypomanic or manic episode (2·59 weeks v. 1·69 weeks). Mean depression ratings across the entire follow-up period did not differ significantly between the two groups, but the intervention group showed a greater decline in depression ratings over time (Z statistic for group-by-time interaction=1·98, p=0·048).

Conclusions. A systematic care program for bipolar disorder significantly reduces risk of mania over 12 months. Preliminary results suggest a growing effect on depression over time, but longer follow-up will be needed.