Psychological Medicine

Although cognitive behavioural therapy (CBT) is claimed to be effective in schizophrenia, major depression and bipolar disorder, there have been negative findings in well-conducted studies and meta-analyses have not fully considered the potential influence of blindness or the use of control interventions.

We pooled data from published trials of CBT in schizophrenia, major depression and bipolar disorder that used controls for non-specific effects of intervention. Trials of effectiveness against relapse were also pooled, including those that compared CBT to treatment as usual (TAU). Blinding was examined as a moderating factor.

CBT was not effective in reducing symptoms in schizophrenia or in preventing relapse. CBT was effective in reducing symptoms in major depression, although the effect size was small, and in reducing relapse. CBT was ineffective in reducing relapse in bipolar disorder.

CBT is no better than non-specific control interventions in the treatment of schizophrenia and does not reduce relapse rates. It is effective in major depression but the size of the effect is small in treatment studies. On present evidence CBT is not an effective treatment strategy for prevention of relapse in bipolar disorder.

Psychiatric co-morbidity is often inadequately controlled for in studies on cognitive functioning in depression. Our recent study established no major deficits in cognition among young adults with a history of pure unipolar depression. The present study extends our previous work by examining the effects of psychiatric co-morbidity and other disorder characteristics on depression-related cognitive functioning.

Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample aged 21–35 years with a lifetime history of unipolar depressive disorders (n=126) and a random sample of healthy controls derived from the same population (n=71). Cognitive functioning was also compared between the subgroups of pure (n=69) and co-morbid (n=57) depression.

The subgroups of pure and co-morbid depression did not differ in any of the cognitive measures assessed. Only mildly compromised verbal learning was found among depressed young adults in total, but no other cognitive deficits occurred. Received treatment was associated with more impaired verbal memory and executive functioning, and younger age at first disorder onset with more impaired executive functioning.

Psychiatric co-morbidity may not aggravate cognitive functioning among depressed young adults. Regardless of co-morbidity, treatment seeking is associated with cognitive deficits, suggesting that these deficits relate to more distress.

Many patients with major depressive disorder (MDD) who experience full symptomatic remission after antidepressant treatment still have residual depressive symptoms. We describe the types and frequency of residual depressive symptoms and their relationship to subsequent depressive relapse after treatment with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Participants in primary (n=18) and psychiatric (n=23) practice settings were openly treated with citalopram using measurement-based care for up to 14 weeks and follow-up for up to 1 year. We assessed 943 (32.8% of 2876) participants who met criteria for remission to determine the proportions with individual residual symptoms and any of the nine DSM-IV criterion symptom domains to define a major depressive episode. At each visit, the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16) and the self-report Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale were used to assessed depressive symptoms and side-effects respectively.

More than 90% of remitters had at least one residual depressive symptom (median=3). The most common were weight increase (71.3%) and mid-nocturnal insomnia (54.9%). The most common residual symptom domains were sleep disturbance (71.7%) and appetite/weight disturbance (35.9%). Those who remitted before 6 weeks had fewer residual symptoms at study exit than did later remitters. Residual sleep disturbance did not predict relapse during follow-up. Having a greater number of residual symptom domains was associated with a higher probability of relapse.

Patients with remission of MDD after treatment with citalopram continue to experience selected residual depressive symptoms, which increase the risk of relapse.

This study examined whether there were associations between individual measures of socio-economic status (SES) and the 12-month prevalence of major depressive disorder (MDD) in representative samples of Blacks, Latinos, Asians and Whites in the USA.

The data used were from the Collaborative Psychiatric Epidemiology Studies (CPES).

There was an association between household income and MDD among Whites. However, the association was not statistically significant. Statistically significant associations were present between educational attainment and MDD among Whites. Among both Whites and Latinos, being out of the labor force was significantly associated with MDD. In analyses by nativity, being out of the labor force was significantly associated with MDD among US-born and foreign-born Latinos.

Significant associations between various measures of SES and MDD were consistently observed among White and, in some cases, Latino populations. Future studies should continue to examine sociopsychological factors related to SES that increase the risk of MDD among people from racial-ethnic communities.

Little research has focused on delineating the specific predictors of emotional over-involvement (EOI) and critical comments (CC) in the early course of psychosis. The purpose of this study was to investigate the differential relationships of EOI and CC with relevant predictors in relatives of first-episode psychosis (FEP) patients.

Baseline patient-related factors including psychotic symptoms, depression and duration of untreated psychosis (DUP) and carer attributes comprising CC, EOI, burden of care and carers' stress and depression were assessed in a cohort of 63 remitted FEP patients and their relatives. Carers were reassessed at 7 months follow-up.

Baseline analysis showed that EOI was more strongly correlated with family stress compared with CC, whereas CC yielded a stronger association with DUP than EOI. Carers' CC at follow-up was not significantly predicted by either baseline family stress, burden of care or patient-related variables. Conversely, baseline EOI predicted both family stress and burden of care at 7 months follow-up. Finally, family burden of care at follow-up was a function of baseline EOI and patients' depressive symptoms.

This study provides preliminary support to the postulate that EOI and CC may be influenced by separate factors early in the course of psychosis and warrant future research and therapeutic interventions as separate constructs. Implications for family interventions in the early phase of psychosis and the prevention of CC and EOI are discussed.

Empirical evidence of the efficacy and effectiveness of psychosocial family intervention and of the specificity of its effects on the course of schizophrenia is limited. The aim was to study the efficacy and effectiveness of psychosocial family intervention with regard to clinical and social functioning and family burden after controlling for compliance and several prognostic factors.

A 2-year randomized controlled trial with blind assessments. Fifty patients with DSM-IV schizophrenia and persistent positive symptoms and/or previous clinical relapse were allocated to psychosocial family intervention, individual counselling and standard treatment versus individual counselling and standard treatment.

Family intervention was associated with fewer clinical relapses, hospitalizations and major incidents, and an improvement in positive and negative symptoms, social role performance, social relations, employment and family burden. The reduction in hospitalizations in the family intervention group was significantly greater than that observed in the group of patients who refused to participate but this was not the case for the control group. The effects of family intervention were independent of compliance and prognostic factors.

Family intervention is effective in severe schizophrenia independently of compliance and prognostic factors.

Recent guidelines for the treatment of irritable bowel syndrome (IBS) emphasize the need for research to facilitate home-based self-management for these patients in primary care. The aim of the current study was to test the efficacy of a manualized cognitive behavioural therapy (CBT)-based self-management programme for IBS in a pilot randomized controlled trial (RCT).

Sixty-four primary-care patients meeting Rome criteria for IBS were randomized into either self-management plus treatment as usual (TAU) (n=31) or a TAU control condition (n=33). The self-management condition included a structured 7-week manualized programme that was self-administered in conjunction with a 1-hour face-to-face therapy session and two 1-hour telephone sessions. The primary outcome measures were the Subject's Global Assessment (SGA) of Relief and the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) assessed at baseline, end of treatment (2 months), and 3 and 6 months post-treatment.

Analysis was by intention-to-treat. Twenty-three (76.7%) of the self-management group rated themselves as experiencing symptom relief across all three time periods compared to seven (21.2%) of the TAU controls [odds ratio (OR) 12.2, 95% confidence interval (CI) 3.72–40.1]. At 8 months, 25 (83%) of the self-management group showed a clinically significant change on the IBS-SSS compared to 16 (49%) of the control group (OR 5.3, 95% CI 1.64–17.26).

This study provides preliminary evidence that CBT-based self-management in the form of a structured manual and minimal therapist contact is an effective and acceptable form of treatment for primary-care IBS patients.

The relationship between metabolic control and cognitive function in adolescents with type 1 diabetes (DM type 1) is not clear. We compared the quality of glycemic control (GC) and cognitive measures in adolescents with DM type 1 to find out if the quality of diabetes management is related to cognitive impairment.

We assessed executive functions (EFs) and other neuropsychological and psychosocial variables in 70 adolescent patients with DM type 1 and 20 age-matched controls. Patients were divided into two groups according to their last hemoglobin A1c (HbA1c): acceptable (HbA1c 5.9–8.0%, mean 6.9%, 36 patients, mean age 14 years) and non-optimal (HbA1c 8.2–11.6%, mean 9.3%, 34 patients, mean age 15.6 years).

We found impaired EFs, mainly problems of concept formation (p=0.038), cognitive flexibility (p=0.011) and anticipation (p=0.000), in the patients with DM type 1. Both groups did not differ in intelligence, most assessed EFs and adjustment to chronic illness (Youth Self-Report; YSR). Younger patients (<15 years) were cognitively less flexible. GC was worse in older patients and in patients with longer duration of the disease. We also found significant differences between patients with diabetes and controls concerning somatic complaints, internalizing problems (Child Behavior Checklist; CBCL) and social activity (CBCL and YSR).

DM type 1 is associated with cognitive deficits in adolescents independent of the quality of metabolic control and the duration of the disease. These deficits are probably related to the disease, especially in patients with early-onset diabetes.

Little is known about the association of eating disorder subtypes across multiple categories of substance use in population-based samples. We examined the association between eating disorders and substance use in a large population-based sample.

Female participants (n=13 297) were from the Swedish Twin Registry [Lichtenstein et al., Twin Research and Human Genetics (2006) 9, 875–882]. Substance use was examined in four defined groups – (1) anorexia nervosa (AN); (2) bulimia nervosa (BN); (3) AN and BN (ANBN); and (4) binge eating disorder (BED) as well as a referent group without eating disorder (no ED). Secondary analyses examined differences between restricting AN (RAN) and binge and/or purge AN (ANBP).

In general, eating disorders were associated with greater substance use relative to the referent. The AN group had significantly increased odds for all illicit drugs. Significant differences emerged across the RAN and ANBP groups for alcohol abuse/dependence, diet pills, stimulants, and polysubstance use with greater use in the ANBP group. Across eating disorder groups, (1) the BN and ANBN groups were more likely to report alcohol abuse/dependence relative to the AN group, (2) the ANBN group was more likely to report diet pill use relative to the AN, BN and BED groups, and (3) the BN group was more likely to report diet pill use relative to the no ED, AN and BED groups.

Eating disorders are associated with a range of substance use behaviors. Improved understanding of how they mutually influence risk could enhance understanding of etiology and prevention.

Worry is considered a key feature of generalized anxiety disorder (GAD), whose neural correlates are poorly understood. It is not known whether the brain regions involved in pathological worry are similar to those involved in worry-like mental activity in normal subjects or whether brain areas associated with worry are the same for different triggers such as verbal stimuli or faces. This study was designed to clarify these issues.

Eight subjects with GAD and 12 normal controls underwent functional magnetic resonance imaging (fMRI) mood induction paradigms based on spoken sentences or faces. Sentences were either neutral or designed to induce worry. Faces conveyed a sad or a neutral mood and subjects were instructed to empathize with those moods.

We found that the anterior cingulate and dorsal medial prefrontal cortex [Brodmann area (BA) 32/23 and BA 10/11] were associated with worry triggered by sentences in both subjects with GAD and normal controls. However, GAD subjects showed a persistent activation of these areas even during resting state scans that followed the worrying phase, activation that correlated with scores on the Penn State Worry Questionnaire (PSWQ). This region was activated during the empathy experiment for sad faces.

The results show that worry in normal subjects and in subjects with GAD is based on activation of the medial prefrontal and anterior cingulate regions, known to be involved in mentalization and introspective thinking. A dysregulation of the activity of this region and its circuitry may underpin the inability of GAD patients to stop worrying.

Most neuroimaging studies of specific phobia have investigated the animal subtype. The blood-injection-injury (BII) subtype is characterized by a unique biphasic psychophysiological response, which could suggest a distinct neural substrate, but direct comparisons between phobia types are lacking.

This study compared the neural responses during the presentation of phobia-specific stimuli in 12 BII phobics, 14 spider (SP) phobics and 14 healthy controls using functional magnetic resonance imaging (fMRI).

Subjective ratings showed that the experimental paradigm produced the desired symptom-specific effects. As in many previous studies, when viewing spider-related stimuli, SP phobics showed increased activation in dorsal anterior cingulate and anterior insula, compared to BII phobics and healthy controls. However, when viewing images of blood-injection-injuries, participants with BII phobia mainly showed increased activation in the thalamus and visual/attention areas (occipito-temporo-parietal cortex), compared with the other two groups. The degree of provoked anxiety and disgust by phobia-relevant images was strongly associated with activation in several common regions across the two phobia groups (thalamus, cerebellum, occipito-temporal regions) but only correlated with activation in the dorsal anterior cingulate gyrus and the anterior insula in the SP phobics.

These results suggest partially distinct neurobiological substrates of animal and BII phobias and support their current classification as two distinct subtypes in the DSM-IV-TR. Further research is needed to better understand the precise neurobiological mechanisms in BII phobia and particularly the fainting response.

Abnormal levels of biomarkers in cerebrospinal fluid (CSF) and atrophy of medial temporal lobe (MTL) structures on magnetic resonance imaging (MRI) are being used increasingly to diagnose early Alzheimer's disease (AD). We evaluated the claim that these biomarkers can detect preclinical AD before behavioural (i.e. memory) symptoms arise.

We included all relevant longitudinal studies of CSF and MRI biomarkers published between January 2003 and November 2008. Subjects were not demented at baseline but some declined to mild cognitive impairment (MCI) or to AD during follow-up. Measures of tau and beta-amyloid in CSF, MTL atrophy on MRI, and performance on delayed memory tasks were extracted from the papers or obtained from the investigators.

Twenty-one MRI studies and 14 CSF studies were retrieved. The effect sizes of total tau (t-tau), phosphorylated tau (p-tau) and amyloid beta 42 (aβ42) ranged from 0.91 to 1.11. The effect size of MTL atrophy was 0.75. Memory performance had an effect size of 1.06. MTL atrophy and memory impairment tended to increase when assessed closer to the moment of diagnosis, whereas effect sizes of CSF biomarkers tended to increase when assessed longer before the diagnosis.

Memory impairment is a more accurate predictor of early AD than atrophy of MTL on MRI, whereas CSF abnormalities and memory impairment are about equally predictive. Consequently, the CSF and MRI biomarkers are not very sensitive to preclinical AD. CSF markers remain promising, but studies with long follow-up periods in elderly subjects who are normal at baseline are needed to evaluate this promise.

Panic disorder (PD) is generally considered to be a chronic or intermittent disorder. This view may be biased because of a lack of general population studies investigating panic from the onset of an episode onwards. Data regarding the course of subthreshold panic disorder (sub-PD) and predictors of its course are lacking.

Using data from a large community-based survey, the Netherlands Mental Health and Incidence Study (NEMESIS), that retrospectively assessed the 2-year course of panic with a Life Chart Interview (LCI), this study investigated remission, chronicity and recurrence in subjects with new episodes of PD or sub-PD. Predictor variables of remission consisted of sociodemographics, psychobiological, environmental, psychiatric and panic-related factors.

In PD, remission of panic attacks occurred in 64.5% of subjects, mean time to remission was 5.7 months, and the remission rate was 5.8/100 person-months. In 43.3% of subjects panic was still present after 1 year. Recurrence of panic attacks occurred in 21.4% of those with PD who had achieved remission and for whom sufficient follow-up time was available. In general, the course of sub-PD was more favourable. Predictors of remission were female gender, the absence of ongoing difficulties, subthreshold panic and a low initial frequency of attacks.

These results suggest that the course of panic is diverse in the general population, thereby underlining the need for accurate predictors. This requires further research including biological data and additional psychological data. In addition, given the large proportion with a relapse, relapse prevention should be part of any treatment programme.

Recent research has documented a link between attention problems at school entry and later academic achievement. Little is known about the association of change in attention problems during the early school years with subsequent change in academic achievement.

A community-based cohort was followed up and assessed for attention problems at ages 6 and 11 (Teacher Report Form; TRF) and for academic achievement in math and reading at ages 11 and 17 (Woodcock–Johnson Psycho-Educational Battery). Complete data were available on 590 children (72% of the initial sample). Ordinary least squares regressions were used to estimate change in academic achievement from age 11 to age 17 in relation to change in TRF-attention problems from age 6 to age 11. Children's IQ and family factors were statistically controlled.

Change in teachers' ratings of attention problems from age 6 to age 11 was negatively associated with change in math and reading from age 11 to age 17, controlling for children's IQ and family factors. Externalizing problems had no significant association with change in math or reading, when added to the multivariable model.

Increases in teacher-rated attention problems from age 6 to age 11 were followed by declines in academic achievement from age 11 to age 17; decreases were followed by gains. The results underscore the need for research on the course of attention problems, the testing of interventions to address children's early attention problems and the evaluation of their effects on subsequent academic achievement.