Key questions remain unaddressed concerning the nature of interpersonal functioning in trauma survivors, including the ability to understand and interpret other people's thoughts and feelings. Here, we investigate theory of mind (ToM) performance of women with PTSD related to childhood abuse in comparison to healthy controls.
Participants completed two ToM tasks, the Interpersonal Perception Task-15 (IPT-15) and the Reading the Mind in the Eyes Task – Revised (RMET).
Relative to controls, women with a history of childhood trauma had difficulty recognizing familial relationships depicted in the IPT-15 (P = 0.005). No other category of the IPT-15 showed significant group differences. In addition, while healthy women displayed faster RMET reaction times to emotionally valenced mental states (positive: P = 0.003; negative: P = 0.016) compared with neutral mental states, the PTSD group showed similar reaction times across all valences. The presence of dissociative symptoms (e.g., disengagement, amnesia, identity dissociation) was strongly associated with hindered accuracy of complex mental state identification and altered perception of kinship interactions.
Women with PTSD stemming from childhood trauma show changes in ToM abilities particularly those often involved in the interpretation of family interactions. In addition, individuals with PTSD showed slower reaction times during the recognition of complex mental states from emotionally salient facial/eye expressions in comparison with healthy subjects.
Treatment of schizophrenia is frequently complicated by patients' ambivalence and lack of insight into the disease, occasionally warranting involuntary treatment. This study aims to describe involuntary treatment in Danish schizophrenia patients.
Patients diagnosed with a lifetime ICD-10 F20 schizophrenia diagnosis and alive in the period 2004–2010 were identified in the Danish Psychiatric Central Research Register, and data were linked to The Registry of Coercive Measures in Psychiatric Treatment.
Within the study period, a total of 18 599 admitted patients were identified, 3078 of which underwent involuntary treatment. The incidence rate for any involuntary treatment was 2.1 per in-patient year and 1.7 and 0.3 per in-patient year for rapid tranquilization and involuntary treatments, respectively. Somatic diseases comprised 34.5% of all involuntary treatments. Psychotropics comprised 56.9% with antipsychotics as the most common drug class (99.5%). Olanzapine was the most commonly used antipsychotic drug (33.2%). Treatment with depot injection and clozapine comprised only 13% and 4.8% of the antipsychotics used, respectively. Electroconvulsive therapy comprised 4.8% of all involuntary treatment.
Involuntary treatment involved a wide range of somatic treatment. Antipsychotic medicine was the most common psychotropic used. Involuntary treatment with depot antipsychotics and clozapine were rare.
The pharmaceutical industry exercises pervasive influence in the mental health field. The internet has become a primary source of mental health information for the public and practitioners. This study therefore compared mental health websites funded and not funded by drug companies.
A systematic literature review of studies examining the role of drug companies in the funding of mental health websites was conducted, followed by a meta-analysis of studies comparing drug company–funded (DCF) sites with sites not funded by the industry.
Mental health websites, in general, overemphasize biogenetic causal explanations and medication. Many mental health websites (42%) are either drug company owned (6%) or receive funding from drug companies (36%). A meta-analysis found that DCF sites are significantly more biased toward biogenetic causes (P < 0.01) and toward medication (P < 0.0001) than sites that are financially independent of the industry.
Practitioners are encouraged to inform patients about the bias inherent in industry-sponsored websites and to recommend, instead, more balanced websites that present a range of evidence-based information about causes and treatments.
This article provides an overview of research on the neurobiological correlates of childhood adversity and a selective review of treatment implications.
Findings from a broad array of human and animal studies of early adversity were reviewed.
Topics reviewed include neuroendocrine, neurotrophic, neuroimaging, and cognitive effects of adversity, as well as genetic and epigenetic influences. Effects of early-life stress on treatment outcome are considered, and development of treatments designed to address the neurobiological abnormalities is discussed.
Early adversity is associated with abnormalities of several neurobiological systems that are implicated in the development of psychopathology and other medical conditions. Early-life stress negatively impacts treatment outcome, and individuals may require treatments that are specific to this condition.
Psychotic symptoms are common in the population and index risk for a range of severe psychopathological outcomes. We wished to investigate functional connectivity in a community sample of adolescents who reported psychotic symptoms (the extended psychosis phenotype).
This study investigated intrinsic functional connectivity (iFC) during resting-state functional magnetic resonance imaging (fMRI; rs-fMRI). Following screening in schools, 11 non-treatment seeking, youth with psychotic symptoms (aged 11–13) and 14 community controls participated in the study. Seed regions of interest comprised brain regions previously shown to exhibit aberrant activation during inhibitory control in adolescents with psychotic symptoms.
Relative to controls, adolescents with psychotic symptoms exhibited reduced iFC between regions supporting inhibitory control. Specifically, they showed weaker iFC between the right inferior frontal gyrus (IFG) and the cingulate, IFG and the striatum, anterior cingulate and claustrum, and precuneus and supramarginal gyrus. Conversely, the psychotic symptoms group exhibited stronger iFC between the superior frontal gyrus and claustrum and IFG and lingual gyrus.
The present findings are the first to reveal aberrant functional connectivity in resting-state networks in a community sample of adolescents with psychotic symptoms and suggest that disruption in integration between distributed neural networks (particularly between prefrontal, cingulate and striatal brain regions) may be a key neurobiological feature of the extended psychosis phenotype.
An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view.
Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task.
Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26–0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression.
This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.
Lithium (Li) is often an effective treatment for mood disorders, especially bipolar disorder (BPD), and can mitigate the effects of stress on the brain by modulating several pathways to facilitate neural plasticity. This review seeks to summarize what is known about the molecular mechanisms underlying Li's actions in the brain in response to stress, particularly how Li is able to facilitate plasticity through regulation of the glutamate system and cytoskeletal components.
The authors conducted an extensive search of the published literature using several search terms, including Li, plasticity, and stress. Relevant articles were retrieved, and their bibliographies consulted to expand the number of articles reviewed. The most relevant articles from both the clinical and preclinical literature were examined in detail.
Chronic stress results in morphological and functional remodeling in specific brain regions where structural differences have been associated with mood disorders, such as BPD. Li has been shown to block stress-induced changes and facilitate neural plasticity. The onset of mood disorders may reflect an inability of the brain to properly respond after stress, where changes in certain regions may become ‘locked in’ when plasticity is lost. Li can enhance plasticity through several molecular mechanisms, which have been characterized in animal models. Further, the expanding number of clinical imaging studies has provided evidence that these mechanisms may be at work in the human brain.
This work supports the hypothesis that Li is able to improve clinical symptoms by facilitating neural plasticity and thereby helps to ‘unlock’ the brain from its maladaptive state in patients with mood disorders.
To review the DSM-5 proposed criteria for mixed depression in light of robust and consistent historical and scientific evidence.
An extensive historical search, a systematic review of the papers used by DSM-5 as reference papers, and a PubMed search were performed.
As Hippocrates, depressive mixed states have been described as conditions of intense psychic suffering, consisting of depressed mood, inner tension, restlessness, and aimless psychomotor agitation. In DSM-5, new criteria are proposed for a mixed features specifier, as part of depression either in major depressive disorder (MDD) or bipolar disorder. Those criteria require, as diagnostically specific, manic/hypomanic symptoms that are the least common kinds of symptoms that actually arise in depressive mixed states. The DSM-5 proposal is based, almost entirely, on a speculative wish to avoid ‘overlapping’ manic and depressive symptoms. Mixed states are, in fact, nothing but overlapping manic and depressive symptoms.
In this article, we review the psychopathology and research on mixed depressive states, and try to demonstrate that the DSM-5 proposal has weak scientific basis and does not identify a large number of mixed depressive states. This may be harmful because of the different treatment required by these conditions.
The aim of this study was to explore any heterogeneity in the 6-month clinical response in patients with antipsychotic drug-naive schizophrenia and to determine predictors of that outcome.
467 patients with antipsychotic drug-naive schizophrenia were included in France nationwide and followed up over 6 months. To identify trajectories of clinical response, a latent class growth analysis (LCGA) was performed using the Clinical Global Impression-Severity (CGI-S) scores at baseline, 1, 3, and 6 months. Regression models were used to identify predictors of trajectory membership.
Five trajectory groups were identified: a rapid response group (n = 45), a gradual response group (n = 204), patients remaining mildly ill (n = 133), patients remaining very ill (n = 23), and a group with unsustained clinical response (n = 62). Predictors of the 6-month clinical response were baseline CGI-S score (odds ratio: 3.1; 95% confidence interval, 2.1–4.4) and negative symptoms (OR, 1.5; 95% CI, 1.2–1.9). The sole predictor of rapid response as compared to gradual response was employment (OR, 2.5; 95% CI, 1.2–4.9).
Clinical response in patients with schizophrenia 6 months after a first-ever antipsychotic drug initiation is heterogeneous. Therapeutic strategies in first episode should take account of symptom severity and early clinical response, to maximize the chances of recovery.
Bipolar disorder has been associated with elevated impulsivity – a complex construct subsuming multiple facets. We aimed to compare specific facets of impulsivity in bipolar disorder, including those related to key psychological correlates of the illness: reward sensitivity and strong emotion.
Ninety-one individuals diagnosed with bipolar I disorder (inter-episode period) and 80 controls completed several well-validated impulsivity measures, including those relevant to reward (Fun-seeking subscale of the Behavioral Activation System scale) and emotion (Positive Urgency and Negative Urgency scales).
Bipolar participants reported higher impulsivity scores than did controls on all of the impulsivity measures, except the Fun-seeking subscale of the Behavioral Activation System scale. Positive Urgency – a measure assessing the tendency to act impulsively when experiencing strong positive emotion – yielded the largest group differences: F(1,170) = 78.69, P < 0.001, partial η2 = 0.316. Positive Urgency was also associated with poorer psychosocial functioning in the bipolar group: ΔR2 = 0.24, b = −0.45, P < 0.001.
Individuals with bipolar I disorder appear to be at particular risk of behaving impulsively when experiencing strong positive emotions. Findings provide an important first step toward developing a more refined understanding of impulsivity in bipolar disorder with the potential to inform targeted interventions.
Impaired insight is an important and prevalent symptom of psychosis. It remains unclear whether cognitive disturbances hamper improvements in insight. We investigated the neurocognitive, social cognitive, and clinical correlates of changes in insight.
One hundred and fifty-four patients with a psychotic disorder were assessed at baseline (T0) and after three years (T3) with the Birchwood Insight Scale, the Positive And Negative Syndrome Scale, measures of neurocognition and social cognition. Linear regression analyses were conducted to examine to what extend neurocognition, social cognition, clinical symptoms and phase of illness could uniquely predict insight change. Subsequently, changes in these factors were related to insight change.
Better neurocognitive performance and fewer clinical symptoms at baseline explained insight improvements. The additional effect of clinical symptoms over and above the contribution of neurocognition was significant. Together, these factors explained 10% of the variance. Social cognition and phase of illness could not predict insight change. Changes in clinical symptoms, but not changes in neurocognitive performance were associated with insight change.
Neurocognitive abilities may predict, in part, the development of insight in psychosis.
To identify differences and similarities between immigrants of Turkish origin and native German patients in therapeutically relevant dimensions such as subjective illness perceptions and personality traits.
Turkish and native German mentally disordered in-patients were interviewed in three psychiatric clinics in Hessen, Germany. The Revised Illness Perception Questionnaire (IPQ-Revised) and the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) were used. Differences of scales and similarities by k-means cluster analyses were estimated.
Of the 362 total patients, 227 (123 immigrants and 104 native Germans) were included. Neither demographic nor clinical differences were detected. Socioeconomic gradients and differences on IPQ-R scales were identified. For each ethnicity, the cluster analysis identified four different patient types based on NEO-FFI and IPQ-R scales. The patient types of each ethnicity appeared to be very similar in their structure, but they differed solely in the magnitude of the cluster means on included subscales according to ethnicity.
When subjective illness perceptions and personality traits are considered together, basic patient types emerge independent of the ethnicity. Thus, the ethnical impact on patient types diminishes and a convergence was detected.
Adults with attention deficit hyperactivity disorder (ADHD) have difficulties processing affective prosody, and research evidence demonstrates the importance of brain serotonin (5-HT) in the neurobiology of ADHD. This study aimed to investigate whether diminished brain 5-HT synthesis, as achieved by acute tryptophan depletion (ATD), can impair the processing of affective prosody in adults with ADHD.
Twenty male patients with ADHD and twenty male healthy controls received ATD and a tryptophan-balanced control condition on separate days in a double-blind within-subject repeated measures crossover design. In both conditions, the Tübingen Affect Battery was administered in which subjects had to name the affective prosody of sentences with neutral, congruent, or incongruent semantic content.
Participants in the group of patients with ADHD perceived affec-tive prosody less accurately than controls. Participants with ADHD showed compromised processing of sentences, committing more errors than healthy controls when identifying affect in instances of incongruent semantic content (P = 0.031). ATD did not contribute to this effect (all P > 0.5).
The difficulties male adults with ADHD have in accurately processing affective prosody may result from impairments in their ability to inhibit unwanted stimuli and impulses. No clear evidence implicates 5-HT as a cause of these impairments.
The high degree of heterogeneity in the development of depression under stress is unaccounted for in traditional statistical modeling. We employ growth mixture modeling to identify classes of individuals at highest risk of depression under stress.
Medical internship was used as a prospective stress model. Interns from US residency programs completed demographic, psychological, and depressive symptom assessments 2 months prior to internship and at 3-month intervals throughout internship year.
A total of 2278 (59%) of interns chose to take part in the study. Three classes of depressive symptoms were identified: i) Stress-resilient class: 62% of participants report low depressive symptoms before and throughout internship year; ii) Stress-neutral class: 22% of participants report mild depressive symptoms before and throughout internship year; and iii) Stress-sensitive class: 16% of participants report low depressive symptoms before internship stress, and high levels of depressive symptoms throughout internship year. Individuals in the Stress-sensitive class were more likely to be female, in a surgical specialty, and have a history of depression, difficulty early family environment and high-neuroticism scores compared with individuals in the Stress-resilient class.
Trajectory-based analysis allows for the identification of a high-risk group, within a heterogeneous population, that accounts for the link between stress and depression.
Growing evidence suggests that patients with bipolar disorder (BD) are impaired in their ability to process non-verbal emotion, although few comprehensive reviews of the behavioural literature exist, and there has been little consideration of methodological issues that may account for discrepant empirical findings. This review examines the behavioural facial, prosodic and multimodal processing literature in BD and discusses methodological issues in the context of this evidence.
Major computer databases including Google Scholar and PsychINFO were consulted to conduct a comprehensive review of quantitative behavioural differences in the emotion-processing literature in BD. Articles were accepted only if the target population sample met criteria for a DSM-III, DSM-IV or ICD-10 diagnosis, and they contained a healthy control group.
The current literature suggests that facial emotion processing is impaired, and there is preliminary evidence for some behavioural impairment in the processing of emotional prosody.
The specificity or generalisability of impairments in facial emotion processing and the effects of mood state are unclear. Similarly, the lack of clarity around the impact of auditory processes on emotional prosody processing warrants a comprehensive examination of the auditory profile in BD.
Progression from cognitive impairment (CI) to dementia is predicted by several factors, but their relative importance and interaction are unclear.
We investigated numerous such factors in the AgeCoDe study, a longitudinal study of general practice patients aged 75+. We used recursive partitioning analysis (RPA) to identify hierarchical patterns of baseline covariates that predicted dementia-free survival.
Among 784 non-demented patients with CI, 157 (20.0%) developed dementia over a follow-up interval of 4.5 years. RPA showed that more severe cognitive compromise, revealed by a Mini-Mental State Examination (MMSE) score < 27.47, was the strongest predictor of imminent dementia. Dementia-free survival time was shortest (mean 2.4 years) in such low-scoring patients who also had impaired instrumental activities of daily living (iADL) and subjective memory impairment with related worry (SMI-w). Patients with identical characteristics but without SMI-w had an estimated mean dementia-free survival time of 3.8 years, which was still shorter than in patients who had subthreshold MMSE scores but intact iADL (4.2–5.2 years).
Hierarchical patterns of readily available covariates can predict dementia-free survival in older general practice patients with CI. Although less widely appreciated than other variables, iADL impairment appears to be an especially noteworthy predictor of progression to dementia.
The First Episode of Psychosis (FEP) represents a period of heightened risk for aggression. However, it is not known whether this risk is significantly altered following contact with mental health services.
Meta-analytic methods were used to estimate pooled prevalence of ‘any’ and ‘serious’ aggression during FEP, while meta-regression analyses were conducted to explore reasons for heterogeneity between studies.
Fifteen studies comprising 3, 294 FEP subjects were analysed. Pooled prevalence of ‘any aggression’ before service contact was 28% (95% CI: 22–34) and following contact 31% (95% CI: 20–42). Pooled prevalence of ‘serious aggression’ was 16% (95% CI: 11–20) before service contact and 13% (95% CI: 6–20) following contact. Four studies reporting repeated assessments within the same cohort revealed that aggression rates did not significantly differ post and pre service contact: Odds Ratios for any aggression: 1.18 (95% CI: 0.46–2.99) and serious aggression: 0.61 (95% CI: 0.31–1.21).
Rates of aggression are high during FEP, both before and following initial service contact, and seem not to alter following contact. This conclusion remains tentative due to considerable heterogeneity between studies and a lack of prospective cohort studies.
To review the literature on psychological and biological findings on resilience (i.e. the successful adaptation and swift recovery after experiencing life adversities) at the level of the individual, and to integrate findings from animal and human studies.
Electronic and manual literature search of MEDLINE, EMBASE and PSYCHINFO, using a range of search terms around biological and psychological factors influencing resilience as observed in human and experimental animal studies, complemented by review articles and cross-references.
The term resilience is used in the literature for different phenomena ranging from prevention of mental health disturbance to successful adaptation and swift recovery after experiencing life adversities, and may also include post-traumatic psychological growth. Secure attachment, experiencing positive emotions and having a purpose in life are three important psychological building blocks of resilience. Overlap between psychological and biological findings on resilience in the literature is most apparent for the topic of stress sensitivity, although recent results suggest a crucial role for reward experience in resilience.
Improving the understanding of the links between genetic endowment, environmental impact and gene–environment interactions with developmental psychology and biology is crucial for elucidating the neurobiological and psychological underpinnings of resilience.
Low diagnostic reliability, the need to meet criteria of two disorders, and its status as residual diagnosis in clinical practice led us to hypothesize that schizoaffective disorder (SAD) is characterized by considerable heterogeneity, particularly in comparison with schizophrenia (SZ) and bipolar disorder (BD). As this has not been investigated the aim of this study is to test whether heterogeneity is larger in SAD than in SZ and BD.
Systematic search for studies simultaneously comparing all three diagnoses regarding demographic, clinical, psychometric (clinical rating scales and IQ tests), and biological parameters; comparison of heterogeneity as measured by standard deviation (SD).
Standard deviation of SAD samples (N = 47) was smaller than in both differential diagnoses. SDs were 7% higher in BD than in SAD (SZ: 2% higher); in studies employing DSM-IIIR/–IV pooled SD was 4% higher in BD (8% lower in SZ). Differences between diagnoses were limited to the comparison of SAD and BD, and became smaller when only psychotic BD was considered.
Heterogeneity of SZ and BD is not smaller than that of SAD. SAD seems not to be more diverse than other functional psychoses. Results are preliminary because of the novelty of the approach and to the small number of studies.
Given the familial influences on schizophrenia, it may be hypothesized that specific symptom domains also cluster within families, and that this applies to both clinical and subclinical levels of expression. This hypothesis was put to the test in a group of patients with a DSM-IV diagnosis of psychotic disorder together with their unaffected siblings, and a group of healthy sib-pairs.
Subclinical positive, negative and depressive symptoms in relatives and healthy controls were assessed with the Community Assessment of Psychic Experiences (CAPE). Positive and negative schizotypy in relatives and controls was measured with the Structured Interview for Schizotypy–Revised. Multilevel linear regression analyses were conducted to investigate clustering of symptom dimensions within patient–relative sib-pairs (N = 811 pairs), healthy sib-pairs of affected families (N = 136 pairs) and healthy control sib-pairs (N = 58 pairs).
Familial clustering of symptoms was found in all three groups. Effect sizes were largest in healthy control sib-pairs, smallest in patient–relative sib-pairs and intermediate in healthy sib-pairs of affected families.
Studies of sibling associations in genetic studies of psychometric expression of psychosis liability need to take into account the fact that the higher levels of background genetic risk and presence of diagnosed illness are inversely associated with sibling associations.
This study examined general medical illnesses and their association with clinical features of bipolar disorder.
Data were cross-sectional and derived from the Lithium Treatment – Moderate Dose Use Study (LiTMUS), which randomized symptomatic adults (n = 264 with available medical comorbidity scores) with bipolar disorder to moderate doses of lithium plus optimized treatment (OPT) or to OPT alone. Clinically significant high and low medical comorbidity burden were defined as a Cumulative Illness Rating Scale (CIRS) score ≥4 and <4 respectively.
The baseline prevalence of significant medical comorbidity was 53% (n = 139). Patients with high medical burden were more likely to present in a major depressive episode (P = .04), meet criteria for obsessive–compulsive disorder (P = .02), and experience a greater number of lifetime mood episodes (P = 0.02). They were also more likely to be prescribed a greater number of psychotropic medications (P = .002). Sixty-nine per cent of the sample was overweight or obese as defined by body mass index (BMI), with African Americans representing the racial group with the highest proportion of stage II obesity (BMI ≥35; 31%, n = 14).
The burden of comorbid medical illnesses was high in this generalizable sample of treatment-seeking patients and appears associated with worsened course of illness and psychotropic medication patterns.
To test whether the association between childhood abuse, cannabis use and psychotic experiences (PEs) was moderated by the COMT (catechol-O-methyltransferase) gene.
Psychotic experiences (PEs), childhood abuse, cannabis use and COMT Val158Met genotypes were assessed in 533 individuals from the general population. Data were analysed hierarchically by means of multiple linear regression models.
Childhood abuse showed a significant main effect on both positive (β = 0.09; SE = 0.04; P = 0.047) and negative PEs (β = 0.11; SE = 0.05; P = 0.038). A significant three-way interaction effect was found among childhood abuse, cannabis use and the COMT gene on positive PEs (β = −0.30; SE = 0.11; P = 0.006). This result suggests that COMT genotypes and cannabis use only influenced PE scores among individuals exposed to childhood abuse. Furthermore, exposure to childhood abuse and cannabis use increased PE scores in Val carriers. However, in individuals exposed to childhood abuse but who did not use cannabis, PEs increased as a function of the Met allele copies of the COMT gene.
Cannabis use after exposure to childhood abuse may have opposite effects on the risk of PEs, depending on the COMT genotypes providing evidence for a qualitative interaction. Val carriers exposed to childhood abuse are vulnerable to the psychosis-inducing effects of cannabis.
To present a systematic review of the evaluation of randomized interventions directed toward improving somatic health for patients with severe mental illness (SMI).
A systematic search in PubMed, Embase, Cinahl, and PsycInfo was performed. The scope of the search was prospective studies for patients aged 18–70, published from January 2000 till June 2011. Randomized interventions directed toward improving somatic health for patients with SMI were selected. We excluded studies on elderly, children, and studies performed before 2000. Information on population, type of intervention, follow-up, outcome measures, and on authors' conclusions were drawn from the original articles.
Twenty-two original studies were included, presenting four types of interventions: health education (n = 9), exercise (n = 6), smoking cessation (n = 5), and changes in health care organization (n = 2). To evaluate the effect of these studies 93 different outcome measures were used in 16 categories.
Many interventions directed toward improving somatic health for patients with SMI have been started. These studies did not apply similar evaluations, and did not use uniform outcome measures of the effect of their interventions. Valuable comparisons on effectiveness are therefore almost impossible.
Animal experiments and studies in adults have shown that the neurotransmitter serotonin (5-HT) plays an important role in learning and memory processes. However, data on this relationship in young persons are scarce, and neurodietary research in this age group is limited compared with the extensive literature on adults. Here, we aimed to explore the effects of a diminished central nervous 5-HT synthesis, which is achieved by acute tryptophan depletion (ATD) Moja-De , on memory function in young males with attention deficit hyperactivity disorder (ADHD).
Twenty-two male patients with ADHD (ages 9–15 years, mean 10.95 ± 1.17 years) received ATD, thus diminishing central nervous 5-HT synthesis, and a tryptophan-balanced amino acid load (BAL) in a randomized, double-blind, within-subject, crossover design study. Approximately 1.7 h after administration of ATD/BAL, verbal declarative memory was assessed using the ‘Auditory Verbal-Learning-Test’ (AVLT).
There were no significant effects of ATD administration on verbal declarative memory function.
In this study, changes in 5-HT neurotransmission were not associated with specific aspects of verbal declarative memory in young persons with ADHD. Future studies with healthy control groups that address effects of covarying attentional processes are warranted.
Personality traits are presumed to endure over time, but the literature regarding older age is sparse. Furthermore, interpretation may be hampered by the presence of dementia-related personality changes. The aim was to study stability in neuroticism and extraversion in a population sample of women who were followed from mid-life to late life.
A population-based sample of women born in 1918, 1922 or 1930 was examined with the Eysenck Personality Inventory (EPI) in 1968–1969. EPI was assessed after 37 years in 2005–2006 (n = 153). Data from an interim examination after 24 years were analysed for the subsample born in 1918 and 1922 (n = 75). Women who developed dementia at follow-up examinations were excluded from the analyses.
Mean levels of neuroticism and extraversion were stable at both follow-ups. Rank-order and linear correlations between baseline and 37-year follow-up were moderate ranging between 0.49 and 0.69. Individual changes were observed, and only 25% of the variance in personality traits in 2005–2006 could be explained by traits in 1968–1969.
Personality is stable at the population level, but there is significant individual variability. These changes could not be attributed to dementia. Research is needed to examine determinants of these changes, as well as their clinical implications.
To date, the impact of the neurotransmitter serotonin (5-HT) on different neuropsychological functions in adults with attention deficit hyperactivity disorder (ADHD) is underinvestigated. We aimed to examine the effects of acute tryptophan depletion (ATD) and the resulting reduction in central nervous 5-HT synthesis on target/non-target discrimination ability and sustained attention in adults with ADHD using an AX-Continuous Performance Test (AX-CPT).
Twenty male patients with ADHD (age: M = 30.25 SD = 9.37) and twenty male healthy controls (age: M = 27.90 SD = 6.01) received ATD on one day and a tryptophan-balanced control condition (BAL) on another day in a double-blind within-subject crossover design. A continuous performance test (AX-CPT) with three conditions (AX, AY, and BX) was administered on both days under depleted and sham-depleted conditions.
In patients omissions increased after ATD when compared with BAL. Patient's reaction time decreased after ATD when compared with BAL, which was contrasted by opposite effects in controls. Patients showed fewer correct responses (AX condition) and showed a higher rate of errors (condition AXE) independent of ATD or BAL intake.
The present preliminary results are indicative of the contribution of serotonergic neurotransmission to attentional processes in adults with ADHD.
Guided Internet-based cognitive behaviour therapy (ICBT) for panic disorder has been shown to be efficacious in several randomized controlled trials. However, the effectiveness of the treatment when delivered within routine psychiatric care has not been studied. The aim of this study was to investigate the effectiveness of ICBT for panic disorder within the context of routine psychiatric care.
We conducted a cohort study investigating all patients (n = 570) who had received guided ICBT for panic disorder between 2007 and 2012 in a routine care setting at an out-patient psychiatric clinic providing Internet-based treatment. The primary outcome measure was the Panic Disorder Severity Scale-Self-report (PDSS-SR).
Participants made large improvements from screening and pretreatment assessments to posttreatment (Cohen's d range on the PDSS-SR = 1.07–1.55). Improvements were sustained at 6-month follow-up.
This study suggests that ICBT for panic disorder is as effective when delivered in a routine care context as in the previously published randomized controlled trials.
Calcium channels are important for converting electrical activity into biochemical events. A single nucleotide polymorphism (SNP) (rs1006737) in the CACNA1C gene has been strongly associated with increased risk for Bipolar disorder (BD) in genome-wide association studies. Recently, this same SNP has been reported to influence executive function in schizophrenia and controls, but it remains unclear whether this SNP affects behaviour, especially cognition in subjects with BD.
A total of 109 BD type I subjects and 96 controls were genotyped for CACNA1C rs1006737 and assessed with an executive function tests battery [Wechsler Adult Intelligence Scale III (WAIS-III) Letter-Number Sequence subtest (WAIS-LNS), digit span (WAISDS), trail making test (TMT), and WCST (Wisconsin Card Sorting Test)].
In patients with BD, the CACNA1C genotype Met/Met was associated with worse performance on all four executive function tests compared to Val/Val. No influence of CACNA1C was observed in the cognitive performance of healthy controls.
Our data indicate for the first time that the CACNA1C risk allele is likely associated with executive dysfunction as a trait in BD, as this association was found regardless the presence of mood symptoms. Larger studies should evaluate the potential influence of CACNA1C on other cognitive domains in BD.
The aim of this study was to examine the association of lay attributions about causes of depression with attitudes and prejudiced behaviour towards people with depression.
Subjects (1631 German-speakers aged 18 and over, randomly selected) were interviewed in two German cities by telephone using a standardized questionnaire. The survey assessed knowledge about depression, stereotypical attitudes and social distance towards persons with depression.
The results indicate that a majority of the respondents holds predominantly non-pejorative attitudes towards persons with depression. The majority estimated psychosocial causes as being most important for the genesis of depression. Stronger social distance was linked to an estimation of personal causes as relevant. Subgroup differences were apparent with respect to age, sex and reported contact to people with depression.
Improvements in the education of the public about depression should be based on a multifactorial model. Future interventions should promote contact with people with depression and place special emphasis on conveying information in a suitable manner depending on the needs of different target groups.
No instrument has been developed and validated across cultures to measure the degree of support provided by informal carers to people with schizophrenia. We aimed to develop such a measure.
The Maristán Scale of Informal Care was developed directly from the views of patients with schizophrenia in six countries. Face-to-face interviews were carried out with participants and 103 were repeated after 30 days. Principal Axis Factoring followed by Promax rotation evaluated the structure of the scale. Horn's parallel combined with bootstrapping determined the number of factors. Cronbach's alpha estimated the scale's internal consistency and intra-class correlation its test-retest reliability.
A total of 164 interviews were undertaken, 103 with re-test. The Horn's Parallel Analysis and the analysis of the Promax rotation revealed one factor. Cronbach's alpha was 0.89. Intra-class correlation coefficient was 0.56 (95% CI 0.42–0.68) and this increased to 0.64 (95% CI 0.51–0.75) after removing two outlying values. Patients from Argentina recorded the lowest scores (poor informal support/care).
The Maristán Scale of Informal Care is a reliable instrument to assess the degree of support provided by informal carers to people with schizophrenia across cultures. A confirmatory factor analysis is needed to evaluate the stability of its factor structure.
Dark-skinned immigrants have a higher risk for schizophrenia and other psychoses than other immigrants. The first British studies reported that first-generation immigrants (FGIs) from the Caribbean presented atypical psychoses. This study examines the characteristics of psychotic episodes in black FGIs to Canada.
The charts of 18 FGIs from Africa and Haiti, extracted from a series of 20 black patients consecutively admitted to Psychiatry, were retrospectively reviewed regarding clinical features, diagnoses and vitamin D levels.
Young FGIs presented acute psychotic episodes with abrupt onset, florid positive symptoms, few negative symptoms and good evolution. The onset was more insidious in older FGIs. Overall, catatonia was very frequent (28%), and mood symptoms still more frequent (44%). No cognitive decline was observed during follow-up. Serum levels of 25-hydroxy vitamin D were in the insufficiency range. Supplementation at 1000 IU/day did not restore normal levels.
The clinical features of psychotic episodes in black FGIs are similar to those reported in dark-skinned FGIs to other countries. They are also observed in other immigrants and in non-immigrants. These atypical psychoses are possibly related to a recent vitamin D deficit. This hypothesis should be tested by clinical trials of sufficient vitamin D supplementation.
This review explores the influence of anxiety and depression on the experience of positive psychotic symptoms, and investigates the possibility of a causal role for anxiety and depression in the emergence and persistence of psychosis.
A systematic literature search was undertaken, producing a number of papers which comment on the links between anxiety and depression, and the experience of delusions and hallucinations. In addition, evidence which could contribute to our understanding of the causal role of anxiety and depression was highlighted.
The findings show that both anxiety and depression are associated in meaningful ways with the severity of delusions and hallucinations, the distress they elicit and their content. However, the cross-sectional nature of the majority of studies and the focus on certain symptom subtypes tempers the validity of the findings. Data from non-clinical samples, studies which track the longitudinal course of psychosis and those which examine the impact of anxiety and depression on the prognosis for people experiencing psychosis, offer some support for the possibility of an influential role for anxiety and depression.
We conclude that anxiety and depression are related to psychotic symptom severity, distress and content and are also linked with sub-clinical experiences, symptom development, prognosis and relapse. These links may imply that anxiety and depression could be targets for therapeutic intervention. The article concludes with suggestions for further research, highlighting avenues which may circumvent the limitations of the body of work as it stands.
The study focuses on the controversial relationship between borderline personality disorder (BPD) and bipolar disorder (BD), defined according to different criteria set, in a world-wide sample of patients with a current major depressive episode (MDE).
A total of 5635 patients with an MDE were enrolled in a multinational study, designed to assess varying definition of hypo/mania and familial and clinical variables associated with bipolarity. Patients with (BPD+) and without (BPD−)comorbid BPD were compared on sociodemographic, familial and clinical characteristics.
Five hundred and thirty-two patients (9.3%) met criteria for BPD. A diagnosis of BD was more frequent in BPD+ than in BPD− using either DSM-IVTR-modified criteria or the bipolar specifier. BPD+ were younger than BPD− depressives with regard to age and age at onset. They also showed more hypomania/mania in first-degree relatives in comparison to BPD− as well as more psychiatric comorbidity, psychotic symptoms, mixed states, atypical features, seasonality of mood episodes, suicide attempts, prior mood episodes and antidepressants-induced hypo/manic switches.
In our sample, selected on the basis of the presence of a mood disorder, the BD-BPD connection is confirmed by the high prevalence of bipolarity in depressive patients with BPD and by the significant association with familial and clinical features classically considered as external validators of bipolarity.
Employment outcome in bipolar disorder is an under investigated, but important area. The aim of this study was to identify the long-term employment outcomes of people with bipolar disorder.
A systematic review using the Medline, PsychInfo and Web of Science databases.
Of 1962 abstracts retrieved, 151 full text papers were read. Data were extracted from 25 papers representing a sample of 4892 people with bipolar disorder and a mean length of follow-up of 4.9 years. Seventeen studies had follow-up periods of up to 4 years and eight follow-up of 5–15 years. Most studies with samples of people with established bipolar disorder suggest approximately 40–60% of people are in employment. Studies using work functioning measures mirrored this result. Bipolar disorder appears to lead to workplace underperformance and 40–50% of people may suffer a slide in their occupational status over time. Employment levels in early bipolar disorder were higher than in more established illness.
Bipolar disorder damages employment outcome in the longer term, but up to 60% of people may be in employment. Whilst further studies are necessary, the current evidence provides support for extending the early intervention paradigm to bipolar disorder.
This study examined crime and violence in patients with schizophrenia with and without comorbid substance-use disorders.
A case-linkage design was used to compare patterns of violence and offending between 4168 schizophrenia patients drawn from a state-wide public mental health register, both with and without comorbid substance-use disorders, and a randomly selected community control group who had never been diagnosed with schizophrenia.
Schizophrenia patients were significantly more likely than controls to be guilty of violent and non-violent offences, and to have been involved in family violence. Even schizophrenia patients without comorbid substance-use disorders had a significantly elevated risk of violence; this group were more than twice as likely as controls to have a violent conviction. The elevation of violence risk in schizophrenia patients was higher in females (OR = 8.59) than males (OR = 2.25).
The increased risk of violent offending in schizophrenia cannot be solely attributed to the effects of comorbid substance misuse, although comorbidity certainly heightens the likelihood of criminality. In addition to offending, people with schizophrenia are more likely than community controls to come to the attention of police via their involvement in family violence incidents. Schizophrenia is a particularly strong risk factor for violence in females.
To explore the relationship between brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), cerebral deep white matter lesions (DWMLs), and measures of white matter integrity in patients with late-onset depression, with respect to vascular risk factors.
We examined 22 patients with late-onset depression and 22 matched controls. Quantification of plasma BDNF and VEGF levels were performed with enzyme-linked immunosorbent assay (ELISA) kits. Measures of white matter integrity comprised apparent diffusion coefficient (ADC) and fractional anisotropy (FA), obtained by diffusion tensor imaging (DTI). Effects of DWMLs, FA, ADC, and vascular risk factors on BDNF and VEGF were assessed using multiple linear regression.
The BDNF and VEGF levels did not differ significantly between groups. With pooled data for patients and controls, the BDNF level was positively associated with both number (t = 2.14, P = 0.039) and volume (t = 2.04, P = 0.048) of prefrontal DWMLs and negatively associated with FA in prefrontal normal-appearing white matter (t = −2.40, P = 0.02), adjusted for age and gender. Smoking and hypercholesterolemia was positively associated with the BDNF (t = 2.36, P = 0.023) and VEGF levels (t = 2.28, P = 0.028), respectively.
Our results suggest a role for BDNF in the complex pathophysiologic mechanisms underlying DWMLs in both normal aging and late-onset depression.
To explore the possibility that autism, catatonia and psychoses in children are different manifestations of a single underlying form of brain pathology – a kind of ‘Iron Triangle’ of symptomatology – rather than three separate illnesses.
Systematic evaluation of historical case literature on autism to determine if catatonic and psychotic symptoms accompanied the diagnosis, as is found in some challenging present-day cases.
It is clear from the historical literature that by the 1920s all three diagnoses in the Iron Triangle – catatonia, autism and childhood schizophrenia – were being routinely applied to children and adolescents. Furthermore, it is apparent that children diagnosed with one of these conditions often qualified for the other two as well. Although conventional thinking today regards these diagnoses as separate entities, the presence of catatonia in a variety of conditions is being increasingly recognized, and there is also growing evidence of connections between childhood-onset psychoses and autism.
Recognition of a mixed form of catatonia, autism and psychosis has important implications for both diagnosis and treatment. None of the separate diagnoses provides an accurate picture in these complex cases, and when given single diagnoses such as ‘schizophrenia’, the standard treatment options may prove markedly ineffective.
To investigate mortality and causes of death of short-lived psychotic disorders, by carrying out a comparison with bipolar disorder and schizophrenia.
Record linkage study to the official register of causes of death of all cases aged 15–64 years who were listed for the first time in the Danish Psychiatric Register between 1995 and 2008 with an ICD-10 diagnosis of ‘acute and transient psychotic disorders’ (ATPDs; n = 4157), bipolar disorder (n = 3200) and schizophrenia (n = 4576).
A total of 232 patients (5.6%) with ATPDs, 172 (5.4%) with bipolar disorder and 233 (5.1%) with schizophrenia had died over a mean follow-up period of 6.6 years. The standardized mortality ratio for all causes, natural causes and unnatural causes was significantly high for the three conditions. Mortality of ATPDs was greater in men, with about two-thirds of all deaths resulting from natural causes mainly cardiovascular, digestive, neoplastic and respiratory diseases. Suicide was the major cause of premature death in patients with ATPDs.
These findings suggest that ATPDs are associated with an increased mortality from both natural causes and suicide.
To evaluate whether the DSM's distinction between uncomplicated (normal) vs. complicated (disordered) bereavement-related depressive episodes can be validly extended to non-bereavement stressor-related depression (SRD). Previous findings supporting the uncomplicated/complicated SRD distinction's discriminant validity were criticized as tautological because of definitional biases (e.g., ‘uncomplicated’ requires brief duration, yet duration was a validator). We tested whether uncomplicated/complicated SRD validator differences are tautological or real.
Using National Comorbidity Survey data, we compared uncomplicated SRDs, complicated SRDs, and endogenous/psychotic MDD on levels of eight pathology validators. We identified definitional biases affecting six validators, and corrected them by deleting the biasing definitional components and recalculating validator levels.
After correction of biases, uncomplicated SRDs had significantly lower pathology levels than both complicated SRDs and endogenous/psychotic MDD on seven of eight validators, disconfirming the tautology hypothesis. Regression analysis revealed that ‘uncomplicated’ cannot be equated with ‘mild’. Extending the ‘uncomplicated’ durational threshold from 2 to 6 months yielded equal or stronger discriminant validity, suggesting the arbitrariness of the current durational criterion.
Uncomplicated SRDs' lower pathology levels are because of real syndromal differences, not definitional tautologies. The uncomplicated/complicated distinction has discriminant validity when extended to non-bereavement SRDs as an indicator of normality vs. disorder.
The aim of this study was to identify psychopathological factors associated with long-term functional outcome in euthymic bipolar disorder patients and to test new measures of mood instability and symptoms intensity.
Fifty-five patients with more than 12 months of follow-up were included. In addition to traditional clinical variables, the time spent ill was documented using a modified life-charting technique based on NIHM life-charting method. New measures, Mood Instability Factor, and Mood Intensity Factor were defined and assessed. Functioning Assessment Short Test (FAST) was used to assess disability.
The follow-up period was 3.00 ± 1.51 years. Weeks with subsyndromal depressive symptoms (β = 0.133, t = 2.556, P = 0.014), weeks with mild manic symptoms (β = 1.441, t = 3.10, P = 0.003), and the Mood Instability Factor (β = 0.105, t = 3.593, P = 0.001) contributed to approximately 46% of the FAST total score variance.
New methodologies including subsyndromal symptoms and mood instability parameters might contribute to understand the worse long-term functional outcome that affects a considerable percentage of BD patients even after episode remission. Concerns about therapeutic approaches are discussed.
Although cannabis use among individuals with psychotic disorder is considerable, little is known about patterns of use and factors contributing to continuation of use. Therefore, we investigated craving in relation to cannabis use in patients with psychotic disorder and healthy controls.
The study included 58 patients with non-affective psychotic disorder and 63 healthy controls; all were frequent cannabis users. Craving was assessed with the Obsessive Compulsive Drug Use Scale (OCDUS) for cannabis, as well as in daily life using the Experience Sampling Method (ESM).
Patients scored higher on the OCDUS (B = 1.18, P = 0.022), but did not differ from controls in ESM indices of craving (all P > 0.05). In daily life, ESM craving predicted cannabis use and this was stronger in controls (χ2 = 4.5, P = 0.033; Bcontrols = 0.08, P < 0.001; Bpatients = 0.06, P < 0.001). In both groups ESM craving was predicted by negative affect, paranoia, and hallucinations (Bnegativeaffect = 0.12, P = 0.009; Bparanoia = 0.13, P = 0.013; Bhallucinations = 0.13, P = 0.028), and followed by an increase in negative affect at non-cannabis-using moments (B = 0.03, P = 0.002).
The temporal dynamics of craving as well as craving intensity in daily life appear to be similar in patients and controls. Further research is needed to elucidate the inconsistencies between cross-sectional and daily-life measures of craving in psychosis.
To determine the effectiveness of agomelatine in routine clinical practice and explore factors associated with response and continuation.
Consecutive patients prescribed agomelatine in participating psychiatric services were included. Patient demographic and outcome data were collected at treatment initiation and then at weeks 4, 8 and 12. Outcomes were analysed with respect to clinical and demographic factors.
A total of 110 patients from nine NHS trusts were followed through 12 weeks of treatment. Agomelatine was largely used in difficult-to-treat or refractory patients: 83 (75%) had failed to respond to, or relapsed on, prior antidepressants. There were high rates of physical (54.5%) and psychiatric (50.0%) comorbidity. At 12 weeks of treatment, 68 (62%) continued agomelatine treatment. Overall, 69 subjects (62.7%) improved by at least one point of the Clinical Global Impression (severity) scale. Of 42 who discontinued, 23 (56%) discontinued because of lack of efficacy and 10 (24%) due to an adverse event. Of all variables examined, only a history of more than five episodes of depression significantly predicted discontinuation of treatment (OR continuation – 0.36, 95% CI 0.14, 0.95).
Agomelatine was effective and generally well tolerated in a cohort of difficult-to-treat patients in clinical practice.
To pursue the previously long-standing but formally untested clinical view that melancholia is preferentially responsive to antidepressant medication in comparison with psychotherapy [specifically Cognitive Behavior Therapy (CBT)]. Second, to determine whether a broader action antidepressant medication sequencing regimen is superior to a Selective Serotonin Reuptake Inhibitor (SSRI) alone.
We sought to recruit a large sample of participants with melancholic depression for a 12-week trial but inclusion criteria compromised recruitment and testing the second hypothesis. The first hypothesis was evaluated by comparing 18 participants receiving antidepressant medication to 11 receiving CBT. Primary study measures were the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Endogenous Subscale (HES), rated blindly, while several secondary measures also evaluated outcome.
Participants receiving medication had a superior 12-week outcome to those receiving CBT, with significant differences present on primary measures as early as 4 weeks. At trial conclusion, the percentage improvement in HAM-D scores was 59.5% vs. 32.5%, respectively [Number Needed to Treat (NNT) = 3.9] and with those in receipt of medication returning non-significantly higher HAM-D responder (66.6% vs. 36.4%, NNT = 3.3) and remission (66.7% vs. 45.4%, NNT = 4.7) rates.
As the sample size was small and participants evidenced only moderate levels of depression severity, the study risked being underpowered and idiosyncratic. Despite the small sample, the superiority of antidepressant medication to CBT in those with a melancholic depression was distinctive in this pilot study.
To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES).
Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively.
Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts.
These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome.
To estimate the risk of developing autism-spectrum disorder (ASD) in children born to immigrants as compared with children of Dutch-born parents.
Retrospective, population-based cohort study of all live births (n = 106 953) between 1998 and 2007 in a circumscribed geographical region in the Netherlands. Cohort members were linked to the Psychiatric Case Register to identify diagnosed cases.
A total of 518 cases of ASD were identified, including 150 children with autism and 368 children with Asperger syndrome or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). Children born to migrants from developing countries were at significantly lower risk of ASD [rate ratio (RR) = 0.6, 95% confidence interval (CI) 0.5–0.9] than children of Dutch-born parents. Within the ASD group, the risk for the subgroup with Asperger syndrome and PDD-NOS was reduced (RR = 0.4, 95% CI 0.3–0.6), whereas that for narrowly defined autism was non-significantly increased (RR = 1.4, 95% CI 0.9–2.4). Migrant groups did not differ in age at diagnosis.
The results echo Swedish findings indicating a reversal of risk gradient in children of parents from developing countries, specifically a decreased risk for high-functioning and increased risk for low-functioning autism.
The aims of the present study were to assess the associations between mood, anxiety and substance use disorders, including their subtypes, and the prevalence of cardiovascular risk factors (CVRFs).
Thorough physical investigations, biological measures and standardized interview techniques were used to assess 3716 subjects of an urban area, aged 35–66 years.
Atypical depression was associated with increased prevalence of overweight, diabetes and the metabolic syndrome (OR = 1.5, 95% C.I. 1.1–2.0; OR = 2.0, 95% C.I. 1.1–3.5, OR = 1.6, 95% C.I. 1.0–2.4 respectively), whereas decreased prevalence of overweight was found in melancholic (OR = 0.7, 95% C.I. 0.6–0.9) and unspecified depression (OR = 0.8, 95% C.I. 0.7–1.0). Alcohol abuse was associated with diabetes (OR = 1.8, 95% C.I. 1.1–2.9) and dyslipidemia (OR = 1.3, 95% C.I. 1.0–1.8), alcohol dependence with dyslipidemia only (OR = 1.4, 95% C.I. 1.0–2.0). Almost all mental disorders were associated with a lifetime history of regular cigarette smoking, and atypical depression, alcohol misuse and drug dependence were associated with inactivity.
To conclude results emphasize the need to subtype depression and to pay particular attention to the atypical subtype. Comorbid alcohol misuse may further increase the cardiovascular risk. Efforts to diminish smoking in subjects with mental disorders could be crucial measures to reduce their high incidence of cardiovascular disease.
The aim of this study was to investigate outcomes of child psychiatric outpatient treatment as usual and to identify outcome predictors, with special regard to attention-deficit/hyperactivity disorder (ADHD), mood disorder, obsessive-compulsive disorder and conduct disorder.
Routinely collected data from 12 613 outpatients between July 2006 and January 2010 in Stockholm, Sweden were analysed. The outcome measure was change in Children's Global Assessment Scale (CGAS) ratings between first visit and case closure (∆CGAS).
CGAS improved during the course of treatment across all diagnostic groups, ranging from a mean change of 4 (mental retardation) to 16 (suicide attempts). ∆CGAS was two times higher in the mood disorder group compared with the ADHD group. In the mood disorder group, several psychotherapies were associated with better outcome but not medication. In the ADHD group, psychotherapeutic interventions were also associated with better outcome, but those who received treatment with central stimulants received less non-medical interventions.
Whereas the functional impairment and the level of improvement in mood disorder corresponded to previous efficacy studies, the ADHD patients were more impaired and improved less after treatment. This should prompt a critical discussion as to whether ADHD patients receive the best available treatment in CAMHS in Stockholm and elsewhere.
Recent epidemiologic studies worldwide have documented a rise in prevalence rates for autism spectrum disorders (ASD). Broadening of diagnostic criteria for ASD may be a major contributor to the rise in prevalence, particularly if superimposed on an underlying continuous distribution of autistic traits. This study sought to determine the nature of the population distribution of autistic traits using a quantitative trait measure in a large national population sample of children.
The Japanese version of the Social Responsiveness Scale (SRS) was completed by parents on a nationally representative sample of 22 529 children, age 6–15.
Social Responsiveness Scale scores exhibited a skewed normal distribution in the Japanese population with a single-factor structure and no significant relation to IQ within the normal intellectual range. There was no evidence of a natural ‘cutoff’ that would differentiate populations of categorically affected children from unaffected children.
This study provides evidence of the continuous nature of autistic symptoms measured by the SRS, a validated quantitative trait measure. The findings reveal how paradigms for diagnosis that rest on arbitrarily imposed categorical cutoffs can result in substantial variation in prevalence estimation, especially when measurements used for case assignment are not standardized for a given population.
This study used voxel-based morphometry (VBM) to investigate brain structural alterations related to trait dissociation and its relationship with post-traumatic stress disorder (PTSD).
Thirty-two subjects either developing (N = 15) or non-developing (N = 17) PTSD underwent MRI scanning and were assessed with the Dissociative Experience Scale (DES), subscales for pathological (DES-T) and non-pathological trait (DES-A) dissociation, and other clinical measures. Gray matter volume (GMV) was analyzed using VBM as implemented in SPM. PTSD and non-PTSD subjects were compared to assess brain alterations related to PTSD pathology, whereas correlation analyses between dissociation measures and GMV were performed on the whole sample (N = 32), irrespective of PTSD diagnosis, to identify alterations related to trait dissociation.
As compared to traumatized controls, PTSD subjects showed reduced GMV in the prefrontal cortex, hippocampus and lingual gyrus. Correlations with dissociation measures (DES, DES-T, and DES-A) consistently showed increased GMV in the medial and lateral prefrontal, orbitofrontal, parahippocampal, temporal polar, and inferior parietal cortices.
PTSD and dissociation seem to be associated with opposite volumetric patterns in the prefrontal cortex. Trait dissociation appears to involve increased GMV in prefrontal, paralimbic, and parietal cortices, with negligible differences between pathological and non-pathological dissociation.
This study compares diagnostic and symptom course trajectories across different anxiety disorders, and examines the role of anxiety arousal vs. avoidance behaviour symptoms in course prediction.
Data were from 834 subjects with a current anxiety disorder from the Netherlands Study of Depression and Anxiety (NESDA) who were re-interviewed after 2 years. DSM-IV-based diagnostic interviews and Life Chart Interviews (LCI) were used to assess the diagnostic and symptom course trajectory over 2 years. Anxiety arousal and avoidance behaviour symptoms were measured with LCI, Beck Anxiety Inventory and Fear Questionnaire.
Prognosis varied across disorders, with favourable remittance rates of 72.5% for panic disorder without agoraphobia and 69.7% for generalized anxiety disorder; gradually declining to 53.5% for social phobia and 52.7% for panic disorder with agoraphobia. Only 42.9% of those with multiple anxiety disorder remitted, and this group showed a more chronic course than pure anxiety disorders. Both baseline duration and severity were course predictors. Avoidance behaviour symptoms predicted the outcome better than anxiety arousal symptoms.
These data suggest that the specific anxiety disorders such as recognized by DSM-IV are useful in predicting the outcome and that this may be determined largely by the relative severity of avoidance behaviour that patients have developed.
To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-β (TGF-β) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls.
Biologic samples were retrieved from the Danish Newborn Screening Biobank. NTFs for 414 ASD cases and 820 controls were measured using Luminex technology. Associations were analyzed with continuous measures (Tobit regression) as well as dichotomized at the lower and upper 10th percentiles cutoff points derived from the controls' distributions (logistic regression).
ASD cases were more likely to have BDNF levels falling in the lower 10th percentile (odds ratios [OR], 1.53 [95% confidence intervals (CI), 1.04–2.24], P-value = 0.03). Similar pattern was seen for TGF-β in females with ASD (OR, 2.36 [95% CI, 1.05–5.33], P-value = 0.04). For NT-4, however, ASD cases diagnosed with ICD-10 only were less likely to have levels in upper 10th percentile compared with controls (OR, 0.22 [95% CI, 0.05–0.98], P-value = 0.05).
Results cautiously indicate decreased NTFs levels during neonatal period in ASD. This may contribute to the pathophysiology of ASD through impairments of neuroplasticity. Further research is required to confirm our results and to examine the potential therapeutic effects of NTFs in ASD.
Biederman J, Petty CR, Spencer TJ, Woodworth KY, Bhide P, Zhu J, Faraone SV. Examining the nature of the comorbidity between pediatric attention deficit/hyperactivity disorder and post-traumatic stress disorder.
Objective: This study sought to address the link between attention deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) in youth by providing a comprehensive comparison of clinical correlates of ADHD subjects with and without PTSD across multiple non-overlapping domains of functioning and familial patterns of transmission.
Method: Participants were 271 youths with ADHD and 230 controls without ADHD of both sexes along with their siblings. Participants completed a large battery of measures designed to assess psychiatric comorbidity, psychosocial, educational, and cognitive parameters.
Results: Post-traumatic stress disorder was significantly higher in ADHD probands vs. controls (5.2% vs. 1.7%, χ2(1) = 4.36, P = 0.04). Irrespective of the comorbidity with PTSD, ADHD subjects had similar ages at onset of ADHD, similar type and mean number of ADHD symptoms, and similar ADHD-associated impairments. PTSD in ADHD probands was significantly associated with a higher risk of psychiatric hospitalization, school impairment, poorer social functioning and higher prevalences of mood, conduct disorder, and anxiety disorders. The mean onset of PTSD (12.6 years) was significantly later than that of ADHD and comorbid disorders (all P < 0.05). Siblings of ADHD and ADHD + PTSD probands had higher prevalences of ADHD vs. siblings of controls (35% vs. 18%, z = 4.00, P < 0.001 and 67% vs. 18%, z = 4.02, P < 0.001 respectively) and siblings of ADHD+PTSD probands had a significantly higher prevalence of PTSD compared with the siblings of ADHD and control probands (20% vs. 3% and 3%, z = 2.99, P = 0.003 and z = 2.07, P = 0.04 respectively).
Conclusion: Findings indicate that the comorbidity with PTSD in ADHD leads to greater clinical severity as regards psychiatric comorbidity and psychosocial dysfunction. ADHD is equally familial in the presence of PTSD in the proband indicating that their co-occurrence is not owing to diagnostic error.
Zetterqvist J, Asherson P, Halldner L, Långström N, Larsson H. Stimulant and non-stimulant attention deficit/hyperactivity disorder drug use: total population study of trends and discontinuation patterns 2006–2009.
Objective: To explore the prevalence and discontinuation of dispensed medications for attention deficit/hyperactivity disorder (ADHD) drugs from 2006 to 2009.
Method: A total population cohort of all individuals aged 6–45 years, alive and registered as residents in Sweden during any calendar year from 2006 to 2009 (N = 5 149 791) included 41 700 patients dispensed with an ADHD drug (methylphenidate, atomoxetine, amphetamine, or dexamphetamine). The dispensing prevalence was calculated for each year, stratified on sex and age. A longitudinal analysis was also performed to compare the rates of treatment discontinuation across the strata.
Results: The dispensing prevalence increased from 2.93 per 1000 in 2006 to 6.98 in 2009 (PR = 2.38, 95% CI = 2.34–2.43). The prevalence ratio (PR) was 3.40 for adults, 22–45 years old; 2.41 for adolescents, 15–21 years old; and 1.90 for children aged 6–14. The increase was also greater in women than in men (PR = 2.92 vs. 2.19). Patients aged 15–21 were the most likely to discontinue treatment; after 3 years and 11 months, 27% of those patients were still under treatment.
Conclusion: From 2006 to 2009, the number of prescriptions dispensed for ADHD drugs increased substantially. The rate of treatment discontinuation in the age interval 15–21 is higher than expected considering the persistence rates of the disorder.
Kötting WF, Bubenzer S, Helmbold K, Eisert A, Gaber TJ, Zepf FD. Effects of tryptophan depletion on reactive aggression and aggressive decision-making in young people with ADHD.
Objective: The neurotransmitter serotonin (5-HT) has been linked to the underlying biological processes related to aggressive behaviour. However, only a few studies on this subject involving young people have been published so far.
Method: We aimed to investigate the effects of acute tryptophan depletion (ATD) on reactive aggression and decision-time for aggressive responses in a sample of young people with Attention deficit hyperactivity disorder (n = 20), a population at risk for aggressive behaviour. The study design was a double-blind within-subject crossover design. Aggression was assessed using a Point subtraction aggression game (PSAG) with high (HP) and low provocation (LP) trials 2.5 h after the intake of ATD and a tryptophan-balanced control condition.
Results: A chi-square comparison was used to identify the effect of ATD on increased aggression after LP. Boys were more likely to respond with an increased aggressive response after HP under ATD as represented by an increased relative risk and odds ratios. Girls had a higher relative risk than boys of an increased point subtraction under ATD after LP. No significant gender differences in decision-time were detected.
Conclusion: An effect of ATD on increased aggression was found in the whole sample after LP. Research involving larger samples is needed to confirm the present preliminary findings.
Attempted suicide and deliberate self-injury can occur before or after presentation with a first-episode of psychosis. The aim of the study is to identify the factors associated with suicide attempts or deliberate self-injury before and after treatment for first-episode psychosis.
A systematic review and meta-analysis of controlled studies of factors associated with either suicide attempts or deliberate self-injury, referred to here as deliberate self-harm (DSH).
The pooled proportion of patients who reported DSH prior to treatment for first-episode psychosis was 18.4% (95% Confidence Interval (CI) 14.4–23.3, N = 18 studies, I2 = 93.8). The pooled proportion of patients with DSH during the period of untreated psychosis was 9.8%, (95% CI 6.7–14.2, N = 5 studies, I2 = 58.9). The pooled proportion of patients committing DSH during periods of follow up of between 1 and 7 years was 11.4%, (95% CI, 8.3–15.5, N = 13 studies, I2 = 89.2). Categorical factors associated with an increased risk of DSH were a prior history of DSH (OR = 3.94), expressed suicide ideation (OR = 2.34), greater insight (OR = 1.64), alcohol abuse (OR = 1.68) and substance use (OR = 1.46). Continuous variables associated with an increased risk of DSH were younger age of onset (Standardized Mean Difference (SMD) = −0.28), younger age at first treatment (SMD = −0.18), depressed mood (SMD = 0.49) and the duration of untreated psychosis (SMD = 0.20). Depressed mood and substance use were associated with DSH both before and after treatment, negative symptoms were associated with DSH after treatment but not before treatment. Positive symptoms and social and global functioning were not associated with DSH. Younger age and the duration of untreated psychosis were associated with DSH before treatment but not after treatment.
Earlier treatment of first-episode psychosis and successful treatment of depression and substance use could prevent some episodes of DSH and might reduce suicide mortality in early psychosis.
To investigate differences in cognitive function and level of psychopathology in patients with schizophrenia (SZ) with or without psychological traumatization/post-traumatic stress disorder (PTSD). We hypothesized that traumatized patients with or without PTSD would have more severe cognitive impairments because of the neuropathological changes associated with PTSD, and more severe psychopathology compared with non-traumatized SZ patients.
Seventy-five SZ patients with traumatization and 217 SZ patients without traumatization were evaluated regarding the symptoms and cognitive functioning, using standard symptom scales (PANSS; CDSS) and a neuropsychological test battery (IQ, verbal memory, attention, working memory, psychomotor speed, and executive functioning).
No significant differences were observed between the groups in cognitive test performance. The patients in the traumatized group with PTSD showed significantly more current depression than the non-traumatized group (P = 0.012).
The findings did not support the hypothesis that the presence of comorbid PTSD/traumatization in SZ is associated with increased cognitive impairment. The increase in current depression in SZ with comorbid traumatization suggests that more severe psychopathology is associated with traumatization.
The objective of this multicenter randomised clinical trial was to examine the effect of exercise versus occupational therapy on mental and physical health in schizophrenia patients.
Sixty-three patients with schizophrenia were randomly assigned to 2 h of structured exercise (n = 31) or occupational therapy (n = 32) weekly for 6 months. Symptoms (Positive and Negative Syndrome Scale) and cardiovascular fitness levels (Wpeak and VO2peak), as assessed with a cardiopulmonary exercise test, were the primary outcome measures. Secondary outcome measures were the Montgomery and Åsberg Depression Rating Scale, Camberwell Assessment of Needs, body mass index, body fat percentage, and metabolic syndrome (MetS).
Intention-to-treat analyses showed exercise therapy had a trend-level effect on depressive symptoms (P = 0.07) and a significant effect on cardiovascular fitness, measured by Wpeak (P < 0.01), compared with occupational therapy. Per protocol analyses showed that exercise therapy reduced symptoms of schizophrenia (P = 0.001), depression (P = 0.012), need of care (P = 0.050), and increased cardiovascular fitness (P < 0.001) compared with occupational therapy. No effect for MetS (factors) was found except a trend reduction in triglycerides (P = 0.08).
Exercise therapy, when performed once to twice a week, improved mental health and cardiovascular fitness and reduced need of care in patients with schizophrenia.
Schennach R, Riesbeck M, Mayr A, Seemüller F, Maier W, Klingberg S, Heuser I, Klosterkötter J, Gastpar M, Schmitt A, Sauer H, Schneider F, Jäger M, Wölwer W, Gaebel W, Möller H-J, Riedel M. Should early improvement be re-defined to better predict the maintenance of response in first-episode schizophrenia patients?
Objective: To evaluate the predictive validity of early response in first-episode schizophrenia within a 1-year follow-up trial and to compare the resulting cutoff to the currently proposed early response definition (20% improvement by week 2).
Method: Receiver operator characteristic (ROC) analyses were used to identify the predictive validity of the psychopathological improvement of treatment from week 1 to week 8, regarding the maintenance of response until week 52 as well as to define the most reasonable cutoff in 132 first-episode patients. The Youden Index (maximum of sensitivity and specificity) was used to compare the newly developed and the commonly used early response definition.
Results: Starting with week 6, a reasonable validity to predict the maintenance of response was found (area under the curve = 0.721) with the best fitting cutoff being a 51.6% PANSS total score improvement. Using this cutoff 74 patients (56%) were correctly identified to become responder and maintain response during follow-up (sensitivity: 0.747). The Youden Index was higher applying the newly developed early response cutoff featuring higher specificity compared to the commonly used early response definition.
Conclusion: Regarding long-term treatment, it seems more appropriate to base predictions of the patient’s maintenance of response not before 6 weeks of treatment.
Nuevo R, Van Os J, Arango C, Chatterji S, Ayuso-Mateos JL. Evidence for the early clinical relevance of hallucinatory-delusional states in the general population.
Objective: To analyze, in a general population sample, clustering of delusional and hallucinatory experiences in relation to environmental exposures and clinical parameters.
Method: General population-based household surveys of randomly selected adults between 18 and 65 years of age were carried out. Setting: 52 countries participating in the World Health Organization’s World Health Survey were included. Participants: 225 842 subjects (55.6% women), from nationally representative samples, with an individual response rate of 98.5% within households participated.
Results: Compared with isolated delusions and hallucinations, co-occurrence of the two phenomena was associated with poorer outcome including worse general health and functioning status (OR = 0.93; 95% CI: 0.92–0.93), greater severity of symptoms (OR = 2.5 95% CI: 2.0–3.0), higher probability of lifetime diagnosis of psychotic disorder (OR = 12.9; 95% CI: 11.5–14.4), lifetime treatment for psychotic disorder (OR = 19.7; 95% CI: 17.3–22.5), and depression during the last 12 months (OR = 11.6; 95% CI: 10.9–12.4). Co-occurrence was also associated with adversity and hearing problems (OR = 2.0; 95% CI: 1.8–2.3).
Conclusion: The results suggest that the co-occurrence of hallucinations and delusions in populations is not random but instead can be seen, compared with either phenomenon in isolation, as the result of more etiologic loading leading to a more severe clinical state.