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Experts have proposed removing obsessive–compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity and familiality data to inform these issues.
Method
Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives).
Results
Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive–compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously.
Conclusions
On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV.
Observed co-morbidity among the mood and anxiety disorders has led to the development of increasingly sophisticated dimensional models to represent the common and unique features of these disorders. Patients often present to primary care settings with a complex mixture of anxiety, depression and somatic symptoms. However, relatively little is known about how somatic symptoms fit into existing dimensional models.
Method
We examined the structure of 91 anxiety, depression and somatic symptoms in a sample of 5433 primary care patients drawn from 14 countries. One-, two- and three-factor lower-order models were considered; higher-order and hierarchical variants were studied for the best-fitting lower-order model.
Results
A hierarchical, bifactor model with all symptoms loading simultaneously on a general factor, along with one of three specific anxiety, depression and somatic factors, was the best-fitting model. The general factor accounted for the bulk of symptom variance and was associated with psychosocial dysfunction. Specific depression and somatic symptom factors accounted for meaningful incremental variance in diagnosis and dysfunction, whereas anxiety variance was associated primarily with the general factor.
Conclusions
The results (a) are consistent with previous studies showing the presence and importance of a broad internalizing or distress factor linking diverse emotional disorders, and (b) extend the bounds of internalizing to include somatic complaints with non-physical etiologies.
Patients with major depressive disorder (MDD) show deficits in processing of facial emotions that persist beyond recovery and cessation of treatment. Abnormalities in neural areas supporting attentional control and emotion processing in remitted depressed (rMDD) patients suggests that there may be enduring, trait-like abnormalities in key neural circuits at the interface of cognition and emotion, but this issue has not been studied systematically.
Method
Nineteen euthymic, medication-free rMDD patients (mean age 33.6 years; mean duration of illness 34 months) and 20 age- and gender-matched healthy controls (HC; mean age 35.8 years) performed the Emotional Face N-Back (EFNBACK) task, a working memory task with emotional distracter stimuli. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure neural activity in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), orbitofrontal cortex (OFC), ventral striatum and amygdala, using a region of interest (ROI) approach in SPM2.
Results
rMDD patients exhibited significantly greater activity relative to HC in the left DLPFC [Brodmann area (BA) 9/46] in response to negative emotional distracters during high working memory load. By contrast, rMDD patients exhibited significantly lower activity in the right DLPFC and left VLPFC compared to HC in response to positive emotional distracters during high working memory load. These effects occurred during accurate task performance.
Conclusions
Remitted depressed patients may continue to exhibit attentional biases toward negative emotional information, reflected by greater recruitment of prefrontal regions implicated in attentional control in the context of negative emotional information.
Electronic medical records (EMR) provide a unique opportunity for efficient, large-scale clinical investigation in psychiatry. However, such studies will require development of tools to define treatment outcome.
Method
Natural language processing (NLP) was applied to classify notes from 127 504 patients with a billing diagnosis of major depressive disorder, drawn from out-patient psychiatry practices affiliated with multiple, large New England hospitals. Classifications were compared with results using billing data (ICD-9 codes) alone and to a clinical gold standard based on chart review by a panel of senior clinicians. These cross-sectional classifications were then used to define longitudinal treatment outcomes, which were compared with a clinician-rated gold standard.
Results
Models incorporating NLP were superior to those relying on billing data alone for classifying current mood state (area under receiver operating characteristic curve of 0.85–0.88 v. 0.54–0.55). When these cross-sectional visits were integrated to define longitudinal outcomes and incorporate treatment data, 15% of the cohort remitted with a single antidepressant treatment, while 13% were identified as failing to remit despite at least two antidepressant trials. Non-remitting patients were more likely to be non-Caucasian (p<0.001).
Conclusions
The application of bioinformatics tools such as NLP should enable accurate and efficient determination of longitudinal outcomes, enabling existing EMR data to be applied to clinical research, including biomarker investigations. Continued development will be required to better address moderators of outcome such as adherence and co-morbidity.
Depression following myocardial infarction (MI) independently increases risk for early cardiac morbidity and mortality. Studies suggest that somatic, but not cognitive, depressive symptoms are responsible for the increased risk. However, the effects of somatic depressive symptoms at follow-up, after sufficient time has elapsed to allow for physical recovery from the initial infarction, are not known. Our aim was to examine the relationship between cognitive and somatic depressive symptom dimensions at baseline and 12 months post-MI and subsequent mortality and cardiovascular morbidity.
Method
Patients were 2442 depressed and/or socially isolated men and women with acute MI included in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial. We used principal components analysis (PCA) of the Beck Depression Inventory (BDI) items to derive subscales measuring cognitive and somatic depressive symptom dimensions, and Cox regression with Bonferroni correction for multiple testing to examine the contribution of these dimensions to all-cause mortality, cardiovascular mortality, and first recurrent non-fatal MI.
Results
After adjusting for medical co-morbidity and Bonferroni correction, the somatic depressive symptom dimension assessed proximately following MI did not significantly predict any endpoints. At 12 months post-MI, however, this dimension independently predicted subsequent all-cause [hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.13–1.81] and cardiovascular mortality (HR 1.60, 95% CI 1.17–2.18). No significant associations were found between the cognitive depressive symptom dimension and any endpoints after Bonferroni correction.
Conclusions
Somatic symptoms of depression at 12 months post-MI in patients at increased psychosocial risk predicted subsequent mortality. Psychosocial interventions aimed at improving cardiac prognosis may be enhanced by targeting somatic depressive symptoms, with particular attention to somatic symptom severity at 12 months post-MI.
Clinical research on subjective determinants of recovery and health has increased, but no instrument has been developed to assess the subjective experience and meaning of psychoses. We have therefore constructed and validated the Subjective Sense in Psychosis Questionnaire (SUSE) to measure sense making in psychotic disorders.
Method
SUSE was based on an item pool generated by professionals and patients. For pre-testing, 90 psychosis patients completed the instrument. Psychometric properties were assessed using methods of classical test theory. In the main study, SUSE was administered to a representative sample of 400 patients. Factor structure, reliability and validity were assessed and confirmatory factor analyses (CFAs) were used for testing subscale coherence and adequacy of the hypothesized factor structure. Response effects due to clinical settings were tested using multilevel analyses.
Results
The final version of SUSE comprises 34 items measuring distinct aspects of the experience and meaning of psychoses in a consistent overall model with six coherent subscales representing positive and negative meanings throughout the course of psychotic disorders. Multilevel analyses indicate independence from clinical context effects. Patients relating psychotic experiences to life events assessed their symptoms and prospects more positively. 76% of patients assumed a relationship between their biography and the emergence of psychosis, 42% reported positive experience of symptoms and 74% ascribed positive consequences to their psychosis.
Conclusions
SUSE features good psychometric qualities and offers an empirical acquisition to subjective assessment of psychosis. The results highlight the significance of subjective meaning making in psychoses and support a more biographical and in-depth psychological orientation for treatment.
It is not known whether first-episode psychosis is characterized by the same prefrontal cortex functional imaging abnormalities as chronic schizophrenia.
Method
Thirty patients with a first episode of non-affective functional psychosis and 28 healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Voxel-based analyses of brain activations and deactivations were carried out and compared between groups. The connectivity of regions of significant difference between the patients and controls was also examined.
Results
The first-episode patients did not show significant prefrontal hypo- or hyperactivation compared to controls. However, they showed failure of deactivation in the medial frontal cortex. This area showed high levels of connectivity with the posterior cingulate gyrus/precuneus and parts of the parietal cortex bilaterally. Failure of deactivation was significantly greater in first-episode patients who had or went on to acquire a DSM-IV diagnosis of schizophrenia than in those who did not, and in those who met RDC criteria for schizophrenia compared to those who did not.
Conclusions
First-episode psychosis is not characterized by hypo- or hyperfrontality but instead by a failure of deactivation in the medial frontal cortex. The location and connectivity of this area suggest that it is part of the default mode network. The failure of deactivation seems to be particularly marked in first-episode patients who have, or progress to, schizophrenia.
Deficits in automatic sensory discrimination, as indexed by a reduction in the mismatch negativity (MMN) and P3a event-related potential amplitudes, are well documented in chronic schizophrenia. However, MMN and P3a have not been sufficiently studied early in the course of psychotic illness. The present study aimed to investigate MMN, P3a and reorienting negativity (RON) across the course of schizophrenia.
Method
MMN, P3a, and RON were assessed in 118 subjects across four groups: (1) individuals at risk for psychosis (n=26); (2) recent-onset patients (n=31); (3) chronic patients (n=33); and (4) normal controls (n=28) using a duration-deviant auditory oddball paradigm.
Results
Frontocentral deficits in MMN and P3a were present in all patient groups. The at-risk group's MMN and P3a amplitudes were intermediate to those of the control and recent-onset groups. The recent-onset and chronic patients, but not the at-risk subjects, showed significant RON amplitude reductions, relative to the control group. Associations between MMN, P3a, RON and psychosocial functioning were present in the chronic patients. In the at-risk subjects, P3a and RON deficits were significantly associated with higher levels of negative symptoms.
Conclusions
Abnormalities in the automatic processes of sensory discrimination, orienting and reorienting of attention are evident in the early phases of schizophrenia and raise the possibility of progressive worsening across stages of the illness. The finding that MMN and P3a, but not RON, were reduced before psychosis onset supports the continued examination of these components as potential early biomarkers of schizophrenia.
Both involuntary dyskinetic movements and psychotic-like experiences (PLEs) are reported to be antecedents of schizophrenia that may reflect dysfunctional dopaminergic activity in the striatum. The present study compared dyskinetic movement abnormalities displayed by children with multiple antecedents of schizophrenia (ASz), including speech and/or motor developmental lags or problems, internalising/externalising problems in the clinical range, and PLEs, with those displayed by children with no antecedents (noASz).
Method
The sample included 21 ASz and 31 noASz children, aged 9–12 years old. None had taken psychotropic medication or had relatives with psychosis. The antecedents of schizophrenia were assessed using questionnaires completed by children and caregivers. A trained rater, blind to group status, coded dyskinetic movement abnormalities using a validated tool from videotapes of interviews with the children.
Results
ASz children reported, on average, ‘certain experience’ of 2.5 PLEs, while noASz children, by definition, reported none. The ASz children, as compared with noASz children, displayed significantly more dyskinetic movement abnormalities in total, and in the facial and the upper-body regions, after controlling for sex and age. Receiver operator characteristics analyses yielded high area under the curve values for the total score (0.94), facial score (0.91) and upper-body score (0.86), indicating that these scores distinguished between the ASz and noASz children with great accuracy.
Conclusions
Brief questionnaires identified children with multiple antecedents of schizophrenia who displayed significantly more involuntary dyskinetic movement abnormalities than children without antecedents. The presence of PLEs and dyskinesias could reflect early disruption of striatal dopamine circuits.
Offspring of patients with schizophrenia exhibit poorer school performance compared with offspring of non-schizophrenic parents. We aimed to elucidate the mechanisms behind this association.
Method
We linked longitudinal national population registers in Sweden and compared school performance among offspring of schizophrenic parents with offspring of non-schizophrenic parents (1 439 215 individuals with final grades from compulsory school 1988–2006). To investigate the mechanisms, we studied offspring of schizophrenic patients and controls within the same extended families. We investigated genetic effects by stratifying analyses of parent–child associations according to genetic relatedness (half-cousins, full cousins and half-siblings). Environmental effects were investigated by comparing school performance of offspring of schizophrenic fathers and of schizophrenic mothers, respectively, and by stratifying the analyses according to environmental relatedness while controlling genetic relatedness (paternal and maternal half-cousins, paternal and maternal half-siblings).
Results
Offspring of parents with schizophrenia had poorer overall school performance than unrelated offspring of non-schizophrenic parents (−0.31 s.d.). Variability in genetic relatedness greatly moderated the strength of the within-family association (β=−0.23 within exposure-discordant half-cousins, β=−0.13 within exposure-discordant full cousins, β=0.04 within exposure-discordant half-siblings), while no evidence was found that the environment affected offspring school performance.
Conclusions
Genetic factors account for poorer school performance in children of parents with schizophrenia. This supports that cognitive deficits found in individuals with schizophrenia and their relatives might be genetically inherited. Early detection of prodromal signs and impaired functioning of offspring of patients with schizophrenia could lead to earlier and better tailored interventions.
Despite increased cardiometabolic risk in individuals with mental illness taking antipsychotic medication, metabolic screening practices are often incomplete or inconsistent.
Method
We undertook a systematic search and a PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) meta-analysis of studies examining routine metabolic screening practices in those taking antipsychotics both for patients in psychiatric care before and following implementation of monitoring guidelines.
Results
We identified 48 studies (n=290 534) conducted between 2000 and 2011 in five countries; 25 studies examined predominantly schizophrenia-spectrum disorder populations; 39 studies (n=218 940) examined routine monitoring prior to explicit guidelines; and nine studies (n=71 594) reported post-guideline monitoring. Across 39 studies, routine baseline screening was generally low and above 50% only for blood pressure [69.8%, 95% confidence interval (CI) 50.9–85.8] and triglycerides (59.9%, 95% CI 36.6–81.1). Cholesterol was measured in 41.5% (95% CI 18.0–67.3), glucose in 44.3% (95% CI 36.3–52.4) and weight in 47.9% (95% CI 32.4–63.7). Lipids and glycosylated haemoglobin (HbA1c) were monitored in less than 25%. Rates were similar for schizophrenia patients, in US and UK studies, for in-patients and out-patients. Monitoring was non-significantly higher in case-record versus database studies and in fasting samples. Following local/national guideline implementation, monitoring improved for weight (75.9%, CI 37.3–98.7), blood pressure (75.2%, 95% CI 45.6–95.5), glucose (56.1%, 95% CI 43.4–68.3) and lipids (28.9%, 95% CI 20.3–38.4). Direct head-to-head pre–post-guideline comparison showed a modest but significant (15.4%) increase in glucose testing (p=0.0045).
Conclusions
In routine clinical practice, metabolic monitoring is concerningly low in people prescribed antipsychotic medication. Although guidelines can increase monitoring, most patients still do not receive adequate testing.
There may be biological plausibility to the notion that cannabis use and childhood trauma or maltreatment synergistically increase the risk for later development of psychotic symptoms. To replicate and further investigate this issue, prospective data from two independent population-based studies, the Greek National Perinatal Study (n=1636) and The Netherlands Mental Health Survey and Incidence Study (NEMESIS) (n=4842), were analyzed.
Method
Two different data sets on cannabis use and childhood maltreatment were used. In a large Greek population-based cohort study, data on cannabis use at age 19 years and childhood maltreatment at 7 years were assessed. In addition, psychotic symptoms were assessed using the Community Assessment of Psychic Experiences (CAPE). In NEMESIS, the Composite International Diagnostic Interview (CIDI) was used to assess psychotic symptoms at three different time points along with childhood maltreatment and lifetime cannabis use.
Results
A significant adjusted interaction between childhood maltreatment and later cannabis use was evident in both samples, indicating that the psychosis-inducing effects of cannabis were stronger in individuals exposed to earlier sexual or physical mistreatment [Greek National Perinatal Study: test for interaction F(2, 1627)=4.18, p=0.02; NEMESIS: test for interaction χ2(3)=8.08, p=0.04].
Conclusions
Cross-sensitivity between childhood maltreatment and cannabis use may exist in pathways that shape the risk for expression of positive psychotic symptoms.
Addicts show both reward processing deficits and increased salience attribution to drug cues. However, no study to date has demonstrated that salience attribution to drug cues can directly modulate inferences of reward value to non-drug cues. Associative learning depends on salience: a more salient predictor of an outcome will ‘overshadow’ a less salient predictor of the same outcome. Similarly, blocking, a demonstration that learning depends on prediction error, can be influenced by the salience of the cues employed.
Method
This study investigated whether salient drug cues might interact with neutral cues predicting financial reward in an associative learning task indexing blocking and overshadowing in satiated smokers (n=24), abstaining smokers (n=24) and non-smoking controls (n=24). Attentional bias towards drug cues, craving and expired CO were also indexed.
Results
Abstaining smokers showed drug cue induced overshadowing, attributing higher reward value to drug cues than to neutral cues that were equally predictive of reward. Overshadowing was positively correlated with expired CO levels, which, in turn, were correlated with craving in abstainers. An automatic attentional bias towards cigarette cues was found in abstainers only.
Conclusions
These findings provide the first evidence that drug cues interact with reward processing in a drug dependent population.
Intrusive re-experiencing in post-traumatic stress disorder (PTSD) comprises distressing sensory impressions from the trauma that seem to occur ‘out of the blue’. A key question is how intrusions are triggered. One possibility is that PTSD is characterized by a processing advantage for stimuli that resemble those that accompanied the trauma, which would lead to increased detection of such cues in the environment.
Method
We used a blurred picture identification task in a cross-sectional (n=99) and a prospective study (n=221) of trauma survivors.
Results
Participants with acute stress disorder (ASD) or PTSD, but not trauma survivors without these disorders, identified trauma-related pictures, but not general threat pictures, better than neutral pictures. There were no group differences in the rate of trauma-related answers to other picture categories. The relative processing advantage for trauma-related pictures correlated with re-experiencing and dissociation, and predicted PTSD at follow-up.
Conclusions
A perceptual processing bias for trauma-related stimuli may contribute to the involuntary triggering of intrusive trauma memories in PTSD.
Early pubertal timing in girls is associated with elevated risk for dieting and eating pathology. The relative importance of biological versus socio-environmental mechanisms in explaining this association remains unclear. Moreover, these mechanisms may differ between objective measures of pubertal development and girls' subjective perceptions of their own maturation.
Method
The sample comprised 924 sister pairs from the National Longitudinal Study of Adolescent Health. Objective pubertal timing (menarcheal age), girls' perceptions of pubertal status and timing relative to peers, dieting and disordered eating behaviors were assessed during a series of confidential in-home interviews.
Results
Behavioral genetic models indicated that common genetic influences accounted for the association between early menarcheal age and increased risk for dieting in adolescence. In contrast, girls' subjective perceptions of their timing relative to peers were associated with dieting through an environmental pathway. Overall, subjective and objective measures of pubertal timing accounted for 12% of the variance in dieting.
Conclusions
Genetic differences in menarcheal age increase risk for dieting among adolescent girls, while girls' perceptions of their maturation represent an environmentally mediated risk.
Data on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated.
Method
After a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale – Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions – Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis.
Results
A total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes.
Conclusions
Improvements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.
Chronic fatigue is a common symptom of multiple sclerosis (MS). A randomized controlled trial (RCT) showed that cognitive behavioural therapy (CBT) was more effective in reducing MS fatigue than relaxation training (RT). The aim of the current study was to analyse additional data from this trial to determine whether (1) CBT compared to RT leads to significantly greater changes in cognitions and behaviours hypothesized to perpetuate MS fatigue; (2) changes in these variables mediate the effect of CBT on MS fatigue; and (3) these mediation effects are independent of changes in mood.
Method
Seventy patients (CBT, n=35; RT, n=35) completed the Cognitive and Behavioural Responses to Symptoms Questionnaire (CBSQ), the Brief Illness Perception Questionnaire (B-IPQ) modified to measure negative representations of fatigue, the Hospital Anxiety and Depression Scale (HADS), and the Chalder Fatigue Questionnaire (CFQ), pre- and post-therapy. Multiple mediation analysis was used to determine which variables mediated the change in fatigue.
Results
Avoidance behaviour and three cognitive variables (symptom focusing, believing symptoms are a sign of damage and a negative representation of fatigue) improved significantly more in the CBT than the RT group. Mediation analysis showed that changing negative representations of fatigue mediated the decrease in severity of fatigue. Change in anxiety covaried with reduction in fatigue but the mediation effect for negative representations of fatigue remained when controlling for improvements in mood.
Conclusions
Change in beliefs about fatigue play a crucial role in CBT for MS fatigue. These beliefs and the role of anxiety deserve more attention in the further development of this intervention.