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There has been increasing interest in the validity and familial transmission of subthreshold psychiatric conditions and the relationship between subthreshold conditions and full syndrome (FS) disorders. However, most of these studies examined a single subthreshold condition and thus fail to take into account the high co-morbidity among subthreshold conditions and between subthreshold conditions and FS disorders.
Method
A family study of subthreshold psychiatric conditions was conducted with 739 community-drawn young adults and their 1744 relatives. We examined (1) whether relatives of probands with subthreshold major depression, bipolar disorder, anxiety disorders, alcohol use, substance use, and/or conduct disorder exhibited an increased rate of the corresponding (homotypic) FS disorder; (2) whether subthreshold disorders were associated with increased familial rates of other (heterotypic) FS disorders; (3) whether subthreshold and FS conditions are associated with similar familial liabilities; and (4) whether these homotypic and heterotypic associations persisted after controlling for co-morbidity.
Results
Significant homotypic associations were observed for subthreshold anxiety, alcohol, conduct, and a trend was observed for major depression. Only the homotypic association for alcohol and conduct remained after controlling for co-morbid subthreshold and FS conditions. Many heterotypic associations were observed and most remained after controlling for co-morbidity.
Conclusions
It is important to broaden the study of subthreshold psychopathology to multiple disorders. In particular cases, controlling for co-morbidity with other subthreshold and FS conditions altered the patterns of familial aggregation. Etiological processes that are common to particular disorders and subthreshold conditions are discussed.
To investigate the extent to which three putative ‘environmental’ risk factors, maternal punitive discipline (MPD), paternal punitive discipline (PPD) and negative life events (NLEs), share genetic influences with, and moderate the heritability of, externalizing behavior.
Method
The sample consisted of 2647 participants, aged 12–19 years, from the G1219 and G1219Twins longitudinal studies. Externalizing behavior was measured using the Youth Self-Report, MPD, PPD and exposure to NLEs were assessed using the Negative Sanctions Scale and the Life Event Scale for Adolescents respectively.
Result
Genetic influences overlapped for externalizing behavior and each ‘environmental’ risk, indicating gene–environment correlation. When controlling for the gene–environment correlation, genetic variance decreased, and both shared and non-shared environmental influences increased, as a function of MPD. Genetic variance increased as a function of PPD, and for NLEs the only interaction effect was on the level of non-shared environment influence unique to externalizing behavior.
Conclusion
The magnitude of the influence of genetic risk on externalizing behavior is contextually dependent, even after controlling for gene–environment correlation.
The cognitive and academic outcomes of infants exposed to radiation after the meltdown at Chornobyl have been intensely debated. Western-based investigations indicate that no adverse effects occurred, but local studies reported increased cognitive impairments in exposed compared with non-exposed children. Our initial study found that at age 11 years, school grades and neuropsychological performance were similar in 300 children evacuated to Kiev as infants or in utero compared with 300 classmate controls, yet more evacuee mothers believed that their children had memory problems. This study re-examined the children's performance and academic achievement at age 19 years.
Method
In 2005–2006, we conducted an 8-year follow-up of the evacuees (n=265) and classmate controls (n=261) assessed in Kiev in 1997. Outcomes included university attendance, tests of intelligence, attention, and memory, and subjective appraisals of memory problems. Scores were standardized using a local population-based control group (n=327). Analyses were stratified by parental education.
Results
Evacuees and classmates performed similarly and in the normal range on all tests, and no differential temporal changes were found. The results were comparable for the in utero subsample. The rates of university attendance and self-reported memory problems were also similar. Nevertheless, the evacuee mothers were almost three times as likely to report that their children had memory problems compared with controls.
Conclusions
Chornobyl did not influence the cognitive functioning of exposed infants although more evacuee mothers still believed that their offspring had memory problems. These lingering worries reflect a wider picture of persistent health concerns as a consequence of the accident.
The association between life events and anxious depression might be due to causality or to gene–environment correlation. We examined unidirectional and reciprocal causality and a gene–environment correlation model, in which genes that influence the vulnerability for anxious depression also increase the risk of exposure to life events. The effect of genes that influence environmental exposure might be mediated through personality and we therefore also examined the association between life events and personality (neuroticism and extraversion).
Method
Information on life events, anxious depression, neuroticism and extraversion was collected in 5782 monozygotic (MZ) and dizygotic (DZ) twins who participated in a longitudinal survey study of the Netherlands Twin Register. To examine causality, data were analysed longitudinally. To examine gene–environment correlation, the co-twin control method was used.
Results
Anxious depression and, to a lesser extent, neuroticism scores increased after exposure to life events. Anxious depression and neuroticism also predicted the experience of life events. Prospectively, extraversion was not associated with life events. Anxious depression, neuroticism and extraversion scores did not differ between the non-exposed subjects of MZ and DZ twin pairs and unrelated subjects discordant for life events.
Conclusions
Our findings suggest that reciprocal causation explains the relationship between life events and anxious depression and between life events and neuroticism. Extraversion is not related to life events. No evidence was found for gene–environment correlation, i.e. the genes that influence anxious depression, neuroticism or extraversion do not overlap with the genes that increase the risk of exposure to life events.
The incidence of schizophrenia and the prevalence of psychotic symptoms in the general adult population are elevated in migrant and ethnic minority groups relative to host populations. These increases are particularly prominent among African-Caribbean migrants to the UK. This study examined the associations of ethnicity and migrant status with a triad of putative antecedents of schizophrenia in a UK community sample of children aged 9–12 years. The antecedent triad comprised: (i) psychotic-like experiences; (ii) a speech and/or motor developmental delay or abnormality; and (iii) a social, emotional or behavioural problem.
Method
Children (n=595) and their primary caregivers, recruited via schools and general practitioners in southeast London, completed questionnaires. Four indices of risk were examined for associations with ethnicity and migrant status: (i) certain experience of at least one psychotic-like experience; (ii) severity of psychotic-like experiences (total psychotic-like experience score); (iii) experience of the antecedent triad; and (iv) severity of antecedent triad experiences (triad score).
Results
African-Caribbean children, as compared to white British children, experienced greater risk on all four indices. There were trends for South Asian and Oriental children to present lowered risk on several indices, relative to white British children. Migration status was unrelated to any risk index.
Conclusion
Prevalence of the putative antecedents of schizophrenia is greater among children of African-Caribbean origin living in the UK than among white British children. This parallels the increased incidence of schizophrenia and elevated prevalence of psychotic symptoms among adults of African-Caribbean origin.
Effectiveness of repetitive transcranial magnetic stimulation (rTMS) for major depression is unclear. The authors performed a randomized controlled trial comparing real and sham adjunctive rTMS with 4-month follow-up.
Method
Fifty-nine patients with major depression were randomly assigned to a 10-day course of either real (n=29) or sham (n=30) rTMS of the left dorsolateral prefrontal cortex (DLPFC). Primary outcome measures were the 17-item Hamilton Depression Rating Scale (HAMD) and proportions of patients meeting criteria for response (⩾50% reduction in HAMD) and remission (HAMD⩽8) after treatment. Secondary outcomes included mood self-ratings on Beck Depression Inventory-II and visual analogue mood scales, Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer-rated cognitive changes. Patients had 6-week and 4-month follow-ups.
Results
Overall, Hamilton Depression Rating Scale (HAMD) scores were modestly reduced in both groups but with no significant group×time interaction (p=0.09) or group main effect (p=0.85); the mean difference in HAMD change scores was −0.3 (95% CI −3.4 to 2.8). At end-of-treatment time-point, 32% of the real group were responders compared with 10% of the sham group (p=0.06); 25% of the real group met the remission criterion compared with 10% of the sham group (p=0.2); the mean difference in HAMD change scores was 2.9 (95% CI −0.7 to 6.5). There were no significant differences between the two groups on any secondary outcome measures. Blinding was difficult to maintain for both patients and raters.
Conclusions
Adjunctive rTMS of the left DLPFC could not be shown to be more effective than sham rTMS for treating depression.
Disinhibition and decision-making skills play an important role in theories on the cause and outcome of addictive behaviors such as substance use disorders and pathological gambling. In recent studies, both disinhibition and disadvantageous decision-making strategies, as measured by neurocognitive tests, have been found to influence the course of substance use disorders. Research on factors affecting relapse in pathological gambling is scarce.
Method
This study investigated the effect of both self-reported impulsivity and reward sensitivity, and neurocognitively assessed disinhibition and decision-making under conflicting contingencies, on relapse in a group of 46 pathological gamblers.
Results
Logistic regression analysis indicated that longer duration of the disorder and neurocognitive indicators of disinhibition (Stop Signal Reaction Time) and decision-making (Card Playing Task) were significant predictors of relapse (explaining 53% of the variance in relapse), whereas self-reported impulsivity and reward sensitivity did not significantly predict relapse. Overall classification accuracy was 76%, with a positive classification accuracy of 76% and a negative classification accuracy of 75%.
Conclusions
Duration of the disorder and neurocognitive measures of disinhibition and decision-making are powerful predictors of relapse in pathological gambling. The results suggest that endophenotypical neurocognitive characteristics are more promising in the prediction of relapse in pathological gambling than phenotypical personality characteristics. Neurocognitive predictors may be useful to guide treatment planning of follow-up contacts and booster sessions.
Internet-based cognitive behaviour therapy (CBT) is a promising new approach for the treatment of depressive symptoms. The current study had two aims: (1) to determine whether, after 1 year, an internet-based CBT intervention was more effective than a waiting-list control group; and (2) to determine whether the effect of the internet-based CBT differed from the group CBT intervention, 1 year after the start of treatment.
Method
A total of 191 women and 110 men (mean age=55 years, s.d.=4.6) with subthreshold depression were randomized into internet-based treatment, group CBT (Lewinsohn's Coping with Depression Course), or a waiting-list control condition. The main outcome measure was treatment response after 1 year, defined as the difference in pretreatment and follow-up scores on the Beck Depression Inventory (BDI). Missing data were imputed using the multiple imputation procedure of data augmentation. Analyses were performed using multiple imputation inference.
Results
In the waiting-list control group, we found a pretreatment to follow-up improvement effect size of 0.69, which was 0.62 in the group CBT condition and 1.22 with the internet-based treatment condition. Simple contrasts showed a significant difference between the waiting-list condition and internet-based treatment (p=0.03) and no difference between both treatment conditions (p=0.08).
Conclusions
People aged over 50 years with subthreshold depression can still benefit from internet-based CBT 1 year after the start of treatment.
The largest clinical epidemiological surveys of psychiatric disorders have been based on unstructured clinical evaluations. However, several recent studies have questioned the accuracy and thoroughness of clinical diagnostic interviews; consequently, clinical epidemiological studies, like community-based studies, should be based on standardized evaluations. The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is the largest clinical epidemiological study using semi-structured interviews assessing a wide range of psychiatric disorders conducted in a general clinical out-patient practice. In the present report we examined the frequency of DSM-IV Axis I diagnostic co-morbidity in psychiatric out-patients.
Method
A total of 2300 out-patients were interviewed with the Structured Clinical Interview for DSM-IV (SCID) upon presentation for treatment.
Results
The mean number of current and lifetime DSM-IV Axis I disorders in the 2300 patients was 1.9 (s.d.=1.5) and 3.0 (s.d.=1.8) respectively. The majority of patients were diagnosed with two or more current disorders, and more than one-third were diagnosed with three or more current disorders. Examination of the most frequent current disorders in the patients with the 12 most common principal diagnoses indicated that the pattern of co-morbidity differed among the disorders. The highest mean number of current co-morbid disorders was found for patients with a principal diagnosis of post-traumatic stress disorder and bipolar disorder.
Conclusions
Clinicians should assume that psychiatric patients presenting for treatment have more than one current diagnosis. The pattern of co-morbidity varies according to the principal diagnosis.
Cannabis use may be a risk factor for schizophrenia. Part of this association may be explained by genotype–environment interaction, and part of it by genotype–environment correlation. The latter issue has not been explored. We investigated whether cannabis use is associated with schizophrenia, and whether gene–environment correlation contributes to this association, by examining the prevalence of cannabis use in groups with different levels of genetic predisposition for schizophrenia.
Method
Case-control study of first-episode schizophrenia. Cases included all non-Western immigrants who made first contact with a physician for schizophrenia in The Hague, The Netherlands, between October 2000 and July 2005 (n=100; highest genetic predisposition). Two matched control groups were recruited, one among siblings of the cases (n=63; intermediate genetic predisposition) and one among immigrants who made contact with non-psychiatric secondary health-care services (n=100; lowest genetic predisposition). Conditional logistic regression analyses were used to predict schizophrenia as a function of cannabis use, and cannabis use as a function of genetic predisposition for schizophrenia.
Results
Cases had used cannabis significantly more often than their siblings and general hospital controls (59, 21 and 21% respectively). Cannabis use predicted schizophrenia [adjusted odds ratio (OR) cases compared to general hospital controls 7.8, 95% confidence interval (CI) 2.7–22.6; adjusted OR cases compared to siblings 15.9 (95% CI 1.5–167.1)], but genetic predisposition for schizophrenia did not predict cannabis use [adjusted OR intermediate predisposition compared to lowest predisposition 1.2 (95% CI 0.4–3.8)].
Conclusions
Cannabis use was associated with schizophrenia but there was no evidence for genotype–environment correlation.
Increased rates of psychiatric disorder have previously been reported in those diagnosed with chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME), although the direction of causation in this relationship has not been established. We aimed to test the hypothesis that individuals with self-reported CFS/ME have increased levels of psychiatric disorder prior to the onset of their fatigue symptoms.
Method
A total of 5362 participants were prospectively followed with various measures of personality, psychiatric disorder and fatigue levels collected over the first 43 years of their life. CFS/ME was identified through self-report during a semi-structured interview at age 53 years.
Results
Thirty-four (1.1%) of the 3035 subjects assessed at age 53 years reported a diagnosis of CFS/ME. CFS/ME was more common among females, but there was no association between CFS/ME and either social class, social mobility or educational level. Those with psychiatric illness between the ages of 15 and 36 years were more likely to report CFS/ME later in life with an odds ratio (OR, adjusted for sex) of 2.65 [95% confidence interval (CI) 1.26–5.57, p=0.01]. Increased levels of psychiatric illness, in particular depression and anxiety, were present prior to the occurrence of fatigue symptoms. There was a dose–response relationship between the severity of psychiatric symptoms and the likelihood of later CFS/ME. Personality factors were not associated with a self-reported diagnosis of CFS/ME.
Conclusions
This temporal, dose–response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have an aetiological role in some cases of CFS/ME.
Although symptoms such as fatigue, headache and pain in bones and muscles are common after disasters, risk factors for these symptoms among disaster survivors have rarely been studied. We examined predisposing, precipitating and perpetuating factors for these physical symptoms among survivors of a man-made disaster. In addition, we examined whether risk factors for physical symptoms differ between survivors and controls.
Method
Survivors completed a questionnaire 3 weeks (n=1567), 18 months and 4 years after the disaster. Symptoms and risk factors were measured using validated questionnaires. A comparison group was included at waves 2 and 3 (n=821). Random coefficient analysis (RCA) was used to study risk factors for symptoms.
Results
Female gender [beta (β)=1.0, 95% confidence interval (CI) 0.6–1.4], immigrant status (β=1.0, 95% CI 0.6–1.4) and pre-disaster psychological problems (β=0.8, 95% CI 0.1–1.4) were predisposing factors for symptoms. Although disaster-related factors were predictors, the relationship between symptoms and disaster-related factors was not very strong and the magnitude of this association was reduced when perpetuating factors were added. Intrusions and avoidance, depression, anxiety and sleeping problems were important perpetuating factors for physical symptoms among survivors and mediated the association between traumatic stress and physical symptoms. Risk factors for symptoms were comparable between survivors and controls.
Conclusions
The results indicate that health-care workers should be alert for physical symptoms among female survivors, immigrant survivors and individuals with a high level of psychological problems both before and after a disaster.
Cognitive models suggest that distress associated with auditory hallucinations is best understood in terms of beliefs about voices. What is less clear is what factors govern such beliefs. This study aimed to explore the way in which traumatic life events contribute towards beliefs about voices and any associated distress.
Method
The difference in the nature and prevalence of traumatic life events and associated psychological sequelae was compared in two groups of voice hearers: psychiatric voice hearers with predominantly negative beliefs about voices (PVH) and non-psychiatric voice hearers with predominantly positive beliefs about voices (NPVH). The data from the two groups were then combined in order to examine which factors could significantly account for the variance in beliefs about voices and therefore levels of distress.
Results
Both groups reported a high prevalence of traumatic life events although significantly more PVH reported trauma symptoms sufficient for a diagnosis of post-traumatic stress disorder (PTSD). Furthermore, significantly more PVH reported experiencing childhood sexual abuse. Current trauma symptoms (re-experiencing, avoidance and hyperarousal) were found to be a significant predictor of beliefs about voices. Trauma variables accounted for a significant proportion of the variance in anxiety and depression.
Conclusions
The results suggest that beliefs about voices may be at least partially understood in the context of traumatic life events.
The ability to appreciate humour is essential to successful human interactions. In this study, we hypothesized that individuals with schizophrenia would have diminished ability to recognize and appreciate humour. The relationship between humour experience and clinical symptoms, cognitive and social functioning was examined.
Method
Thirty patients with a DSM-IV diagnosis of schizophrenia were compared with 30 age-, gender-, IQ- and ethnicity-matched healthy controls. Humour recognition was measured by identification of humorous moments in four silent slapstick comedy film clips and calculated as d-prime (d′) according to signal detection theory. Humour appreciation was measured by self-report mood state and funniness ratings. Patients were assessed for clinical symptoms, theory of mind ability, executive function [using the Wisconsin Card Sorting Test (WCST)] and social functioning [using the Life Skills Profile (LSP)].
Results
Patient and control groups did not differ in the funniness ratings they attributed to the video clips. Patients with schizophrenia had a lower d′ (humour) compared to the controls, after controlling for (1) the performance of a baseline recognition task with a non-humorous video clip and (2) severity of depressive symptoms. In patients, d′ (humour) had significant negative correlation with delusion and depression scores, the perseverative error score of the WCST and the total scores of the LSP.
Conclusions
Compared with controls, patients with schizophrenia were less sensitive at detecting humour but similarly able to appreciate humour. The degree of humour recognition difficulty may be associated with the extent of executive dysfunction and thus contribute to the psychosocial impairment in patients with schizophrenia.