Self-guided online cognitive behavioural therapy for insomnia: A naturalistic evaluation in patients with potential psychiatric comorbidities.

BACKGROUND: Insomnia is the most prevalent sleep disorder worldwide, and regularly co-occurs with anxiety and depression. Cognitive behavioural therapy is the gold standard treatment for insomnia (CBT-I), however demand for treatment providers drastically exceeds supply. Internet-delivered programs for insomnia (iCBT-I) improve treatment access. However the effects of unguided iCBT-I for individuals with comorbidities within a naturalistic setting remains unexplored. We developed a novel unguided iCBT-I program and evaluated its impact on insomnia, psychological distress, and wellbeing when accessed by the public. METHODS: 317 participants experiencing insomnia for over 3 months enrolled in the program. The program consisted of 4 lessons delivered online with automated web support. Insomnia symptoms, psychological distress, and general wellbeing were assessed at lesson 1 and 4. Intention-to-treat linear mixed models were used to examine effects on insomnia, distress, and wellbeing. RESULTS: Participants experienced large (g = 1.11) and significant reductions in insomnia, moderate (g = 0.55) and significant reductions in distress, and small (g = 0.37) but significant improvements in wellbeing. 65% of participants who reported pre-treatment insomnia severity at clinical levels remitted following treatment. LIMITATIONS: To examine the program in a naturalistic setting, we did not employ a control group or follow participants beyond the completion of treatment. CONCLUSIONS: Unguided iCBT-I is effective for individuals in the community who experience insomnia and are likely experiencing comorbid mental health problems. These effects in the absence of guided contact strengthen the utility of unguided iCBT-I as a scalable and cost-effective method of disseminating treatments for this disorder.

DSM-IV post-traumatic stress disorder among World Trade Center responders 11-13 years after the disaster of 11 September 2001 (9/11).

BACKGROUND: Post-traumatic symptomatology is one of the signature effects of the pernicious exposures endured by responders to the World Trade Center (WTC) disaster of 11 September 2001 (9/11), but the long-term extent of diagnosed Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) post-traumatic stress disorder (PTSD) and its impact on quality of life are unknown. This study examines the extent of DSM-IV PTSD 11-13 years after the disaster in WTC responders, its symptom profiles and trajectories, and associations of active, remitted and partial PTSD with exposures, physical health and psychosocial well-being. METHOD: Master's-level psychologists administered sections of the Structured Clinical Interview for DSM-IV and the Range of Impaired Functioning Tool to 3231 responders monitored at the Stony Brook University World Trade Center Health Program. The PTSD Checklist (PCL) and current medical symptoms were obtained at each visit. RESULTS: In all, 9.7% had current, 7.9% remitted, and 5.9% partial WTC-PTSD. Among those with active PTSD, avoidance and hyperarousal symptoms were most commonly, and flashbacks least commonly, reported. Trajectories of symptom severity across monitoring visits showed a modestly increasing slope for active and decelerating slope for remitted PTSD. WTC exposures, especially death and human remains, were strongly associated with PTSD. After adjusting for exposure and critical risk factors, including hazardous drinking and co-morbid depression, PTSD was strongly associated with health and well-being, especially dissatisfaction with life. CONCLUSIONS: This is the first study to demonstrate the extent and correlates of long-term DSM-IV PTSD among responders. Although most proved resilient, there remains a sizable subgroup in need of continued treatment in the second decade after 9/11.

Reductions in the internalising construct following internet-delivered treatment for anxiety and depression in primary care.

Depressive and anxiety disorders are different manifestations of a latent internalising construct. To date, efficacy studies have tended to focus on disorder-specific outcomes, rather than underlying dimensions. This study examined the effect of a transdiagnostic internet-delivered cognitive behavioural therapy (iCBT) on the internalising construct in a primary care sample. Participants included 635 patients aged 18 years or over who were prescribed a six lesson transdiagnostic iCBT program for anxiety and depression by their primary healthcare professional. All patients completed the Patient Health Questionnaire 9, the Generalised Anxiety Disorder 7-Item Scale, the Mini Social Phobia Inventory and the Panic Disorder Severity Self-Report Scale at baseline. 325 of these patients completed the program and provided data on each of these scales during the final lesson. Reductions in the latent internalising construct were assessed within a longitudinal factor analysis framework that compared internalising factor means before and after treatment. The within group mean reduction in the latent internalising construct was large (ES = 1.23, SE = 0.09; p < 0.001). Due to the lack of a control group, between group reductions in the latent internalising construct could not be investigated. This study demonstrated that there are clinically significant reductions in the latent internalising construct following transdiagnostic iCBT for anxiety and depression.

Psychotic-like experiences in a community sample of 8000 children aged 9 to 11 years: an item response theory analysis.

BACKGROUND: Psychotic-like experiences (PLEs) in the general population are common, particularly in childhood, and may constitute part of a spectrum of normative development. Nevertheless, these experiences confer increased risk for later psychotic disorder, and are associated with poorer health and quality of life. METHOD: This study used factor analytic methods to determine the latent structure underlying PLEs, problem behaviours and personal competencies in the general child population, and used item response theory (IRT) to assess the psychometric properties of nine PLE items to determine which items best represented a latent psychotic-like construct (PSY). A total of 7966 children aged 9-11 years, constituting 95% of eligible children, completed self-report questionnaires. RESULTS: Almost two-thirds of the children endorsed at least one PLE item. Structural analyses identified a unidimensional construct representing psychotic-like severity in the population, the full range of which was well sampled by the nine items. This construct was discriminable from (though correlated with) latent dimensions representing internalizing and externalizing problems. Items assessing visual and auditory hallucination-like experiences provided the most information about PSY; delusion-like experiences identified children at more severe levels of the construct. CONCLUSIONS: Assessing PLEs during middle childhood is feasible and supplements information concerning internalizing and externalizing problems presented by children. The hallucination-like experiences constitute appropriate items to screen the population to identify children who may require further clinical assessment or monitoring. Longitudinal follow-up of the children is required to determine sensitivity and specificity of the PLE items for later psychotic illness.

Neurocognitive disorders: cluster 1 of the proposed meta-structure for DSM-V and ICD-11.

BACKGROUND: In an effort to group mental disorders on the basis of aetiology, five clusters have been proposed. In this paper, we consider the validity of the first cluster, neurocognitive disorders, within this proposal. These disorders are categorized as 'Dementia, Delirium, and Amnestic and Other Cognitive Disorders' in DSM-IV and 'Organic, including Symptomatic Mental Disorders' in ICD-10. METHOD: We reviewed the literature in relation to 11 validating criteria proposed by a Study Group of the DSM-V Task Force as applied to the cluster of neurocognitive disorders. RESULTS: 'Neurocognitive' replaces the previous terms 'cognitive' and 'organic' used in DSM-IV and ICD-10 respectively as the descriptor for disorders in this cluster. Although cognitive/organic problems are present in other disorders, this cluster distinguishes itself by the demonstrable neural substrate abnormalities and the salience of cognitive symptoms and deficits. Shared biomarkers, co-morbidity and course offer less persuasive evidence for a valid cluster of neurocognitive disorders. The occurrence of these disorders subsequent to normal brain development sets this cluster apart from neurodevelopmental disorders. The aetiology of the disorders is varied, but the neurobiological underpinnings are better understood than for mental disorders in any other cluster. CONCLUSIONS: Neurocognitive disorders meet some of the salient criteria proposed by the Study Group of the DSM-V Task Force to suggest a classification cluster. Further developments in the aetiopathogenesis of these disorders will enhance the clinical utility of this cluster.

Neurodevelopmental disorders: cluster 2 of the proposed meta-structure for DSM-V and ICD-11.

BACKGROUND: DSM-IV and ICD-10 are atheoretical and largely descriptive. Although this achieves good reliability, the validity of diagnoses can be increased by an understanding of risk factors and other clinical features. In an effort to group mental disorders on this basis, five clusters have been proposed. We now consider the second cluster, namely neurodevelopmental disorders. METHOD: We reviewed the literature in relation to 11 validating criteria proposed by a DSM-V Task Force Study Group. RESULTS: This cluster reflects disorders of neurodevelopment rather than a 'childhood' disorders cluster. It comprises disorders subcategorized in DSM-IV and ICD-10 as Mental Retardation; Learning, Motor, and Communication Disorders; and Pervasive Developmental Disorders. Although these disorders seem to be heterogeneous, they share similarities on some risk and clinical factors. There is evidence of a neurodevelopmental genetic phenotype, the disorders have an early emerging and continuing course, and all have salient cognitive symptoms. Within-cluster co-morbidity also supports grouping these disorders together. Other childhood disorders currently listed in DSM-IV share similarities with the Externalizing and Emotional clusters. These include Conduct Disorder, Attention Deficit Hyperactivity Disorder and Separation Anxiety Disorder. The Tic, Eating/Feeding and Elimination disorders, and Selective Mutisms were allocated to the 'Not Yet Assigned' group. CONCLUSION: Neurodevelopmental disorders meet some of the salient criteria proposed by the American Psychiatric Association (APA) to suggest a classification cluster.

Emotional disorders: cluster 4 of the proposed meta-structure for DSM-V and ICD-11.

BACKGROUND: The extant major psychiatric classifications DSM-IV, and ICD-10, are atheoretical and largely descriptive. Although this achieves good reliability, the validity of a medical diagnosis would be greatly enhanced by an understanding of risk factors and clinical manifestations. In an effort to group mental disorders on the basis of aetiology, five clusters have been proposed. This paper considers the validity of the fourth cluster, emotional disorders, within that proposal. METHOD: We reviewed the literature in relation to 11 validating criteria proposed by a Study Group of the DSM-V Task Force, as applied to the cluster of emotional disorders. RESULTS: An emotional cluster of disorders identified using the 11 validators is feasible. Negative affectivity is the defining feature of the emotional cluster. Although there are differences between disorders in the remaining validating criteria, there are similarities that support the feasibility of an emotional cluster. Strong intra-cluster co-morbidity may reflect the action of common risk factors and also shared higher-order symptom dimensions in these emotional disorders. CONCLUSION: Emotional disorders meet many of the salient criteria proposed by the Study Group of the DSM-V Task Force to suggest a classification cluster.

Where should bipolar disorder appear in the meta-structure?

BACKGROUND: The extant major psychiatric classifications, DSM-IV and ICD-10, are purportedly atheoretical and largely descriptive. Although this achieves good reliability, the validity of a medical diagnosis is greatly enhanced by an understanding of both risk factors and clinical history. In an effort to group mental disorders on the basis of risk factors and clinical manifestations, five clusters have been proposed. The purpose of this paper is to consider the position of bipolar disorder (BPD), which could be either with the psychoses, or with emotional disorders, or in a separate cluster. METHOD: We reviewed the literature on BPD, unipolar depression (UPD) and schizophrenia in relation to 11 validating criteria proposed by the DSM-V Task Force Study Group, and then summarized similarities and differences between BPD and schizophrenia on the one hand, and UPD on the other. RESULTS: There are differences, often substantial and never trivial, for 10 of the 11 validators between BPD and UPD. There are also important differences between BPD and schizophrenia. CONCLUSION: BPD has previously been classified together with UPD, but this is the least justifiable place for it. If it is to be recruited to a 'psychotic cluster', there are several important respects in which it differs from schizophrenia, so the cluster would have a division within it. The alternative would be to allow it to be in an intermediate position in a cluster of its own.

Elevation of endogenous nucleophiles in rat lung by cysteine and glutathione esters in vitro.

In this study, we have compared the uptake of L-cysteine (L-CySH), D-cysteine (D-CySH), L-cysteine isopropyl ester (L-CIPE) and D-cysteine isopropyl ester (D-CIPE) in rat lung slices and tracheal sections and determined the effectiveness of glutathione (GSH), GSH isopropyl monoester, GSH isopropyl diester, gamma-glutamylcysteine (gamma-glu-cys) isopropyl monoester and gamma-glu-cys isopropyl diester to elevate and prolong intracellular GSH concentrations in rat lung slices. Lung slices were incubated with 1.0 mM of thiol and the concentrations determined intracellularly and extracellularly with time. Slices incubated with GSH, GSH isopropyl diester and gamma-glu-cys isopropyl diester had cellular GSH concentrations increased by up to 60%, 95% and 58%, respectively, whereas GSH isopropyl monoester and gamma-glu-cys isopropyl monoester did not increase the intracellular GSH concentration. Extracellularly, the GSH concentration had decreased by 15%, GSH isopropyl diester by 27%, gamma-glu-cys isopropyl diester by 66% and both isopropyl monoesters by over 90% at 120 min. Lung slices and tracheal sections incubated with L- or D-CySH at 37 degrees had increased cellular concentrations of L- and D-CySH which ranged between 0.88-1.25 nmol mg(-1) and 1.35-2.25 nmol mg(-1) , respectively. Reducing the incubation temperature to 4 degrees had little effect on the accumulation of D-CySH; however, L-CySH concentrations increased progressively in the trachea and lung to reach 2.73 and 2.63 nmol mg(-1) at 90 min, respectively. Lung slices incubated with L- or D-CIPE had increased L- or D-CySH concentrations up to a max of 13.7 and 11.1 nmol mg(-1) and tracheal sections up to a max of 5.56 and 11.09 nmol mg(-1). In the lung slice medium, L- and D-CIPE levels had decreased by 75.2% and 74.0% at 90 min, respectively, and from the tracheal section medium, L- and D-CIPE concentrations had decreased by 66.7% and 32.7%, respectively. Preincubation of lung slices and tracheal sections with the carboxylesterase inhibitor, bis (p-nitrophenyl) phosphate (BNPP), almost completely prevented the disappearance of L- and D-CIPE extracellularly and greatly reduced the appearance of cellular L- and D-CySH. GSH, GSH isopropyl diester and gamma-glu-cys isopropyl diester elevated and prolonged GSH concentrations in rat lung slices, but GSH isopropyl monoester and gamma-glu-cys isopropyl monoester did not increase GSH levels. The uptake of L-CySH, but not D-CySH, is temperature sensitive in rat lung slices and tracheal sections and carboxylesterases appear to have a major influence on the uptake and metabolism of L- and D-CIPE by rat lung slices and tracheal sections.

The effect of sulphur mustard on glutathione levels in rat lung slices and the influence of treatment with arylthiols and cysteine esters.

1. Sulphur mustard reacts directly with benzenethiols and cysteine esters in aqueous medium. 2. Benzenethiols diffuse into lung slices in short term culture. 3. Treatment of lung slices in short term culture with benzenethiols does not protect cellular glutathione from conjugation with sulphur mustard. 4. Following uptake of cysteine ester into lung slices cysteine is elevated but this does not protect cellular glutathione from sulphur mustard.

Anatomy of diplegia: an hypothesis.

Periventricular leukomalacia (PVL) occurring in relation to the body of the lateral ventricle could account for damage to the corticospinal tracts. However, PVL in this location is relatively rare, and the view that it causes the diplegia of preterm birth is challenged on the anatomical grounds that the corticospinal tracts to the legs are some distance away from the main sites of PVL, which are at the collateral trigone and near to the interventricular foramen. If PVL lesions do cause permanent nerve damage, it is surprising that cortical blindness in diplegia is so uncommon. A dying-back neuropathy caused by selective damage to corticospinal neurons could be considered as an alternative hypothesis to account for the paralysis of diplegia.

Structure-activity relationships of cysteine esters and their effects on thiol levels in rat lung in vitro.

Pretreatment with cysteine esters increases cysteine (CySH) levels in rat lung and protects against the lethal effects of inhaled perfluoroisobutene in vivo. There are marked differences in the duration of protection achieved with different cysteine esters. In this study we have compared the uptake and metabolism of CySH, N-acetyl cysteine (NAc), cysteine esters and cystine esters in vitro using rat lung and liver homogenates and lung slices. Liver homogenates metabolized CySH and cysteine esters faster than lung homogenates. The half life (T1/2) of CySH in lung was 58.8 +/- 17.3 min and in liver was 14.0 +/- 1.6 min (mean +/- SEM). T1/2 of the esters in lung ranged between 6.5 and 12.1 min and in liver between 1.9 and 5.3 min. Cysteine tertiary butyl ester, which does not protect in vivo, was not hydrolysed to CySH by lung or liver homogenates. All esters increased and prolonged intracellular CySH concentrations in lung slices to a much greater extent than CySH itself. NAc did not raise intracellular CySH above that of the controls and no NAc appeared within the slice. After CySH incubation intracellular CySH was 0.9 +/- 0.1 nmol/mg wet wt at 10 min whereas after incubation with the esters it ranged between 2.60 and 3.65 nmol/mg wet wt. Cysteine cyclohexyl ester prolonged the increase of CySH the longest and cysteine methyl ester the shortest. CySH levels with cysteine cyclohexyl ester were 2.74 +/- 0.15 and 4.13 +/- 0.37 nmol/mg wet wt at 10 and 60 min, respectively, whereas with cysteine methyl ester, CySH levels were 2.60 +/- 0.5 and 1.25 +/- 0.08 nmol/mg wet wt at similar times. Cystine esters increased intracellular concentrations of both cystine and CySH. CySH concentrations ranged between 2.92 and 3.19 nmol/mg wet wt and cystine between 1.39 and 1.47 nmol/mg wet wt at 60 min. The elevation and duration of CySH in lung slices is well correlated with the duration of protection against perfluoroisobutene achieved in vivo.