Hyper- and Hypomentalizing in Patients with First-Episode Schizophrenia: fMRI and Behavioral Studies.

BACKGROUND: Historically, research investigating neural correlates of mentalizing deficits in schizophrenia has focused on patients who have been ill for several years with lengthy exposure to medication. Little is known about the neural and behavioral presentations of theory-of-mind deficits in schizophrenia, shortly after the first episode of psychosis. METHODS: We investigated social cognition in 17 recently diagnosed first-episode schizophrenia (FES) patients with little or no exposure to antipsychotic medication and 1:1 matched healthy controls. We recorded behavioral and neural responses to the Animated Triangles Task (ATT), which is a nonverbal validated mentalizing task that measures the ascription of intentionality to the movements of objects. RESULTS: FES patients under-interpreted social cues and over-interpreted nonsocial cues. These effects were influenced by current intelligence (IQ). Control group and FES neural responses replicated earlier findings in healthy adults. However, a region of anterior medial prefrontal cortex (amPFC) of FES patients showed a different response pattern to that of controls. Unlike healthy controls, patients increased activity in this social cognition region while studying "random" movements of shapes, as compared to the study of movements normally interpreted as "intentional". CONCLUSIONS: Mentalizing deficits in FES consists of hypo- and hypermentalizing. The neural pattern of FES patients is consistent with deficits in the ability to switch off mentalizing processes in potentially social contexts, instead increasing them when intentionality is not forthcoming. Overall, results demonstrate complexities of theory of mind deficits in schizophrenia that should be considered when offering social cognitive training programs.

Patient preferences for medicine administration for acute agitation: results from an internet-based survey of patients diagnosed with bipolar disorder or schizophrenia in two Nordic countries.

The objective was to elicit patient preferences for medicine administration method in the management of acute agitation episodes among patients diagnosed with bipolar disorder or schizophrenia. The patients' experiences of acute agitation episodes and their management of episodes were also explored. Data were collected via an anonymous, internet-based survey of residents in Denmark or Sweden with schizophrenia or bipolar disorder (October 2014 to December 2014). Inclusion criteria were having a diagnosis of schizophrenia or bipolar disorder, and being above 18 years of age. The questionnaire included questions about preferences for medication attributes, experiences with pharmacological treatment for agitation and involvement in treatment plans. A total of 237 diagnosed patients (61 with schizophrenia; 176 with bipolar disorder) completed the questionnaire. Agitation episodes were experienced by 90% of the respondents. In total, 83% of the respondents reported having received treatment with tablets. When patients were presented with the attributes of an inhalation method, respondents stated that the fast onset of action, low risk of adverse reactions and least invasive form of drug delivery were positive attributes of treatment with inhalation. Inhalation is a new delivery route for treatment of acute agitation in patients diagnosed with bipolar disorder or schizophrenia. Inhalation is the preferred treatment method for acute agitation among Danish and Swedish patients with bipolar disorder or schizophrenia.

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II).

OBJECTIVE: To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years of treatment as usual. DESIGN: Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site. SETTING: Participants were recruited from six OPUS teams in Denmark between 2009 and 2012. OPUS teams provide SEI treatment to all patients diagnosed with a schizophrenia spectrum disorder in Denmark. PARTICIPANTS: 400 participants (51% women) with a mean age of 25.6 (standard deviation 4.3) were randomised to five years of SEI (experimental intervention; n=197) or to two years of SEI plus three years of treatment as usual (control; n=203). INTERVENTIONS: OPUS treatment consists of three core elements-modified assertive community treatment, family involvement, and social skill training-with a patient-case manager ratio of no more than 12:1. For participants randomised to five years of OPUS treatment, the treatment was largely unchanged. Participants randomised to the control group were mostly referred to community health centres after two years of SEI treatment. MAIN OUTCOMES: Follow-up assessments were conducted five years after start of OPUS treatment. Primary outcome was negative symptoms measured on the scale for assessment of negative symptoms (avolition-apathy, anhedonia, alogia, and affective blunting). Secondary outcomes were remission of both negative and psychotic symptoms, psychotic symptoms, suicidal ideation, substance abuse, compliance with medical treatment, adherence with treatment, client satisfaction, days in hospital care, and labour market affiliation. RESULTS: Levels of negative symptoms did not differ between the intervention group and control group (1.72 v 1.81 points; estimated mean difference -0.10 (95% confidence interval -0.33 to 0.13), P=0.39). Participants receiving five years of OPUS treatment were more likely to remain in contact with specialised mental health services (90.4% v 55.6%, P<0.001), had higher client satisfaction (estimated mean difference 2.57 points (95% confidence interval 1.36 to 3.79), P<0.001), and had a stronger working alliance (estimated mean difference 5.56 points (95% confidence interval 2.30 to 8.82), P=0.001) than the control group. CONCLUSIONS: This trial tests SEI treatment for up to five years for patients with first episode schizophrenia spectrum disorder; previous trials have found treatment effects for programmes lasting from one to three years. The prolonged SEI treatment had few effects, which could be due to the high level of treatment provided to control participants and the late start of specialised treatment.Trial registration Clinicaltrial.gov NCT00914238.

The effect of the medicine administration route on health-related quality of life: Results from a time trade-off survey in patients with bipolar disorder or schizophrenia in 2 Nordic countries.

BACKGROUND: Agitation episodes are common among patients with schizophrenia or bipolar disorder. Oral and intramuscular administration methods are commonly used in pharmacological treatment of acute agitation. Recently, an innovative inhalation product with loxapine(Adasuve®)has become available for treatment of acute agitation episodes associated with bipolar disorder or schizophrenia. The objective for the present study was to investigate the impact of the pharmacological treatment's administration methods on the health-related quality of life (HRQoL) in patients with bipolar disorder or schizophrenia in Denmark and Sweden using a time trade-off (TTO) approach. METHODS: The TTO methodology was used to examine the HRQoL impact of administration method of pharmacological treatment of acute agitation. Data were collected via an internet-based survey, using an existing panel of respondents with schizophrenia or bipolar disorder. RESULTS: Respondents considered living with schizophrenia/ bipolar disorder, having one yearly agitation episode treated with inhaler better than living with the same conditions and receiving treatment with tablet or injection. The utility value was 0.762 for inhalable treatment, 0.707 for injection and 0.734 for tablet treatment. CONCLUSIONS: Patients' preference for treatment delivery options showed that inhalation was associated with a significant utility gain when compared to injection or tablets. Inhalable loxapine may be a new tool for control of agitation episodes for strengthening the patient provider alliance when taking patient's preference for delivery method into consideration.

A retrospective study of clinical usage of quetiapine XR and quetiapine IR in outpatients with schizophrenia in Denmark.

OBJECTIVES: The atypical antipsychotic quetiapine is a first-line treatment for schizophrenia. This non-interventional study (NCT01212575) evaluated the clinical use of its two formulations, extended release (XR) and immediate release (IR), in outpatients with schizophrenia spectrum disorder. METHODS: Patients who had received at least one dose of quetiapine XR and/or IR were included. A dosage ≥400 mg/day was defined as antipsychotic. Medical records data were collected retrospectively. RESULTS: Of 186 enrolled patients, 99 (53%) and 87 (47%) received quetiapine XR and IR, respectively. Use in antipsychotic dosage was seen for 89% XR versus 63% IR patients (mean daily dose ≥400 mg/day; p < 0.0001). 75% XR and 53% IR patients used dosages ≥600 mg/day (p = 0.0019). Quetiapine XR was used at higher mean daily dosages than IR (748 vs 566 mg/day; p = 0.006). Forty-three patients (23%) used both formulations concomitantly; 55 patients (30%) used either XR or IR. Quetiapine IR was used as-needed in 44 patients (23%); one patient used XR as-needed. CONCLUSIONS: Quetiapine XR was used more often in higher (antipsychotic) dosages; quetiapine IR more frequently on an as-needed administration basis. Concomitant use was seen. These findings probably reflect the different profiles of XR/IR and advocate the need for both formulations to offer treatment choice.

Augmenting clozapine with sertindole: a double-blind, randomized, placebo-controlled study.

Clozapine augmentation with antipsychotic drugs is widely used despite sparse evidence supporting this strategy. Sertindole is a nonsedating atypical antipsychotic drug with low affinity for cholinergic receptors, which makes it potentially suitable for augmentation of clozapine. The study design was a 12-week, double-blind, randomized, placebo-controlled study including patients with International Statistical Classification of Diseases, 10th Revision schizophrenia (F20.0-F20.3) and treated with clozapine for at least 6 months who had not achieved sufficient response. Patients were randomized 1:1 to either sertindole 16 mg or placebo, and assessment was done at baseline and after 6 and 12 weeks. Assessment included the Positive and Negative Syndrome Scale, Clinical Global Impression, Udvalg for Kliniske Undersøgelser, World Health Organization Quality of Life Brief, Drug Attitude Inventory, fasting glucose, lipids, and electrocardiogram. Clozapine augmentation with sertindole was not superior to placebo regarding total score or subscale score of the Positive and Negative Syndrome Scale, Clinical Global Impression, World Health Organization Quality of Life Brief, or Drug Attitude Inventory. No increased adverse effects compared with placebo were found. Four patients randomized to sertindole experienced a significant worsening of psychosis, and 2 of them required psychiatric admission. Metabolic parameters were unchanged during the study, but augmentation of clozapine with sertindole was associated with a 12-millisecond (SD, 20-millisecond) QTc prolongation compared with 0 millisecond (SD, 20 milliseconds) in the placebo group (P < 0.03). Augmentation with sertindole showed no benefits compared with placebo. Psychiatrists should be aware that augmentation might not add any benefits for the patients and in some cases worsen psychosis.

Patients with eating disorders. A high-risk group for fractures.

PURPOSE: To analyze fracture risk and bone mineral density in patients with eating disorders (anorexia nervosa, bulimia nervosa, and other eating disorders). DESIGN: Clinical overview. FINDINGS: Bone mineral density is decreased and fracture risk increased in patients with anorexia nervosa. In patients with bulimia nervosa, bone mineral is only marginally decreased and fracture risk marginally increased. In patients with other eating disorders (eating disorders not otherwise specified), bone mineral density is decreased and fracture risk increased. CONCLUSIONS: Fracture risk is increased in patients with eating disorders. An eating disorder should be suspected in severely underweight young individuals (primarily girls) presenting with fractures, especially low-energy fractures.

Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders--a nationwide register study.

OBJECTIVE: To study fracture risk in patients with anorexia nervosa (AN), bulimia nervosa (BN), or eating disorders not otherwise specified (EDNOS). METHOD: Cohort study including all Danes diagnosed with AN (n = 2,149), BN (n = 1,294), or EDNOS (n = 942) between 1977 and 1998. Each patient was compared with three randomly drawn age- and gender-matched control subjects. RESULTS: Fracture risk was increased in AN after diagnosis compared to controls (incidence rate ratio: 1.98, 95% CI: 1.60-2.44), but not before. The increased fracture risk persisted more than 10 years after diagnosis. A significant increase in fracture risk was found before diagnosis in BN (1.31, 95% CI: 1.04-1.64), with a trend towards an increase after diagnosis (1.44, 95% CI: 0.93-2.22). EDNOS patients had a significant increase in fracture risk before (1.39, 95% CI: 1.06-1.81) and after diagnosis (1.77, 95% CI: 1.25-2.51). DISCUSSION: The increased fracture risk many years after diagnosis indicates permanent skeletal damage.

Mortality in concurrent type 1 diabetes and anorexia nervosa.

OBJECTIVE: Previous studies in this field report early occurrence of diabetic complications, but excess mortality, though expectable, has not been reported. We combined information from earlier studies to estimate the mortality for this group of patients. RESEARCH DESIGN AND METHODS: The observed mortality is analyzed using crude mortality rate (a percentage), standardized mortality ratio (SMR), incidence rate ratio, risk difference, and survival analysis. RESULTS: After approximately 10 years of follow-up, 13 of 510 females with type 1 diabetes, 43 of 658 females with anorexia nervosa (AN), and 8 of 23 concurrent case subjects had died. Mortality rate was 2.2 (per 1,000 person-years) for type 1 diabetes, 7.3 for AN cases, and 34.6 for concurrent cases. Crude mortality rates were 2.5, 6.5, and 34.8%, respectively. SMR was 4.06 in type 1 diabetes, 8.86 in AN, and 14.5 in concurrent cases. Survival analysis indicated between-group differences in mortality. CONCLUSIONS: Concurrent type 1 diabetes and AN is a rare but serious condition in females. All indexes of mortality evidence excess mortality in this preliminary study. Vigorous and well-directed treatment efforts seem vital for this subpopulation. Collaboration between diabetologists and eating disorder specialists is warranted. The implications of other eating disorders and subclinical eating disorders in diabetic populations need to be analyzed, especially because these conditions are more frequent than clinical eating disorders.