Effect of trehalose and melibiose on crystallization of amorphous paracetamol.

This paper investigates the solid-state behavior of two-phase solid dispersions involving small molecules. The effect of two sugars, trehalose and melibiose, on the recrystallization of amorphous paracetamol, and vice versa, was investigated. The solid dispersions were prepared via heating and quench-cooling, and then stored at a temperature of 38.5 ± 0.5 °C and relative humidities of 3 ± 1% and 75 ± 1%. X-ray powder diffraction (XRPD) confirmed that the solid dispersions were amorphous, while Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) revealed that the solid dispersions were two-phase systems with drug-rich and excipient-rich regions. XRPD was used to qualitatively and quantitatively study the crystallization of the components, and revealed that, despite the existence of two phases, the sugars hindered the crystallization of paracetamol. In contrast, once the paracetamol crystallization started, it accelerated the crystallization of the sugars. Overall, the study demonstrates that small-molecule solid-dispersions need not be single-phase to observe mutual influences between the components in crystallization behavior, and that these effects are likely mediated through interactions at the phase interfaces, as well as alterations in water sorption and mechanical effects.

Three new species of Krogia (Ramalinaceae, lichenised Ascomycota) from the Paleotropics.

Krogiaborneensis Kistenich & Timdal, K.isidiata Kistenich & Timdal and K.macrophylla Kistenich & Timdal are described as new species, the first from Borneo and the two latter from New Caledonia. The new species are supported by morphology, secondary chemistry and DNA sequence data. Krogiaborneensis and K.isidiata contain sekikaic and homosekikaic acid, both compounds reported here for the first time from the genus. Krogiamacrophylla contains an unknown compound apparently related to boninic acid as the major compound. DNA sequences (mtSSU and nrITS) are provided for the first time for Krogia and a phylogeny of the genus based on 15 accessions of five of the six accepted species is presented. Krogiaantillarum is reported as new to Brazil, Guatemala and Mexico.

Content of Orthopedic Patient Education Provided by Nurses in Seven European Countries.

Patients' and their significant others' education during the perioperative phase is an important and challenging aspect of care. This study explored the content of education provided by nurses to arthroplasty patients and their significant others. Data were collected with the Education of Patients-NURSE content (EPNURSE-Content), Received Knowledge of Hospital Patient (RKhp), and Received Knowledge of Significant Other (RKso) scales. The results showed that the content of education emphasized biophysiological and functional needs, differed between countries, and was related to how physically demanding nurses found their job to be and the amount of education provided. There is congruence between the received knowledge of patients and their significant others in relation to the content of education provided by nurses. The findings can support nurses in developing aid material for patients and significant others explaining the nature of education and advising them what to expect and how to optimize their participation in the process.

Obstetric complications as risk factors for schizophrenia spectrum psychoses in offspring of mothers with psychotic disorder.

BACKGROUND: Obstetric complications have predicted future development of schizophrenia in previous studies, but they are also more common in mothers with schizophrenia. The aims of this study were to compare the occurrence of obstetric complications in children of mothers with schizophrenia spectrum psychoses and control children, and to investigate whether obstetric complications predicted children's psychiatric morbidity. METHOD: The Helsinki High-Risk (HR) Study monitors females born between 1916 and 1948 and treated for schizophrenia spectrum disorders in Helsinki psychiatric hospitals, their offspring born between 1941 and 1977, and controls. We examined information on obstetric complications and neonatal health of 271 HR and 242 control offspring. We compared the frequency of obstetric complications and neonatal health problems in the HR group vs controls and in HR children who later developed psychotic disorders vs healthy HR children. A Cox regression model was used to assess whether problems in pregnancy or delivery predicted psychiatric morbidity within the HR group. RESULTS: Few differences between HR and control offspring were found in obstetric complications. Within the HR group, infections (hazard rate ratio [HRR] 3.73, 95% CI 1.27-11.01), hypertension during pregnancy (HRR 4.10, 95% CI 1.15-14.58), and placental abnormalities (HRR 4.09, 95% CI 1.59-10.49) were associated with elevated risk of schizophrenia spectrum psychoses. CONCLUSIONS: Common medical problems during pregnancy were associated with increased risk of schizophrenia spectrum psychoses in offspring of mothers with schizophrenia spectrum psychoses. These results underline the role of the prenatal period in the development of schizophrenia and the importance of careful monitoring of pregnancies of mothers with psychotic disorder.

Increased use of antidepressants in women decreases suicides in men: an ecological study.

OBJECTIVE: The suicide rate has decreased in many countries, while the use of antidepressants has increased. In our previous study, the decrease in suicide rate between 1994 and 2001 was greater in men than in women, but the increase in use of antidepressants was greater in women than in men. We hypothesized that the increase in the use of antidepressants in women associates with the decrease in suicide rate in men. METHOD: Population-based suicide rate and reimbursed antidepressant prescriptions, an indicator of antidepressant use, between 1994 and 2001 in Finland were analyzed in the whole population. Variance in the suicide rates in men and women was explained by antidepressant prescriptions for men and women, age, time period, and geographical region in Poisson regression analyses. RESULTS: The decrease in suicide rate in men associated significantly with the increase in antidepressant prescriptions in women even though the model took into account the effect of increased antidepressant prescriptions in men, as well as the effects of age, time, and region (risk ratio [RR] = 0.70, P = .004, in the model without age; RR = 0.89, P = .048 in the complete model). However, the decrease in suicide rate in women did not associate with the increase in antidepressant prescriptions in men. CONCLUSIONS: Increased prescription of antidepressants in women associates with a decreased suicide rate in men. Increased use of antidepressive medication in women may decrease depressiveness in their microsocieties and thereby reduce the risk of suicides also in men.

Effects of antidepressant drug treatment and psychotherapy on striatal and thalamic dopamine D2/3 receptors in major depressive disorder studied with [11C]raclopride PET.

Antidepressant drug treatment and psychotherapy are both effective in treating major depression, but there are no published studies comparing the effects of these two treatments on the dopaminergic neurotransmitter system in major depression. We conducted a randomized comparative study on the effects of fluoxetine medication and short-term psychodynamic psychotherapy on striatal and thalamic dopamine D(2/3) receptors in patients with major depression. Duration of the treatment was 4 months, and dopamine D(2/3) receptor binding was quantified before and after treatment as the binding potential (BP (ND)) using [(11)C]raclopride and 3D positron emission tomography. Both treatments were clinically effective in treating major depression, as shown by substantial decreases in symptom ratings. Yet, there were no effects on D(2/3) receptor availability in the ventral striatum or other subdivisions of the striatum. Fluoxetine but not psychotherapy increased [(11)C]raclopride BP (ND) in lateral thalamus (+7.74%, p = 0.002) but this increase was not correlated with clinical improvement. In conclusion, this preliminary study does not support the involvement of ventral dopaminergic neurotransmission in the antidepressant effects of fluoxetine or psychodynamic psychotherapy. The effects of fluoxetine on thalamic dopamine systems need to be further explored.

Personality traits and recovery from major depressive disorder.

OBJECTIVE: To study the correlation of personality traits measured by the Temperament and Character Inventory (TCI) with the prognosis of major depressive disorder in patients treated with either fluoxetine or short-term psychodynamic psychotherapy in a randomized comparative study. METHOD: 35 patients with DSM IV-defined major depressive disorder of mild or moderate severity were randomized to receive either short-term psychodynamic psychotherapy or fluoxetine treatment for 16 weeks. Prior to beginning of the therapy, patients were assessed with TCI. The Hamilton Depression Rating Scale (HDRS) was used as the outcome measure completed at the baseline and follow-up at 4 months. RESULTS: In the combined group (n=35), Harm Avoidance was associated with the severity of the depression measured by the HDRS at the baseline (P=0.01) and baseline Self-Directedness with the HDRS at 4 months follow-up (P=0.03). In the fluoxetine treatment group, Reward Dependence (P=0.03), Self-Directedness (P=0.01) and Cooperativeness (P=0.02) at the baseline associated with HDRS at 4 months follow-up. No statistically significant associations between personality traits and depression scores at the follow-up were found in the patients treated with psychotherapy. CONCLUSION: In this whole cohort of depressive patients, baseline high Self-Directedness predicted higher depression scores after 4 months of treatment. In the fluoxetine treatment group, subjects with high baseline Reward Dependence, Self-Directedness or Cooperativeness were likely more severely depressed at the 4 months follow-up. We suggest that associations between personality traits and remaining depressive symptoms after 4 months treatment with fluoxetine could be caused by the potential differences in the placebo effect.

Health-related quality-of-life profiles in nonalexithymic and alexithymic subjects from general population.

OBJECTIVE: Earlier studies have shown an association between alexithymia and health-related quality of life (HRQoL). There has been some controversy as to whether this is attributable solely to psycho-social domains of HRQoL or also to physical domains. Furthermore, there are no studies on HRQoL profiles in representative general population samples controlling for sociodemographic variables, mental health and somatic health. METHODS: The study forms part of the Health 2000 Study. Altogether 5090 participants from general population, aged 30-97 years, filled in the 20-item Toronto Alexithymia Scale and the 15D HRQoL scale. Depressive and anxiety disorders were assessed in a structured psychiatric interview. Physical health was examined by physicians. The 15-dimension HRQoL profiles of both alexithymic and non-alexithymic subjects were obtained by analysis of covariance, controlling for sociodemographic and health-related variables. RESULTS: The alexithymic group had significantly (P<.001) lower mean scores on every dimension of the 15D even after controlling for confounding demographic variables, somatic diagnoses and depressive and anxiety disorders. The differences were greatest in the psycho-social domains. CONCLUSIONS: Alexithymia seems to be a personality trait with a statistically significant association to every dimension of HRQoL, not only to psychosocial domains. However, the associations between alexithymia and some somatic dimensions may be of little clinical significance.

[Update on current care guidelines. Depression, current care guideline]. / Depressio.

The treatment of depression is based on careful diagnostic evaluation. In the acute phase of treatment, brief psychotherapies (cognitive, interpersonal, psychodynamic or problem-solving) are effective in cases of mild to moderate depression. Antidepressants are also effective, their importance increasing alongside the level of severity. Electroconvulsive therapy (ECT) is effective for severe or psychotic depression. After the acute phase, antidepressants must be continued for at least six months to prevent a relapse; maintenance antidepressant treatment must be considered after three lifetime episodes. Primary health care is responsible for the majority of mild to moderate cases of depression, but psychiatric consultation services and nurse case managers are required to fulfill this task.

Does defense style or psychological mindedness predict treatement response in major depression?

BACKGROUND: The aim of this study was to define the impact of defense style and psychological mindedness (PM) on the prognosis of major depressive disorder (MDD) in patients treated with either fluoxetine (FLX) or short-term psychodynamic psychotherapy (STPP) in a randomized comparative study. METHOD: 50 patients with MDD received either STPP or FLX treatment for 16 weeks. The Hamilton Depression Rating Scale (HDRS) was the outcome measure completed at baseline and in the follow-ups at 4- and 12-months. Patients completed the Psychological Mindedness Scale (PMS) and the Defense Style Questionnaire at the baseline. RESULTS: In the FLX group recovery measured by the decrease in the HDRS during the 4-month follow-up associated with baseline mature defense style (r=-.59, P=.015). There were no correlations between the PMS-scores and the outcome measures in either treatment groups nor defense status and the outcome in the STPP group. CONCLUSION: Mature defense style predicts good response to FLX therapy in major depression. This association was not found in the psychotherapy group. The results may imply that patients with immature defenses benefit relatively more from brief psychotherapy than medication. PM measured by the PMS was not useful in predicting recovery in MDD.

Alexithymia and health-related quality of life in a general population.

BACKGROUND: Alexithymia is thought to reflect a deficit in the cognitive processing of emotion, and, therefore, it may predispose individuals to both psychological and somatic symptoms. OBJECTIVE: The authors investigated the relationship between alexithymia and health-related quality of life (HRQoL) in a nationally representative population sample of 5,418 subjects, age 30 to 97 years. METHOD: Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20) and HRQoL measured with the 15D, a generic HRQoL measure. RESULTS: Alexithymia was significantly associated with lower HRQoL independently of other variables. The TAS-20 subfactor Difficulties Identifying Feelings was the strongest common denominator between alexithymia and HRQoL. CONCLUSION: Alexithymia may be a predisposing factor to poorer HRQoL.

Short-term psychodynamic psychotherapy and fluoxetine in major depressive disorder: a randomized comparative study.

BACKGROUND: There are few studies comparing the efficacy of short-term psychodynamic psychotherapy (STPP) and pharmacotherapy in major depressive disorder. We conducted a comparative study on the efficacy of STPP versus fluoxetine treatment in patients with major depressive disorder in a primary care setting. METHODS: Fifty-one patients with major depressive disorder (DSM-IV) of mild or moderate severity were recruited through occupational health services providing primary health care. Patients were randomized to receive either STPP (1 session/week) or fluoxetine treatment (20-40 mg/day) for 16 weeks. The outcome measures included the Hamilton Depression Rating Scale (HDRS), the Beck Depression Inventory (BDI), and the Social and Occupational Functioning Assessment Scale (SOFAS). RESULTS: Intent-to-treat analyses indicated that both treatments were highly effective in reducing the HDRS (p < 0.0001) and BDI (p < 0.0001) scores, as well as in improving functional ability (SOFAS; p < 0.0001), with no statistically significant differences between the treatments. Of those 40 subjects who completed the follow-up, 57% in the psychotherapy group and 68% in the fluoxetine group showed full remission (HDRS

Alexithymia and somatization in general population.

OBJECTIVE: Even though the association between alexithymia and somatization seems plausible according to several studies with selected populations, it has not been verified in carefully controlled and nationally representative population studies. We conducted such a study to find out whether alexithymia is associated with somatization at population level. METHODS: This study was a part of the Finnish Health 2000 Study. The nationally representative sample comprised 5129 subjects aged 30 to 97 years. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20) and somatic symptom reporting with the 12-item somatization scale derived from the Hopkins Symptom Checklist. Sociodemographic and health-related variables, including depressive and anxiety disorders, and physician verified somatic diagnoses, were treated as confounders in multivariate analyses. RESULTS: Alexithymia was associated with somatization independently of somatic diseases, depression and anxiety and confounding sociodemographic variables. The TAS-20 factor scale "Difficulties Identifying Feelings" was the strongest common denominator between alexithymia and somatization. CONCLUSIONS: This was the first time the independent association between alexithymia and somatization was established in a large, nationally representative nonclinical sample of both young and old adults with and without mental disorders and somatic diseases.

Striatal dopamine D2 receptors in medication-naive patients with major depressive disorder as assessed with [11C]raclopride PET.

RATIONALE: Among other monoamine neurotransmitters, dopamine is implicated in the pathophysiology of major depression. Experimental studies suggest the involvement of the mesolimbic dopamine system in the mechanism of action of antidepressant drugs. Previous in vivo imaging studies have studied striatal dopamine D2 receptor availability in depression but the results are equivocal thus far. OBJECTIVE: To study the striatal and thalamic dopamine D2 receptor availability in drug-naive patients with major depression was the aim of this study. MATERIALS AND METHODS: Caudate, putamen, and thalamic dopamine D2 receptor availability was estimated using positron emission tomography and [11C]raclopride in 25 treatment-seeking drug-free patients (of whom 24 were drug-naive) with major depression (primary care patients) as well as in 19 demographically similar healthy control subjects. Receptor availability was expressed as the binding potential (BP ND), and analyses were carried out based on both regional and voxel-level BP ND estimates. RESULTS: No statistically significant differences in [11C]raclopride BP ND were observed between the groups either in the caudate nucleus (+1.7%, CI -4.8% to +8.3%), putamen (-1.0%, CI -7.2% to 5.1%), thalamus (-2.4%, CI -8.7% to 4.0%), or ventral striatum (-3.8%, CI -9.3% to +1.6%). In the patients, depressive symptoms were not associated with [11C]raclopride BP ND in any region. CONCLUSIONS: The findings in this sample of treatment-seeking, drug-naive and predominantly first-episode patients with major depression do not support the involvement of striatal dopamine D2 receptors in the pathophysiology of the illness, but do not exclude the potential importance of dopaminergic mechanisms in antidepressant drug action.

Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WAY-100635.

Serotonin (5-HT) is involved in the pathophysiology of major depressive disorder (MDD). Among the numerous serotonergic receptors, the 5-HT1A receptor subtype is of interest because of its involvement in cognition, hippocampal neurogenesis, and mechanism of action of antidepressant drugs. Previous imaging studies have suggested altered availability of 5-HT1A receptors in MDD but prior antidepressant medication and chronicity of the illness may confound the interpretation. We examined 21 drug-naive primary-care patients with MDD using positron emission tomography (PET) imaging with [carbonyl-11C]WAY-100635, a radioligand for 5-HT1A receptors, along with 15 healthy control subjects. Binding to receptors was assessed both regionally and at voxel level with the binding potential (BP) that was estimated using arterial blood input. Compared with healthy controls, the BP of [carbonyl-11C]WAY-100635 was reduced in patients with MDD in most brain regions, ranging from -9% to -25%. Voxel-level analysis confirmed this finding by showing a widespread reduction of [carbonyl-11C]WAY-100635 BP. No statistically significant associations were observed between BP and total HAMD scores in the patients, but lower BP was associated with higher likelihood of insomnia. This study demonstrated a widespread reduction in the availability of serotonin 5-HT1A receptors in a relatively large sample of drug-naive primary-care patients with MDD, suggesting the involvement of this receptor subtype in the pathophysiology of the illness. Lack of correlation with overall severity of the illness may relate to a largely trait-like nature of this abnormality in depressive disorders.

Alexithymia and occupational burnout are strongly associated in working population.

OBJECTIVE: The relationship between alexithymia and occupational burnout has not previously been studied. We investigated the association between alexithymia and occupational burnout in a representative nationwide population health study. METHODS: This study was a part of the Finnish Health 2000 Study. The nationally representative sample comprised 3322 employees aged 30-64 years. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20) and occupational burnout with the Maslach Burnout Inventory-General Survey. Sociodemographic and health-related variables including depression were treated as confounders in the logistic regression analyses, which were performed alternately with TAS-20 total score and the scores of the three TAS-20 factor scales as alexithymia variables. RESULTS: Alexithymia and its three facets were significantly associated with occupational burnout even when controlled for confounding factors. CONCLUSIONS: Even though both alexithymia and depression are associated with burnout, alexithymia may be an independent risk factor for occupational burnout.

Use of antidepressants and suicide rate in Finland: an ecological study.

OBJECTIVE: The suicide rate has decreased in many countries, while the use of antidepressants has increased greatly. The aim of this study was to investigate the associations between use of antidepressants and suicide rate. METHOD: Population-based suicide rates and reimbursed prescriptions of antidepressants between 1994 and 2001 in Finland were analyzed in the whole population, and separately by gender, age, and geographical region. RESULTS: There were significant differences in suicide rates between men and women (p < .0001), but there were no differences between different regions of the country. The decline in the suicide rate was significantly associated with use of antidepressants among men aged 15 to 44 (p < .0001), 45 to 64 (p = .0005), and 75 years and over (p = .001) and men in 3 regions (p < .001). The decline in the suicide rate was significantly associated with the use of antidepressants among 15- to 44-year-old women (p = .008) and women in 1 region (p = .013). Use of antidepressants had a significant association with the decrease in the suicide rate (risk ratio = 0.08, 95% CI 0.02 to 0.30, p < .001), despite the effect of background variables, their interaction, and the course of time. CONCLUSIONS: An increase in the use of antidepressants may decrease the suicide rate. Baseline suicide rate and access to health care may influence this association.

Age is strongly associated with alexithymia in the general population.

OBJECTIVE: We studied the prevalence of alexithymia, its distribution in different age groups in a wide age range, its association with sociodemographic and health-related variables, and its co-occurrence with depression. METHODS: The study forms part of the Health 2000 Study. The original sample comprised 8028 subjects representing the general adult population of Finland. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20), and depression was measured with the 21-item Beck Depression Inventory. Altogether, 5454 participants filled in TAS-20 in their mother tongue. RESULTS: The prevalence of alexithymia was 9.9%. Men (11.9%) were more commonly alexithymic than women (8.1%). Alexithymia was associated with male gender, increasing age, low educational level, poor perceived health, and depression. CONCLUSIONS: The findings were in line with earlier population studies. For the first time, it was possible to analyze the prevalence of alexithymia in a wide age range (30-97 years). International comparative studies are needed.

Occupational Functioning Scale (OFS)--an instrument for assessment of work ability in psychiatric disorders.

The aim was to present the content of the newly developed observer rating scale of work ability--The Occupational Functioning Scale (OFS)--and its basic psychometric properties. Psychiatric disorders cause functional impairment in several domains, including occupational functioning. The assessment of work-related functioning is often neglected in psychiatric research, partly due to a lack of reliable and valid instruments. The validity of OFS was evaluated by comparing it with other work ability measures (SAS-work, Work Ability Index, sickness absence) and to non-work-ability related measures [Inventory of Interpersonal Problems (IIP), Symptom Check List - General Symptomatic Index (SCL-90-GSI)] in 150 patients with depressive or anxiety disorders. Reliability was determined by 39 videotaped interviews rated by four judges. OFS showed excellent inter-rater reliability (intraclass correlation = 0.91) and good criterion validity by being more strongly related to other scales of occupational functioning (mid R:rmid R: = 0.39-0.47) than to measures of general distress (SCL-90-GSI) and interpersonal problems (IIP)(mid R:rmid R: = 0.26 and 0.12). OFS is a simple, reliable and clinically meaningful instrument for assessment of work ability in depressive and anxiety disorders.