Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

[Guideline-conform inpatient psychiatric psychotherapeutic treatment of chronic depression: Normative personnel requirements]. / Leitlinienentsprechende stationäre psychiatrisch-psychotherapeutische Behandlung der chronischen Depression : Normative Personalbedarfsermittlung.

BACKGROUND: Chronic depression is a frequent mental disorder representing a significant subjective and economic burden. Effective disorder-specific treatment of chronic depression presupposes sufficient funding of treatment resources. OBJECTIVE: Definition of normative needs of personnel resources for guideline-compliant and evidence-based inpatient treatment of chronic depression based on treatment duration and intensity. The personnel resources determined were compared to the resources provided on the basis of the existing reimbursement system (Psych-PV) in Germany. MATERIAL AND METHODS: Resources determined according to national treatment guidelines and empirical evidence were compared to personnel resources dictated by the German Psych-PV reimbursement algorithm. RESULTS: The current funding algorithm greatly underestimates the resources needed for a guideline-compliant and evidence-based treatment program, even if healthcare providers received 100 % reimbursement of the sum determined by the Psych-PV algorithm. DISCUSSION: The results clearly show that even in the case of a full coverage of the current German reimbursement algorithm, funding allocation for evidence-based inpatient treatment of chronic depression is insufficient. In addition, the difficulties of specific coding of chronic depression in the ICD-10 system generates a major problem in the attempt to measure the current resources needed for sufficient treatment.

[Guideline-adherent psychiatric-psychotherapeutic hospital care: Normative definition of staff required using the example of depression]. / Leitliniengerechte psychiatrisch-psychotherapeutische Krankenhausbehandlung : Normative Personalermittlung am Beispiel Depression.

BACKGROUND: Unipolar depression is of high relevance in German inpatient treatment. An effective psychiatric psychotherapeutic hospital treatment also requires sufficient staff for carrying out psychotherapeutic treatment. AIMS AND OBJECTIVES: The aim of this study was to define the staff requirements for guideline-adherent psychiatric-psychotherapeutic inpatient treatment of depression on the basis of a weekly treatment schedule for a 5-week admission period. A further aim was to compare the staff required with the resources defined by the German psychiatric staffing regulations (Psych-PV). MATERIAL AND METHODS: The weekly schedule was normatively defined on the basis of the current evidence for treatment efficacy and effectiveness. The staff required was calculated on the basis of the weekly schedule. The time for psychotherapy defined by the Psych-PV was calculated using the treatment classification provided by a large nationwide database. RESULTS: Regarding psychotherapy, 280 min per week is regarded as necessary and usually sufficient according to the current evidence. The results showed clearly higher requirements of working time of psychiatrists and psychologists than those defined by the Psych-PV. In particular, the Psych-PV allows only 72 min for psychotherapy per patient and week and only a limited amount of direct patient contact with psychiatrists. CONCLUSION: The figures provided impressively show that the Psych-PV does not allow effective guideline-adherent hospital treatment within a reasonable length of hospital stay. Despite its evidential effectiveness, psychotherapeutic treatment cannot be sufficiently provided under the current financing circumstances.

[Interpersonal psychotherapy for work-related stress depressive disorders]. / Interpersonelle Psychotherapie bei arbeitsstressbedingten depressiven Erkrankungen.

In general work involves health promoting functions but can also have hazardous impacts on well-being. Due to a massive change in working conditions it has become increasingly more recognized that depressive disorders are highly prevalent at the workplace and that work stress belongs to the most common triggers of depressive disorders, particularly in men. It is relevant to differentiate between subjectively experienced burnout and clinical depression. The best investigated psychosocial work stressors include increased job demands in connection with low control possibilities and lack of gratification, interpersonal conflicts, role stress and social isolation. For the treatment of work-related clinical depression, an additional focus of interpersonal psychotherapy (IPT) of depression, namely "work-related stress and burnout experience" was conceptualized based on a vulnerability-stress model and the fact that work usually takes place in an interpersonal context. This new problem area focuses on role stress and conflicts at work and the reduction of stressful working conditions. Interpersonal psychotherapy has so far been useful for the treatment of depression due to problems at work; however, further studies are needed to evaluate the efficacy of this newly designed problem area.

Long-term effect of combined interpersonal psychotherapy and pharmacotherapy in a randomized trial of depressed patients.

OBJECTIVE: Evaluation of the long-term benefits of combined pharmacological and psychotherapeutic depression treatment and the differential impact of early childhood trauma. METHOD: A randomized trial was conducted in 124 in-patients with a diagnosis of major depressive disorder comparing 5 weeks of interpersonal psychotherapy plus pharmacotherapy (IPT) with medication plus clinical management (CM). The study included a prospective, naturalistic follow-up 3, 12 and 75 months after in-patient treatment. The Hamilton Rating Scale for Depression (HRSD) served as the primary outcome measure. RESULTS: Patients in both treatments reduced their depressive symptoms between baseline and 5-year follow-up significantly with a faster decrease early in the follow-up phase. The time rate of change and acceleration on the HRSD was higher for patients in the combination therapy group. The contrast between the conditions at year 5 was non-significant. However, 28% of the IPT patients showed a sustained remission compared with 11% of the CM patients (P = 0.032). Early adversity was found to be a moderator of the relationship between treatment and outcome. CONCLUSION: In the long-term, a combination of psycho- and pharmacotherapy was superior in terms of sustained remission rates to standard psychiatric treatment. Early trauma should be assessed routinely in depressed patients.

[Differential indications for psychotherapy exemplified by depression]. / Differenzielle Indikation für Psychotherapie am Beispiel der Depression.

The general efficacy of psychotherapeutic approaches in the treatment of mental disorders has been demonstrated by meta-analyses. Disorder-specific methods are increasingly dominating the field. In the field of depression psychological interventions have proven to be as equally effective as pharmacotherapy in mild and moderate depressives but with longer lasting effects after termination of treatment. The combination of both methods is particularly relevant for the therapy of severe and chronic depression. The indications should be differentiated beyond the severity and course of the disorder, e.g. according to previous traumatization, comorbidity, patient difficulty and the empirical evidence of the different approaches.

[Affective disorders. The significance of psychotherapeutic approaches]. / Depressive Störungen. Stellenwert psychotherapeutischer Verfahren.

The use of psychotherapeutic strategies is essential in the treatment of affective disorders. Psychotherapy proved to be at least equivalent to antidepressant medication in the treatment of mild to moderate depression. In severe cases, the combination of both treatments is considered by guidelines to be the standard treatment. Psychotherapeutic approaches show a longer latency than antidepressants; however, the effects are longer lasting. Regarding the effectiveness of pharmacotherapy sobering results have been published recently. Therefore, the further development of psychotherapy deserves special attention. Cognitive behavioral therapy and interpersonal therapy provide the highest evidence. The empirical basis for psychodynamic psychotherapies is still limited. In the treatment of chronic depression a new approach--cognitive behavioral analysis system of psychotherapy--is gaining importance. There is a trend towards an increasing specification of psychotherapy for distinct subgroups of depressed patients. Challenges for the future include increasing treatment efficacy, investigating mechanisms of efficacy and predictors for a differential indication, and making effective approaches generally available to all patients.

[Interpersonal psychotherapy and pharmacotherapy for post-stroke depression. Feasibility and effectiveness]. / Interpersonelle Psychotherapie und Pharmakotherapie bei Post-Stroke-Depression. Machbarkeit und Effektivität.

BACKGROUND: Only few studies investigated the effectiveness of psychotherapy in post-stroke depression (PSD). The aim of this feasibility study was to compare interpersonal psychotherapy, pharmacotherapy, and their combination regarding depression and rehabilitation outcome. PATIENTS AND METHODS: Post-stroke depression was found in 35% of 485 stroke patients examined. Seventy-four PSD patients were randomised to one of three treatment conditions. Severity of depression was measured by the Hamilton Depression Rating Scale and the Hospital Anxiety and Depression Scale. The Barthel Index and a questionnaire for health-related quality of life were used as measurements of rehabilitation outcome. RESULTS: There were no significant differences between the three groups in patient mood or rehabilitation outcome. Concerning the severity of depression, quality of life, and social support, all patients showed benefits from antidepressive treatment. In addition a correlation was found between rehabilitation outcome and depression. CONCLUSION: In this feasibility study all antidepressive treatments were successfully implemented in the rehabilitation of post-stroke depressed patients. Combination therapy (interpersonal psychotherapy plus medication) was as effective as one of those elements alone. Because of the small sample size however, further randomized trials are required.

Determination of the ionization potentials of security-relevant substances with single photon ionization mass spectrometry using synchrotron radiation.

Several ionization potentials (IPs) of security relevant substances were determined with single photon ionization time of flight mass spectrometry (SPI-TOFMS) using monochromatized synchrotron radiation from the "Berliner Elektronenspeicherring-Gesellschaft für Synchrotronstrahlung" (BESSY). In detail, the IPs of nine explosives and related compounds, seven narcotics and narcotics precursors, and one chemical warfare agent (CWA) precursor were determined, whereas six IPs already known from the literature were verified correctly. From seven other substances, including one CWA precursor, the IP could not be determined as the molecule ion peak could not be detected. For these substances the appearance energy (AE) of a main fragment was determined. The analyzed security-relevant substances showed IPs significantly below the IPs of common matrix compounds such as nitrogen and oxygen. Therefore, it is possible to find photon energies in between, whereby the molecules of interest can be detected with SPI in very low concentrations due to the shielding of the matrix. All determined IPs except the one of the explosive EGDN were below 10.5 eV. Hence, laser-generated 118 nm photons can be applied for detecting almost all security-relevant substances by, e.g., SPI-TOFMS.

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10-3) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe.

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

Test-retest reliability and validity of the Structured Interview for Sleep Disorders According to DSM-III-R.

OBJECTIVE: The purpose of this study was to evaluate the reliability of sleep disorder diagnoses in DSM-III-R by using a newly developed interview, the Structured Interview for Sleep Disorders According to DSM-III-R (SIS-D) and to evaluate the concordance between these diagnoses and sleep laboratory data. In addition, the sources of disagreements between two interviewers in the diagnoses given to the same patient were determined. METHOD: Two different interviewers used the SIS-D to diagnose 68 patients with complaints of sleep disorders. The concordance between these interviewers' diagnoses and polysomnographic findings was investigated by using kappa statistics. RESULTS: There were excellent reliabilities for almost all current main diagnostic categories and good concordance between diagnoses made on the basis of the structured interview and polysomnographic data. The main source of disagreement between interviewers was found in the symptom information given by the patient. CONCLUSIONS: These findings provide support for the utility of DSM-III-R sleep disorder diagnoses and for their retention in DSM-IV. These findings also accord well with a recent literature review of the DSM-III-R diagnosis of primary insomnia by the DSM-IV Work Group on Sleep Disorders. The good concordance between interview diagnoses and polysomnographic data suggests that a structured interview such as the SIS-D may be a useful screening instrument. The authors discuss the implications of these findings for the polysomnographic evaluation of chronic insomnia.

Long-term, high-fat-sucrose diet alters rat femoral neck and vertebral morphology, bone mineral content, and mechanical properties.

Short-term exposure to diets high in fat and sucrose can induce hyperinsulinemia, affect calcium and magnesium metabolism, and alter bone mineralization and mechanical properties. The current study focused on the morphological and structural changes that result from long-term exposure to a high-fat sucrose (HFS) diet. Inbred, female Fischer 344 rats were assigned randomly to a low-fat, complex-carbohydrate (LFCC) diet group or a HFS diet for 24 months. At the end of the 2 years, each femoral neck (FN) was tested to failure in cantilever-bending, the sixth lumbar vertebra (L6) was tested in compression, and geometrical characteristics of the bones were determined. Although the HFS rats were significantly fatter and heavier than the LFCC rats, the HFS L6 had a significantly smaller average cross-sectional area. When L6 structural properties were normalised with respect to body mass, the HFS L6 had significantly lower loads, energies, and stiffnesses. The HFS L6 stress and strain energy density values were also significantly less than the LFCC L6. Compared to the LFCC FN, the HFS FN had a smaller cortical shell and larger trabecular core. The HFS FN also had significantly lower mass-normalised loads, energies, and stiffnesses. These results suggest that a long-term HFS diet has a significant adverse effect on rat bone morphology and mechanics.

Sleep onset insomnia, sleep maintaining insomnia and insomnia with early morning awakening--temporal stability of subtypes in a longitudinal study on general practice attenders.

The present study investigated the temporal stability of insomnia patterns during a 4-month study period, classifying insomnia as sleep-onset insomnia, sleep-maintaining insomnia or insomnia with early morning awakening. In a longitudinal study design, 2,512 general practice attenders were investigated at the time of the first inquiry (T1) with a questionnaire. Four months later (T2), all patients complaining of difficulties in initiating and/or maintaining sleep and/or early morning awakening (n = 328) were again contacted by mail and received the same questionnaire as at T1. According to the reported symptoms, patients were assigned to the different subtypes of insomnia. The diagnosis at T1 was then compared with the diagnosis at T2 4 months later. Only about half of all patients who complained of difficulties in initiating sleep at T1 still exclusively reported sleep-onset insomnia 4 months later, whereas the remaining patients were distributed to different subtypes. The stability of sleep-maintaining insomnia and insomnia with early morning awakening was even lower. Comorbidity with a somatic or psychiatric disorder at T1 and change in hypnotic treatment did not account for the instability of the respective subgroup of insomnia. These findings illustrate that cross-sectional studies focusing on subtypes of insomnia, e.g. sleep-onset insomnia, may lead to erroneous results.

Physicochemical properties, pharmacokinetics, and biodistribution of gadoteridol injection in rats and dogs.

RATIONALE AND OBJECTIVES: The physicochemical properties of gadoteridol, a macrocyclic nonionic gadolinium complex, were studied together with its pharmacokinetics and biodistribution in rats and dogs. METHODS: Studies in rats were conducted after single intravenous injections at 0.1 or 0.35 mmol/kg using 153Gd-labeled gadoteridol or with seven daily doses of 0.1 mmol/kg to examine the levels of residual gadolinium in organs. Nonradioactive biodistribution and excretion studies were performed in dogs following injection at 0.1 mmol/kg. RESULTS: After injection, the dose was rapidly cleared from rat blood and excreted such that more than 90% of the dose appeared in the urine within 4 hr of injection. At 7 and 14 days postinjection, only extremely low levels of gadolinium were observed in liver and bone; these levels were two to eight times lower than the levels reported after the injection of gadopentetate dimeglumine. CONCLUSION: The extracellular distribution and rapid urinary excretion of gadoteridol is in agreement with data obtained with other gadolinium-containing chelates used as intravascular magnetic resonance imaging contrast agents. Differences observed in the long-term retention of gadolinium between gadoteridol and gadopentetate dimeglumine were consistent with the reported greater in vivo resistance to transmetallation of gadolinium macrocycles compared with the linear gadolinium chelate molecules.

Biophysiological effects of Ukrain therapy in a patient with breast cancer (case report).

The effects on different biophysiological parameters and subjective impressions were studied in a patient with breast cancer who was not previously given any therapy before receiving Ukrain. Daily measurements of pulse, blood pressure, temperature and various laboratory examinations were carried out. Development and course of subjective and objective phenomena seem to be typical for patients in whom Ukrain could induce long-term complete remission. The patient described here has had to data 12 years without any oncopathological symptoms.

Role of psychotherapy in the management of psychiatric diseases.

Psychotherapy plays an essential role in the treatment of mental disorders. The use and research of psychological treatment strategies increased drastically over the past decade. The general efficacy of psychotherapy for the treatment of psychiatric diseases is proved and documented in several meta-analyses. Psychotherapy re-searchers have found solutions for acceptable study designs which account for the special character of these interventions and studied the efficacy of psychotherapeutic treatment in more than 1000 intervention trials.Meanwhile evidence-based psychotherapy approaches tailored to a specific diagnosis are dominating the field and question the basis of psychotherapy schools.A new field of research in psychotherapy is the neurobiological basis of mental disorders and the demonstration of neurobiological changes with psycho-therapeutic treatment.