Neurophysiologische, neuropsychologische und strukturelle Auffälligkeiten im Prodromalstadium der Schizophrenie

Schizophrenie ist eine psychische Störung mit biologischen und kognitiven Auffälligkeiten. In dieser Dissertation wurden Arbeiten zur Abnahme der grauen Substanz, der Amplitude der P300 sowie neuropsychologische Testleistungen bei prodromalen und schizophrenen Patienten im Vergleich mit Gesunden vorgestellt. Unsere Ergebnisse zeigten, dass neurobiologische und strukturelle Veränderungen bereits im Prodromalstadium vorhanden waren. Dagegen wiesen intellektuell leistungsfähige Prodromalpatienten keine kognitiven Einschränkungen auf. Zudem konnten wir in einer Pilotstudie zeigen, dass Prodromalpatienten von einem kognitiven Training mehr profitierten als erkrankte Menschen. Die Ergebnisse lassen darauf schließen, dass kognitive und strukturelle Veränderungen bereits im Prodromalstadium vorhanden sind, und dass Prodromalpatienten von kognitiven Trainings profitieren

Alice Karakterinin Yaşantılarının Mahler’in Kuramına Göre Ben Gelişimindeki Rolü

Bu çalışmada Alice Harikalar Ülkesinde ve Aynanın İçinden (devam romanı) romanlarındaki Alice karakterinin Mahler’in ayrışma - bireyleşme kuramı ışığında duygu, düşünce ve davranışlarının ben gelişimindeki rolünün incelenmesi amaçlanmıştır. Mahler’e göre yaşamın ilk altı ayı normal otistik evre ve normal ortakyaşamsal evre olmak üzere iki evreden oluşur. Altıncı aydan sonraki evre ayrışma - bireyleşme evresi olarak değerlendirilmiştir. Ayrışma-bireyleşme evresi; farklılaşma, alıştırma, yeniden yakınlaşma ve bireyliğin pekişmesi ve coşkusal nesne sürekliliğinin başlangıcı olarak dört alt evreden oluşmaktadır. Her iki roman da Alice karakterinin rüyaları üzerine kurulmuştur. Bu sebeple, romanlardaki imgeler üzerinden yorumlama yapılmıştır. Bu çalışmada Mahler’in kuramının yanında birçok literatür bulgusundan destek alınarak, özellikle Alice karakterinin bireyleşmesi ve ben gelişimine odaklanılmıştır. Alice karakterinin maceralar boyunca yaşadıkları doğrultusunda bireyleşmesinin tamamlandığı düşünülmüştür.In the current paper, it was aimed to understand and conceptualize the role of Alice’s emotions, thoughts, and behaviors in her self-development through Mahler's separation – individuation theory and other relevant literature. According to Mahler, the first six months of life consists of two stages, namely, normal autistic phase and normal symbiotic phase. The stage after the sixth month was considered as separation - individuation phase. Separation - individuation phase consists of four sub-stages differentiation, practice, re-rapprochement and consolidation of individuals and continuity of enthusiastic objects. The novels entitled as “Alice in Wonderland” and “Alice Looking through Glasses” were evaluated for these aim. Both novels are based on the dreams of Alice. Therefore, interpretations are based on symbols or images in the novels. Alice’s self-development and individuation were emphasized. It was thought that Alice approached her separation – individuation throughout her adventures

A Critical Review of “Alice in Wonderland” based on Mahler’s Theory: The Role of Alice’s Adventures in Self-Development

Bu çalışmada Alice Harikalar Ülkesinde ve Aynanın İçinden (devam romanı) romanlarındaki Alice karakterinin Mahler’in ayrışma - bireyleşme kuramı ışığında duygu, düşünce ve davranışlarının ben gelişimindeki rolünün incelenmesi amaçlanmıştır. Mahler’e göre yaşamın ilk altı ayı normal otistik evre ve normal ortakyaşamsal evre olmak üzere iki evreden oluşur. Altıncı aydan sonraki evre ayrışma - bireyleşme evresi olarak değerlendirilmiştir. Ayrışma-bireyleşme evresi; farklılaşma, alıştırma, yeniden yakınlaşma ve bireyliğin pekişmesi ve coşkusal nesne sürekliliğinin başlangıcı olarak dört alt evreden oluşmaktadır. Her iki roman da Alice karakterinin rüyaları üzerine kurulmuştur. Bu sebeple, romanlardaki imgeler üzerinden yorumlama yapılmıştır. Bu çalışmada Mahler’in kuramının yanında birçok literatür bulgusundan destek alınarak, özellikle Alice karakterinin bireyleşmesi ve ben gelişimine odaklanılmıştır. Alice karakterinin maceralar boyunca yaşadıkları doğrultusunda bireyleşmesinin tamamlandığı düşünülmüştür.In the current paper, it was aimed to understand and conceptualize the role of Alice’s emotions, thoughts, and behaviors in her self-development through Mahler's separation – individuation theory and other relevant literature. According to Mahler, the first six months of life consists of two stages, namely, normal autistic phase and normal symbiotic phase. The stage after the sixth month was considered as separation - individuation phase. Separation - individuation phase consists of four sub-stages differentiation, practice, re-rapprochement and consolidation of individuals and continuity of enthusiastic objects. The novels entitled as “Alice in Wonderland” and “Alice Looking through Glasses” were evaluated for these aim. Both novels are based on the dreams of Alice. Therefore, interpretations are based on symbols or images in the novels. Alice’s self-development and individuation were emphasized. It was thought that Alice approached her separation – individuation throughout her adventures

Test-performance after cognitive training in persons at risk mental state of schizophrenia and patients with schizophrenia

This exploratory study aims to examine the differential effects of a computer-based cognitive training in 'prodromal' patients (mean age 27.20 years, S.D. 5.31 years) compared with patients with full-blown schizophrenia (mean age 30.13 years, S.D. 7.77 years). Ten patients at risk for schizophrenia and 16 patients suffering from schizophrenia underwent a computerized cognitive training program (Cogpack). Cognitive functioning before and after a total of 10 training sessions was assessed by different tests controlling for memory, attention, and logical thinking. Prodromal patients turned out to be able to significantly improve their long-term memory functions and their attention after cognitive training with the Cogpack software package whereas in the group of patients with schizophrenia no improvement occurred (e.g. continuous performance test, identical pairs-subtest 'shapes': improvement from 0.73 to 0.88 in persons at risk of schizophrenia vs. no improvement in patients with schizophrenia (0.55 to 0.53). Cognitive training using Cogpack is helpful for the improvement of cognitive functioning in persons at risk of schizophrenia. Thus, the application of cognitive training should be provided as early as possible in the prodromal phases of schizophrenia in order to use the full rehabilitative potential of the patients. These results should be confirmed by further investigations including larger sample sizes

Early Mood Swings as Symptoms of the Bipolar Prodrome: Preliminary Results of a Retrospective Analysis

Background/Aims: Temperament and mood swings are promising indicators for the characterization of mood spectrum vulnerability. The aim of this study was to investigate the relationship between affective temperament and mood swings in bipolar disorder. We explored these clinical features retrospectively. Methods: Patients who met the criteria for bipolar I disorder were enrolled in the study. Exclusion criteria were partial remittance and a full affective or psychotic episode. Data concerning illness and family history, mood swings (semistructured interview for mood swings) and depression (Beck, Depression Inventory) were obtained. We examined premorbid temperament with the validated German version Temps-M of the original version Temps-A. Patients with and without mood swings were compared with respect to the dominant temperament. Results: Out of 20 bipolar patients, 6 subjects reported mood swings prior to the onset of affective disorder. Subjects with mood swings prior to the onset of bipolar disorder significantly correlated with a positive family history of affective disorders. Concerning cyclothymic and irritable temperament, bipolar affective patients with mood swings had higher scores. No differences were found between males and females. Conclusion: Our findings go in line with previous results that mood swings, as represented by the cyclothymic temperament, are present prior to the first onset of bipolar disorder in a subset of patients. These traits may represent vulnerability markers and could presumably be used to identify individuals at high risk for developing bipolar disorder in order to prevent this illness. Further studies are indicated to clarify the correlation with genetic risk factors

Reduction of auditory event-related P300 amplitude in subjects with at-risk mental state for schizophrenia

Neurophysiological methods allow the examination of cognitive-cortical functioning in patients with schizophrenia in its prodromal states. As revealed by previous studies, event-related potential components such as auditory evoked P300 associated with cognitive processes, such as attention and orientation, are known to be reduced in amplitude in acute and chronic as well as in medicated and unmedicated patients. It is, however, unclear whether a P300 amplitude reduction occurs before the schizophrenic psychosis is fully manifested. We studied patients in the prodromal phase of the schizophrenic disorder (i.e. subjects with an at-risk mental state showing attenuated psychotic symptoms or brief limited intermittent symptoms) as well as first-episode patients and chronic patients with schizophrenia and compared these groups to healthy subjects. The event-related P300 was recorded during an auditory oddball paradigm. Groups differed significantly from each other in the P300 amplitude at Pz (F(3/149)=2.532, p=0.02). Post-hoc tests revealed significantly lower P300 amplitudes of non-medicated prodromal (p=.03), first-episode (p=.01) and chronic patients (p=.001) compared to the healthy controls. The study revealed that there are neurophysiological changes as the reduction in P300 amplitudes begins early in schizophrenia at the prodromal phase, i.e. before a manifestation of full-blown psychosis, and that these changes seem to have a progressive course from prodromal to chronic state of schizophrenia as assumed in this cross-sectional study

Real-World Systemic Treatment Patterns after Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma in the United States

Real-world (RW) evidence is needed to evaluate atezolizumab plus bevacizumab (atezo + bev) utilization for hepatocellular carcinoma (HCC) in clinical practice. This retrospective cohort study used administrative claims databases to evaluate treatment patterns in individuals with HCC ≥18 years of age who were initiated on atezo + bev between June 2020 and June 2022. The endpoints of this study were the proportion of individuals who discontinued atezo + bev and received subsequent systemic therapies, time to discontinuation (TTD), and time to next treatment. Overall, 825 individuals were eligible (median age 67 years; 80% male). Over a median follow-up of 15.3 months, most (72%) discontinued atezo + bev, with a median TTD of 3.5 months. A minority (19%) received subsequent therapies, with the most common second-line agents being lenvatinib (6%), cabozantinib (4%), and nivolumab (4%). The median time from index to next treatment post-atezo + bev was 5.4 months. Further research is needed to identify the patients who are most likely to benefit from atezo + bev as well as later-line HCC therapies to optimize overall survival

Ventral striatal activation during reward processing in subjects with ultra-high risk for schizophrenia

Background: Early dysfunction of the brain reward system in schizophrenia might be already recognized in the prodromal phase of this illness. We used functional magnetic resonance imaging to assess the blood oxygen level-dependent response in the ventral striatum (VS) of subjects with ultra-high risk for psychosis during the presentation of reward-indicating and loss-indicating stimuli. Methods: Thirteen prodromal patients (mean age: 25.5 ± 4.6 years) and 13 age-matched healthy volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus will gain money, avoid losing money or have no consequence. Results: Compared with the neutral condition, anticipation of reward loss-avoidance elicited significant activation of the VS in both healthy subjects and subjects with ultra-high risk for psychosis, but there was only a statistical tendency for less activation during loss-avoidance anticipation in prodromal compared to healthy subjects. Discussion: This study provides a first weak hint, as revealed by functional magnetic resonance imaging, for impaired activation of a central area of the mesolimbic dopaminergic brain reward system, the VS, already in subjects with ultra-high risk for psychosis, which is in line with results of patients with full-blown schizophrenic psychosis. This pilot study has, however, strong limitations, and its results need to be replicated first before they can be used e.g. for early recognition of patients in the schizophrenic prodrome