Negative symptoms in alcohol use disorder: A pilot study applying the two-factor model of negative symptoms to patients with alcohol use disorder

Background and aimsAlcohol Use Disorder (AUD) is characterized by a reduction in goal-directed behavior, with alcohol use taking precedence over other areas of life. These features in AUD resemble negative symptoms in schizophrenia, especially the reduction in motivation and pleasure (MAP). Given the clinical similarities of negative symptoms across diagnostic categories, it comes as a surprise that there are few investigations on negative symptoms in alcohol and other substance use disorders. To our knowledge, our study is the first to assess negative symptoms in AUD based on a two-factorial approach, and to investigate the interrelation of these dimensions with the severity of AUD, and alcohol craving.Materials and methodsWe examined a sample of 42 patients with AUD at the Psychiatric University Hospital in Zurich. Participants provided self-report and interview-based measures of the severity of AUD, negative symptoms, and alcohol craving. Finally, we used data from the electronic health records of the patients.ResultsPatients with AUD show negative symptoms to a similar extent as patients with schizophrenia or bipolar disorder. We found a positive correlation between the extent of impairment within the MAP factor and overall severity of AUD. Furthermore, MAP negative symptoms were correlated with alcohol craving. In a linear regression, negative symptoms predicted alcohol craving whereas depression did not.SummaryNegative symptoms as conceptualized for schizophrenia are prevalent in patients with AUD and associated with the severity of AUD. More specifically, severity of AUD correlates with diminished motivation and pleasure, highlighting the importance of disturbances in motivational functions in AUD. This is further supported by the correlation between negative symptoms and craving, a hallmark of AUD. Taken together, our findings suggest that negative symptoms might be a highly relevant but hitherto often neglected therapeutic target in AUD

Immunocytochemical Differentiation of Mucosa And Skin Cells in Forensic Traces

Die vorliegende Doktorarbeit beschreibt eine neu entwickelte Methode zur immuncytochemischen Identifizierung von Schleimhautzellen in forensischen Spuren. Zunächst wurden aus der Vielzahl an Cytokeratinen und den entsprechenden Antikörpern diejenigen identifiziert, die spezifisch für Schleimhautepithelzellen sind. Der nächste Schritt bestand in der Modifikation der immunhistochemischen Färbeprotokolle, die ursprünglich für Gewebeschnitte konzipiert waren, für den Einsatz an cytologischen Präparaten. Zudem mussten geeignete Fixations- und Permeabilisationsverfahren gefunden und angepasst werden. In einer Vielzahl von Vorversuchen kristallisierte sich für den forensischen Einsatz Cytokeratin 4 als schleimhautspezifischer Zellbestandteil heraus. Mit CytoRich Red konnte eine geeignete Fixationslösung gefunden werden. Die Verwendung von Trypsin zur Permeabilisierung der cytologischen Präparate führte zu ausgezeichneten Färberesultaten, ohne die morphologische Integrität der Zellen zu beeinträchtigen. Mittels der entwickelten Färbetechnik gelang es erstmals, menschliche Schleimhautzellen in forensischen Spuren sicher zu identifizieren. Die gemäß den entwickelten Vorschriften gefärbten Zellen konnten in einem nächsten Schritt mittels Laser-Mikrodissektion selektiv gewonnen werden. Es gelang in mehreren Stichproben die Erstellung einer DNA-Typisierung, dem sogenannten „genetischen Fingerabdruck“. Schließlich gelang es mittels Real-Time-quantitative-PCR Unterschiede in der relativen Expression von Cytokeratin 4 zwischen Vaginal- und Wangenschleimhaut festzustellen. Dieser Ansatz stellt einen ersten Schritt zur eindeutigen Unterscheidung der beiden Schleimhaut-Typen dar, was einen weiteren Mosaikstein in der Auswertung biologischer Spuren darstellen kann.This doctoral thesis describes a newly developed method for the identification of mucous cells in forensic traces by means of immunocytochemical staining. Among the variety of cytokeratins that exist in human cells, it was possible to find a few which were specific for mucosa. Subsequently, existing immunohistochemical staining protocols which were initially designed for tissue sections were modified for use on cytological preparations. In addition, suitable procedures for fixation and permeabilization had to be found and adjusted. In a large number of preliminary tests, cytokeratin 4 (CK4) emerged as a cell component specific for mucous cells suitable for forensic use. In CytoRich Red a suitable fixation solution could be found. The use of trypsin for permeabilization resulted in excellent staining results without compromising the morphological integrity of the cells. By means of the developed staining method, it was possible for the first time to reliably identify human mucous cells in forensic samples. As a next step, those cells that were stained according to the newly developed protocols could be obtained via laser microdissection. In a number of sample tests, it was possible to realise a DNA-typing from the thus obtained cells. Finally, differences in the relative expression of cytokeratin 4 between vaginal and buccal mucosa could be found via real-time quantitative PCR. This approach constitutes a first step towards a clear distinction of the two kinds of mucosa, which can added to the mosaic of forensic trace analysis

The fear of being laughed at as additional diagnostic criterion in social anxiety disorder and avoidant personality disorder?

Social anxiety disorder (SAD) is the most common anxiety disorder and has considerable negative impact on social functioning, quality of life, and career progression of those affected. Gelotophobia (the fear of being laughed at) shares many similarities and has therefore been proposed as a subtype of SAD. This hypothesis has, however, never been tested in a clinical sample. Thus, the relationship between gelotophobia, SAD and avoidant personality disorder (APD) was investigated by examining a sample of 133 participants (64 psychiatric patients and 69 healthy controls matched for age and sex) using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (4th edition) and an established rating instrument for gelotophobia (GELOPH). As expected, gelotophobia scores and the number of gelotophobic individuals were significantly higher among patients with SAD (n = 22) and APD (n = 12) compared to healthy controls and other psychiatric patients. Furthermore, gelotophobia scores were highest in patients suffering from both SAD and APD. In fact, all patients suffering from both disorders were also suffering from gelotophobia. As explained in the discussion, the observed data did not suggest that gelotophobia is a subtype of SAD. The findings rather imply that the fear of being laughed at is a symptom characteristic for both SAD and APD. Based on that, gelotophobia may prove to be a valuable additional diagnostic criterion for SAD and APD and the present results also contribute to the ongoing debate on the relationship between SAD and APD

The fear of being laughed at as additional diagnostic criterion in social anxiety disorder and avoidant personality disorder?

Social anxiety disorder (SAD) is the most common anxiety disorder and has considerable negative impact on social functioning, quality of life, and career progression of those affected. Gelotophobia (the fear of being laughed at) shares many similarities and has therefore been proposed as a subtype of SAD. This hypothesis has, however, never been tested in a clinical sample. Thus, the relationship between gelotophobia, SAD and avoidant personality disorder (APD) was investigated by examining a sample of 133 participants (64 psychiatric patients and 69 healthy controls matched for age and sex) using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (4th edition) and an established rating instrument for gelotophobia (GELOPH). As expected, gelotophobia scores and the number of gelotophobic individuals were significantly higher among patients with SAD (n = 22) and APD (n = 12) compared to healthy controls and other psychiatric patients. Furthermore, gelotophobia scores were highest in patients suffering from both SAD and APD. In fact, all patients suffering from both disorders were also suffering from gelotophobia. As explained in the discussion, the observed data did not suggest that gelotophobia is a subtype of SAD. The findings rather imply that the fear of being laughed at is a symptom characteristic for both SAD and APD. Based on that, gelotophobia may prove to be a valuable additional diagnostic criterion for SAD and APD and the present results also contribute to the ongoing debate on the relationship between SAD and APD

Scatter plot depicting the relationship between the number of SCID diagnoses of SAD and APD and the GELOPH<15> score.

<p>The dashed horizontal line illustrates the cut-off for gelotophobia (GELOPH<15> score > 2.5).</p

Multiple linear regression predicting GELOPH<15> scores in patients and controls (<i>n</i> = 123).

<p>Multiple linear regression predicting GELOPH<15> scores in patients and controls (<i>n</i> = 123).</p

Scatter plot depicting the relationship between the number of SCID diagnoses of SAD and APD and the GELOPH<15> score.

<p>The dashed horizontal line illustrates the cut-off for gelotophobia (GELOPH<15> score > 2.5).</p

Demographic and gelotophobia data of healthy controls and psychiatric patients (with exception of sex, education and gelotophobia present, <i>means</i> and <i>SD</i> are shown).

<p>Demographic and gelotophobia data of healthy controls and psychiatric patients (with exception of sex, education and gelotophobia present, <i>means</i> and <i>SD</i> are shown).</p

The fear of being laughed at as additional diagnostic criterion in social anxiety disorder and avoidant personality disorder?

Social anxiety disorder (SAD) is the most common anxiety disorder and has considerable negative impact on social functioning, quality of life, and career progression of those affected. Gelotophobia (the fear of being laughed at) shares many similarities and has therefore been proposed as a subtype of SAD. This hypothesis has, however, never been tested in a clinical sample. Thus, the relationship between gelotophobia, SAD and avoidant personality disorder (APD) was investigated by examining a sample of 133 participants (64 psychiatric patients and 69 healthy controls matched for age and sex) using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (4th edition) and an established rating instrument for gelotophobia (GELOPH). As expected, gelotophobia scores and the number of gelotophobic individuals were significantly higher among patients with SAD (n = 22) and APD (n = 12) compared to healthy controls and other psychiatric patients. Furthermore, gelotophobia scores were highest in patients suffering from both SAD and APD. In fact, all patients suffering from both disorders were also suffering from gelotophobia. As explained in the discussion, the observed data did not suggest that gelotophobia is a subtype of SAD. The findings rather imply that the fear of being laughed at is a symptom characteristic for both SAD and APD. Based on that, gelotophobia may prove to be a valuable additional diagnostic criterion for SAD and APD and the present results also contribute to the ongoing debate on the relationship between SAD and APD