Thesis defense Mario Braakman (Donders Series 130)

18 September 2013

Promotors: Prof.dr. F.A.M. Kortman, Prof.dr. W. van den Brink.

Copromotors: Dr. R.J. Verkes, dr. M.W.J. Koeter

Posttraumatic stress disorder with secondary psychotic features. A diagnostic validity study among refugees in the Netherlands

The study presented in this thesis originated from a clinical observation. During our clinical work in a psychiatric inpatient treatment facility for traumatized refugees and asylum seekers in the Netherlands we encountered many patients suffering from symptoms of posttraumatic stress disorder (PTSD) in conjunction with symptoms of chronic psychosis, especially delusions and hallucinations. These patients had developed PTSD and subsequently, sooner or later, psychotic symptoms as well.  They had a remarkable poor response to antipsychotic medication. The goal of this thesis was to find evidence for the validity of this complex clinical picture as a separate diagnostic entity or to refute it. Is PTSD with secondary psychotic features a diagnostic entity on its own or could this syndrome appropriately be described by familiar and already existing diagnostic categories? First we studied the present state of knowledge by an extensive survey of the literature. PTSD-SP emerged as a syndrome that consists of posttraumatic stress disorder, joined by one or more psychotic features, especially hallucinations and delusions. The psychotic features were not confined to only the episodes of re-experiencing, but persisted continuously. The content of these psychotic features was generally paranoid in nature, and no first rank Schneiderian psychotic features appeared to be present. There was no history of psychotic episodes prior to the traumatic event(s). In first degree relatives of PTSD-SP patients there was an increased prevalence of major depression but no increased prevalence of psychotic disorders, which would be expected in cases of schizophrenia. Positive correlations of the secondary psychotic features in PTSD-SP patients were found with ethnicity (African-American and Hispanic), with co-morbid depressive disorder, with the enzyme-activity of DβH and with cerebrospinal fluid concentrations of CRF, blood platelet serotonine and MAO B activity. There were specific smooth pursuit eye movement deficits. Positive and negative psychotic symptoms did respond in uncontrolled pre-post comparisons with antipsychotics in some studies but not significantly compared to placebo in another study. Three principal research questions came forward out of this review of the literature: 1. Can chronic psychosis in PTSD-SP be distinguished from psychosis in schizophrenia by clinical features and trauma history?; 2. Can the presence of psychotic features in PTSD-SP be explained by psychiatric comorbidity, by more severe PTSD re-experiencing-symptoms, or by more severe or a specific type of traumatic events?; 3. Is plasma dopamine beta-hydroxylase activity increased in posttraumatic stress disorder with secondary psychotic features? To answer these questions we designed a cross sectional study in which we recruited adult refugee patients from two mental health hospitals in the Netherlands. We found that the clinical features of PTSD-SP can be distinguished from those of schizophrenia. Patients of the PTSD-SP group had considerably less negative symptoms and less disorganisation than is commonly seen in schizophrenia and furthermore they had more affective distress and more stress due to auditory hallucinations than patients in the schizophrenia group in this study. In addition, patients in the PTSD-SP group had more comorbid disorders than patients in the schizophrenia group. Patients with PTSD-SP suffered more from depressed and anxious feelings than patients who suffered from schizophrenia and they were more frequently traumatized. In males the first psychotic symptoms in PTSD-SP patients started more than 10 years later than in schizophrenia. Major depressive disorder was the most common comorbid condition in the PTSD-SP group. Therefore we explored the associations between psychotic features in PTSD-SP and other comorbid psychiatric conditions, especially major depressive disorder. Our data indicated that the presence of psychotic symptoms was not attributable to comorbid major depressive disorder. Finally we aimed to validate a previous study by Hamner and Gold who reported an increased level of blood plasma activity of dopamine-β-hydroxylase (DβH) in patients with PTSD and psychotic symptoms compared to healthy controls and PTSD patients without psychotic features. We wanted to validate these findings in a larger, mixed gender, multi-ethnic sample and included also patients with schizophrenia. In addition, we evaluated DBH -1021C>T (rs1611115) genotype because DβH plasma levels are under strong genetic control. We found that DBH -1021C>T genotype was strongly associated with plasma DβH activity in the ethnically heterogeneous sample. Mean plasma DβH activity in patients with PTSD-SP was not different from that of patients with schizophrenia or PTSD or from that of health individuals, even after taking DBH -1021C>T genotype into account. The presence or absence of major depressive disorder in patients with PTSD-SP was not related to plasma DβH activity either. We concluded that we have obtained numerous facts indicating that PTSD-SP should be considered as a (severe) subtype of PTSD or as a separate diagnostic entity. Nevertheless more studies are needed to address a number of unresolved issues. For example, little is known about the course of PTSD-SP or about its pathophysiology. And there is a paucity of family studies as well as neuroimaging data, nor do we have studies about the etiology and risk factors of PTSD-SP. This all might contribute to find more adequate and effective treatment options for this clinical syndrome.