Μελέτη συννόσησης μετατραυματικής και καταθλιπτικής διαταραχής
Authors: Κωστάρας Παναγιώτης 
Published: September 2021

Objective: Post-Traumatic Stress Disorder (PTSD) is a mental disorder that develops in some people after a serious traumatic event and is characterized by symptoms of re-experiencing, avoidance, arousal and distorted beliefs and emotions. According to epidemiological studies, about 50% of the general population will experience such a traumatic event, like a life threatening situation or serious injury and 20% of will eventually suffer from PTSD. Most people usually recover after a few months and within the first year after one traumatic event, without the need of any therapeutic intervention. However, one out of three patients with PTSD continue to suffer from PTSD-symptoms for over 3 years and show comorbidity with a series of mental disorders. Epidemiological studies in patients with PTSD suggest that lifetime comorbidity with other mental disorders can be as high as 90%, regarding a bright spectrum of mental disorders like major depressive disorder (MDD), anxiety and panic disorders, personality disorders and substance abuse. PTSD-MDD comorbidity rates vary between 37% and 48% in community samples, while in clinical samples these rates are even higher, reaching 68%. PTSD-MDD comorbidity is related with poor prognosis, more frequent hospitalizations and higher rates of suicide. Recent comorbidity studies focus on three possible explanations about the frequently observed PTSD-MDD comorbidity: 1. Symptom overlap between PTSD and MDD in combination with a difficulty of modern classification systems to distinguish efficiently between these two disorders, 2. Shared risk factors and 3. The possibility that one disorder is predisposing factor for the other. Concerning the first hypothesis, it has been shown that, in traumatized patients, symptom overlap between MDD and PTSD was very frequent and that the only reliable factor to distinguish effectively between PTSD and MDD was the criterion A of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), that defines trauma. As for the possibility that both disorders share common risk factors, there is strong evidence that trauma is such an important etiological factor. Neuroendocrionological research suggest that persistent and repeated stressful life events early in life, can cause permanent dysfunctions of the stress response system in the hypothalamus, impairing the negative feedback of stress hormones, resulting in hyper-secretion of CRF, prolonged stress reactions and predisposition to depressive-like behavior, stress-related disorders, substance abuse and even physical diseases such as cardiovascular disease, stroke, diabetes mellitus, inflammatory diseases, autoimmune disorders etc. Regarding the possibility that the one disorder may be a causal factor for the other, findings are rather inconclusive. One recent meta-analysis suggests that PTSD is a possible risk factor for MDD and that the opposite is less possible. Large-scale community studies suggested earlier that pre-existing MDD predisposes an individual to PTSD. Other studies conclude that both disorders are manifestations of a broader syndrom that is related to stress, while others suggest that both disorders are independent sequelae of trauma and their relation differs among genders. There are also a few studies who show that both PTSD as a single diagnosis and PTSD-MDD comorbidity are a common psychopathological entity, different from MDD as a single diagnosis after a traumatic event, which has unique risk factors. It thus seems that there is a certain ambiguity about the causes of the frequently observed of PTSD-MDD comorbidity and, more specifically, whether one disorder displays a risk factor for the other or whether both disorders share common risk factors. Taking however the most recent neurophysiological research into account as well as epidemiological studies regarding PTSD-MDD comorbidity, it seems that stressful life events and especially those that happen early in life, display a significant risk factor for both PTSD and MDD, explaining, in part, the high rates of PTSD-MDD comorbidity. And while PTSD-MDD comorbidity is extensively studied among individuals who were exposed to a traumatic event or with higher possibilities of being exposed to one (i.e. war veterans), there are only few studies who were conducted on outpatients with MDD. A large study which evaluated comorbidity between MDD and anxiety disorders including PTSD, found that MDD-PTSD comorbidity was 24.1%, with 14.4% suffering from a major depressive episode (MDE) at the time of the evaluation. In another study, the prevalence of PTSD among patients with psychotic MDD was 57% and was related with earlier onset of MDD and poor prognosis. In another study, who was carried out on 275 inpatients with severe mental disorders found that 119 individuals (43%) had also PTSD, while only three of them had a documented PTSD diagnosis on their records. PTSD comorbidity rates were higher among patients with MDD (58%) and were related to the number of traumatic events reported by each individual, especially those involving sexual violence during childhood. The main objective of our study was the evaluation of depressive outpatients with regard to PTSD comorbidity and trauma history. More specifically we aimed: a. to illustrate the characteristics of individuals with MDD-PTSD comorbidity, like the prevalence of MDD-PTSD comorbidity and the disorder that usually precedes the other, demographic and socio-ecomomic parameters, traumatic history like the age of exposure to trauma and its nature, psychiatric history like the age of symptom onset, chronicity of symptoms, presence of psychotic symptoms, suicide attempts, hospitalizations etc., medical history like physical comorbidity, b. to compare those characteristics with patients with monopolar MDD, in order to illustrate the consequences of MDD-PTSD comorbidity, the possibility of her neglection in clinical practice, and parameters that may play part in MDD-PTSD comorbidity, c. to study the characteristics with trauma history regardless of MDD-PTSD comorbidity and to compare with those without trauma history in order to illustrate its socio-economic and clinical consequences and d. to access the characteristics of individuals with trauma history who never suffered from comorbid PTSD in order to evaluate parameters involved in the manifestation of a so-called post-traumatic depression. Methods: Our sample consisted of 101 adult outpatients diagnosed with MDD, as documented in their medical files. Those were retrieved from two distinct outpatient units of the University of Athens Medical School, 1st Department of Psychiatry, Aiginiteion Hospital. Patients with bipolar disorder, schizoaffective disorders and organic mental disorders were excluded. Each of them underwent a semi-structured clinical interview, in which data from the socio-economic, medical and psychiatric background were retrieved, as well as data regarding trauma history. For the evaluation of traumatic life events the Life Events Checklist was used. For each traumatic experience, individuals were accessed about possible PTSD in the aftermath of that experience. For the presence of depressive and post-traumatic psychopathology we relied on the Greek version of the MINI. Global functionality was accessed by the GAF. After completion of the semi-structured interview patients were categorized in three groups: A. patients with MDD without trauma history, B. patients with MDD and trauma history without PTSD comorbidity and C. patients with MDD-PTSD comorbidity. Multiple logistic rergression models were applied for exploring the discrimination between MDD-PTSD and MDD-nonPTSD patients in order to explore possible factors that are involved in MDD-PTSD comorbidity. Similarly, we compared patients with and without trauma history (group A), in order to evaluate possible consequences of trauma in our sample. We also compared patients in group B with the rest of our sample to access parameters involved in a so called post-traumatic depression. The list of the independent variables considered in that models were variables that showed an p-value <0.200 from the simple regression models. IBM SPSS Statistics 21.0 was used for analysis and a level of acceptance of null hypothesis was set at 0.05. Results: The majority of our sample were women (n= 78, 77.2%) and the mean age was 50.0 ± 12.6 years. On average, the duration of studies, including years of basic education, was 12.1 ± 4.4 years. The mean age of psychiatric symptom onset, as reported from our subjects, were 33.5 ±15.5 years. The mean age of the first MDE onset was 37.9 ±13.6 years. The mean age of exposure to a traumatic event was 21.8 ±15.8 years. Sixty patients (59.4%) had actual ongoing depressive symptoms, according to the MINI. The mean total duration of MDE was 3.7 ±5.1 years. Sixty five patients (64.4%) reported at least one traumatic event in their past, which fulfilled the criterion A of the DSM IV- TR diagnostic criteria for PTSD. The prevalence of PTSD after a traumatic experience was 46.0% (n=64). The trauma most frequently related to PTSD was the experience of the sudden or violent death, followed by physical violence. Lifetime prevalence of MDD-PTSD comorbidity in our sample (group C) was 39 subjects (38.6%), while almost one out of four patients suffered from ongoing MDD-PTSD comorbidity. Only 11 patients (28.2%) with MDD-PTSD comorbidity had a documented PTSD diagnosis in their records. In most cases of MDD-PTSD comorbidity PTSD preceded MDD by 6.2 ±14.6 years. Multiple logistic regression analysis showed increased odds ratio (OR) of MDD-PTSD comorbidity with chronic depression, prolonged or repeated trauma and male gender. Years of education, age of symptom onset and GAF had in increased OR with MDD-PTSD comorbidity. There was also an increased OR of borderline significance between MDD-PTSD comorbidity and number of comorbid physical diseases. Group A consisted of 36 subjects (35.6%). Multiple logistic regression analysis showed that trauma history has a higher OR with smoking and the number of comorbid physical diseases. Fewer years of education had a lower OR with trauma history. Finally, group B, i.e. patients with MDD with trauma history who never suffered from PTSD, consisted of 26 (25.7%) subjects. Multiple logistic regression analysis showed that post traumatic depression had a higher OR with single trauma and financial independency and a lower OR with married status and chronic depression. Discussion: The prevalence of current MDD-PTSD comorbidity was 26.7%, while the percentage of lifetime MDD-PTSD comorbidity was 38.6%. These rates are almost twice as those reported in outpatients with anxiety disorders and similar to those reported in inpatients with depression and other severe mental disorders. In our study, only 28.2% of patients with MDD-PTSD comorbidity had a documented PTSD diagnosis on their records, a rate that is nevertheless much higher than that reported by others. This means that PTSD diagnosis is usually missed. Taking into account the average PTSD duration which was about 16 years, we may conclude that many patients with MDD suffer from a lasting condition of continuous psychopathology without receiving proper treatment, leading to worse living conditions, mental and physical health. Patients with MDD-PTSD comorbidity for example had an earlier onset of MDD, longer lasting depressive episodes and a worse functionality. They also had unfavorable living standards, given that almost half of them were in need of financial support, while the lower level of education was found to be a significant predictive factor for the group of patients with MDD-PTSD comorbidity. Initially, there was a strong relation between suicide attempts and MDD-PTSD comorbidity, as other recent studies have shown, which vanished, however, after controlling for the age of psychiatric symptom onset. MDD-PTSD comorbidity patients tend to show more physical comorbidity, a finding that most probably is related to trauma per se than to PTSD comorbidity. Some studies suggest that there is a linear relationship between trauma exposure and physical comorbidity. We found that the number of additional physical diseases predicted significantly the presence of psychological trauma in our patients, which supports the above hypothesis. Seeking for possible explanations for this finding, we could take the hypersensitivity of the Hypothalamus-Pituitary-Adrenal axis into account, as a long term consequence of early trauma. By searching for possible causes for the fact that MDD-PTSD comorbidity is frequently overlooked, clinical practice and published literature show that psychiatrists are reluctant to ask about past traumatic experiences and that routine psychopathological examination does not involve questions about flashbacks, dissociation, hyperarousal and other symptoms that are indicative of PTSD. Patients may also avoid talking about traumatic experiences, while mental health professionals may find it difficult to assess and treat the sequelae of a trauma, especially if they lack sufficient knowledge in the field psychotraumatology. Further, if a patient reports the death of a close relationship, the clinician may start examining the possibility of MDD without thinking about PTSD as well. Our study, as well as recent literature suggests however that the experience of a sudden or violent death of another person is a trauma that frequently leads to PTSD. It therefore seems important to look after probable PTSD in individuals who report the loss of a significant person, especially if this incident occurred in a sudden or violent manner. The most significant predictive factors for PTSD were chronic depression, prolonged or repeated trauma, male gender, lower level of education, lower level of global functioning and younger age of psychiatric symptom onset. The relation between lower education and psychopathology is well established and is regarded rather as consequence of psychopathology rather than cause. The same is true for lower functionality in patients with comorbid psychopathology. Patients with chronic depression were 8 times more likely to suffer from MDD-PTSD comorbidity. Other researches on PTSD comorbidity in patients with anxiety disorders came to similar conclusions, underlying thus the crucial role of psychological trauma in chronic depression. This finding may prove useful in clinical praxis, guiding a clinician to probable PTSD comorbidity in a patient with persistent depressive symptoms for over 2 years. The strong relation between chronic depression and PTSD may be explained by the fact that PTSD is frequently overlooked, functioning thus as a trigger for further psychopathology. The initially strong relation between childhood trauma and MDD-PTSD comorbidity vanished after controlling for repeated and/or prolonged trauma. The latter proved to be a significant predictor of MDD-PTSD comorbidity. One possible explanation would be that most cases of childhood trauma in our study were of a repetitive and prolonged nature. Moreover, in animal experiments concerning neurobiological effects of early trauma, the applied stressful stimuli were almost always of a repetitive nature, whether it was achieved with the application of painful stimuli or the deprivation of maternal care. Thus, the repetition of a certain stressful experience early in life may contribute to the sensitization of the HPA axis, predisposing the subject to PTSD and MDD later in life. Repetitive stress is also linked to alterations in brain plasticity in animal models, leading for example to a volume reduction of the hippocampus and the medial prefrontal cortex, commonly observed in PTSD and MDD. Of course, the link between prolonged or repeated trauma and MDD-PTSD comorbidity needs to be investigated further. Male gender predicting PTSD-MDD co-morbidity was unexpected, since it is generally accepted that females are twice as likely to develop PTSD after trauma than males. Due to the fact, however, that our sample consisted of treatment-seeking subjects only, we could hypothesize that depressed males are more likely to seek psychiatric treatment, if their symptoms are attributable to an external event rather to an internal vulnerability, thus complying to traditional sociocultural demands of masculinity, which are more prominent in individuals with poor socio-economic status, as in our group of MDD-PTSD patients. Yet another known factor facilitating treatment-seeking behavior in response to mental illness is co-morbidity. We also found that the risk for MDD-PTSD comorbidity is reduced by 9% as the age at psychiatric symptom onset increases by one year. Younger age at psychiatric symptoms onset in patients with comorbid PTSD was also recently reported in patients with bipolar disorder. These findings may indicate that trauma-related psychopathology usually precedes and is casually related to comorbid affective disorders, since traumatic events tend to occur early in life. We may assume that psychopathology with late onset, may be linked to endogenous factors rather than traumatic experiences. When looking for a probable cause regarding MDD-PTSD co-morbidity, we have to consider that in most cases PTSD preceded or began simultaneously with MDD, but remained mainly undiagnosed and hence untreated, predisposing the patient to serious socio-economic decline, a diminished level of functioning and, consequently, to other mental disorders. It thus seems that PTSD is rather a risk factor for MDD; not the opposite. Some authors propose a model in which PTSD mediates the effects of trauma in serious mental disorders both directly by the continuous presence of underlying symptoms of hyperarousal, avoiding and re-experiencing the trauma, symptoms that are frequently overlooked, and indirectly by the devastating effects of PTSD in social and occupational functioning. Our study showed that patients with MDD without history of trauma (group C) were older and in a much higher proportion married. This finding can be explained by the fact that, in our study, most traumatic events took place at a mean age of 22 years, where sexual and interpersonal relations are beginning to shape and possibly hindered in their development to mature relationships, due to trauma. Predictive factors for a trauma-history in our patients were fewer years of education, smoking and physical comorbidity, all of whom are considered as consequences rather risk factors for trauma exposure. Regarding physical comorbidity, our study showed that for each additional physical disease, the probability of being exposed to a serious traumatic event increased about 2,5 times. This finding underlines the importance of psychological trauma and its pathophysiological consequences that may lead to physical comorbidity. Our study also showed that a single traumatic event may predispose a subject to MDD, which may occur years after its first impact; single trauma proved to be the most significant predictive factor for patients in group B (patients with MDD and trauma-history without history of PTSD). These results support the hypothesis of a distinct, trauma-related depressive disorder which has different characteristics than MDD-PTSD comorbidity or MDD without trauma-history, as other authors suggested. More studies are needed in order to validate this hypothesis and to evaluate the differences between a post-traumatic depression and MDD without trauma-history in more detail.