Post-traumatic Stress and Depressive Symptoms in Women With Ovarian Cancer 3-6 Months After Diagnosis.

BACKGROUND/AIM: The potentially traumatic role of severe life-threatening medical conditions is still debated in psychiatry and not yet recognized, particularly among post-traumatic stress disorders. However, increasing evidence suggests the psychopathological impact of severe medical conditions related to their poor prognosis, high lethality, treatments heaviness and invasiveness. Ovarian cancer (OC) is one of the malignancies with the highest mortality and the aim of this study was to investigate post-traumatic stress and depressive symptoms in women 3 to 6 months after diagnosis. PATIENTS AND METHODS: A sample of 83 women diagnosed with OC at different stages (from AI to IV) was recruited and assessed by means of the: Structural Clinical Interview for Mental Disorders according to DSM-5 (SCID-5), Trauma and Loss Spectrum Self-Report (TALS-SR), Impact Event Scale-Revised (IES-R), Hamilton Rating Scale for Depression (HAM-D), Mood Spectrum-Self Report (MOOD-SR), Work and Social Adjustment Scale (WSAS). RESULTS: Full data on the psychiatric assessments were available for 45 patients: 13 (28.9%) patients reported a diagnosis of PTSD. Patients with PTSD reported statistically significant higher depressive symptoms and more severe impact on work and social functioning compared to those without PTSD. CONCLUSION: Our results highlight the need to carefully assess the potentially traumatic burden of a diagnosis of OC and its association with depressive symptoms for their impact on patients' global functioning, in order to provide appropriate preventive and therapeutic interventions.

Metabolic and Inflammatory Response in Post-Traumatic Stress Disorder (PTSD): A Systematic Review on Peripheral Neuroimmune Biomarkers.

Several heterogeneous pathophysiology pathways have been hypothesized for being involved in the onset and course of Post-Traumatic Stress Disorder (PTSD). This systematic review aims to summarize the current evidence on the role of inflammation and immunological dysregulations in PTSD, investigating possible peripheral biomarkers linked to the neuroimmune response to stress. A total of 44 studies on the dysregulated inflammatory and metabolic response in subjects with PTSD with respect to controls were included. Eligibility criteria included full-text publications in the English language, human adult samples, studies involving both subjects with a clinical diagnosis of PTSD and a healthy control group. The research was focused on specific blood neuroimmune biomarkers, namely IL-1ß, TNF-α, IL-6 and INF-γ, as well as on the potential harmful role of reduced antioxidant activity (involving catalase, superoxide dismutase and glutathione peroxidase). The possible role of the inflammatory-altered tryptophan metabolism was also explored. The results showed conflicting data on the role of pro-inflammatory cytokines in individuals with PTSD, and a lack of study regarding the other mediators investigated. The present research suggests the need for further studies in human samples to clarify the role of inflammation in the pathogenesis of PTSD, to define potential peripheral biomarkers.

Improving physical activity and diet in patients with severe mental disorders: Results from the LIFESTYLE multicentric, real-world randomized controlled trial.

Aims of the present study are to test the efficacy of a lifestyle group intervention, compared to a brief psychoeducational intervention, on levels of physical activity and dietary habits in a real-world sample of patients with severe mental disorders. The study, funded by the Italian Ministry of Education, has been carried out in six Italian University psychiatric outpatient units. All patients were randomly assigned to the experimental or control group and were assessed through standardized assessment instruments at baseline and six months after randomization. Of the 401 recruited patients, 43.3% had a diagnosis of bipolar disorder, 29.9% of psychosis and 26.9% of major depression. Patients were mainly female (57%), with a mean age of 45.6±11.8 years. Treated patients have almost 8 times the likelihood to show an increase of the total MET (OR: 8.02; p < .001) and of the walking MET (OR: 7.68; p < .001) and are more likely to increase the weekly consumption of vegetables (OR= 1.98, p < .05) and to reduce that of junk food (OR:0.23; p < .05). The present study support the notion that patients with severe mental disorders can improve their lifestyle behaviours and that, with appropriate support, they can achieve a healthy living.

The Complex Interplay Between Physical Activity and Recovery Styles in Patients With Severe Mental Disorders in a Real-World Multicentric Study.

Compared with the general population, people with severe mental disorders have significantly worse physical health and a higher mortality rate, which is partially due to the adoption of unhealthy lifestyle behaviors, such as heavy smoking, use of alcohol or illicit drugs, unbalanced diet, and physical inactivity. These unhealthy behaviors may also play a significant role in the personal and functional recovery of patients with severe mental disorders, although this relationship has been rarely investigated in methodologically robust studies. In this paper, we aim to: a) describe the levels of physical activity and recovery style in a sample of patients with severe mental disorders; b) identify the clinical, social, and illness-related factors that predict the likelihood of patients performing physical activity. The global sample consists of 401 patients, with a main psychiatric diagnosis of bipolar disorder (43.4%, N = 174), psychosis spectrum disorder (29.7%; N = 119), or major depression (26.9%; N = 118). 29.4% (N = 119) of patients reported performing physical activity regularly, most frequently walking (52.1%, N = 62), going to the gym (21.8%, N = 26), and running (10.9%, N = 13). Only 15 patients (3.7%) performed at least 75 min of vigorous physical activity per week. 46.8% of patients adopted sealing over as a recovery style and 37.9% used a mixed style toward integration. Recovery style is influenced by gender (p < 0.05) and age (p < 0.05). The probability to practice regular physical activity is higher in patients with metabolic syndrome (Odds Ratio - OR: 2.1; Confidence Interval - CI 95%: 1.2-3.5; p < 0.050), and significantly lower in those with higher levels of anxiety/depressive symptoms (OR: 0.877; CI 95%: 0.771-0.998; p < 0.01). Globally, patients with severe mental disorders report low levels of physical activities, which are associated with poor recovery styles. Psychoeducational interventions aimed at increasing patients' motivation to adopt healthy lifestyle behaviors and modifying recovery styles may improve the physical health of people with severe mental disorders thus reducing the mortality rates.

Prescribing Tamoxifen in Patients With Mood Disorders: A Systematic Review of Potential Antimanic Versus Depressive Effects.

PURPOSE/BACKGROUND: Tamoxifen is a selective estrogen receptor modulator widely used for treatment and prevention of estrogenic receptor-positive breast cancer. Tamoxifen is an object of growing interest in psychopharmacology as an antimanic drug, because it inhibits the protein kinase C, a molecular target of bipolar disorder. Consistently, the potential depressive effect of tamoxifen has been repeatedly reported. METHODS/PROCEDURES: This article systematically reviews studies examining tamoxifen impact on mood, exploring either its potential therapeutic use as antimanic agent or its potential depressive effect. FINDINGS: Eight studies explored tamoxifen antimanic properties, all, but one, reported a rapid and efficacious antimanic action. As to the depressive effect, 9 cohort studies emerged among which 4 pointed out an increased risk of depression. Seven case reports described the onset or exacerbation of depressive episodes besides 1 case series study reported a high rate of depressive symptoms. In addition, 1 case report study described a tamoxifen-induced manic episode. IMPLICATIONS/CONCLUSIONS: The present review highlights tamoxifen treatment as a possible trigger of mood symptoms onset or exacerbation in vulnerable patients. Accordingly, patients with a history of mood disorders may require a close clinical surveillance during tamoxifen use. At the same time, the use of tamoxifen as an antimanic agent in psychiatric settings requires caution, as available evidence came from small-sample studies with short observation time. More studies are needed to define how long-term tamoxifen use may affect the course of bipolar disorder.

Suicidality and Illness Course Worsening in a Male Patient with Bipolar Disorder during Tamoxifen Treatment for ER+/HER2+ Breast Cancer.

PURPOSE: Tamoxifen is a selective estrogenic receptor modulator (SERM) drug. In addition to its common use in breast cancer ER+, Tamoxifen has been object of growing interest in psychiatry as antimanic drug. At the same time, clinical concerns about Tamoxifen's depressogenic effect have been repeatedly raised even without reaching univocal conclusions. We discuss the case of a 45-year-old-male with a diagnosis of Bipolar Disorder type II, treated with Tamoxifen as relapse prevention treatment after surgery for a ER+/HER2+ breast cancer. The patient required two psychiatric admissions in a few-month time span since he showed a progressive worsening of both depressive and anxiety symptoms, with the onset of delusional ideas of hopelessness and failure up to suicidal thoughts. The clinical picture showed poor response to treatment trials based on various associations of mood-stabilising, antidepressants, and antipsychotic drugs. During the second hospitalization, after a multidisciplinary evaluation, the oncologists agreed on Tamoxifen discontinuation upon the severity of the psychiatric condition. The patient underwent a close oncological and psychiatric follow-up during the following 12 months. METHODS: Psychiatric assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAM-D), the Columbia Suicide Severity Rating Scale (C-SSRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). All questionnaires were administered at the time of the second hospitalization and in a one-year follow-up. RESULTS: Suicidal ideation fully remitted and depressive symptoms markedly and rapidly improved in the aftermath of Tamoxifen discontinuation. The symptomatological improvement remained stable across one-year follow-up. CONCLUSIONS: Male patients with a mood disorder history constitute a high-risk group as to Tamoxifen psychiatric side effects. The onset or worsening of depressive symptoms or suicidality should be carefully addressed and promptly treated, and clinicians should be encouraged to consider the possibility of discontinue or reduce Tamoxifen therapy after a multidisciplinary evaluation.

Naturalistic 6-month antidepressants follow-up in patients with fibromyalgia: impact on somatic and mood spectrum symptoms.

OBJECTIVES: Literature shows high rates of comorbidity between fibromyalgia (FM) and mood disorders, especially major depressive disorder (MMD), reported in more than half of the cases. Consistently, patients with FM also present high rates of mood spectrum symptoms, despite scant data are still available on the relationship with antidepressant treatment outcomes. The present study was aimed at exploring the clinical outcome of patients with FM-MDD comorbidity naturalistically treated with antidepressant drugs, besides the relationships between mood spectrum symptoms and the treatment response. METHODS: A total sample of 40 patients with FM and MDD, who started a treatment with an antidepressant drug, was recruited at the Rheumatology Unit of the University of Pisa, Italy. Patients were evaluated at baseline and after 1 (T1) and 6 months (T2) of the treatment with an antidepressant drug. Assessments included: the Mood Spectrum-Self Report (MOODS-SR) for mood spectrum symptoms, the Short Form Health Survey (SF-36) for the global functioning and the Clinical Global Impression (CGI) for the clinical severity and improvement. All instruments were administered at baseline and the SF-36 and CGI were repeated at T1 and T2. RESULTS: Twenty-eight (70%) patients reported an improvement at the CGI at T2. At T1 and T2 the CGI item-1 and most of the SF-36 domain scores significantly improved with respect to the T0, with the exception of the "role physical" and "role emotional" subscales. Improved patients reported higher scores in the energy depressive MOODS-SR domain. Furthermore, correlations emerged between several MOODS-SR domains and the CGI or SF-36 subscales scores at T0. CONCLUSIONS: Our results corroborate previous findings on the role of antidepressant drugs in the management not only of MDD symptoms, but also of the painful component of FM. FM patients should be investigated for Mood Spectrum symptomatology considering its prominent role on the manifestations of the disorder and treatment outcome.

Adult Autism Subthreshold spectrum correlates to Post-traumatic Stress Disorder spectrum in patients with fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is an increasingly prevalent disorder that usually shows a chronic course and a disappointing therapeutic response in which psychiatric features seem to play a relevant role. Most recently, the relationship between FM and Post-traumatic Stress Disorder (PTSD) has gained interest since several studies demonstrated a higher rate of PTSD, both full blown and partial, and Post-traumatic Stress spectrum symptoms. While the relationship between higher burden of autistic symptoms and PTSD is reported in literature, the relationship between FM and autism spectrum symptoms is still unexplored. In this study we investigated both post-traumatic and autistic spectrum in a sample of FM patients with the aim of exploring the relationships between these dimensions. METHODS: One hundred and nineteen patients with FM, diagnosed according the American College of Rheumatology 2010 criteria, were consecutively enrolled at the Unit of Rheumatology, University of Pisa, Italy. Assessments included: the Trauma And Loss Spectrum-Self Report (TALS-SR), for the post-traumatic stress spectrum symptomatology, the Adult Autism Subthreshold spectrum (AdAS spectrum) for the assessment of subthreshold autism spectrum. The scores reported to AdAS (total and per domain) by the entire sample and subgroups with PTSD diagnosis, partial PTSD and no PTSD were compared in order to detect a relation between Autistic Traits (ATs) and post-traumatic spectrum in this clinical sample. RESULTS: Our results show that FM patients with PTSD report an AdAS total score significantly higher than those reported by patients without PTSD. Moreover, through an examination of the correlation between AdAS spectrum and TALS-SR scores, significant correlations between the total score of the two instruments has emerged. The correlation resulted to be particularly significant between TALS-SR scores and non-verbal communication domain of the AdAS and between hyper-hypo reactivity to sensory input domain and several TALS-SR domains. CONCLUSIONS: These results highlight the clinical relevance of autistic traits in FM patients with PTSD. In this regard, we may claim a potential role of abnormal processing of sensory input and deficits in non-verbal communication in explaining this association.

Potentially traumatic events, post-traumatic stress disorder and post-traumatic stress spectrum in patients with fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is defined as a severe, chronic, non-articular rheumatic condition characterised by widespread musculoskeletal pain, hyperalgesia and generalised tender points, in the absence of inflammatory or structural musculoskeletal abnormalities. Pain is the predominant symptom, allodynia and hyperalgesia are common signs. Extreme fatigue, impaired cognition and non-restorative sleeping difficulties coexist in addition to other somatic symptoms. Several studies suggest there is a meaningful relationship between FM and the psychological symptoms of depression and post-traumatic stress disorder (PTSD). PTSD is a mental disorder that can develop after a person has been exposed to a traumatic event, characterised by a specific set of symptoms including re-experiencing of the event, avoidance and numbing and arousal. The present study investigates the impact of lifetime potentially traumatic events, including losses, and of post-traumatic stress symptoms on the severity of illness in patients with fibromyalgia (FM). METHODS: Sixty-one patients with FM, diagnosed according to the American College of Rheumatology criteria, were consecutively enrolled at the Unit of Rheumatology, University of Pisa, Italy. Assessments included: the SCID-5 and the Trauma and Loss Spectrum Self-Report (TALS-SR) lifetime version. RESULTS: 21.3% of the subjects (n=13) met the criteria for "partial" PTSD: 57.4% criterion B, 42.6% criterion C, 31.1 criterion D and 44.3% criterion E. Fibromyalgia patients without PTSD reported significantly lower scores in all domains compared to the patients with partial PTSD, the latter ones reporting significantly lower scores in all domains compared to full PTSD with the exception of domain I. In particular, these differences were noticeable in Domain VI and Domain VIII. CONCLUSIONS: The results of the study show that fibromyalgic patients with PTSD report more potentially traumatic events, avoidance symptoms, numbing, arousal, maladaptive coping and personality characteristics compared to patients with partial or without PTSD; these results could indicate that loss and/or trauma events represent a risk factor for the development of symptoms of FM in genetically predisposed individuals.

Personality Traits in Fibromyalgia (FM): Does FM Personality Exists? A Systematic Review.

INTRODUCTION: Fibromyalgia (FM) is the second most common rheumatic disease with many effects on patient's quality of life. It has been described as a chronic condition characterized by widespread musculo-skeletal pain, sleep disorders and prominent fatigue. Regarding the role of personality factors in fibromyalgia, researchers have focused both on personality traits and psychopathological aspects showing inconsistent results. In particular, several studies have examined the role of alexithymia in FM patients, a trait of personality characterized by difficulty in identification, recognition and description of emotions and feelings, while others have focused on a specific type of personality, such as type D personality (distressed personality). Other studies investigated personality in FM patients referring to Cloninger's model, a psychobiological model of personality that includes both temperamental and character dimensions of personality. Analyzing scientific literature on this subject seems well suited to provide a critical review of the latest studies and their results. METHODS: The method used for this review satisfies the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). We identified PsycInfo and PubMed as databases for our research. RESULTS: Personality is studied under many aspects and a reference model is not always present. Many studies underline high levels of alexithymia and type D personality in FM patients but when depression is controlled, these results do not differ from those of healthy controls. CONCLUSION: Studies that use a comprehensive model of personality present a different theoretical approach and use alternatively the Big-Five model, Eysenck's and Cloninger's models. The use of a comprehensive model of personality and the control of psychopathological disorders, such as anxiety and depression, seem to be very relevant for a better understanding of a specific personality profile associated with fibromyalgia.

Post-traumatic Stress Disorder in patients with ovarian cancer.

Ovarian cancer (OC) is one of the deadliest malignancies. The impact of this diagnosis is, therefore, highly traumatic, and affected women are prone to significant distress during the whole course of the disease. The present paper is aimed to review extant literature about the relationship between OC and Post-traumatic Stress Disorder (PTSD).

The management of fibromyalgia from a psychosomatic perspective: an overview.

Fibromyalgia (FM) is a central sensitization syndrome characterized by chronic widespread pain. FM is often comorbid with psychiatric disorders, as well as psychological distress that worsens the quality-of-life of people affected. The aim was to collect current evidence about the management of FM from a psychosomatic perspective. The literature was synthesized and summarized in a narrative format. The literature search was carried out in PubMed; review articles, meta-analysis, overview, and guidelines published in the last 10 years written in English were included. Five main topics (Diagnostic criteria of FM; Pathogenesis of chronic widespread pain in FM; Early stress and trauma as predisposing factors for central sensitization; FM and Psychiatric comorbidity; Implications for treatment) were pointed out and discussed. Much evidence underlies the importance of considering and treating the comorbidity of FM with psychiatric disorders and psychological factors that affect pain management. Validation of FM as a central sensitization syndrome by a clinician facilitates therapeutic strategies that involve patients as active participants in the pain management process, likely leading to improved outcomes.

Transdiagnostic factors across fibromyalgia and mental disorders: sleep disturbances may play a key role. A clinical review.

Sleep disturbances, affective disorders, pain and fatigue are often present in individuals affected by fibromyalgia (FM). The pathophysiology of FM is not yet well understood and, to date, no treatment has been proven to be fully effective in alleviating all symptoms. Adopting a transdiagnostic perspective could thus be useful for clinicians: treatment would target a transdiagnostic process across a range of disturbances, not just a single disorder. The aim of this review is to revise the available literature about the potential role of sleep disturbances as a transdiagnostic process in FM symptomatology and mood or anxiety disorders comorbidity. We are proposing a model under which sleep disturbances can play a central role. Because conditions of sleep loss are related to the activation of the stress system, including the activation of the inflammation system, we propose this mechanism as a key one: it can be shared by mental, sleep disturbances and pain in FM and it may explain, in part, the high levels of comorbidity between them. In this frame-work sleep disturbances may play a key role and be the target of therapeutic strategies across FM symptomatology and mental disorders.

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome.

OBJECTIVES: The present paper aimed at reviewing literature data on the inflammatory hypothesis of mood spectrum, as well as the overlapping features with some chronic rheumatologic disorders, in particular fibromyalgia and chronic fatigue syndrome. METHODS: A literature search was carried out for English papers published in the years 2000-2014, while using the following words: mood spectrum, depression, bipolar disorders, fibromyalgia, chronic fatigue syndrome, neurotransmitters, inflammation, neuroinflammation, cytokines. RESULTS: Overlapping features were highlighted between mood spectrum, fibromyalgia and chronic fatigue syndrome suggesting common underlying mechanisms at pathophysiological level involving both central nervous and the immune systems. CONCLUSIONS: Taken together, the literature would suggest that the borders between different medical domains should be reconsidered in the light of common processes linking them.

Cyclic adenosine monophosphate responsive element binding protein in post-traumatic stress disorder.

OBJECTIVES: The cyclic adenosine monophosphate responsive element binding (CREB) protein is a transcription factor involved in different neural processes, such as learning, neuroplasticity and the modulation of stress response. Alterations in the CREB pathway have been observed in the brains and lymphocytes of patients affected by depression and alcohol abuse. Given the lack of information, our study aimed at investigating the levels of total and activated CREB protein in lympho-monocytes of 20 drug-free patients suffering from post-traumatic stress disorders (PTSD), as compared with 20 healthy control subjects. METHODS: Blood samples were collected from patients and healthy control subjects on the same time and lympho-monocytes were isolated according to standardized methods. CREB protein levels and activation were measured by means of immunoenzymatic techniques. RESULTS: The results showed that PTSD patients had statistically lower levels of total CREB protein in lympho-monocytes than healthy control subjects. On the contrary, no difference in the activated CREB protein was detected. CONCLUSIONS: These findings, albeit preliminary, would suggest that the CREB pathway might be involved in the pathophysiology of PTSD. Future studies should clarify if specific PTSD symptom clusters might be related to the CREB pathway.

Lifetime manic-hypomanic symptoms in post-traumatic stress disorder: relationship with the 18 kDa mitochondrial translocator protein density.

Initially explored in military settings, post-traumatic stress disorder (PTSD) has shown increasing prevalence in the general population. The high comorbidity rates between bipolar disorder (BD) and PTSD have raised the issue of whether some characteristics of BD could represent risk factors for PTSD. In combat-related PTSD, the 18 kDa mitochondrial translocator protein (TSPO), essential for steroid synthesis, was found to be decreased. Aims of the present study were: 1) the assessment of the TSPO mitochondrial density in lymphomonocytes from civilian patients with non-combat-related PTSD, without current or lifetime Axis I mood comorbidity, versus controls; 2) the exploration of the correlations between TSPO density and the presence of comorbid manic/hypomanic lifetime spectrum symptoms. Assessments included the Structured Clinical Interview for DSM-IV (SCID), the Impact of Event Scale (IES), and the lifetime Mood Spectrum Self-Report (MOODS-SR). Blood samples were processed to assess TSPO binding parameters in lymphomonocyte mitochondrial membranes. PTSD patients showed a significant decrease in TSPO density, without changes in mitochondrial citrate synthase activity. Further, TSPO density correlated with the number of lifetime manic/hypomanic spectrum symptoms. For the first time, TSPO density was found to be decreased in non-war-related PTSD and such decreases correlated with comorbid manic/hypomanic spectrum symptoms, indicating a possible role of sub-threshold bipolar comorbidity in PTSD-related neurobiological dysregulation.

Serotonin-mediated cyclic AMP inhibitory pathway in platelets of patients affected by panic disorder.

Cyclic adenosine monophosphate (cAMP) pathway abnormalities have been suggested to be involved in anxiety disorders including panic (PD). The present study sought at investigating the downstream inhibitory adenylyl cyclase (AC) pathway activated by 5-HT in platelets obtained from 22 patients with a diagnosis of PD versus 22 healthy volunteers. In PD patients, a significant impairment of 5-HT potency to inhibit AC was observed. One month of treatment with paroxetine induced a significant increase of 5-HT potency in T1 patients close to the control values. [(35)S]GTPgammaS binding studies showed that in PD patients, a reduction of 5-HT receptor-G protein coupling occurred without any significant changes in G protein levels. These findings demonstrated that (1) a reduction of the inhibitory AC pathway activated by 5-HT occurred in platelets from PD patients; (2) the reduced 5-HT responsiveness in PD was related to an impairment of 5-HT receptor-G protein coupling, and (3) after 1 month of treatment with paroxetine, such a dysfunction significantly reversed together with a significant improvement of clinical symptoms.