The Clinical, Biological, Psychological and Psychiatric Impact of the Diagnosis of Breast Cancer in Women.

OBJECTIVE: Psychosocial factors are correlated with the risk of breast cancer, by the lack of externalization of feelings and aggressive tendencies, or with a negative prognosis, by the presence of a high level of stress and reduced coping abilities. Impairment of psychological status should be assessed early to identify quantifiable psychooncological changes, such as depression, anxiety, and self-esteem. These indicators, measured in this study, may become psychometric markers for predicting the existence of the neoplastic process, prior to histopathological evaluations. METHODS: 58 patients diagnosed with breast cancer and in different stages of evolution and 61 breast lumps patients were evaluated for depression, anxiety and self-esteem. RESULTS: The correlation of depression and anxiety levels according to the evolutionary stage of the disease was as follows: in stage I cases of severe depression with significant anxiety predominate, in stage II mild depression predominates with insignificant anxiety, in stage III depression predominates moderate with significant anxiety, while in stage IV moderate depression with significant anxiety predominates. CONCLUSIONS: The presence of significant anxiety in the uncertainty phase and the anxious-depressive clinical picture can be an alarm signal for the initiation of specific psychotherapeutic strategies, to increase the adaptive potential and resilience to the disease to ensure a therapeutic collaboration of the patient by increasing adherence and compliance. the proposed therapeutic plan. Relatively sudden anxiety in a young woman, risk factors for breast cancer, and deficient cognitive impairment require intensified clinical and paraclinical investigations to confirm early oncological diagnosis.

Impairment of the cardiac ejection fraction by blocking dopamine D2 receptors induced by long-acting injectable antipsychotic treatment.

INTRODUCTION: Atypical antipsychotics have numerous benefits compared to conventional ones in respect to the possible adverse effects. However, like the other ones, they may induce direct cardiovascular alterations, probably through the apoptotic effect of dopamine receptor D2 (DRD2) blockade. The main objective of the study was to assess the cardiac ejection fraction (EF) using transthoracic speckle tracking echocardiography (TSTE) in patients treated with long-acting injectable (LAI) atypical antipsychotics. PATIENTS, MATERIALS AND METHODS: This cross-sectional study was conducted on 123 patients with schizophrenia or schizoaffective disorder divided in four samples according to their treatment: Aripiprazole, Olanzapine, Paliperidone and Risperidone. We analyzed socio-demographic data, the intensity of psychiatric symptoms, the duration of psychosis and of LAI treatment, and the cardiac EF measured with TSTE. RESULTS: We found no statistically significant differences between the four antipsychotics regarding the values of the EF. Nevertheless, we observed a trend indicating that patients treated with an antipsychotic associated with a lower affinity for the DRD2, such as Olanzapine, have higher EF values than patients treated with antipsychotics with a stronger binding to the DRD2, such as Paliperidone and Risperidone. Patients receiving Aripiprazole, which has the strongest affinity for the DRD2 from all four antipsychotics but is also a partial DRD2 agonist, display higher EF values than those on Paliperidone and Risperidone. CONCLUSIONS: Antipsychotics with a lower affinity for the DRD2 or a partial agonism for it may be associated with higher EF. Cardiac monitoring should be performed periodically in patients on LAI antipsychotic therapy.

The role of personality dimensions and trait anxiety in increasing the likelihood of suicide ideation in women during the perinatal period.

INTRODUCTION: Increasing amount of data reveal that suicide risk is a real phenomenon among perinatal women, determined by several other psychopathological conditions with depression being just one of them. This study aimed to investigate the role of personality dimensions on the occurrence of suicide ideation during the perinatal period. METHODS: A longitudinal prospective study was performed in pregnant women who were monitored at university-based obstetrical care units in our county. Recruited women were reassessed between 6 and 8 weeks into their postnatal period. Trait and state anxiety, five-factor based dimensions of personality, and depressive symptoms were assessed using established psychometric measures. Appropriate statistical analyses were conducted, depending on the distribution of variables. RESULTS: Significant levels of state anxiety (33.7% vs. 15.5%), depressive symptoms (19.8% vs. 8.5%), and suicide risk (13.9% vs. 6.3%) have halved in the postnatal period compared to the antenatal assessment. A lower level of education was associated with the presence of postnatal suicide ideation (p = .041), while an unemployed professional status was more frequent in pregnant women presenting antenatal suicide ideation (p = .021). Trait anxiety was predictive for the appearance of suicide ideation within the entire perinatal period assessed (p < .001 and p = .007, respectively). Agreeableness and conscientiousness predicted antenatal suicide ideation (p = .033 and p = .032, respectively). DISCUSSIONS: Different dimensions of personality may play a contributing role in the development of suicide ideation in perinatal women. Consequently, personality dimensions and trait anxiety, not only depressive symptoms, should be investigated when attempting to identify perinatal women at risk of suicide.

Mild TBI in the elderly - risk factor for rapid cognitive impairment in Alzheimer's disease.

In recent decades, traumatic brain injury (TBI) has become one of the most important health problems worldwide and is a major cause of morbidity, mortality and economic losses. Mild traumatic brain injury (mTBI) is less considered, with clinical underestimation leading to an epidemiological underevaluation of its incidence. Many of the signs and symptoms induced by mTBI are difficult to highlight clinically, especially those related to cognitive, behavioral, or emotional impairment. The complexity of the biological mechanisms induced by mTBI in the elderly determines synchronous pathogenic actions in which the vascular, inflammatory and neurodegenerative elements are intertwined. It is difficult to highlight a major pathogenic factor, since they act simultaneously, multimodally, in a real pathogenic cascade. The identification of mTBI and cerebral vascular changes by neuroimaging techniques, transcranial Doppler (TCD) or biological markers, suggests a potential prophylactic intervention by using neuroprotective factors as early as possible. Proper prophylaxis measures with neurotrophic treatment, rebalancing the gamma-aminobutyric acid (GABA)∕glutamate balance and combating the chronic inflammatory process, can become important pharmacological therapeutic targets.

SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine.

Patients with serious mental illness are a high-risk category of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with schizophrenia are not participatory and have increased mortality and morbidity, patients with dementia cannot be cared for while depression, anxiety, bipolar tubing are associated with low immune status. Social stress is amplified by social isolation, amplifying depression and the mechanisms of decreased immunity. Hygiene measures and prophylactic behavior are impossible to put into practice in conditions of chronic mental illness. In coronavirus disease 2019 (COVID-19), the risk for severe development is associated with the presence of comorbidities and immune system deficiency. Prothrombotic status, cytokine storm and alveolar destruction are mechanisms that aggravate the evolution of patients, especially in the context in which they have dysfunction of the autonomic system. The activity of proinflammatory cytokines is accentuated by hyperglutamatergia, which potentiates oxidative stress and triggers the mechanisms of neural apoptosis by stimulating microglial activation. Activation of M1-type microglia has an important role in pathogenesis of major psychiatric disorders, such as major depression, schizophrenia or bipolar disorder, and may associate hippocampal atrophy and disconnection of cognitive structures. Memantine and Amantadine, N-methyl-D-aspartate (NMDA) glutamate receptor inhibitors, have demonstrated, through their pharmacological profile, psychotropic effects but also antiviral properties. In the conditions of the COVID-19 pandemic, based on these arguments, we suggest that they can be associated with the therapy with the basic psychotropics, Memantine or Amantadine, for the control of neuropsychiatric symptoms but also as adjuvants with antiviral action.

Depression and anxiety in recurrent giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a benign neoplasia more frequently encountered in young females. The pathogenic and evolutionary dynamics of the disease is strongly influenced by the presence of depression and cellular mechanisms, especially proinflammatory and immune. Although it is not a malignant tumor, it is often recurrent, which determines a high level of depression, anxiety, and fear of the patients. Cytokine mechanisms, especially through increased tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6), as well as the involvement of the receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANK-L) system, can be correlated with the risk of malignancy. Unfavorable evolution is associated with persistent pain, difficulties of movement and body dysmorphic symptoms. The diagnosis is based mainly on histopathological (HP) assessment. The patients can be treated with pharmacological agents (Denosumab), surgery with tumor excision, reconstruction or osteosynthesis, and radiotherapy. Patients with GCTB require HP and imaging evaluations, especially of relapses, to detect the risk of metastasis or malignancy, simultaneously with psychological and psychiatric monitoring to detect depression, addictive behaviors, and suicide risk. It is necessary to evaluate in a multidisciplinary team to avoid unfavorable oncological and psychiatric developments. Through its clinical, HP, and therapeutic features, GCTB has multiple connections with the psychological and psychopathological dimension.

Current understanding of psycho-neurobiology in depressive disorders with suicidal thoughts - translational models.

Epidemiological data confirm the rising incidence of depression associated with suicidal ideation and cardiovascular comorbidities of coronary type. In contradiction with the large number of antidepressant drugs, the therapeutic results are not satisfactory, with numerous existing incomplete remissions characterized by maintained cellular dysfunctionalities that amplify the cognitive deterioration and the risk of several somatic comorbidities. The surprising fact is the relatively high number of deaths in this type of patients due to acute coronary disease (myocardial infarction - MI). The vulnerability of hippocampal and frontal cortex cerebral structures is presented as obtained on animal model consecutive to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and on theoretical model where the hypothalamic disconnectivity determines the activation in the sympathetic autonomic nervous system, leading to heart disorders: high blood pressure, left ventricular hypertrophy and coronary illness. Identifying the association of psychological risk factors, patients fitting in a model of psychosomatic dominant personality traits, where the main risk factors are represented by inflexibility, guilt and self-accusation feelings, associated with increase of biological indicators (proinflammatory factors, endothelial dysfunction and cytokine aggressiveness) and neuroimaging indicators (frontal, temporal, hippocampal atrophy, ventriculomegaly, cerebellum atrophy). Changes identified post-mortem in the arterioles from the frontal cortex were found also in the coronary vessels, suggesting a symmetric evolution The highlighted personality factors are responsible for the decrease of adherence and compliance both in the psychiatric and the cardiologic treatment, the patient being exposed to behavioral risks regarding life style and nutrition, factors that increase the risk for acute coronary accident. The psycho-neurobiological inspired theoretical models argument the importance of a differentiated and customized approach of the patients with depressive disorder and suicidal ideation, and they can be the base for initiating strategies for prevention of unfavorable evolution and risk of death by MI.

Difficulties in histopathology diagnosis and treatment of depressive disorder of breast cancer in male - clinical case presentation.

Breast cancer is less common among men than among women (about 1 in 100) and it is considered a rare disease but the evolution is significantly influenced by depression and distress. We present the case of a 63-year-old patient that was diagnosed in another Clinic with squamous skin carcinoma, but, after complete resection in our Hospital, it was proven to be breast cancer. At diagnosis, computed tomography (CT) scan showed local disease. Adjuvant treatment, consisting in chemotherapy and radiotherapy, was administered. At the beginning of hormonal therapy, the patient had a new CT scan that showed liver and bone metastases. The patient started palliative hormonal treatment with bisphosphonates. The aim of the study was to highlight both the importance of early diagnosis and treatment and the aggressiveness of male breast cancer compared with female. Depressive disorder and social distress worsens the prognosis and quality of life. Male with breast cancer has identity difficulties, body image disturbances and secondary distress.

Cardiovascular anomalies and evolutionary risk factors in schizophrenia - multifactorial approach.

Schizophrenia is a functional psychosis with a multifactorial etiopathogeny involving genetic, endocrine and immunological risk factors. The main pathogenic hypothesis involves dopamine dysregulation, with hyperfunction in the limbic system and hypofunction in the prefrontal cortex. Normal dopamine activity is critical for cognitive and emotional processing, but also for autonomic and immune regulation. Co-morbidity between schizophrenia and cardiovascular anomalies is complex. Genetic factors influence the development of brain, cardiac and vascular structures, as well as the activity of enzymes involved in dopamine synaptic turnover. Autoimmunity triggered by infections or related to systemic diseases affects both brain and heart in a direct manner through autoantibodies and/or indirectly through microvascular injury. In most cases, the co-morbidity between schizophrenia and cardiac diseases is secondary to metabolic dysfunctions induced by psychotropic medication or psychosis itself. Because of their diverse pharmacodynamic profiles, antipsychotics differ in their propensity to facilitate the development of the metabolic syndrome. The distress associated with acute psychotic symptoms or a sedentary lifestyle due to negative symptoms may have a negative impact on the energetic metabolism or cardiac function. Conclusions: An interdisciplinary approach is required between neurosciences and cardiology not only at the research level, but also in the clinical practice. Cardiac co-morbidity in subjects with schizophrenia may critically affect the survival rates of these patients. Moreover, the nature of the cardiac co-morbidity may guide the clinician in better understanding and differentiating functional psychoses from organic ones. The multifactorial approach can identify cardiovascular risk factors based on clinical, biological and neuroimaging markers.

Translational approaches in treatment-resistant depression based on animal model.

An intensively researched and yet poorly understood phenomenon, both at clinical and neurobiological level, is the determinism of treatment-resistant depression. Even more controversial are the stages of approaching therapeutically this pathology because there are no evidence-based recommendations stating that a pharmacological agent is superior to another, on medium and long-term. Due to the lack of "golden standard" approaches, physician's experience, therapeutic alliance and a close monitoring stand as the most useful good practices in the treatment of resistant depression. The neurobiology of this pathology is incompletely characterized, and the current paper will present data derived from single-photon emission computed tomography as arguments for a better understanding of the treatment-resistance in major depression. These data have been compared with the existing data in the literature and arguments in favor of using this investigational method have been formulated. All the three cases presented are patients diagnosed with treatment-resistant major depression, each case with its own psychiatric and somatic background, and therefore with its own therapeutic approach. In all these cases, structured interviews and psychometric scales were applied in order to allow a flexible pharmacological regimen, adjusted to the patient's dynamic needs. Measurements for health-related quality of life were considered necessary for treatment-resistant depression monitoring because low values registered in this domain have important prognostic significance. Translational studies on animal models of depression support the existence of cerebral structural dysfunctions or lesions which can be correlated with clinical and neuroimaging data, allowing for the formulation of neurobiological and psychopharmacological models for treatment-resistant depression.

Neurobiological arguments for a pathogenic multifactorial disconnective model of cognitive disorders from Alzheimer's disease in elderly people.

Incidence of Alzheimer's disease (AD) in people over 75 years is much higher, and the progression of cognitive deficit become faster, leading to a decrease of quality of life for patients and their families. In this context, it is proposed a multifactorial pathogenic model of disconnected cognitive circuits, which is combined with genetic and vascular-cerebral vulnerability elements, allowing an aggressive progression of neurodegenerative factors, favoring onset of dementia. Data from research studies on animal model (rat) highlighted central role of cerebral cholinergic deficit (which is amplified by cerebral ischemia) on the background of apolipoprotein E4 (ApoE4) genotype, favoring multifactorial disconnected mechanisms, by excess of beta-amyloid (ß-A) or increase of vascular dysfunction. Depressive disorder, social stress and traumatic brain injury are favoring the excess in production of ß-A. Hippocampal structure disconnects the cognitive circuits, and from a neuropsychological point of view can be many patterns, which are correlated with neuroimaging (hippocampal atrophy, cerebral siderosis, white matter hyperintensity, ventriculomegaly) or biological (hyperhomocysteinemia) factors. Identifying the pathogenic model of multifactorial disconnectivity in the rapid evolution of cognitive deficit in patients with AD may create the premises for an early diagnosis and treatment, based on the biological, neuropsychological and clinical elements.

Clinical and biological outcomes of prolonged treatment with haloperidol in schizophrenia.

Paranoid schizophrenia with long-term course is a challenge for the clinical and therapeutic research, particularly because chronic course is difficult to identify due to the high rate of mortality in this category of patients. The therapeutic stability on an antipsychotic molecule (haloperidol) is indeed an exception, since the current trend in the case of unfavorable course is based on therapeutic versatility and polypharmacy. Haloperidol is the first-generation antipsychotic that is referred in the therapeutic guidelines as the "golden standard" regarding its efficacy on positive symptoms. The research in fundamental and molecular psychopharmacology has shown the aggressivity of this molecule on the secondary and tertiary signaling chains, including mitochondrial alterations. On male patients with paranoid schizophrenia (positive symptoms) and a chronic course of more than 35 years who received exclusively haloperidol, our study demonstrated an negative outcome with the loss of social functioning, persistence of positive symptoms, chronic extrapyramidal symptoms and mild cognitive impairment. The neuroimaging evaluations have shown atrophy in the temporal poles, posterior ventriculomegaly, cerebellar atrophy and calcification on choroid plexus and pineal gland. The difference between the histological changes induced by haloperidol on animal model and the ones on the patients in our study is located in the frontal cortex, thus suggesting the presence of two neurobiological models of schizophrenia in men: fronto-striatal and temporal-limbic-striatal. The persistence of extrapyramidal symptoms during the treatment with haloperidol may be considered as a clinical marker of the risk for negative outcome and a potential indication for the therapeutic switch.

The microvascular alterations in frontal cortex during treatment with antipsychotics: a post-mortem study.

INTRODUCTION: Schizophrenia is the most severe psychiatric illness, with a biological support in the brain. There is evidence that the adequate dopamine balance in the frontal cortex is associated with a better outcome of the disorder, while the alteration of dopamine mechanism at this level may affect the vascular system leading to secondary neuronal alterations. Our study was conducted post-mortem and its objective was to identify the alterations in the neuronal architecture, in the integrity of the microvascular unit in the frontal cortex of patients treated with potent and excessive D2-blocking antipsychotics. MATERIALS AND METHODS: We studied post-mortem sections of the frontal cortex of three patients (two women and one man) diagnosed with schizophrenia or schizophrenia-spectrum disorders and treated with antipsychotics for the last 24 months. The slides were prepared according to the classical histopathological protocols. RESULTS: Various alterations were found at the neural and vascular levels in the frontal cortex. The most significant was the neural loss as the result of severe changes in the microvessels (diameter reduction, hyaline and collagen deposits, edema, pinocytosis and vacuolization). DISCUSSION: The evidences shown in our study highlight the fact that antipsychotics with potent antagonist action on D2 receptors may affect the neurovascular unit and small vessels in frontal cortex by altering the balance vasoconstriction-vasodilatation, thus reducing the blood flow and metabolism and generating structural microvascular changes proportional with the level of apoptosis at this level. The functional integrity of the dopaminergic system in frontal cortex depends on the vascular support and the capabilities of the neurovascular unit and any dysfunction increases the neuronal loss with clinically significant changes. CONCLUSIONS: The pathological data of our study raises the hypothesis for the pathogenic stages at the level of microvessels in the frontal cortex of the patients with schizophrenia or schizophrenia-spectrum disorders treated with D2-blocking antipsychotics: a stage with functional, reversible alterations that may be correlated with the impairments of working memory and presence of extrapyramidal symptoms and a lesional, irreversible stage with significant deterioration of cognition and global functioning. Further studies are needed to verify this hypothesis.

Prenatal depression and stress - risk factors for placental pathology and spontaneous abortion.

Prenatal stress and depression affects 10-25% of pregnant women and is associated with disruption of fetal neurodevelopment, higher rates of placental abnormalities, preeclampsia, spontaneous abortion, or preterm birth. Markers of genetic vulnerability are catechol-O-methyltransferase, monoamine oxidase-A, variation of serotonin transporters, low levels of dopamine-beta-hydroxylase, and brain derived neurotrophic factor Val66Met (BDNF), while hyperactivity of HPA (hypothalamic-pituitary-adrenal) axis and massive release of endogenous cortisol, regulated by metalloproteinase-1, -2, -3 and -9, and are involved both in depressive symptoms and neurodevelopmental abnormalities in fetus. In women with prenatal stress and depression which suffered spontaneous abortion were observed placental abnormalities as regular shape and necrotic villi, decidua with large areas of necrosis, acute inflammation and effusion areas correlated with increase in proinflammatory factors, immune deficit and infections, hyaline type fibrosis, intervilos and deciduous intense hemorrhage, associated with increase of vascular endothelial growth factor. Taking into account the important societal and economic costs becomes important for an interdisciplinary approach, in which pregnancy and its risks are a central point for women mental health.

Choroid plexus calcification: clinical, neuroimaging and histopathological correlations in schizophrenia.

Schizophrenia is recognized as a psychiatric disorder that causes the most pronounced disturbances of cognition and social integration. In the etiopathogenesis of the disease, genetic, neurobiological and vascular factors are involved. Functional integrity of the brain can be correlated with the integrity of the blood-brain barrier (BBB), and the dysfunction of this barrier is an indicator that suggests neurodevelopmental abnormalities, injuries of various etiologies and dysfunctions within the small vessels of the brain that disrupt the calcium homeostasis. Neuroimaging shows that in patients with poor evolution, cognitive dysfunction and therapeutic resistance, the presence of choroid plexus calcification associated with hippocampal, frontal, temporoparietal and cerebellar atrophies. Antipsychotics with high capacity to block D2 dopamine receptors (haloperidol model) can aggravate apoptotic mechanisms of the brain areas involved in cognition and disrupts the functional integrity of the BBB due to decreased of choroid plexus blood flow because of the narrowing of cerebral small vessels. Choroid plexus calcification may be a predictive indicator of poor evolution or of a neurodegenerative type.

Comparative study of neuroprotective effect of tricyclics vs. trazodone on animal model of depressive disorder.

The neurobiological model of depressive disorder may be correlated with the animal model on rat, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the increase of cortisol level being specific to the model of depression in women. The neurobiological model of depression in women presents vulnerabilities for some cerebral structures (hippocampus, frontal cortex, cerebral amygdala). A decrease of frontal cortex and hippocampus volumes are recognized in depressive disorder in women, depending on duration of disease and antidepressant therapy. Neurobiological vulnerability may be pronounced through cholinergic blockade. The purpose of the study was to highlight the cytoarchitectural changes in the frontal cortex and hippocampus by comparing two antidepressant substances: amitriptyline with a strong anticholinergic effect and trazodone, without anticholinergic effect. The superior neuroprotective qualities of trazodone for the frontal cortex, hippocampus and dentate gyrus are revealed. The particular neurobiological vulnerability of depression in women requires a differentiated therapeutic approach, avoiding the use of antidepressants with anticholinergic action.