The Impact of Emotional Responses on Female Reproduction: Fibrinolysis in the Spotlight.

Fibrinolytic enzymes modify various substrates required for tissue remodeling, playing a crucial role in mechanisms underlying resilience, reward processing, ovulation, embryo implantation, and placentation. Individuals with low resilience and reduced reward responsiveness, when exposed to chronic stress, are at increased risk of experiencing a range of negative emotions. Chronic anxiety and melancholia are examples of negative emotions associated with hypercortisolism, while fear and atypical depression are characterized by systemic inflammation.

Silicone breast implants may contribute to early-onset fetal growth restriction.

Introduction: There are many studies showing that silicone breast implants may affect lactation, but few analyzed whether these implants affect placentation. We observed that many mothers with growth-restricted pregnancies had inflammatory conditions, such as silicone breast implants or giardiasis.

Methods: This single-center cohort study assessed the prevalence of inflammatory conditions in normotensive growth-restricted singleton pregnancies.

The Fibrinolytic System in Peripartum Depression.

The relationship between depression and reduced fibrinolytic activity reflects the role of tissue plasminogen activator and plasmin in brain remodeling underlying resilience, depression remission, and reward processing, rather than the dissolution of fibrin clots. Individuals who experience depression demonstrate hippocampal and prefrontal cortex atrophy, as well as impaired neuronal connectivity. Brain-derived neurotrophic factor (BDNF), synthesized as a precursor that is activated through cleavage by tissue plasminogen activator and plasmin, influences adult neurogenesis and neuronal plasticity in the hippocampus and prefrontal cortex.

Mechanisms affecting brain remodeling in depression: do all roads lead to impaired fibrinolysis?

Fibrinolysis occurs when plasminogen activators, such as tissue plasminogen activator (tPA), convert plasminogen to plasmin, which dissolves the fibrin clot. The proteolytic activity of tPA and plasmin is not restricted to fibrin degradation. In the extravascular space, these two proteases modify a variety of substrates other than fibrin, playing a crucial role in physiological and pathological tissue remodeling.

Panic Disorder and Chronic Caffeine Use: A Case-control Study.

Background: Acute administration of caffeine produces panic attacks in most Panic Disorder (PD) patients, but little is known about chronic caffeine use in these patients.

Objective: To assess caffeine use in patients with PD and to ascertain if caffeine consumption is associated with sociodemographic or clinical features.

Methods: 65 adults with PD and 66 healthy controls were included in the current study.

Antidepressants: bleeding or thrombosis?

The contribution of depression to the pathogenesis of cardiovascular disease includes autonomic disturbances, endothelial dysfunction, inflammation, smoking, sedentary lifestyle, carbohydrate craving, and impaired fibrinolysis. There is evidence that serotonergic antidepressants (selective serotonin reuptake inhibitors and serotonin and noradrenaline reuptake inhibitors) restore the fibrinolytic profile. Contrary to common belief, such antidepressants do not affect platelet aggregation induced by adenosine diphosphate or adrenaline but reduce platelet adhesion to collagen.

Autism spectrum disorders: let's talk about glucose?

Autism spectrum disorders (ASD) are characterized by disconnectivity due to disordered neuronal migration, and by neuronal mitochondrial dysfunction. Different pathways involved in neuronal migration are affected by intrauterine hyperglycemia and hyperinsulinemia, while prolonged neonatal hypoglycemia may cause mitochondrial dysfunction. Our hypothesis was that conditions leading to intrauterine hyperglycemia or neonatal hypoglycemia would influence ASD pathogenesis.

Anxiety-Related Bleeding and Thrombosis.

Anxiety, a normal response to stressful situations, is characterized by increased levels of factor VIII, fibrinogen, and von Willebrand factor, and by enhanced platelet aggregability. One would expect acute anxiety to be a prothrombotic state, but since acute mental stress induces tissue plasminogen activator (tPA) release from endothelial and chromaffin cells, fibrinolysis counteracts procoagulant stimuli. It could be said that procoagulant changes accompanying the fight-or-flight response reduce the risk of bleeding in case of potential injuries, while activation of fibrinolysis counteracts activation of hemostasis to prevent intravascular thrombus formation before injuries occur.

May maternal lifestyle have an impact on neonatal glucose levels?

Neonatal glucose levels correlate negatively with umbilical cord levels of C-peptide, a polypeptide secreted with insulin. In other words, neonatal hypoglycemia results from excessive insulin secretion from fetal/neonatal beta cells. Given that insulin causes fat to be stored rather than to be used for energy, one would expect that chronic hyperinsulinemia would result in large-for-gestational-age neonates.

Improvement of Psychotic Symptoms and the Role of Tissue Plasminogen Activator.

Tissue plasminogen activator (tPA) mediates a number of processes that are pivotal for synaptogenesis and remodeling of synapses, including proteolysis of the brain extracellular matrix, degradation of adhesion molecules, activation of neurotrophins, and activation of the N-methyl-d-aspartate receptor. Abnormalities in these processes have been consistently described in psychotic disorders. In this paper, we review the physiological roles of tPA, focusing on conditions characterized by low tPA activity, which are prevalent in schizophrenia.

Adverse obstetric and neonatal outcomes in women with mental disorders.

The brain and the placenta synthesize identical peptides and proteins, such as brain-derived neurotrophic factor, oxytocin, vascular endothelial growth factor, cortisol, and matrix metalloproteinases. Given the promiscuity between neurochemistry and the mechanism of placentation, it would be expected that mental disorders occurring during pregnancy would increase the risk of adverse obstetric and neonatal outcomes. Indeed, expectant mothers with anxiety disorders, post-traumatic stress disorder, schizophrenia, or depressive disorders are at higher risk of preterm birth, low-birth-weight and small-for-gestational-age infants than controls.

Low activity of plasminogen activator: a common feature of non- iatrogenic comorbidities of schizophrenia.

Understanding the pathogenesis of non-iatrogenic comorbidities of schizophrenia may provide insights into the pathogenesis of schizophrenia itself. First-episode, drug-naïve schizophrenia patients are at high risk of thromboembolic events, diseases related to substance abuse, sexual dysfunction, reproductive disorders, inflammatory and autoimmune diseases, as well as complications of hyperinsulinemia or hyperhomocysteinemia. This review focuses on the role of reduced plasminogen activator activity in non-iatrogenic comorbidity of schizophrenia.

A role for tissue plasminogen activator in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by generalized microvascular occlusion. TTP has been related to severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor multimers into less adhesive molecules. However, ADAMTS13 deficiency correlates poorly with severity of thrombocytopenia or microangiopathic hemolysis, with the frequency of neurologic complications or the response to plasma exchange.

Coagulation and mental disorders.

The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders.

Markers of low activity of tissue plasminogen activator/plasmin are prevalent in schizophrenia patients.

Introduction: Clot buster tissue plasminogen activator (tPA) and its end-product plasmin play a well-defined role in neurochemistry. They mediate a number of events that culminate in tolerance against excitotoxicity, hippocampal neurogenesis, synaptic remodeling, neuronal plasticity, cognitive and emotional processing. Abnormalities in these processes have been implicated in schizophrenia pathogenesis.

Are the antiplatelet and profibrinolytic properties of selective serotonin-reuptake inhibitors relevant to their brain effects?

The serotonin transporter (SERT) is found in neuron and platelet membranes. Selective serotonin-reuptake inhibitors (SSRIs) are widely prescribed for severe depression. They may at least partly counteract the effects of serotonin on the vascular biology system, can lower agonists-induced platelet activation, aggregation and procoagulant activity in vitro, thus modulating platelet thrombogenicity.

Mental disorders and thrombotic risk.

Patients with psychosis, severe depression, or chronic stress are at increased risk for thromboembolism. Evidence suggests that tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) imbalance may play an important role in pathophysiology of mental and thromboembolic disorders. tPA facilitates clot dissolution and participates in several brain functions, including response to stress, learning, and memory.

Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy.

Electroconvulsive therapy is an important treatment option for major depressive disorders, acute mania, mood disorders with psychotic features, and catatonia. Several hypotheses have been proposed as electroconvulsive therapy's mechanism of action. Our hypothesis involves many converging pathways facilitated by increased synthesis and release of tissue-plasminogen activator.

Multiple roles of tissue plasminogen activator in schizophrenia pathophysiology.

Schizophrenia, a disabling mental disorder, is characterized by brain atrophy, especially in the superior temporal gyrus and the medial temporal lobe, which includes the hippocampus and the amygdala. The model that better explains brain atrophy includes a trigger and a predisposing condition. The trigger is exemplified by illicit drugs or environmental stressors that promote release of substances harmful to the neurons, such as glucocorticoids or noradrenalin.

Psychiatric remission with warfarin: Should psychosis be addressed as plasminogen activator imbalance?

Background: Psychotic patients are at increased risk of thromboembolism that cannot be ascribed to physical restraint or medication. Patients with chronic schizophrenia or long-term depressive illness do not display ischemic brain injuries on magnetic resonance imaging, as expected in patients with thrombotic tendency, but atrophy of specific brain regions, which indicates abnormal neuronal plasticity.

Hypotheses: We postulate that a relationship between psychosis pathophysiology and thrombotic tendency may comprise proteins that participate not only in the anticoagulation-fibrinolysis mechanism, but also in neuronal plasticity.