Бисфенол А, эндокринная дисфункция и патогенез шизофрении

In recent years, numerous substances have been identified as so-called ‘‘endocrine disruptors’’ because exposure to them results in disruption of normal endocrine function with possible adverse health outcomes. The pathologic and behavioral abnormalities attributed to exposure to endocrine disruptors like bisphenol-A (BPA) have been studied in animals. Mental conditions ranging from cognitive impairment to autism have been linked to BPA exposure by more than one investigation. Concurrent with these developments in BPA research, schizophrenia research has continued to find evidence of possible endocrine or neuroendocrine involvement in the disease. Sufficient information now exists for a comparison of the neurotoxicological and behavioral pathology associated with exposure to BPA and other endocrine disruptors to the abnormalities observed in schizophrenia. This review summarizes these findings and proposes a theory of endocrine disruption, like that observed from BPA exposure, as a pathway of schizophrenia pathogenesis

BPA is a common ingredient of many plastic and resin products including food and drink containers, internal linings of food cans, and dental enamels. Also known as 2,2-bis(4-hydroxyphenyl) propane, BPA was invented in the 20th century and is manufactured by combining acetone and phenol. Emerging research indicates BPA is an estrogenic EDC that alters or interferes with normal endocrine development in various vertebrate and invertebrate species.

Effects of Bisphenol-A and Other Endocrine Disruptors Compared With Abnormalities of Schizophrenia: An Endocrine-Disruption Theory of Schizophrenia

Отсутствие эффективности в РКИ: зипрасидон при биполярной депрессии и ламотриджин при депрессии

Both bipolar depression and refractory unipolar depression are highly difficult to treat. Because few randomized controlled trials (RCTs) address these conditions, clinicians often try medications either from the same class as proven-effective agents or that are effective for related conditions. These two large, well-conducted RCTs remind us that such clinical strategies may be neither sound nor effective.

What Lamotrigine and Ziprasidone Are Not Good For 

Предиктор эффективности терапии эсциталопрамом

A recent Loyola study found that the blood test for a protein called vascular endothelial growth factor (VEGF) could help predict successful treatment. The researchers found that among depressed patients who had higher than normal levels of VEGF, more than 85 percent experienced partial or complete relief after taking escitalopram (Lexapro).

 Blood Test May Predict Antidepressant Effectiveness

Ранняя диагностика шизофрении

The study of the preventive potential of pre-onset or psychosis-risk intervention requires a common and reliable diagnosis of a risk syndrome with which to construct samples that we can track and treat and that can be replicated by independent clinical investigators. Yung and McGorry10 created the Comprehensive Assessment of At-Risk Mental States (CAARMS), a structured interview for diagnosing the psychosis-risk syndrome. Our team at Yale developed the Structured Interview for Psychosis-Risk Syndromes (SIPS); this tool is used to rate the severity/frequency of key prodromal symptoms and can be used to determine the presence or absence of several psychosis-risk syndromes. It can also be used to estimate the severity of these symptoms and syndromes, including the boundary of transition from the prodrome to psychosis, called “conversion.”
The interrater reliability of the SIPS is satisfactory. Moreover, the SIPS has proved to be a valid predictor of psychosis insofar as psychosis developed over the next 2.5 years in approximately 33% of a large sample of treatment-seeking persons meeting SIPS criteria. In essence, approximately 1 of 3 persons who met an SIPS prodromal diagnosis became psychotic, which amounts to a risk for psychosis that is more than 400 times the risk for the average individual. Some of the remaining two-thirds of the sample who met an SIPS prodromal diagnosis and in whom psychosis did not develop remained prodromally symptomatic and eventually met criteria for schizotypal personality disorder; in others, Axis I disorders, such as depression, developed; and in many, prodromal symptoms remitted with time without sequelae (J. Addington et al, unpublished data, 2010).

Treatment research in psychosis risk has just begun, and initial findings show promise. Combined antipsychotic (risperidone) and individual psychotherapy, antipsychotic therapy alone (olanzapine), and psychotherapy (cognitive-behavioral therapy) alone all show that onset of psychosis in prodromal samples can be delayed, but often with substantial adverse effects (eg, weight gain with olanzapine). Most recently, a randomized trial of v-3 fatty acids delayed onset of psychosis with virtually no adverse effects. In this study, the risk to benefit ratio is remarkably good, and if the results can be replicated, they should essentially eliminate concerns about untoward adverse effects in false-positive cases. Overall, however, many more treatment studies are needed before integrated guidelines can be formulated.

Early Antecedents and Detection of Schizophrenia

Оланзапин при резистентной мании

Objective

To examine the safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania.
Method

Subjects (n = 18) who were acutely manic, did not respond to lithium, anticonvulsants, and neuroleptics, and/or had intolerable side effects to them in previous manic episodes were openly treated with olanzapine monotherapy (5–40 mg/d) for 12 weeks. The primary and secondary outcomes included the change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score, Clinical Global Impression for Bipolar Disorder-Severity Scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D) and Positive and Negative Syndrome Scale (PANSS), and response and remission rate.
Results

The mean change in YMRS total score from baseline to endpoint was −23.3 ± 8.4 (p < 0.001). Fifteen (88.5%) patients achieved response (≥50% reduction in YMRS total score) and 14 (77.8%) achieved remission (YMRS total score ≤9 at endpoint). Mean changes from baseline to endpoint in CGI-S for mania and PANSS total score were significant, but not the changes in HAM-D total score or CGI-S for depression. The most common adverse events were sedation, self-reported weight gain, ≥7% increase in body weight, dizziness, and akathisia.

Safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania: a 12-week open-label study

РКИ варениклина при шизофрении

The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the α4β2 and full agonist at the α7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2–8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline–placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p=0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p=0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p=0.008) and Stroop Interference (p=0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes.

Adjunctive Varenicline Treatment with Antipsychotic Medications for Cognitive Impairments in People with Schizophrenia: A Randomized Double-Blind Placebo-Controlled Trial

Галлюцинации

Hallucinations: Common features and causes

Ухудшение депрессивной симптоматики у группы больных в исследовании дулоксетина

New research shows that while many antidepressants help most people who take them, a small group of people who take them will actually feel more depressed than if they had just been taking a placebo or sugar pill.

 Some People Feel Worse on Antidepressants Like Cymbalta

Do Antidepressants Make Some People Worse?

Взаимодействие рецепторов серотонина и глутамата как возможный механизм психоза

Serotonin (5HT) and glutamate are two neurotransmitters. Up until now, it was thought that they acted independently. A given neuron might have receptors for both serotonin and glutamate, but they didn't interact: serotonin would never affect the glutamate receptors, and vice versa.
The new research overturns that view. Authors Miguel Fribourg and colleagues ofMount Sinai School of Medicine show, in a series of elegant experiments in mice, that different receptors can cluster together, forming a complex. The two receptors, serotonin's 5HT2A and glutamate's mGluR2, can talk to each other.

A Psychedelic Tale of Two Neurotransmitters