Default mode and task-positive networks connectivity during the N-Back task in remitted depressed patients with or without emotional residual symptoms.

Clinical remission of depression may be associated with emotional residual symptoms. We studied the association of emotional blunting, rumination with neural networks dynamics in remitted depressed patients and cognitive performance during an N-Back task. Twenty-six outpatients in remission of depression (Hamilton Depressive rating scale score <7) performed an N-Back task during fMRI assessment. All patients had been treated by paroxetine for a minimum of 4 months. Two subgroups of patients [Nonemotionally blunted (NEB) = 14 and emotionally blunted (EB) = 12] were determined. To identify functional network maps across participants, the Network Detection using Independent Component Analysis approach was employed. Within and between Task Positive Network (TPN) and Default Mode Network (DMN) connectivity were assessed and related to variability of performance on the N-Back task and rumination. EB and NEB patients were not different for the level of accurate responses at the N-Back. However over the entire working memory task, the negative correlation between DMN and TPN was significantly lower in the EB than NEB group and was differently related to cognitive performance and rumination. The stronger the negative correlation between DMN and TPN was, the less variable the reaction time during 3-Back task in NEB patients. Moreover the greater the negative correlation between DMN and TPN was, the lower the rumination score in EB patients. Emotional blunting may be associated with compromised monitoring of rumination and cognitive functioning in remitted depressed patients through altered cooperation between DMN and TPN. The study suggests clinical remission in depression is associated with biological heterogeneity. Hum Brain Mapp 38:3491-3501, 2017. © 2017 Wiley Periodicals, Inc.

Urban environment and psychiatric disorders: a review of the neuroscience and biology.

Most of the world's population now lives in cities. While living in cities have both health risks and benefits, mental health has been usually considered to be negatively affected by urbanicity. While mental health disorders have complex etiology and multiple causes, it has been shown in multiple observational studies that mood and anxiety disorders are more prevalent in urban centers and incidence has been increasing. In addition, the incidence of schizophrenia is strongly increased in people born and raised in cities. Studies on the effects of urbanicity on the brain, however, are more challenging to conduct, since individual and environmental factors are hard to distinguish. The main objective of this article is to review studies on how specific neural processes mediate those associations between urbanicity and psychiatric disorders and how environmental factors affect genetic regulation (epigenetics). Neuroimaging studies have shown how urban stressors might affect the brain by conducting experiments using functional magnetic resonance imaging (fMRI). There have been demonstrations that urban upbringing and city living have dissociable impacts on social evaluative stress processing in humans. City living was associated with increased amygdala activity and the urban upbringing has been shown to affect the perigenual anterior cingulate cortex, a key region for regulation of amygdala activity, negative affect and stress. In addition, studies on epigenetics have shown associations between exposure to features of the environment and methylation patterns. The goal of understanding how urban environments act as a risk factor for mental disorders may be pursued on several levels. It can be approached by measuring the effects of economic factors (unemployment, socioeconomic status), social condition (social network support), environmental exposures (toxins, air pollution, noise, light), that must be weighed to identify how it contributes to mental disorders.

A pathophysiological paradigm for the therapy of psychiatric disease.

Despite enormous progress in fundamental knowledge in neuroscience, no revolutionary therapies in psychiatry (and neurology) have emerged in the past ten years. Most drugs alleviate symptoms, rather than restoring the 'set point' of brain function from a pathological position to a more normal one. We propose a hypothesis-driven, systems-level approach to drug discovery and development that is based on pathophysiology and which uses new animal models.

The future of psychiatry: brain devices.

Recent advances in deep brain stimulators and brain-machine interfaces have greatly expanded the possibilities of neuroprosthetics and neuromodulation. Together with advances in neuroengineering, nanotechnology, molecular biology and material sciences, it is now possible to address fundamental questions in neuroscience in new, more powerful ways. It is now possible to apply these new technologies in ways that range from augmenting and restoring function to neuromodulation modalities that treat neuropsychiatric disorders. Recent developments in neuromodulation methods offer significant advantages and potential clinical benefits for a variety of disorders. Here we describe the current state of the art in neuromodulation methods, and some advances in brain-machine interfaces, describing the advantages and limitations of the clinical applications of each method. The future applications of these new methods and how they will shape the future of psychiatry and medicine, along with safety and ethical implications, are also discussed.

Sleep disorders in psychiatry.

Sleep is an active state that is critical for our physical, mental, and emotional well-being. Sleep is also important for optimal cognitive functioning, and sleep disruption results in functional impairment. Insomnia is the most common sleep disorder in psychiatry. At any given time, 50% of adults are affected with 1 or more sleep problems such as difficulty in falling or staying asleep, in staying awake, or in adhering to a consistent sleep/wake schedule. Narcolepsy affects as many individuals as does multiple sclerosis or Parkinson disease. Sleep problems are especially prevalent in schizophrenia, depression, and other mental illnesses, and every year, sleep disorders, sleep deprivation, and sleepiness add billions to the national health care bill in industrialized countries. Although psychiatrists often treat patients with insomnia secondary to depression, most patients discuss their insomnia with general care physicians, making it important to provide this group with clear guidelines for the diagnosis and management of insomnia. Once the specific medical, behavioral, or psychiatric causes of the sleep problem have been identified, appropriate treatment can be undertaken. Chronic insomnia has multiple causes arising from medical disorders, psychiatric disorders, primary sleep disorders, circadian rhythm disorders, social or therapeutic use of drugs, or maladaptive behaviors. The emerging concepts of sleep neurophysiology are consistent with the cholinergic-aminergic imbalance hypothesis of mood disorders, which proposes that depression is associated with an increased ratio of central cholinergic to aminergic neurotransmission. The characteristic sleep abnormalities of depression may reflect a relative predominance of cholinergic activity. Antidepressant medications presumably reduce rapid eye movement (REM) sleep either by their anticholinergic properties or by enhancing aminergic neurotransmission. Intense and prolonged dreams often accompany abrupt withdrawal from antidepressant drugs, a reflection of an REM rebound after drug-induced REM deprivation. The postulated link between sleep and psychiatric disorders has been reinforced by the findings of modern neurobiology.

[Brain aging, biological and psychosocial aspect]. / Vieillissement cérébral, aspects biologiques et psychosociaux.

The world population is aging The frontier between physiological and pathological brain aging is somewhat unclear. Pathological aging can cause both mild cognitive impairments and dementias (vascular and Alzheimer). It is important to understand brain aging in order to identify risk factors and develop protective measures. Proper lifetime brain protection could improve quality of life in old age.

Biomarkers of psychiatric diseases: current status and future prospects.

Abnormal behavior and disturbed cognition, often assumed to represent psychiatric illness, may actually result from some form of occult organic brain disease that can be detected by means of one or more biomarkers. This truth was discovered more than a century ago by Aloysius Alzheimer, a German psychiatrist and neuropathologist. As a psychiatrist, he described the behavioral manifestations of "senile dementia" in a 51-year-old female; as a neuropathologist, he was the first to recognize the significance of the senile plaques and neurofibrillary tangles found in her brain after her death at age 55 years. It was Alzheimer who made the connection between these "biomarkers" and the symptoms of the increasingly prevalent disease that now bears his name. In recent years, the search for psychiatry-relevant biomarkers of major depression, schizophrenia, bipolar disease, and other important psychiatric/neuropsychiatric disorders has intensified. Biomarkers in psychiatry and neuropsychiatry have the potential of clarifying the etiology of an ambiguous clinical presentation-making it possible, for example, to detect underlying differences between psychological maladies that have confusingly similar symptoms. In addition, attempts are now being made to classify mental disorders on the basis of biomarkers. Biomarkers may also disclose the presence of a previously unsuspected physical explanation for behavior(s) originally presumed to be "psychiatric" in origin. Although clinically usable biomarkers in the diagnosis and treatment of mental illness await validation, candidate genomic biomarkers and protein profiling of candidate biomarkers in psychiatry are rapidly gaining ground as areas of interest, with considerable future potential. This review considers biomarker-related issues germane to psychiatry and neuropsychiatry in the context of new data that can be used to tailor therapies to the individual psychiatric patient.

From restoration of neuroplasticity to the treatment of depression: clinical experience.

The adult brain has more plasticity than previously believed. Neurogenesis, growth and branching of dendrites, and remodeling of synaptic contacts in different regions of the brain occur continuously. Numerous studies have reported a decrease in neuroplasticity in depressed patients and/or in animals subjected to stress and to different models of depression. This has led to the proposal of a new approach to the pathophysiology of depression: depression could be the result of the decrease in neuroplasticity in brain structures involved in the control of mood. This new approach to the pathophysiology of depression can lead to better understanding of, or the proposal of more solid hypotheses about, some issues such as the impact of genetics and environmental factors on the occurrence of depressive episodes, the increased risk of depression in patients with somatic diseases in which there are alterations of neuroplasticity, or the increased risk of depressive relapse in depressed patients in partial remission in whom we suspect that neuroplasticity is only partially restored. These observations have also led to the proposal of new hypotheses concerning the mode of action of antidepressant drugs. In this regard, tianeptine is of particular interest. Tianeptine's pharmacological and clinical properties have been extensively studied. Tianeptine has specific neurotrophic properties, and its antidepressant properties have been well demonstrated. Tianeptine provides early relief of anxious symptoms without sedation in depressed patients. The acceptability and safety profiles of tianeptine are appreciated by both physicians and patients; for instance, tianeptine does not induce sexual dysfunction, nausea, or weight gain. It is of interest to focus on what we already know about tianeptine's pharmacological and clinical properties, and to create mechanistic hypotheses about the similarities and differences observed in clinical practice between tianeptine and other antidepressants.

Personalized medicine in psychiatry: new technologies and approaches.

Psychiatric patients tend to exhibit significant interindividual variability in their responses to psychoactive drugs, as well as an irregular clinical course. For these (and other) reasons, increasing numbers of psychiatrists are turning to genotyping for help in selecting the psychopharmacologic agents best suited to an individual patient's distinctive metabolic characteristics and clinical presentation. Fortunately, routine genotyping is already available for gene variations that code for proteins involved in neurotransmission, and for drug-metabolizing enzymes involved in the elimination of many medications. Thus, genotyping-based personalized psychiatry is now in sight. Increasing numbers of clinically useful DNA microarrays are in the development stage, including a simplified procedure for genotyping patients for CYP2D6, which metabolizes a high proportion of the currently prescribed antidepressants and antipsychotics. It has been pointed out that psychiatric disease is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of complex intracellular networks in the brain. Thus, analysis of functional neuronal networks is becoming an essential component of drug development strategies. The integrated use of technologies such as electroencephalography, magnetoencephalography, functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI), in combination with pharmacogenetics, promises to transform our understanding of the mechanisms of psychiatric disorders and their treatment. The concept of network medicine envisions a time to come when drugs will be used to target a neural network rather than simply components within the network. Personalized medicine in psychiatry is still at an early stage, but it has a very promising future.

Autism, a brain developmental disorder: some new pathopysiologic and genetics findings.

Autism is a severe neurodevelopmental disorder that is typically diagnosed by 3 years of age. Core symptoms of autism include profound deficits in social interaction and communication, restricted interests, stereotyped responses, and other repetitive patterns of behavior. Other abnormalities include mental retardation and comorbid epilepsy. These symptoms underscore the consequences of genetic inheritance for brain function and behavior. The etiology of autism may involve an interaction between genetic susceptibility (mediated by multiple genes) and environmental factors influencing brain development.

Decanoato de haloperidol: um novo neuroléptico de açäo prolongada no tratamento de manutençäo de pacientes esquizofrênicos / Haloperidol decanoate: a new neuroleptic of prolonged action in maintenance treatment of schizophrenic patients

Os autores estudaram 29 pacientes esquizofrênicos crônicos e hospitalizados, sob tratamento com neurolépticos por via oral, nos quais esta medicaçäo foi substituída por decanoato de haloperidol, por via intramuscular aplicada a cada quatro semanas. Os pacientes foram avaliados, antes, durante e após o tratamento, através da BPRS, escala clínica global e escala de efeitos colaterais de BORDELEAU. A grande maioria dos pacientes recebeu 100mg IM cada quatro semanas, equivalente, aproximadamente, a 20 vezes a dose diária de haloperidol ou dose correspondente de outro neuroléptico. Concluíram que o decanoato de haloperidol, administrado nestas condiçöes, mostrou-se um medicamento seguro e eficaz, tornando-se uma opçäo prática e confortável para o tratamento de manutençäo de esquizofrênicos crônicos

Tratamento a longo prazo de pacientes psicóticos com a risperidona: um estudo brasileiro multicêntrico aberto / Long-term treatment of psychotic patients with risperidone: an open Brazilian multicentre study

Em um estudo aberto multicêntrico, 154 esquizofrênicos (DSM-III - R) com um escore total > 60 na PANSS foram tratados durante 7 meses com a risperidona depois de um período de "wash-out". As doses foram aumentadas até 3 mg duas vezes por dia na primeira semana e de forma flexível, de acordo com a ICG, a dose podia ser aumentada até 16 mg/dia no final do primeiro mês. A partir daí, foi recomendado manter-se dose estável nos próximos 6 meses do tratamento. Os parâmetros de eficácia foram: ICG aplicada mensalmente e PANSS aplicada nos meses 1, 4 e 7. A segurança da risperidona foi avaliada por meio de exame físico, testes laboratoriais, ECG e sinais vitais (PS,PD e FC). As reaçoes adversas foram registradas em todas as visitas do estudo, os sintomas extrapiramidais (SEP) foram avaliados segundo a Extrapyramidal Symptom Rating Scale (ESRS) e também ICG para gravidade de parkinsonismo e discinesia. Cerca de 77 porcento dos pacientes completaram o estudo e em apenas 9 porcento o térmico precoce foi atribuído a falta de eficácia. De uma maneira geral, a risperidona foi eficaz (diminuiçao da sintomatologia > 20 porcento) em cerca de 70 porcento dos pacientes. As reaçoes adversas mais freqüentes foram insônia (14,1 porcento ) e ganho de peso (10,9 porcento). A risperidona nao causou nenhuma alteraçao importante nos testes laboratoriais realizados antes do início e no final do tratamento. Durante o período de tratamento houve uma diminuiçao dos SEP apesar de ter havido um aumento da dose média diária. Isto foi atribuído à tolerância. A dose ótima foi de 6 a 8 mg/dia, contudo, para alguns pacientes mais pode ser necessário se aumentar a dose. Em conclusao, nossos dados sugerem que a risperidona é um medicamento seguro, tem um rápido início de açao e na dose média de 6 a 8 mg/dia foi eficaz tanto em sintomas positivos como negativos; a resposta terapêutica tende a aumentar ao longo do tratamento enquanto que os SEP, além de poucos, mant6em-se estáveis ou tendem a diminuir.