One-Year Follow-Up of Healthy Older Adults with Electroencephalographic Risk for Neurocognitive Disorder After Neurofeedback Training.

BACKGROUND: In healthy older adults, excess theta activity is an electroencephalographic (EEG) predictor of cognitive impairment. In a previous study, neurofeedback (NFB) treatment reinforcing reductions theta activity resulted in EEG reorganization and cognitive improvement. OBJECTIVE: To explore the clinical applicability of this NFB treatment, the present study performed a 1-year follow-up to determine its lasting effects. METHODS: Twenty seniors with excessive theta activity in their EEG were randomly assigned to the experimental or control group. The experimental group received an auditory reward when the theta absolute power (AP) was reduced. The control group received the reward randomly. RESULTS: Both groups showed a significant decrease in theta activity at the training electrode. However, the EEG results showed that only the experimental group underwent global changes after treatment. These changes consisted of delta and theta decreases and beta increases. Although no changes were found in any group during the period between the posttreatment evaluation and follow-up, more pronounced theta decreases and beta increases were observed in the experimental group when the follow-up and pretreatment measures were compared. Executive functions showed a tendency to improve two months after treatment which became significant one year later. CONCLUSION: These results suggest that the EEG and behavioral benefits of this NFB treatment persist for at least one year, which adds up to the available evidence contributing to identifying factors that increase its efficacy level. The relevance of this study lies in its prophylactic features of addressing a clinically healthy population with EEG risk of cognitive decline.

LncRNA-MYL2-2 and miR-124-3p Are Associated with Perioperative Neurocognitive Disorders in Patients after Cardiac Surgery.

BACKGROUND: Perioperative neurocognitive disorders (PND) resulting from cardiac surgery is a complication with high morbidity and mortality. However, the pathogenesis is unknown. METHODS: For the sake of investigating the risk factors and mechanism of PND, we collected the characteristics and neurological scores of patients undergoing cardiac surgery in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and Affiliated Hospital of Southwest Medical University from Jan 1, 2016 to Dec 11, 2018. RESULTS: We found that age and left atrial thrombus are independent risk factors for PND after cardiac surgery. Furthermore, the serum of 29 patients was collected on the 7th day after cardiac surgery for detecting the expression of lncRNA-MYL2-2 and miR-124-3p. Increased lncRNA-MYL2-2 and decreased miR-124-3p in serum were associated with the decline of patients' cognition. CONCLUSIONS: LncRNA-MYL2-2 and miRNA-124-3p may jointly participate in the occurrence and development of PND after cardiac surgery. These important findings are advantaged to further understand the pathogenesis of PND and prevent it, provide new biomarkers for the diagnosis and monitoring of PND.

Comparison of two electronic screening tests (culturally neutral & culturally customized) for major and minor neurocognitive disorders.

INTRODUCTION: While attempting to test the population for Mild and Major Neurocognitive Disorders (M. - M. N.D.) there are tests in conventional and electronic form which are applied. However, a large proportion of elderly avoids being tested as the process itself causes stress and fatigue. The structure of the tests is often irrelevant to the experiences and life of the elderly as it focuses on the standard arraying of the diagnostic criteria. OBJECTIVES: A) the introduction of a culturally oriented screening test based on folk tradition. B) exploiting the advantages of technology in an electronic version of this test, in order: To be administered by non-specialist and/or people of the elderly's environment. To be given to people with sensory impairments of vision or hearing - speech. METHODOLOGY: 1. Automation of the delivery and evaluation process in order to avoid the bias effect due to differences between examiners. Use of multimedia and innovative interfaces. 2. Application of the electronic version to a sample of 300 people of both sexes and 60+ years old. The evaluation of the culturally customized test will be done on the following axes: Metric Capacity in detection of Major and Mild ND. For this case, the reference point are normalized screening tests. Evaluation of usability and acceptance by examinees, examiners, caregivers and health professionals using normalized tools and interviews. 3. Comparative study with an electronic state-of-the-art screening test (TAB CAT) for M-MND in a sample of 120 individuals aiming in comparing the tests for ease of use and acceptance by the test subjects.All participants will be from 60 years old and above, having the Greek language as native language, without any limitations on the educational level. Participants will be divided into 3 groups according to their diagnosis (normal, Mild ND, Major ND) Expected Benefits: The potential effectiveness of the innovative screening method for Mild - Major ND is expected to increase the number of elderlies who treated for neurocognitive impairment while reducing examination costs.

Guided meditation as an adjunct to enhance postoperative recovery after cardiac surgery: study protocol for a prospective randomized controlled feasibility trial.

BACKGROUND: Cardiac surgical procedures are associated with postoperative neurological complications such as cognitive decline and delirium, which can complicate recovery and impair quality of life. Perioperative depression and anxiety may be associated with increased mortality after cardiac surgeries. Surgical prehabilitation is an emerging concept that includes preoperative interventions to potentially reduce postoperative complications. While most current prehabilitation interventions focus on optimizing physical health, mind-body interventions are an area of growing interest. Preoperative mind-body interventions such as Isha Kriya meditation, may hold significant potential to improve postsurgical outcomes. METHODS: This is a prospective, randomized controlled feasibility trial. A total of 40 adult patients undergoing cardiac surgery will be randomized to one of three study groups. Participants randomized to either of the two intervention groups will receive meditative intervention: (1) commencing two weeks before surgery; or (2) commencing only from the day after surgery. Meditative intervention will last for four weeks after the surgery in these groups. Participants in the third control group will receive the current standard of care with no meditative intervention. All participants will undergo assessments using neurocognitive, sleep, depression, anxiety, and pain questionnaires at various time points in the perioperative period. Blood samples will be collected at baseline, preoperatively, and postoperatively to assess for inflammatory biomarkers. The primary aim of this trial is to assess the feasibility of implementing a perioperative meditative intervention program. Other objectives include studying the effect of meditation on postoperative pain, sleep, psychological wellbeing, cognitive function, and delirium. These will be used to calculate effect size to design future studies. DISCUSSION: This study serves as the first step towards understanding the feasibility of implementing a mind-body intervention as a prehabilitative intervention to improve postoperative surgical outcomes after cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03198039 . Registered on 23 June 2017.

Mindfulness-Based Stress Reduction for Older Adults With Stress Disorders and Neurocognitive Difficulties: A Randomized Controlled Trial.

OBJECTIVE: To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints. To explore decreased hypothalamic-pituitary-adrenal (HPA) axis activity as a possible mechanism. METHODS: 103 adults aged 65 years or older with an anxiety or depressive disorder (diagnosed according to DSM-IV criteria) and subjective neurocognitive difficulties were recruited in St. Louis, Missouri, or San Diego, California, from September 2012 through August 2013 and randomly assigned in groups of 5-8 to mindfulness-based stress reduction (MBSR) or a health education control condition matched for time, attention, and credibility. The primary outcomes were memory (assessed by immediate and delayed paragraph and list recall) and cognitive control (Delis-Kaplan Executive Function System Verbal Fluency Test and Color Word Interference Test). Other outcomes included clinical symptoms (worry, depression, anxiety, and global improvement). HPA axis activity was assessed using peak salivary cortisol. Outcomes were measured immediately post-intervention and (for clinical outcomes only) at 3- and 6-month follow up. RESULTS: On the basis of intent-to-treat principles using data from all 103 participants, the mindfulness group experienced greater improvement on a memory composite score (P = .046). Groups did not differ on change in cognitive control. Participants receiving MBSR also improved more on measures of worry (P = .042) and depression (P = .049) at posttreatment and on worry (P = .02), depression (P = .002), and anxiety (P = .002) at follow-up and were more likely to be rated as much or very much improved as rated by the Clinical Global Impressions-Improvement scale (47% vs 27%, χ² = 4.5, P = .03). Cortisol level decreased to a greater extent in the mindfulness group, but only among those participants with high baseline cortisol. CONCLUSIONS: In this population of older adults with stress disorders and neurocognitive difficulties, a mindfulness intervention improves clinical outcomes such as excessive worry and depression and may include some forms of immediate memory performance. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01693874.

A retrospective classification of diagnoses in terms of DSM-5 for patients included in randomized controlled trials of Ginkgo biloba extract EGb 761(®).

When the early trials of Ginkgo biloba extract EGb 761(®) were conducted, different terms were used to denote ageing-associated neurocognitive disorders. With the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a taxonomy covering dementia and pre-dementia stages of such disorders became available. DSM-5 diagnostic criteria for neurocognitive disorders (NCDs) were applied to patients with any type of ageing-associated cognitive impairment, including dementia, enrolled in randomized controlled clinical trials of EGb 761(®), taking into account the reported inclusion and exclusion criteria and patient characteristics at baseline. For 23 of 31 trials (74 %), the inclusion diagnoses could be classified as NCD in accordance with DSM-5. Thirteen trials enrolled patients with major NCD, four trials enrolled patients with mild NCD and six trials enrolled patients with NCD, who could not be classified unambiguously as having mild or major NCD. Although various terms were formerly used for neurocognitive disorders, the patients enrolled in the majority of clinical trials with EGb 761(®) could be classified retrospectively using modern DSM-5 diagnostic criteria.

Delirium em idosos em unidades de terapia intensiva: revisão integrativa da literatura / Delirium en ancianos en unidades de cuidados intensivos: revisión integradora de la literatura / Delirium in the elderly in intensive care units: an integrative literature review

Objective: conducting a survey about delirium in the elderly in an Intensive Care Unit (ICU). Method: an integrative review of the literature held in databases MEDLINE and IBECS, in May 2012, whose inclusion criteria were: to be published between May 2007 to May 2012, available in full and in Portuguese, English and Spanish. Results: there were found 68 productions and selected 16, which were categorized into: 1) Incidence and prevalence of delirium in the elderly in ICU; 2) Factors predisposing and precipitating risk of delirium in the elderly in ICU and 3) Strategies for preventing modifiable risk factors of delirium in the elderly patients in the ICU. Conclusion: the scientific production about delirium is incipient in Brazil,health professionals, especially nurses, need to improving the recognition of this syndrome and implementing strategies for risk prevention factors for delirium.

Objetivo: realizar um levantamento acerca do delirium em idosos em Unidade de Terapia Intensiva (UTI). Método: revisão integrativa da literatura, nas bases de dados MEDLINE e IBECS, em maio de 2012, cujos critérios de inclusão foram publicados entre maio de 2007 a maio de 2012, com disponibilidade na íntegra,e nos idiomas português, inglês e espanhol. Resultados: foram encontradas 68 produções e selecionadas16, as quais foram categorizadas em: 1) Incidência e prevalência de delirium em Idosos na UTI; 2) Fatores de risco precipitantes e predisponentes do delirium em idosos na UTI e 3) Estratégias de prevenção de fatores de risco modificáveis do delirium em idosos nas UTIs. Conclusão: a produção científica acerca do delirium no Brasil é incipiente, os profissionais de saúde, especialmente os da enfermagem, necessitam melhorar o reconhecimento desta síndrome e implementar estratégias de prevenção dos fatores de risco para delirium.

Objetivo: realizar un estudio acerca del delirium en los ancianos en la Unidad de Cuidados Intensivos (UCI). Método: revisión integradora en bases de datos MEDLINE e IBECS, en mayo de 2012, cuyos criteriosde inclusión fueron: ser publicados entre mayo 2007 a mayo 2012, disponible en su totalidad en portugués, inglés y español. Resultados: se encontraron 68 producciones y seleccionadas 16, que fueron clasificadas en: 1) Incidencia y prevalencia de delirium en ancianos en la UCI; 2) Factores de riesgo precipitantes y predisponentes del delirium en ancianos en la UCI y 3) Estrategias de prevención de factores de riesgo modificables del delirium en ancianos en las UCI. Conclusión: la producción científica acerca del delirio es incipiente en Brasil, los profesionales de la salud, especialmente las enfermeras, tienen que mejorar el reconocimiento de este síndrome y poner en práctica estrategias para prevenir los factores de riesgo para el delirium.

[Psychotic disorder induced by Fahr's syndrome: a case report]. / Trouble psychotique secondaire à un syndrome de Fahr: à propos d'une observation.

UNLABELLED: Fahr's syndrome is a rare disorder characterized by abnormal deposits of calcium in areas of the brain that control movement, including the basal ganglia and the cerebral cortex associated with many neurological and psychiatric abnormalities such as a rigid hypokinetic syndrome, mood disorders and cognitive impairment. Fahr's syndrome is secondary to some disorders, such as hypoparathyroidism. CASE REPORT: We report the case of a 56 year-old man, with a history of cataract, who was admitted to our psychiatric hospital for the first time in his life because of psychotic symptoms associated with irritability and aggressiveness. Since the age of 38 the patient had become nervous, 10 years later he developed tonic-clonic seizures. Two months ago, he began expressing delusions of persecution against his wife and sons and making fugues. According to his family during this period, he was agitated, aggressive, and suffered from insomnia and anorexia. The general and psychiatric examination showed an upright and bronzed patient with neglected hygiene. He was indifferent to his environment and expressed poor mimics and gestures. He was anxious, suspicious and not very talkative. He was conscious but his attention was slightly decreased. Moreover, he was not aware of his problems. The neurological examination showed extrapyramidal syndrome with postural tremor and cerebellar ataxia. A cranial computed tomography brain scan found bilateral, symmetric basal ganglia calcifications, in favour of Fahr's syndrome. Phosphocalcic investigations revealed low concentration of serum calcium at 1.01mmol/L (normal 2.15 to 2.57mmol/L) and hyperphosphoremia at 2.69mmol/L (normal 0.81 to 1.55mmol/L). He also had low concentrations of 25-OH vitamin as well as decreased urinary levels of phosphate and calcium. The blood level of parathyroid hormone was 0ng/L. The diagnosis of Fahr's syndrome, revealing a hypoparathyroidism was posed. He was supplemented with calcium and alpha cholecalciferol and treated with clozapine (100mg per day). After four weeks, psychotic symptoms responded well to this treatment without expressing any side effects, notably seizures. DISCUSSION: Psychotic symptoms seen in Fahr's disease include auditory and visual hallucinations, complex perceptual distortions, delusions, and fugue state. Some of them were manifest in this patient. It is likely that the psychosis in both Fahr's disease and schizophrenia share a similar pathology. Positive psychotic symptoms, hallucinations, and paranoia are not necessarily generated by the classical hypothesis of dopamine-mediated attachment of salience to internally generated stimuli. Still, there is some evidence that disruption of the cortex involved in the pathophysiology of schizophrenia is also seen in Fahr's disease, particularly in areas of the limbic system. CONCLUSION: Psychiatrists should consider Fahr's syndrome as a differential diagnosis in the evaluation of psychosis associated with seizures. This case, along with others in the literature, further emphasizes the importance of the role of neuro-imaging and the search for disrupted phosphocalcic metabolism in patients with atypical psychotic symptoms. Moreover, further research should focus on pharmacologic interventions. The efficacy and risks of neuropharmacologic and psychopharmacologic interventions in Fahr's syndrome, and correlates of good and poor outcome with these interventions remain to be defined.

Issues related to symptomatic and disease-modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy.

Many symptoms of neurologic or psychiatric illness--such as cognitive impairment, depression, anxiety, attention deficits, and migraine--occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure.

Psychiatric symptoms in systemic lupus erythematosus: a systematic review.

OBJECTIVE: Systemic lupus erythematosus (SLE) presents with psychiatric symptoms in most patients that often remain undiagnosed and untreated. This study evaluates the prevalence of psychiatric symptoms in SLE on the basis of clinical trials that fulfilled diagnostic criteria specified by the American College of Rheumatology (ACR). Current hypotheses explaining the pathogenesis of psychiatric symptoms of lupus are reviewed to gain new insights into the neuroimmune pathogenesis of other psychiatric disorders. DATA SOURCE: A MEDLINE search of the literature (English language only) from April 1999 to August 2011 was performed using the search terms lupus and psychiatric to identify studies of neuropsychiatric SLE. STUDY SELECTION: Of 163 publications, 18 clinical studies were selected that focused on psychiatric symptoms, had a sample size of at least 20, and included patients of any age or gender as long as they fulfilled ACR criteria for neuropsychiatric SLE. DATA EXTRACTION: The following data were extracted: author name, year of publication, psychiatric diagnostic method, total number of patients with SLE, and percentage of patients with individual psychiatric diagnoses. The point prevalence of psychiatric symptoms was calculated for neuropsychiatric SLE diagnoses in every study included. RESULTS: Psychiatric symptoms are present in the majority of patients with SLE. Depression (in up to 39% of patients) and cognitive dysfunction (up to 80%) are the most common psychiatric manifestations. Genetic and environmental factors (eg, ultraviolet light, retroviruses, and medications) may play a role in the pathogenesis. In addition, the patient's reaction to the illness may result in anxiety (up to 24%) and depression. Currently known biomarkers are nonspecific for neuropsychiatric SLE and indicate inflammation, microglial activation, ischemia, oxidative stress, mitochondrial dysfunction, and blood-brain barrier dysfunction. CONCLUSIONS: Identification of lupus-specific biomarkers of psychiatric symptoms is a high priority. Our current diagnostic assessment methods need improvement. Development of evidence-based guidelines is needed to improve diagnosis, prevention, and treatment of disabling psychiatric complications in lupus.

Síndrome de Otelo (delirio celotípico monosintomático) inducido por agonistas dopaminérgicos / Othelo syndrome (monosymptomatic jealousy delusion) related with dopaminergic agonists

La enfermedad de Parkinson (EP) es un trastorno neurodegenerativo crónico que produce un grado variable de destrucción de neuronas de los ganglios basales, con la consecuente reducción de la transmisión dopaminérgica. Clínicamente se traduce principalmente en temblor de reposo, rigidez muscular, bradicinesia y alteraciones de la marcha. También aparecen otros síntomas motores y no motores. Entre los no motores se encuentra un amplio espectro de sintomatología psiquiátrica, entre la que destacan la depresión, la ansiedad, la agitación, el delirium, los trastornos del sueño, la hipersexualidad, los trastornos del control de impulsos y diversos síntomas psicóticos. Estos últimos presentan una prevalencia del 45-60% en la EP, predominando los «síntomas menores» (ilusiones visuales y sensaciones de presencia) sobre las alucinaciones y delirios. Entre los delirios destacamos el síndrome de Otelo (SO), un trastorno delirante con síntomas celotípicos poco frecuente en pacientes con EP. Su aparición se relaciona con el tratamiento agonista dopaminérgico, y en la mayoría de los casos se resuelve tras la disminución de la dosis del fármaco agonista. Solo en algunos casos es necesario añadir tratamiento antipsicótico, siendo de elección los atípicos. Por último, nuevos fármacos como la pimavanserina (un agonista inverso selectivo 5-HT2A) están siendo estudiados en el tratamiento de la psicosis asociada a la EP, con resultados prometedores. Presentamos un caso de EP que, tras varios años de tratamiento agonista dopaminérgico, desarrolló un SO que se resolvió tras recibir tratamiento antipsicótico atípico y ajustar el tratamiento antiparkinsoniano (AU)

Parkinson disease (PD) is a chronic, neurodegenerative disorder that produces a degeneration of the basal ganglia, with a variable reduction of dopamine neurotransmission activity. In a clinical point of view, these impairments are translated into tremor, rigidity, bradykinesia, and shuffling gait. Both motor and nonmotor symptoms are characteristics of PD. Nonmotor symptoms include a wide spectrum of psychiatric features: depression, anxiety, delirium, sleep disorders, hipersexuality, impulsivity disorders, and psychotic symptoms. Prevalence of psychotic symptoms in PD is high (45-60%), although "minor symptoms" (visual illusions and "sense of presence") are more frequent than "major" ones (hallucinations and delusions). Considering the delusional disorders, Othelo syndrome (OS) (jealousy delusion) represents a scarce clinical presentation in PD. Jealousy delusion has been related with dopaminergic agonists, and a reduction of dose is the first-line treatment. In several cases, it may be also necessary to add atypical antipsychotics as complementary therapy. Finally, pimavanserine (a selective, inverse agonist 5-HT2A) is currently on research, and it may be a promising option in the treatment of PD related-psychosis in the next future. We present a case-report of PD which developed an OS after several years of agonistic dopaminergic treatment. The dose-adjustment of antiparkinsonian drugs plus atypical antipsychotics was the option played, obtaining resolution of jealousy delusion (AU)

[Psychiatric disorders in juvenile myoclonic epilepsy]. / Troubles psychiatriques dans l'épilepsie myoclonique juvénile.

Mild personality problems have been described in patients with juvenile myoclonic epilepsy (JME), but clinical practice shows that JME can be diagnosed in patients with more or less severe psychiatric disorders (PD). The presence in JME patients of personality disorders has been described repeatedly, but never quantified. We thus decided to evaluate, using the DSM IV, the current prevalence and types of PD in a large series of consecutive, newly referred patients with JME. Among 170 consecutive JME cases referred to two departments of epileptology (Marseilles and Nice) between 1981 and 1998 (66 males, 104 females; aged 11.7-70; mean+/-SD 32.4+/-10.4 follow-up 12.7+/-10 [0.5-52]), we found 45 patients (26.5p.100) with PD. According to the DSM IV, they could be classified as severe mental retardation (main diagnosis) (one case); pervasive developmental disorders (2 cases); tic disorder (1 case); enuresis (1 case); psychotic disorders (5 cases, including schizophrenia paranoid type (1 case), disorganized type (1 case), delusional disorder (1 case), unspecified (2 cases)); depressive disorders (3 cases); generalized anxiety (6 cases); anorexia nervosa (2 cases); personality disorders (24 cases, including borderline personality (11 cases), dependent personality (5 cases), histrionic personality (2 cases), obsessive-compulsive personality (1 case), not specified (5 cases)). Sudden unexplained death occurred in 2 cases (borderline personality and pervasive developmental disorder not otherwise specified, respectively) and death due to pneumonia in 1 cases (anorexia). Although uncommonly severe cases of JME may have been selected in our referral centers, it appears that JME may be associated with PD. Comparatively mild personality disorders are the most common finding, and may be part of the clinical picture to some extent, while severe PD are less common, and probably coincidental. The presence of PD does not exclude the diagnosis of JME, and PD may represent a further challenge in the comprehensive care of these patients.

Perinatal complications and abnormal proton metabolite concentrations in frontal cortex of adolescents seen on magnetic resonance spectroscopy.

OBJECTIVE: The relation of perinatal complications to metabolism of orbitofrontal cortex was studied in 12 normal adolescents aged 13 to 17 years. BACKGROUND: Perinatal complications are associated with both (a) behavioral signs of frontal lobe dysfunction and (b) increased risk for mood disorders and schizophrenia. Perinatal complications are not usually sufficient to produce these disorders, however, suggesting an etiologic model in which perinatal complications interact with a second, familial, liability factor. The present study tested a key prediction of this "two-factor" model, namely, that perinatal complications will be associated with physiologic signs of frontal dysfunction, even in persons who have no personal or family history of these psychiatric disorders. METHODS: Subjects were screened by structured interviews with the Kiddie Schedule for Affective Disorders and Schizophrenia and had no personal or family history of psychiatric disorder. Ratios of choline and N-acetyl aspartate to creatine in orbitofrontal cortex were measured using proton magnetic resonance spectroscopy. Perinatal complications were scored with the examiners blinded to magnetic resonance spectroscopy data, applying published scales to hospital records on subjects' gestations and births. RESULTS: Perinatal complications were significantly correlated with reduced concentrations of choline and N-acetyl aspartate. CONCLUSIONS: Our results complement earlier findings of significant relations between perinatal complications and signs of frontal lobe dysfunction, as well as elevated rates of these two types of variables in mood disorders and schizophrenia.

Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms.

All research on schizophrenia depends on selecting the correct phenotype to define the sample to be studied. Definition of the phenotype is complicated by the fact that there are no objective markers for the disorder. Further, the symptoms are diverse, leading some to propose that the disorder is heterogeneous and not a single disorder or syndrome. This article explores an alternative possibility. It proposes that schizophrenia may be a single disorder linked by a common pathophysiology (a neurodevelopmental mechanism), which leads to a misconnection syndrome of neural circuitry. Evidence for disruption in a specific circuit is explored: the cortical-thalamic-cerebellar-cortical circuit (CCTCC). It is suggested that a disruption in this circuit leads to an impairment in synchrony, or the smooth coordination of mental processes. When synchrony is impaired, the patient suffers from a cognitive dysmetria, and the impairment in this basic cognitive process defines the phenotype of schizophrenia and produces its diversity of symptoms.

Absence of the adhesio interthalamica as a marker of early developmental neuropathology in schizophrenia: an MRI and postmortem histologic study.

Several recent studies have reported an association between midline cerebral malformations (e.g., corpus callosum, cavum septum pellucidum) and schizophrenia. The authors investigated whether absence of the adhesio interthalamica (AI), a midline structure that develops in concert with prominent features of the ventricular system soon after the bridge from the late embryonic stages to early fetal life, might constitute a marker of early developmental neuropathologic changes in schizophrenia. Eighty-two patients (54 men, 28 women) with a diagnosis of first-episode schizophrenia (FES) were recruited from consecutive admissions to a psychiatric inpatient service. Fifty-two healthy control subjects (30 men, 22 women) were recruited and matched to the patient sample on distributions of sex and age. Magnetic resonance imaging studies were performed, and the presence versus absence of the AI was determined for each subject. The length and volume of the third ventricle were measured for each subject. The AI was found to be absent more often among patients with FES compared with control subjects, and patients without an observable AI also had larger third-ventricle volumes. These differences in presence or absence of the AI observed in vivo (but not in a comparable postmortem sample of histologically fixed and prepared brain slices), which are likely related to third-ventricle enlargement, may represent yet another early developmental marker of cerebral malformation among patients with FES.

Magnetic resonance imaging volumetric and phosphorus 31 magnetic resonance spectroscopy measurements in schizophrenia.

The purpose of this study was to examine the relationship between phosphorus magnetic resonance spectroscopy (31P MRS) parameters and left prefrontal volumes in both patients with schizophrenia and healthy subjects. 31P MRS parameters and magnetic resonance imaging (MRI) volumetric data were collected in the left prefrontal region in 10 patients with schizophrenia and 10 healthy subjects of comparable age, handedness, sex, educational level, and parental educational level. No correlations were found between any MRS parameter and grey matter volumes in the combined subjects. Phosphomonoester (PME) and grey matter volumes, however, were both correlated negatively with age. PMEs were found to be decreased, and calculated intracellular magnesium ([Mg2+]intra) was found to be increased in the patients with schizophrenia compared with healthy subjects after adjusting for left prefrontal grey and white matter, total brain volume, and age. These findings suggest that cortical grey and white manner volumes are not directly related to PME and [Mg2+]intra abnormalities in schizophrenia patients.

[Role of the cytokine network in the CNS and psychiatric disorders]. / Die Rolle des Zytokinnetzwerks im ZNS und psychische Störungen.

There is a strong interrelationship between the immune system, the central nervous system and psychological processes that are suggested to play a pivotal role in the pathogenesis of psychiatric disorders. In schizophrenia and depression, activation of the immune system has been observed repeatedly. Cytokines play a key role in immune activation. They are actively transported into the CNS, but also released from activated glia cells. Cytokines activate glia cells in the CNS to produce other cytokines, and a cascade of cytokine effects may be initiated by this mechanisms. During the past few years, the influence of the cytokines on dopaminergic, noradrenergic and serotonergic neurotransmission and also on the hormones of the hypothalamus-pituitary-adrenal axis has been elucidated. It suggests a pivotal role in psychological processes and psychiatric disorders. For example, in schizophrenia the IL-2 cerebrospinal fluid concentration shows a stronger relationship to the relapse probability than catecholamine metabolites. Although the hypersecretion of IL-2 in schizophrenia and of IL-6 in depression are suggested to play key roles for these disorders, a specificity of certain cytokines for certain psychiatric disorders seems unlikely. Psychomotor, sleep and sickness behavior are influenced by IL-1, disturbances of memory and attention by IL-2, but also by TNF-alpha. From the distribution of cytokine receptors in the CNS conclusions can be drawn regarding the influence of cytokines on psychological processes. The finding that norepinephrine stimulates activated astrocytes to produce IL-6 implies that the cytokine cascade may be activated by neuronal processes under certain conditions. This can lead to a molecular biological explanation of the influences of stress on the immune system. Lastly, influences of the cytokines on blood-brain barrier disturbances and further consequences resulting from the role of the cytokine network in the CNS are discussed.

Persisting childish behavior after bilateral thalamic infarcts.

We report a case with bilateral paramedian thalamic infarcts. The patient showed a dramatic personality change characterized by childish behavior and euphoria; which remained unchanged for 2 years after the onset. 'Vorbeireden' characterized by approximate answers was also observed. Anterograde amnesia had quite improved after 2 years, while retrograde amnesia for 1 year prior to the stroke onset and vertical gaze palsy remained unchanged. An MRI scan demonstrated bilateral medial thalamic and right midbrain infarcts without other lesions in the brain. A position emission tomography study showed that cerebral metabolic rate for glucose was markedly decreased in both thalami and in the cerebellum, and only slightly decreased in the parietal and occipital cortical regions. Cerebral metabolic rates of glucose in the frontal and temporal cortices were within normal range. The paramedian thalamic lesions per se may be responsible for the patient's personality change, 'Vorbeireden', and amnesia.