Chronic Neuropsychiatric Disorders Research Articles

Attention-deficit/hyperactivity symptoms and personal strengths in adults

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent chronic neuropsychiatric disorders in children and adolescents; however, it continues into adulthood in 4-77% of the cases. Due to executive dysfunction, adults with ADHD may have deficits in personal strengths, as well as difficulties utilizing existing strengths in challenging situations, which may add to the functional impairments associated with ADHD in adults.ObjectivesTherefore, we aimed to explore the association between personal strengths and ADHD symptoms in a community sample of adults.MethodsFive hundred and twenty-eight adults (mean age = 21.41 years, SD = 2.29, range: 18 ̶ 28, female: N = 488, 92.4%) filled out an online questionnaire after giving their informed consent. Personal strengths were assessed using Bernstein’s Strengths Scale (BSS) which measures sixteen positive attributes grouped into four higher-order factors: self-directedness (Identity, Self-reflection, Self-confidence, Self-assertion, Imagination/Creativity), self-regulation (Emotional balance, Resilience, Self-control, Self-care, Reality testing), connection (Empathy, Compassion, Humour, Responsibility), and transcendence (Gratitude and Wisdom). ADHD symptoms were measured by the screening version (Part A) of the Adult ADHD Self-Report Scale (ASRS).ResultsParticipants who were screened positive in ASRS (N = 247, 46.7%) scored lower in all but four BSS subscales than participants who were screened negative (N = 280, 53.3%). Effect sizes reached the medium level (Cohen’s d > .5) for Self-confidence, Self-care, Responsibility and Wisdom, and were small (Cohen’s d > .2) for Identity, Self-assertion, Imagination, Resilience, Reality-testing, Emotional balance, and Gratitude. However, no group differences were found in the Self-reflection, Empathy, Compassion, and Humour subscales of the BSS.ConclusionsOur results suggest that ADHD symptoms in adults may be associated with deficits in personal strengths; that is, adults with ADHD may have difficulties, especially in trusting in their abilities, qualities, and judgements, in taking care of their own emotional and physical well-being, in taking responsibilities and in being open to learning from their experiences. Addressing personal strengths in psychosocial interventions for adult ADHD may improve patients’ functioning.This research has been supported by the National Research, Development, and Innovation Office, OTKA-PD-134849 and ÚNKP-22-2-I-ELTE-854 grants.Disclosure of InterestNone Declared

Insomnia in Forensic Detainees: Is Salience Network the Common Pathway for Sleep, Neuropsychiatric, and Neurodegenerative Disorders?

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. Since the brain salience network is likely the common denominator for insomnia, neuropsychiatric and neurodegenerative disorders, here, we focus on the pathology of this neuronal assembly and its likely driver, the dysfunctional neuronal and mitochondrial membrane. We also discuss potential treatment strategies ranging from membrane lipid replacement to mitochondrial transplantation. The aims of this review are threefold: 1. Examining the causes of insomnia in forensic detainees with severe mental illness, as well as its role in predisposing them to neurodegenerative disorders. 2. Educating State hospital and prison clinicians on frontotemporal dementia behavioral variant, a condition increasingly diagnosed in older first offenders which is often missed due to the absence of memory impairment. 3. Introducing clinicians to natural compounds that are potentially beneficial for insomnia and severe mental illness.

A Fiber Sensor for Long-Term Monitoring of Extracellular Potassium Ion Fluctuations in Chronic Neuropsychiatric Diseases.

The extracellular potassium ion concentration in the brain exerts a significant influence on cellular excitability and intercellular communication. Perturbations in the extracellular potassium ion level are closely correlated with various chronic neuropsychiatric disorders including depression. However, a critical gap persists in performing real-time and long-term monitoring of extracellular potassium ions, which is necessary for comprehensive profiling of chronic neuropsychiatric diseases. Here, a fiber potassium ion sensor (FKS) that consists of a soft conductive fiber with a rough surface and a hydrophobic-treated transduction layer interfaced with a potassium ion-selective membrane is found to solve this problem. The FKS demonstrates stable interfaces between its distinct functional layers in an aqueous environment, conferring an exceptional stability of 6 months in vivo, in stark contrast to previous reports with working durations from hours to days. Upon implantation into the mouse brain, the FKS enables effective monitoring of extracellular potassium ion dynamics under diverse physiological states including anesthesia, forced swimming, and tail suspension. Using this FKS, tracking of extracellular potassium ion fluctuations that align with behaviors associated with the progression of depression over months is achieved, demonstrating its usability in studying chronic neuropsychiatric disorders from a new biochemical perspective.

Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

Coadministration of tianeptine alters behavioral parameters and levels of neurotrophins in a chronic model of Maple Syrup Urine disease.

Maple Syrup Urine Disease (MSUD) is caused by the deficiency in the activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), resulting in the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, and their respective branched-chain α-keto acids. Patients with MSUD are at high risk of developing chronic neuropsychiatric disorders; however, the pathophysiology of brain damage in these patients remains unclear. We hypothesize that MSUD can cause depressive symptoms in patients. To test our hypothesis, Wistar rats were submitted to the BCAA and tianeptine (antidepressant) administration for 21days, starting seven days postnatal. Depression-like symptoms were assessed by testing for anhedonia and forced swimming after treatments. After the last test, the brain structures were dissected for the evaluation of neutrophins. We demonstrate that chronic BCAA administration induced depressive-like behavior, increased BDNF levels, and decreased NGF levels, suggesting a relationship between BCAA toxicity and brain damage, as observed in patients with MSUD. However, the administration of tianeptine was effective in preventing behavioral changes and restoring neurotrophins levels.

Neuroinflammation in a Rat Model of Tourette Syndrome.

ObjectiveTourette syndrome (TS) is a group of childhood-onset chronic neuropsychiatric disorders characterized by tics, i.e., repetitive, sudden, and involuntary movements or vocalizations, which is often associated with various psychopathological and/or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders and have a worse prognosis. The mechanism of TS is still not clear. The relationship between immune activation, neuroinflammation, and neuropsychiatric disorders has attracted much attention in the past two decades. To explore the underlying mechanism in TS, the relationship between neuroinflammation and behavioral alterations in TS rats was investigated in this study.MethodsA total of 36 Sprague-Dawley male rats were divided into three groups randomly as follows: the TS, control (CON), and drug intervention groups. The TS rat group was treated with haloperidol (Hal) (the TS + Hal group). The TS rat model was established using 3,3-iminodipropionitrile (IDPN), which is a well-known animal model of TS. The behavioral syndromes, brain tissue cytokines, like interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), and microglial activation of the three groups were assessed.ResultsThe behavioral scores of rats in the TS group and the TS + Hal group were higher than those in the CON group (P < 0.05), but the scores of behavioral tests in the TS + Hal group were lower than those in the TS group (P < 0.05). The levels of IL-6 and TNF-α in the rat brain tissue were significantly higher in the TS group than in the CON group (P < 0.05), while no significant differences were found between the CON group and the TS + Hal group (P > 0.05). The microglia was significantly activated in the TS group and slightly activated in the TS + Hal group, which was considerably less than that in the TS group.ConclusionThe IDPN-induced TS rats had significant neuroinflammation in the brain, and the interaction between dopamine (DA) dysregulation and immune dysfunction may play a vital role in the pathogenic mechanisms of TS.

Electrocardiogram Monitoring Practices for Hospitalized Adults Receiving Antipsychotics: A Retrospective Cohort Study.

Antipsychotics are frequently used for managing both acute and chronic neuropsychiatric disorders. While antipsychotics are known to be associated with increased mortality due to cardiac arrhythmia, there is a lack of consensus on the timing and frequency of electrocardiogram (ECG) monitoring. The goal of this study was to examine current ECG monitoring practices for adults receiving antipsychotics, specifically during hospital admission. The study involved a multisite retrospective chart review of adults admitted across 8 hospitals between January 2010 and December 2015 who received antipsychotics during hospitalization. The primary outcome was the presence of an ECG after receiving an antipsychotic. During the study period, there were 26,353 hospitalizations during which adults received antipsychotic medication; the average age of the patients was 61.4 years, 50.1% were female, and 64.8% were white. The average comorbidity score was 1.4 with a median length of stay of 8.3 days. Of the 26,353 patients who were hospitalized, 60.6% (n=15,977) of patients in the sample had an ECG during their hospitalization, and 41.2% (n=10,865) had the ECG following antipsychotic administration. Patients who received a follow-up ECG had a longer length of stay (median: 11.3 d) compared with those who did not receive a follow-up ECG (median: 7.0 d). Follow-up ECGs were more likely among patients who had a history of heart failure [odds ratio (OR)=1.17, 95% confidence interval (CI): 1.06-1.30, P=0.002], who were receiving multiple antipsychotics (OR=1.3, 95% CI: 1.24-1.36, P<0.001) or other QT-prolonging medications (OR=1.09, 95% CI: 1.07-1.1, P<0.001), who were receiving risperidone (OR=1.12, 95% CI: 1.004-1.25, P=0.04), and who showed an increase in QTc duration (OR per 10 ms increase=1.02, 95% CI: 1.01-1.04, P=0.003). Follow-up ECGs were less likely to be administered to patients who were receiving antipsychotics before admission (OR=0.93, 95% CI: 0.87-0.997, P=0.04). This study demonstrated that, in a large health system, ECG monitoring is not routinely practiced for hospitalized patients receiving antipsychotics. Further studies are needed to identify patients who would most benefit from ECG monitoring in the acute care setting.

Арт-терапія у комплексному лікуванні хворих на хронічні психоневрологічні захворювання

Стаття присвячена психологічним механізмам, що змінюють структуру особистості у пацієнтів із хронічними психоневрологічними захворюваннями, і психотерапевтичній роботі з даними станами. Акцент зроблений на втраті пацієнтами своєї ідентичності і формуванні «спаяності» з хворобою. Докладно описані система використання арт-терапії та деякі техніки когнітивної терапії у комплексному лікуванні пацієнтів.

Estrogen pendulum in schizophrenia and Alzheimer’s disease: Review of therapeutic benefits and outstanding questions

Although produced largely in the periphery, gonadal steroids play a key role in regulating the development and functions of the central nervous system and have been implicated in several chronic neuropsychiatric disorders, with schizophrenia and Alzheimer’s disease (AD) most prominent. Despite major differences in pathobiology and clinical manifestations, in both conditions, estrogen transpires primarily with protective effects, buffering the onset and progression of diseases at various levels. As a result, estrogen replacement therapy (ERT) emerges as one of the most widely discussed adjuvant interventions. In this review, we revisit evidence supporting the protective role of estrogen in schizophrenia and AD and consider putative cellular and molecular mechanisms. We explore the underlying functional processes relevant to the manifestation of these devastating conditions, with a focus on synaptic transmission and plasticity mechanisms. We discuss specific effects of estrogen deficit on neurotransmitter systems such as cholinergic, dopaminergic, serotoninergic, and glutamatergic. While the evidence from both, preclinical and clinical reports, in general, are supportive of the protective effects of estrogen from cognitive decline to synaptic pathology, numerous questions remain, calling for further research.

Rhynchophylline Attenuates Tourette Syndrome via BDNF/NF-κB Pathway In Vivo and In Vitro

Tourette syndrome (TS) is characterized by one of the chronic neuropsychiatric disorders in multiple children, and the pathogenesis of Tourette syndrome (TS) has not been previously elucidated.The aim of this study was designed to investigate the effects of rhynchophylline (RH) on Tourette syndrome (TS) in rats.TS model was established in rats and BV2 cells by the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior evaluations including stereotypy recording and autonomic activity test were performed. Inflammatory cytokine levels such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum, striatum, and cell supernatant were detected. The expression levels of BDNF/NF-κB pathway in striatum and BV2 cells were measured by Western blot. Dopamine (DA) and dopamine receptor D 2 (D2) in striatum were also measured.Data indicated that RH significantly decreased IL-6, IL-1β, and TNF-α in serum, striatum, and cell supernatant of TS model, with altered expression of P-NF-κBp65, P-IκBα, and BDNF in TS rats, and DOI-induced BV2 cells, as evidenced by Western blot analysis and immunohistochemistry analysis. RH also significantly reduced the levels of DA and D2 in striatum.Our results shown that the regulation of BDNF/NF-κB pathway might be involved in the effects of RH on TS model.

Molecular Imaging of mGluR5 Availability with [11C]ABP68 in Glutaminase Heterozygous Mice.

Many PET tracers enable determination of fluctuations in neurotransmitter release, yet glutamate specifically can not be visualized in a noninvasive manner. Several studies point to the possibility of visualizing fluctuations in glutamate release by changes in affinity of the mGluR5 radioligand [11C]ABP688. These studies use pharmacological challenges to alter glutamate levels, and so probe release, but have not measured chronic alterations in receptor occupancy due to altered neurotransmission relevant to chronic neuropsychiatric disorders or their treatment. In this regard, the GLS1 heterozygous mouse has known reductions in activity of the glutamate-synthetic enzyme glutaminase, brain glutamate levels and release. We imaged this model to elucidate glutamatergic systems. Dynamic [11C]ABP688 microPET scans were performed for mGluR5. Western blot was used as an ex vivo validation. No significant differences were found in BPND between WT and GLS1 Hets. SPM showed voxel-wise increased in BPND in GLS1 Hets compared to WT consistent with lower synaptic glutamate. This was not due to alterations in mGluR5 levels, as western blot results showed lower mGluR5 levels in GLS1 Hets. We conclude that because of the chronic glutaminase deficiency and subsequent decrease in glutamate, the mGluR5 protein levels are lowered. Due to these decreased endogenous glutamate levels, however, there is increased [11C]ABP688 binding to the allosteric site in selected regions. We speculate that lower endogenous glutamate leads to less conformational change to the receptors, and thus higher availability of the binding site. The lower mGluR5 levels, however, lessen [11C]ABP688 binding in GLS1 Hets, in part masking the increase in binding due to diminished endogenous glutamate levels as confirmed with voxel-wise analysis.

Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics.

Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs.

Evidence of the dopamine-2 receptor mediated inhibition of the hypothalamic-pituitary-adrenal system; a rodent model of hypercortisolism in chronic neuropsychiatric disorders

Evidence of the dopamine-2 receptor mediated inhibition of the hypothalamic-pituitary-adrenal system; a rodent model of hypercortisolism in chronic neuropsychiatric disorders

A New Level A Type IVIVC for the Rational Design of Clinical Trials Toward Regulatory Approval of Generic Polymeric Long-Acting Injectables.

Chronic neuropsychiatric disorders and diabetes mellitus affect millions of patients and require long-term supervision and expensive medical care. Although repeated drug administration can help manage these diseases, relapses and re-hospitalization owing to patient non-adherence and reduced therapeutic efficacy remain challenging. In response, long-acting injectables, which provide sustained drug release over longer periods at concentrations close to therapeutic ranges, have been proposed. Recent advancements include polymeric long-acting injectables (pLAIs), in which the active pharmaceutical ingredient (API) is encapsulated within U.S. Food and Drug Administration (FDA)-approved biocompatible polymers, such as poly(lactic-co-glycolic acid), or PLGA. Despite significant progress and development in the global pLAI market, FDA guidance for the approval of complex drug products, such as generic pLAIs, is not clearly defined. Although in vitro to in vivo correlation (IVIVC) can facilitate the identification of critical quality attributes (CQAs), drug formulations, and in vitro test platforms for evaluating drug performance in vivo, the application of IVIVC in order to shortlist time- and resource-intensive clinical trials for generic pLAIs has not been reported. Here, we propose a new Level A Type IVIVC that directly correlates the in vitro outcomes, such as drug dissolution, of candidate generic formulations with the clinical characteristics, such as drug absorption, of a reference listed drug (RLD), to help identify the specific generic pLAI formulations with clinical absorptions that are likely to be similar to that of the RLD, thereby reducing the number of clinical trials required for evaluation of clinical bioequivalence (BE). Therefore, the scope of the proposed method is intended only for the rational design of clinical trials, i.e., to shortlist the specific pLAI generic formulations for clinical BE evaluation, and not necessarily to analyze drug performances (i.e., drug safety and effectiveness) in the shortlisted clinical trials or post-approval. Once validated, this method will be of great value to developers of generic pLAIs and regulatory bodies to accelerate their approval of these generic pLAIs.

Adult Attention Deficit Hyperactivity Disorder Symptoms, Perceived Stress, and Well-Being: The Role of Early Maladaptive Schemata.

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent chronic neuropsychiatric disorders, severely affecting the emotional well-being of children as well as of adults. It has been suggested that individuals who experience symptoms of ADHD develop maladaptive schemata of failure, impaired self-discipline, social isolation, and shame. These schemata may then contribute to impaired emotional well-being by increasing unhelpful responses to stressful life events. However, to date, no empirical research has tested this theoretical proposition. In a sample of 204 nonclinical adults, we conducted a serial multiple mediator analysis, which supported the proposed model. More severe ADHD symptoms were associated with higher levels of perceived stress both directly and indirectly through stronger maladaptive schemata, which, in turn, were related to lower levels of emotional well-being. Results suggest that identifying and modifying maladaptive schemata may be an important addition to psychotherapy for adult ADHD patients.

Chronic Subdural Hematoma and Neuropsychiatric Disorders: Report of a Case

Introduction Organic disorders can mimic all kinds of psychiatric illnesses. Some neurological diseases including front location are misleading when psychiatric manifestations represent the beginning shape or dominate the clinical. It may be dementia, mental confusion, mood disorders and psychotic disorders. Objectives the aim of this study was to point out through the study of a clinic observation, discuss the importance of the importance of organicity to psychiatric disorders and the resulting difficulties of diagnostic and therapeutic order. Methods We report the case of a 72 year old man without chronic disease identified, consulted in February 2013 emergency following a head injury with loss of initial knowledge . The brain scanner (TDM) was normal. In July 2013, the patient began to exhibit behavioral problems in such wandering, memory problems, slow ideation, delusions of persecution with audiovisual hallucinations. This table psychotic moved in a very insidious and fluctuating intensity. The patient was seen in psychiatry at the worsening of symptoms. Exploration has confirmed the diagnosis of chronic subdural hematoma (HSDC) without signs of compression. The surgery consisted of an enlarged trepanation and evolution was favorable. Conclusion It appears from this case and review of the literature that various psychiatric manifestations may reveal an HSDC and that, in the elderly, neuroimaging should be systematic, even for minor symptoms. The total resorption led to the disappearance of psychiatric symptoms in most patients, but this remains a topic of discussion for patients who retain residual symptoms, even after resorption of the mass.

Anatomical Brain Images Alone Can Accurately Diagnose Chronic Neuropsychiatric Illnesses

ObjectiveDiagnoses using imaging-based measures alone offer the hope of improving the accuracy of clinical diagnosis, thereby reducing the costs associated with incorrect treatments. Previous attempts to use brain imaging for diagnosis, however, have had only limited success in diagnosing patients who are independent of the samples used to derive the diagnostic algorithms. We aimed to develop a classification algorithm that can accurately diagnose chronic, well-characterized neuropsychiatric illness in single individuals, given the availability of sufficiently precise delineations of brain regions across several neural systems in anatomical MR images of the brain.MethodsWe have developed an automated method to diagnose individuals as having one of various neuropsychiatric illnesses using only anatomical MRI scans. The method employs a semi-supervised learning algorithm that discovers natural groupings of brains based on the spatial patterns of variation in the morphology of the cerebral cortex and other brain regions. We used split-half and leave-one-out cross-validation analyses in large MRI datasets to assess the reproducibility and diagnostic accuracy of those groupings.ResultsIn MRI datasets from persons with Attention-Deficit/Hyperactivity Disorder, Schizophrenia, Tourette Syndrome, Bipolar Disorder, or persons at high or low familial risk for Major Depressive Disorder, our method discriminated with high specificity and nearly perfect sensitivity the brains of persons who had one specific neuropsychiatric disorder from the brains of healthy participants and the brains of persons who had a different neuropsychiatric disorder.ConclusionsAlthough the classification algorithm presupposes the availability of precisely delineated brain regions, our findings suggest that patterns of morphological variation across brain surfaces, extracted from MRI scans alone, can successfully diagnose the presence of chronic neuropsychiatric disorders. Extensions of these methods are likely to provide biomarkers that will aid in identifying biological subtypes of those disorders, predicting disease course, and individualizing treatments for a wide range of neuropsychiatric illnesses.

Rages—What Are They and Who Has Them?

The purpose of this study was to examine rages and define their associated clinical and diagnostic conditions systematically. Children's severe anger outbursts, sometimes called "rages," have been associated with many disorders, including mania, "severe mood dysregulation," and oppositional defiant/conduct disorder. Although reactive aggression has been studied extensively, there are almost no data on this important and disabling clinical phenomenon. A total of 130 different 5-12 year olds were hospitalized over 151 consecutive admissions were evaluated diagnostically with information from parents, children, doctors, nursing staff, and teachers. Rages were operationally defined as agitated/angry behaviors requiring seclusion or medication because the child could not be verbally redirected to "time out." Rage behaviors were categorized as they occurred with the specially designed Children's Agitation Inventory. Hypotheses were that rages would be associated with prior treatment failure, and that children with rages would have the most co-morbidities, including learning/language disorders. We did not expect narrow-phenotype bipolar disorder to be specifically associated with rages. Of 130 children, 71 (54.6%) were admitted for rages. Preadmission rages and admission taking an atypical antipsychotic significantly predicted the subsequent number of in-hospital rages. Attention-deficit/hyperactivity disorder with learning/language disorder significantly predicted the occurrence and number of rages. Bipolar disorder was the referring diagnosis in 17/49 (34.7%) admissions with rages and 15/102 (14.7%) of admissions without rages (odds ratio [OR] 3.05, confidence interval [CI] 1.36, 6.80). However, a consensus diagnosis of bipolar disorder occurred in 5 (9.1%) of the sample with rages and 5 (5.8%) in the rest of admissions. Psychiatrically hospitalized children with multiple rages have complex, chronic neuropsychiatric disorders and have failed prior conventional treatment. One third of children with rages had been given a bipolar diagnosis prior to admission. However, only 9% of children with rages were given that diagnosis after careful observation.

Scalp recordings of mid-latency AEP and auditory gating in the Göttingen minipig: a new animal model in information processing research

Early central information processing, measured in humans by the gating of the middle latency auditory evoked potential (AEP) P50 and the effect of attention on AEP N100, is affected in schizophrenia. Exploring the possibility of using miniature pigs in longitudinal studies of chronic neuropsychiatric disorders, we present a method for recording seven channel surface middle latency AEP in the awake animal. The AEP and the AEP gating measured in a paired stimulus paradigm similar to the P50 gating paradigm used in humans, were recorded in six adult male minipigs in two sessions. The AEP had a stable N40/P60/N120/P200 configuration and in the gating paradigm the difference between stimulus one (S1) and two (S2) P60 and N120 amplitudes were significant. Mean AEP P60 gating ratio (S2/S1) at the posterior central electrode was 0.66 (std 0.29) range 0.21–1.08 and corresponding N120 was 0.60 (std 0.19) range 0.28–0.76. The method presented is feasible for scalp recordings of middle latency evoked potentials in the awake animal, but further studies of interval sensitivity and the effect of arousal manipulation are needed to assess the equivalence of the pig components to those of the human at similar latencies.

Implications of the neuroprotective effects of lithium for the treatment of bipolar and neurodegenerative disorders.

Bipolar disorder is increasingly recognized as an illness that may progress to impairment in neurocognitive functioning and cell loss in cortical and limbic brain regions. Glutamatergic damage and/or damage due to high glucocorticoid levels that inhibit adult neurogenesis are likely contributing mechanisms. Drug treatments with possible neuroprotective effects are becoming increasingly important both clinically and as research tools. Mood stabilizing drugs and lithium in particular may act to prevent neuronal damage and tissue loss that may occur in the brain of patients with bipolar disorders. Lithium has been shown to exert neuroprotective effects in vitro and to stimulate neurogenesis in the hippocampus. Animal studies have demonstrated pharmacological effects of lithium suggestive of its role in neuroprotection, which range from reducing excitotoxicity through increased glutamate uptake, to regulation of a number of signal transduction intermediates such as myo-inositol, protein kinase C, phosphotidylinositol-3 kinase (PI-3K)/protein kinase B (Akt), ras-mitogen-activated protein kinase (MAPK), glycogen synthase kinase (GSK)-3alpha and -3beta and calcium. It remains to be established whether lithium treatment protects against possible cell damage in the same manner as it protects against recurrences of the illness. We propose to examine the effect of long-term lithium treatment on neurocognitive functioning of bipolar patients and the use of lithium in the treatment of chronic neuropsychiatric disorders.