bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical significance of atypical antipsychotics
Authors: Boer J.A. Den , Westenberg H.G.M. , Louwerens J.W. , Slooff C.J.
Published: July 2016

A concise review is given of the importance of the atypical antipsychotic drugs clozapine, sulpiride, remoxipride and raclopride. Both the concept of atypicality and the pharmacological profile of these compounds is discussed. The newly developed atypical antipsychotic remoxipride has been studied in several double blind studies. In virtually all of these studies a reduced propensity for the induction of extrapyramidal symptoms was found.

These findings implicate that atypical antipsychotics may also not induce tardive dyskinesia. In addition to the treatment of acute schizophrenia, these compounds might be of use in the treatment of treatment resistent schizophrenia (clozapine), tardive dyskinesia and psychosis during the course of Parkinson's disease.
Meta-analysis of 38 placebo-controlled studies examining the antidepressant-induced analgesic effect
Authors: Onghena P. , van Houdenhove B.
Published: July 2016

For all controlled studies that bear upon the analgesic-effect of antidepressants, a meta-analysis was conducted to get an estimation of the effect size and to get a sight on the possible modes of action. For this purpose both content and methodological variables were coded for each study. The mean size of the analgesic effect is 0.63. This means that the average patient getting an antidepressant has less pain than 74% of the patients getting a placebo. However because of selective drop-out and the use of psychometri-cally inadequate pain scales, this may be an over-estimation. Real analgesic qualities of antidepressive agents seem to offer the most plausible explanation for the effect, but the importance of serotonin reuptake blocking is not confirmed. A main objection, however, is that in all studies the depression variable was insufficiently controlled at inclusion. Because both the estimation of the effect size as the explanation of the effect are confounded with methodological doubts, it is concluded that further studies need to be done to overcome these difficulties.
Diagnostic and classification systems with special emphasis on the Minicompendium
Authors: Bech P.
Published: July 2016

With the introduction of major tranquillizers more than three decades ago symptom rating scales were soon accepted as the method of evaluating their clinical effects. The Mini-compendium is a collection of rating scales for measuring outcome of antianxiety drugs, antidepressants, antimanics, and anti-psychotics. The scales have been selected by their “cash values”, i.e. the scales most frequently used for the respective dimensions. These scales have been further developed in terms of strict item definitions. The simple sum of the individual scale items has been considered as a sufficient statistic if they fulfilled latent structure analysis of shared phenomenology.
The flexible brain. On mind and brain, neural darwinism and psychiatry
Authors: den Boer J.A.
Published: July 2016

A theoretical introduction is given in which several theoretical viewpoints concerning the mind-brain problem are discussed. During the last decade philosophers like Searle, Dennett and the Churchlands have taken a more or less pure materialistic position in explaining mental phenomena.

Investigators in biological psychiatry have hardly ever taken a clear position in this discussion, whereas we believe it is important that the conclusions drawn from biological research are embedded in a theoretical framework related to the mind-brain problem.

In this article the thesis is defended that the theory of neural darwinism represents a major step forward and may bridge previous distinctions between biological, clinical and social psychiatry.
Focal neurocognitive dysfunctions in abstinence delirium: a case report
Authors: Mariën P. , Borggreve F. , Spanoghe W. , Saerens J. , Pickut B.A. , Deyn P.P. De
Published: July 2016

Due to abrupt interruption of hidden benzodiazepine-use, a 68-year-old woman developed a full-blown abstinence delirium characterized by epileptic seizures and progressive focal neurocognitive symptoms. The evolution of such rare neuro-linguistic phenomena as an echoism, palilalia and glossomania associated with a progressive visuo-perceptive syndrome and a visual hallucinosis are for the first time reported within the context of withdrawal. Notwithstanding the lack of any neuroradiological evidence for a morphological lesion in the clinically expected brain regions, the anatomo-clinical hypothesis of a focal frontal and parieto-occipital dysfunction was explicitly corroborated by repeated 99mTc-HMPAO SPECT findings.
Literatuuronderzoek naar intacte cognitieve vaardigheden bij patiënten met dementie van het Alzheimer-type
Authors: Jelicic M. , Bonebakker A.E.
Published: July 2016

De onlangs overleden Willem de Kooning wordt alom beschouwd als één der grootste beeidende kunstenaars van de 20e eeuw. Hij werd in 1904 in Nederland geboren en emigreerde in 1926 naar de Verenigde Staten. Daar ontwikkelde de Kooning eind jaren veertig, samen met Jackson Pollock, Franz Kline en Mark Rotko, een nieuwe stroming binnen de schilderskunst: het abstract expressionisme. Het waren vooral zijn opzienbarende, semi-abstracte schilderijen over vrouwen die destijds veel stof deden opwaaien. Op 78-jarige leeftijd werd bij hem de ziekte van Alzheimer vastgesteld. Een jaar eerder, in 1981, was de Kooning, na enkele jaren zo goed als gestopt te zijn, wederom begonnen met schilderen. Tussen 1981 en 1986 produceerde hij zo'n 250 abstracte doeken.
Manic episode, thyroid gland function and lithium
Authors: Foeken K. , van de Wetering B.J.M.
Published: July 2016

This paper addresses the issue of (recurrent) mania in relation to an increased T4-value, whether or not influenced by lithium. Lithium has an anti-TSH-effect on the thyroid gland by inhibiting the intracellular enzyme adenylate cyclase. This might cause hypothyroidism. Moreover, lithium is also known to have a direct stabilizing effect on (behavioral manifestations) of dopamine receptor supersensitivity.

The hypothesis regarding the relation between thyroid function and affective disturbances is that the altered thyroid function may cause a change in the availability of the central dopamine receptors. Dopamine is known to be able to cause a manic state. TSH and TRH are also involved in this mechanism. It is, therefore, very likely that an increased thyroid function, whether or not caused by discontinuation of lithium-therapy, could induce a (recurrent) mania.
The effect of stress and psychosocial variables on natural killer cells: a review
Authors: Gerits P. , de Brabander B.
Published: July 2016

In this review we discuss the results of studies about the effect of stress, depression, anxiety, social support and various psychosocial treatments on numbers and activity of Natural Killer (NK) cells. In general a suppressive effect is observed among depressive persons and persons who react to stressfull events with feelings of helplessness and anxiety. Lack of social support also seems to engender immunosuppression including NK suppression. Various forms of psychosocial care seem to be able to undo these negative consequences. However, the real clinical relevance of these findings is still a matter of dispute.
The use of thyroid hormone in the treatment of depression: a review
Authors: Vegt M. , Bruijn J.A. , Birkenhäger T.K.
Published: July 2016

The writers of this paper made an inventory of the studies on the use of thyroid hormone in the treatment of depression. Fifteen clinical trials (353 patients), published between 1969 and 1987. were found, that can be described, as to their design, in two seperate groups:

One group (7 studies) administers thyroid hormone simultaneously with a tricyclic antidepressant to reach a faster effect of the antidepressant. The other group (8 studies) adds thyroid hormone to a tricyclic antidepressant in patients who fail to respond to this treatment, with the aim to convert therapeutic failure to success. After studying the literature we think we are able to conclude that it can be usefull to combine the antidepressant with thyroid hormone in view of the fact that, in a number of depressed patients, it shortens the duration of the illness. The augmentation of tricyclics by thyroid hormone needs further study.
Psychofarmakologikum VI
Authors: Pieters G.
Published: July 2016

Inleiding

In deze rubriek zal worden ingegaan op recente observaties betreffende de psychofarmakologie in de breedst mogelijke zin. Vaak zullen zaken uit de Literatuur worden behandeld. De gekozen onderwerpen dienen altijd klinische relevantie te hebben. Ook zal deze rubriek gaan over gewoontes die in psychofarmakologische behandeling of in onderzoek zijn geslopen die volgens de auteur lang niet altijd logisch zijn. Soms zal deze rubriek een oproep bevatten om te reageren op een bijdrage gepubliceerd in dit of in een ander tijdschrift. Ook zal de lezer worden aangemoedigd hier zijn eigen ervaringen mee te delen. Het is niet de bedoeling in deze rubriek onderzoeken uitvoerig te rapporteren. Daarvoor staan andere pagina's van de Acta Neuropsychiatrica voor u open.
A rare complication of carcinoÏd carcinoma
Authors: Broek W.W. Van Den , Pepplinkhuizen L.
Published: July 2016

In this case report of a patient with carcinoid carcinoma we discuss the normal metabolism of tryptophan, one of the essential amino acids.

We also examined the changes of this metabolism due to the metastasis of the carcinoid carcinoma and its psychiatric complications based on a central tryptophan deficiency.

A less frequent complication of the changes in the tryptophan metabolism due to carcinoidosis is the disease pellagra. This disease is always accompanied with psychiatric symptoms. It plays an important role in the development of the transmethylation hypothesis of schizophrenia.
Klinefelter syndroom en psychiatrische stoornissen: Twee gevalsbeschrijvingen en een literatuuroverzicht
Authors: Michielsen P.J.S. , Verhoeven W.M.A. , de Blécourt C.V.
Published: July 2016

Klinefelter syndrome is a genetically determined disorder characterized by an additional X-chromosome. Apart from the phenotypical features, the literature about this disorder mentiones a psychopathological phenotype comprising mainly psychoses, depressive diseases and personality disorders. A substantial number of patients presents with mild to moderate mental retardation.

In this paper, two case reports are described and their psychopathology is compared with the data from the existing literature.
Genetics of bipolar disorders
Authors: Souery D. , Massat I. , Mendlewicz J.
Published: July 2016

Advances towards the understanding of the etiological mechanisms involved in mood disorders provide interesting yet diverse hypotheses and promising models. In this context, molecular genetics has now been widely incorporated into genetic epidemiological research in psychiatry. Affective disorders and, in particular, bipolar affective disorder (BPAD) have been examined in many molecular genetic studies which have covered a large part of the genome, specific hypotheses such as mutations have also been studied. Most recent studies indicate that several chromosomal regions may be involved in the aetiology of BPAD. Other studies have reported the presence of anticipation in BPAD. This phenomenon describes the increase in clinical severity and decrease in age of onset observed in successive generations. This mode of transmission correlates with the presence of specific mutations (Trinucleotide Repeat Sequences) and may represent a genetic factor involved in the transmission of the disorder. In parallel to these new developments in molecular genetics, the classical genetic epidemiology, represented by twin, adoption and family studies, provided additional evidence in favour of the genetic hypothesis in mood disorders. Moreover, these methods have been improved through models to test the gene-environment interactions. While significant advances have been made in this major field of research, it appears that integrative models, taking into account the interactions between biological (genetic) factors and social (psychosocial environment) variables offer the most reliable way to approach the complex mechanisms involved in the etiology and outcome of mood disorders.
Epidemiology and pathobiology of bipolar disorder, and their exploration within a complete catchment area population
Authors: Scully P.J. , Owens J.M. , Kinsella A. , Waddington J.L.
Published: July 2016

Epidemiological and pathobiological findings in bipolar disorder [BP] have often been limited by selection bias and lack of epidemiological representativeness. In a rural, circumscribed catchment area, ‘all’ patients with BP were identified and assessed. On preliminary analysis, morbid risk [MR] for BP over the area as a whole was 5.0 ± 0.6/1000. The distribution of MR for BP over geographical subregions showed no significant deviation from a statistical model for random occurrences in space by place at birth, in contrast to schizophrenia [SZ], and varied only modestly among males by place at onset. These results imply different etiological factors acting in BP in comparison with SZ, particularly with regard to the role of early versus later life events. In preliminary analyses of psychotic and cognitive features, current severity of positive symptoms was predicted in BP only by increasing dominance of the left hand; negative symptoms by duration of illness and current anticholinergic exposure; poorer general and frontal cognitive function by older age at onset of illness, increasing duration of illness, and current anticholinergic exposure. The finding on handedness suggests disturbance of cerebral asymmetry associated with positive symptoms in BP, while both negative symptoms and cognitive impairment may involve progressive processes. Further analysis of this epidemiologically complete population, including systematic comparisons of BP with schizoaffective disorder and SZ, continues.
Towards a new model for cellular pathophysiology in affective disorder
Authors: Normann C.
Published: July 2016

The mode of action of serotonin in depression is unclear. We tested the modulation of hippocampal long-term plasticity, a model for learning and memory, by 5-HT and found a selective impairment of long-term depression resulting in a positive modification of synaptic network properties. We hypothetize a role for long-term plasticity in emotional regulation and the pathophysiology of affective disorders.
Pediatric mania: a developmental subtype of bipolar disorder?
Authors: Biederman J. , Mick E. , Faraone S.V. , Spencer Th. , Wilens T. , Wozniak J.
Published: July 2016

Despite ongoing controversy, the view that pediatric mania is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include:

- its pattern of comorbidity may be unique by adult standards, especially its overlap with ADHD, aggression and conduct disorder;

- its overlap with substance use disorders;

- its association with trauma and adversity;

- its response to treatment is atypical by adult standards.

These issues will be reviewed in the presentation.
Neural mechanisms of childhood-onset bipolar illness
Authors: Post R.M. , Leverich G.S. , Speer A.M. , Xing G. , Weiss S.R.B.
Published: July 2016

Substantial evidence exists for a cohort effect (earlier onset and increased prevalence) for both unipolar and bipolar affective disorder in every generation born since World War II. This effect could be related to inherited mechanisms (e.g., bi-Hneal pedigrees or genetic anticipation) or to environmental/experiential effects on gene expression (e.g., stressor effects on the induction of transcription and growth factors, enzymes, hormones and their receptors, and signal transduction molecules) as documented in preclinical models of neonatal maternal separation.

This laboratory evidence is summarized and new clinical data on the impact of severe stressors on the unfolding course of bipolar illness are noted. The reported occurrence of childhood or adolescent physical or sexual abuse, compared to those who report their absence, is associated with: earlier bipolar illness onset; faster cycling (including ultradian) patterns; increased Axis I and II comorbidities; and increased time ill in a prospective year of follow-up. Selectively, physical abuse was associated with a reported pattern of increasingly severe mania and sexual abuse with increased numbers of serious suicide attempts.

In a retrospective survey of parents of children with an approximate average age of 13 who were diagnosed with bipolar illness (compared to those with other diagnoses and those with no diagnosis), a cluster of symptoms related to irritability and dyscontrol differentiated the bipolar children earliest. These symptoms included: temper tantrums, irritability, inattention, hyperactivity, impulsivity, poor frustration tolerance, and increased aggression.

Given the growing evidence that episodes of affective dysfunction can not only convey morbidity and mortality, but may also sensitize to further recurrence and thus change the course of illness, opportunities abound for early recognition and intervention in childhood onset bipolar illness. Such a successful endeavor would both allow a more normal psychobiological development and allow the possibility of preventing the unfolding of more full-blown bipolar illness altogether.
Different modes of action of alprazolam in the treatment of panic attacks
Authors: Gool Dominique Van
Published: July 2016

Alprazolam (a benzodiazepine in the group of the triazolo-benzodiazepines) is a potent drug for the treatment of panic disorder. This is possible due to four different interactions with neurotransmitter systems. First, it facilitates, as all diazepines, the inhibitory acitivity of gamma-amino-butyricacid (GABA). The chemical structure differs from the benzodiazepines by incorporation of the triazoloring. Due to this triazoloring, the drug has three additional modes of action. These modes of action inhibit the locus coeruleus which plays a role in the origin of panic disorder. A first specific action is a stimulation of the serotonergic system. Triazolobenzodiazepines are also α2-adrenoreceptor agonists. Both mechanisms are responsible for inhibition of the locus coeruleus. Triazolo-benzodiazepines inhibit the platelet-activating-factor (PAF). PAF stimulates the corticotropin-releasing-hormone (CRH). This hormone stimulates the locus coeruleus. CRH in patients with panic attacks is elevated. This could be a result of hyperactive metabolism of the right parahippocampal area, which is observed in patients with panic attacks. Triazolo-benzodiazepines decrease the activity of the locus coeruleus because of a low CRH-level due to inhibited PAF.
Neurologic and psychiatric symptoms following chronic phenytoin intoxication
Authors: Boermans J.A.J. , Nijdam JR.
Published: July 2016

Reported (ir)reversibility of neurological and psychiatric symptoms induced by Phenytoin intoxication is being discussed by means of a case report concerning a 40-year old man who sets fire to his house during a psychosis. Observation after admission to a general psychiatric hospital, following a short period of detention, leads to diagnosing neurological and psychiatric symptoms due to chronic Phenytoin intoxication. Discontinuation of Phenytoin supply induces partial remission of the symptoms. Literature on the subject is being revised.
Brain alterations in depression
Authors: Hoogendijk Witte J.G. , Meynen Gerben , Eikelenboom Piet , Swaab Dick F.
Published: July 2016

This article describes a number of studies by our research group to find brain structures that may be involved in the symptoms of idiopathic depression, depression in Alzheimer's disease and depression in Parkinson's disease. Until recently, idiopathic depression has generally been related to deficiencies of aminergic systems. In Alzheimer patients we found a strong decrease in the number of neurons in the locus coeruleus and brain noradrenaline concentrations, but in depressed Alzheimer patients we did not find an extra de crease. This is in agreement with the finding that there is no cell loss in the locus coeruleus in idiopathic depression. We did find, however, that the number of corticotropin-releasing hormone-, vasopressin- and oxytocin expressing neurons, the number of corticotropin-releasing hormone neurons co-expressing vasopressin and the amount of corticotropin-releasing hormone -mRNA in idiopathic depression were strongly increased in the paraventricular nucleus of the hypothalamus. This result supports the hypothesis on the pathogenetic involvement of the hypothalamo-pituitary-adrenal axis in depression and is of clinical relevance, since it may provide a theoretical rationale for antidepressive therapy with CRH antagonists.
Cardiopsychiatry
Authors: Honig A.
Published: July 2016

Affective disorders cluster in patients with cardiac diseases, in particular in coronary artery disease (CAD) which has become one of the most prevalent chronic disorders in the western world. Affective dysregulation has been recognized as a major riskfactor for cardiac death in patients with CAD. Therefore treatment of affective dysregulation is important from both the psychiatric and cardiac perspective. An evidence based treatment algorithm for affective disorders is as yet not available. In this paper a possible etiological model for the relationship between affective and cardiac dysregulation is proposed, based on the stress-diathesis model.
Whiplash associated disorders: is there a place for psychiatrists and psychologists?
Authors: Verhey F.R.J. , Stapert S.Z. , Jolles J.
Published: July 2016

Between 25 and 30% of the victims of a whiplash injury have complaints after one year. This condition is referred to as late whiplash syndrome. This syndrome is characterized by pain of the neck, headache, forgetfulness, poor concentration, mental fatigue, and affective symptoms. The causes of the persistent symptoms are unknown. In all, the evidence that late-whiplash syndrome is a neurological disorder is flimsy. Current opinion holds that the acute basis is the painful injury of the neck. In the months following the accident, pain is the substrate on which psychological and social factors may act. Emotional symptoms such as lability of affect and disturbed mood, or posttraumatic stress disorders are common after whiplash. Although there is definitely a place for psychiatrists and psychologists in the treatment of late whiplash syndrome, these professionals are not involved in late whiplash disorder as much as they should be. Brief psychological treatment has proven to significantly reduce the severity and duration of symptoms. Optimal management must cover the treatment of pain, depression, anxiety, and fatigue; adequate psycho-education, stressing the good long-term outcome; and education of patients and relatives on possible cognitive symptoms.
Positron emissie tomografie (PET) bij stemmingsstoornissen: een overzicht
Authors: Van Eyken N. , D'haenen H.
Published: July 2016

Positron emission tomography is one of the most important techniques of functional imaging in psychiatry. This paper gives a synopsis of the findings in mood disorders: determination of brain glucose metabolism, cerebral blood flow and receptor studies. Investigation in a resting state as well as after activation are discussed.

Although findings are somewhat discrepant hypometabolism, and/or hypoperfusion, most often in frontal and limbic areas are frequently described. Further research is needed, and standardization of the methodology would be most wellcome.
Therapeutic drug monitoring
Authors: Noten J.B.G.M. , Verhoeven W.M.A. , Tuinier S. , Touw D.
Published: July 2016

The cytochrome P450 iso-enzyme system plays a key role in the biotransformation of many drugs, including psychotropics. Its activity is determined by both genetic and environmental factors. The most important iso-enzymes for psychiatry in general are P450 IID6, 3A4 and 1A2. Knowledge about the involvement of these enzymes and biotransformation processes is mandatory because of the individual variability in their metabolic capacity. Regular measurement of plasmaconcentrations of (psycho)pharmacological compounds is therefore essential. In addition, the potential value of pheno- and/or genotyping has to be investigated.
Integratie van opleiding en onderzoek in de opleiding tot psychiater
Authors: Verhoeven W.M.A. , Goessens L.F.M. , van den Berg Y.W.M.M. , Tuinier S.
Published: July 2016

In the training program for residents in psychiatry, scientific education and participation in research projects are relatively underdeveloped. This may result in a gap between recently acquired scientific knowledge and its implementation in clinical practice.

Since the start of the residency training in psychiatry in 1989 in the Vincent van Gogh Institute for Psychiatry, several research lines have been developed especially concerning dimensional diagnostic procedures, evaluation of treatment effects, stress and psychopathology, pharmacokinetics of psychotropic compounds and disordered impulse and aggression regulation. It is concluded that active participation in research projects by both psychiatrists and residents in psychiatry is increasingly mandatory due to social-economic en scientific developments. Despite several countervailing factors, the Vincent van Gogh Institute for Psychiatry has succeeded in the creation of a scientific orientation in the residency program resulting in a number of publications.
Leeftijdsgeassocieerde cognitieve functiestoornissen: Cognitive aging in a longitudinal perspective: the Maastricht Aging Study (MAAS)
Authors: Jolles J. , Boxtel M.P.J. van , Ponds R.W.H.M. , Metsemakers J.F.M. , Houx P.J.
Published: July 2016

Cognitive dysfunctions in old individuals can be a precursor of dementia. The Maastricht Aging Study (MAAS) was designed to characterize the usual and pathological aging of cognitive function. The study involves a group of 1,900 initially healthy individuals who will be followed-upfor a period of 12 years with respect to health characteristics and neurocognitive status. For this purpose a sample was drawn from a patient register of collaborating family practices, stratified for age (range 24 to 81 years), sex and general ability level. Rationale and design of MAAS are discussed and also some findings from the cross-sectional baseline measurement: general aspects of memory and attention, cognitive functioning after brain trauma and general anesthesia, physical condition (fitness, morbidity and vascular risk factors) as predictor of cognitive function, and finally cognitive complaints and metamemory.
Psychobiological aspects of Sensation Seeking Behavior
Authors: te Riele Y.L.M. , Colon EJ.
Published: July 2016

Samenvatting

Sensation Seekers zijn personen die vrijwillig levensgevaarlijke situaties opzoeken. Sensation Seeking gedrag kan sociaal en lichamelijk schadelijke effecten hebben. In vergelijking met controlegroepen zijn bij Sensation Seekers significante ver-schillen aangetoond in verscheidene psychobiologische reacties die optreden bij informatieverwerking.
The significance of the expression of Fos protein in the brain for the classification of antipsychotics
Authors: Korf J. , Sebens J.B.
Published: July 2016

Samenvatting

In de afgelopen zes jaar is veel onderzoek verficht naar de effecten van antipsychotica op de regionale c-fos-expressie in de hersenen. Deze benadering biedt in een dierexperimentele proefopzet de mogelijkheid op cellulair niveau de effecten van psychofarmaca te bestuderen. Het fos-gen behoort tot de groep ‘immediate early genes’. Dit zijn genen die de transcriptie van andere, vaak onbekende genen reguleren. Een aantal aspecten van dit mechanisme wordt in deze bijdrage beschreven. Het onderzoek naar de effecten van antipsychotica op c-fos-expressie wordt samengevat en de betekenis voor de classificatie van antipsychotica benadrukt. Het blijkt dat deze farmaca effectief zijn in zowel de (meso)limbische gebieden (als nucleus accumbens, septum en amygdala) als ook in de basale ganglia. De relatieve effecten, wat betreft de c-fos-reactie, van de atypische antipsychotica (als clozapine en risperidon) zijn hoger in de limbische structuren, vergeleken met de effecten van de typische (als haloperidol). De potentie van de c-fos-methodiek voor verdere ontwikkelingen in dit gebied wordt aangegeven.
Obsessive compulsive disorder: Opportunities within and beyond the serotonergic domain
Authors: Zohar J. , Sasson Y.
Published: July 2016

Abnormality of the serotonin (5-hydroxytryptamine – 5-HT) system and particularly hypersensitivity of postsynaptic 5-HT receptors remained the leading hypothesis for the underlying pathophysiology of obsessive compulsive disorder (OCD) during the 1980s. A number of lines of evidence supported this serotonergic hypothesis, not least the treatment studies which demonstrated clearly and consistently that anti-obsessional efficacy was a function of serotonin re-uptake inhibition. Studies of markers and biological probes provided further evidence: platelet studies, for example, linked reductions in 5-HT activity with clinical response, and treatment response was correlated with decreased 5-hydroxyindolacetic acid (5-HIAA) levels within the cerebrospinal fluid of OCD patients.

Added to this was the evidence from the behavioral or physiological responses observed following serotonergic challenge with the serotonin agonists meta-chlorophenylpiperazine, a compound with high affinity for 5-HT1A-, 5-HT1D- and 5-HT2C-receptors.
Age-related cognitive decline and the borderland between normal aging and dementia
Authors: Jolles J.
Published: July 2016

It is now generally agreed that healthy individuals are characterized by cognitive decline during the later decades of adult life. The acquisition of new information becomes less efficient, which, coupled with a diminished retention of this information for later use, results in substantially poorer memory performance. The ability to plan new activities, solve problems and make complex decisions, as well as cognitive flexibility is noticeably diminished. In addition, attentional processes appear to be invariably poorer in old subjects than in young subjects (for review). While it is quite clearly established that elderly subjects (i.e. after 65 years of age) show a deterioration of cognitive functioning, there is also evidence that this deterioration may start in middle age (40 years). There is large individual variance in age groups; for instance, some old individuals perform on many neurocognitive tests as well as young individuals do. Rowe and Kahn proposed in their influential article to discern between successful aging and usual aging. Successful aging would be due to the effect of chronological age, whereas additional factors would be responsible for usual aging. An important point is the nature of the borderland between usual cognitive aging and pathological conditions such as dementia. Various health-related factors are thought to be important in this respect. They may be a determinant for the transition between successful aging to normal aging and into the borderland with dementia. The Brain & Behavior Research Institute in Maastricht investigates the determinants of successful and pathological aging in a number of related and multidisciplinary projects. This paper describes some major findings of this research programme and gives a theory on the interaction of vulnerability factors and protective factors in their effect on cognitive aging.
The role of the ‘central’ cholecystokinin-B receptor in panic disorder
Authors: Megen H.J.G.M. Van , Westenberg H.G.M. , Boer J.A. Den
Published: July 2016

Research investigating the neurobiological underpinnings of anxiety disorder have mainly been focused on dysfunction of the GABA, noradrenergic and serotonergic (5-HT) neuronal systems. Just recently, in both animal and human studies, evidence has been found for a possible role of the cholecystokinin (CCK) neuronal system in the pathogenesis of anxiety disorder.

Behaviorally, animal studies revealed anxiogenic-like properties for the ‘central’ CCKB receptor agonists, while CCKB receptor antagonists displayed intrinsic anxiolytic properties. Similarly, in man, CCKB receptor agonists, like pentagastrin and CCK4, were found to be able to elicited panic attacks in both panic disorder (PD) patients and healthy volunteers. These effects appear due to stimulation of the CCKB receptor. In addition, clinically effective panicolytic agents reduce the sensitivity to CCK4 in PD patients. Taken together, these findings may suggest a role for CCK in the neurobiology of PD. On the other hand, there is circumstantial evidence for involvement of several other neuronal systems, such as the serotonergic, noradrenergic and GABA-ergic system, in the regulation of anxiety. Interestingly, evidence has been found for an interaction between CCK and 5-HT and that this interaction plays a role in the mediation of anxiety.

This presentation will critically discuss the evidence for the role of the CCKB receptor in anxiety and in addition, will focus on the putative evidence that the role of CCK in anxiety is mediated by its interaction with the serotonergic neuronal system.
Benzodiazepinen in perspectief (I): De GABAA-benzodiazepine-receptor
Authors: Vermeulen P.J.L. , Zitman F.G.
Published: July 2016

In this first part of a review on recent insights into the structure and function of the γ-aminobuty rie acid type A - benzodiazepine receptor system, the γ-aminobutyric acid type A (GABAA) receptor and the different types of benzodiazepine (BDZ) receptors known at this moment are dicussed. GABAA- and BDZ receptors are coupled in a supramolecular GABAA-BDZ-ionophore receptor complex, each consisting of five acidic glycoprotein molecules called subunits. These subunits can be classified into five groups: α, β, γ, σ and ρ. Present evidence indicates the existence of multiple subtypes of these subunits. Multiple GABAA-BDZ receptors exist in the brain that show differential distribution and developmental patterns. These receptors differ from their subunit composition. The final functional properties of the receptor are determined by the different subunits constituting this receptor. Heterogeneity among α- subunits may determine the diversity of BDZ pharmacology in different regions of the nervous system.
The immune system mediates blood-brain barrier damage; possible implications for pathophysiology of neuropsychiatric illnesses
Authors: Werf Y.D. Van Der , Jongste M.J.L. De , Horst G.J. Ter
Published: July 2016

In this investigation the effects of immune activation on the brain are characterized. In order to study this, we used a model for chronic immune activation, the myocardial infarction, and intravenous injections with the pro-inflammatory cytokine Tumour Necrosis Factor alpha (TNF-α). The incentive for this study is the observation that myocardial infarction is accompanied by behavioural and neuronal abnormalities. The effects of myocardial infarction on the brain and its functioning are widespread. In order to examine the mechanism through which this interaction occurs, a group of rats underwent an experimentally induced myocardial infarction whereafter immunohistochemistry was performed on slices of the brain. This experiment revealed regional serum protein extravasation, pointing to leakage of the blood-brain barrier. This process occurred in certain cortical, subcortical and hindbrain areas in discrete patches. The leakage was co-localized with the expression of the immune activation marker ICAM-1. A second group of rats was therefore injected with TNF-α, a major pro-inflammatory cytokine, to assess the involvement of the immune system in the effects shown. This procedure rendered the same results. It is concluded that myocardial infarction may interfere with the integrity of the blood-brain barrier and possibly with brain functioning through activation of the immune system. The relevance for pathophysiological processes is discussed.
Melatonine en stemmingsstoornissen
Authors: Beullens J.
Published: July 2016

Melatonin is a hormone secreted by the pineal gland mainly during the night. The discovery that this melatonin secretion decreases under the influence of bright light, gave rise to the use of light therapy in some affective disorders. The literature on the relationship between melatonin secretion and mood is reviewed concerning seasonal affective disorder, non-seasonal affective disorder and premenstrual syndrome. Light therapy could reduce an abnormal high melatonin secretion back to normal proportions. None of the affective disorders, however, is accompanied by an unusual high melatonin level. Nevertheless, light therapy as well as other therapies that suppress melatonin have a therapeutic effect. This is not the case with the administration of melatonin. Mood is not affected by extra melatonin in seasonal affective disorder but it is in both other affective disorders. Melatonin plays a part in the pathogenesis of the affective disorders but it is not yet clear which one.
Circadian tuning of motivation. A little organ of yesterday?
Authors: Daan S.
Published: July 2016

The analysis of motivational systems underlying temporal organisation in animal behaviour has relied primarily on two conceptual functional frameworks: Homeostasis and biological clocks. Homeostasis is one of the most general and influential concepts in physiology. Walter Cannon introduced homeostasis as a universal regulatory principle which animals employ to maintain constancy of their ‘internal milieu’ in the face of challenges and perturbations from the external environment. Cannon spoke of “The Wisdom of the Body”, the collective of responses designed to defend the ideal internal state against those perturbations.
An interpersonal view on depression
Authors: Bouhuys A.L. , Geerts E. , Mersch P.P.A. , Jenner J.A.
Published: July 2016

Cognitive and behavioural processes may constitute a risk for onset and persistence of depression. People who become depressed frequently show enduring negative cognitions which predispose them to depression. In addition, interpersonal processes are supposed to contribute to the etiology and maintenance of depression. Depression-prone persons are presumed to display deficient or problematic social behaviours that elicit negative reactions in others, finally resulting in withdrawal by family and friends.

About 60% of human communication is non-verbal. An ethological approach may therefore contribute to reveal behavioural and cognitive vulnerability factors for depression onset or persistence. Various studies support this presumption: High levels of patients' observed behaviour indicating involvement in the interaction between depressives and clinicians at admission are related with persistence of depression.
Treatment indications for light therapy
Authors: Kasper S. , Neumeister A.
Published: July 2016

Light therapy (LT) has become increasingly popular in various countries around the world in the last decade. For instance, according to a recent survey carried out in Germany in 1992, 13% (n = 56) of all German psychiatric hospitals (n = 422) used LT for different treatment indications and another 8% indicated their interest to do so. Among university facilities LT is even more popular, with a percentage of 57%. Although the most frequently used treatment indication for LT is seasonal affective disorder (SAD) or its subsyndromal form (S-SAD) it is apparent that other forms of depression e.g. non-seasonal forms, either acute or chronic are also a target for this new treatment modality. There is a number of studies supporting the use of LT for SAD (for review), however there are just a few studies for non-seasonal depression or for the other treatment indications (for review).
Suppressing Electron Exposure Artifacts: An Electron Scanning Paradigm with Bayesian Machine Learning
Authors: Hujsak Karl , Myers Benjamin D. , Roth Eric , Li Yue , Dravid Vinayak P.
Published: July 2016

Electron microscopy of biological, polymeric, and other beam-sensitive structures is often hampered by deleterious electron beam interactions. In fact, imaging of such beam-sensitive materials is limited by the allowable radiation dosage rather that capabilities of the microscope itself, which has been compounded by the availability of high brightness electron sources. Reducing dwell times to overcome dose-related artifacts, such as radiolysis and electrostatic charging, is challenging due to the inherently low contrast in imaging of many such materials. These challenges are particularly exacerbated during dynamic time-resolved, fluidic cell imaging, or three-dimensional tomographic reconstruction—all of which undergo additional dosage. Thus, there is a pressing need for the development of techniques to produce high-quality images at ever lower electron doses. In this contribution, we demonstrate direct dose reduction and suppression of beam-induced artifacts through under-sampling pixels, by as much as 80% reduction in dosage, using a commercial scanning electron microscope with an electrostatic beam blanker and a dictionary learning in-painting algorithm. This allows for multiple sparse recoverable images to be acquired at the cost of one fully sampled image. We believe this approach may open new ways to conduct imaging, which otherwise require compromising beam current and/or exposure conditions.
Volcanic Eruptions Stir an Already Complex Atmosphere
Authors: Crane Leah
Published: July 2016

A study of Earth's atmospheric response to major volcanic eruptions seeks to reconcile contradictions between observations and climate models.
The ERK signaling target RNF126 regulates anoikis resistance in cancer cells by changing the mitochondrial metabolic flux
Authors: Yoshino Seiko , Hara Toshiro , Nakaoka Hiroki J , Kanamori Akane , Murakami Yoshinori , Seiki Motoharu , Sakamoto Takeharu
Published: July 2016

Loss of anchorage to the extracellular matrix leads to apoptosis (anoikis) in normal cells, but cancerous cells are usually resistant to such stress. Here we report the pivotal role of an E3 ubiquitin ligase, ring-finger protein 126 (RNF126), in the resistance of cancer cells to the stress associated with non-adherent conditions. Non-adherent cancer cells exhibited increased flux through the tricarboxylic acid cycle via increased conversion of pyruvate to acetyl-CoA. RNF126 was found to act as a ubiquitin ligase for pyruvate dehydrogenase kinases (PDKs), resulting in their proteasomal degradation. This decrease in PDK levels allowed pyruvate dehydrogenases to catalyze the conversion of pyruvate to acetyl-CoA. Moreover, depletion of RNF126 or increased expression of PDK1 in cancer cells suppressed colony formation in soft agar as well as tumorigenicity in mice. RNF126 expression in cancer cells was found to be under the control of the extracellular signal-regulated kinase signaling pathway, which is essential for anoikis resistance. Thus, RNF126 is an attractive molecule for treating cancer by selectively targeting anchorage-independent growth.
Healthy ageing of cloned sheep
Authors: Sinclair K. D. , Corr S. A. , Gutierrez C. G. , Fisher P. A. , Lee J.-H. , Rathbone A. J. , Choi I. , Campbell K. H. S. , Gardner D. S.
Published: July 2016

The health of cloned animals generated by somatic-cell nuclear transfer (SCNT) has been of concern since its inception; however, there are no detailed assessments of late-onset, non-communicable diseases. Here we report that SCNT has no obvious detrimental long-term health effects in a cohort of 13 cloned sheep. We perform musculoskeletal assessments, metabolic tests and blood pressure measurements in 13 aged (7–9 years old) cloned sheep, including four derived from the cell line that gave rise to Dolly. We also perform radiological examinations of all main joints, including the knees, the joint most affected by osteoarthritis in Dolly, and compare all health parameters to groups of 5-and 6-year-old sheep, and published reference ranges. Despite their advanced age, these clones are euglycaemic, insulin sensitive and normotensive. Importantly, we observe no clinical signs of degenerative joint disease apart from mild, or in one case moderate, osteoarthritis in some animals. Our study is the first to assess the long-term health outcomes of SCNT in large animals.
Dengue virus infection induces interferon-lambda1 to facilitate cell migration
Authors: Hsu Yu-Lin , Wang Mei-Yi , Ho Ling-Jun , Lai Jenn-Haung
Published: July 2016

A marked increase in the rate of dengue virus (DENV) infection has resulted in more than 212 deaths in Taiwan since the beginning of 2015, mostly from fatal outcomes such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms of these fatal manifestations are poorly understood. Cytokines induce an overwhelming immune reaction and thus have crucial roles. Interferon-lambda (IFN-λ), a newly identified IFN subtype, has antiviral effects, but its immunologic effects in DENV infection have not been investigated. In the present study, we show that DENV infection preferentially induced production of IFN-λ1 in human dendritic cells (DCs) and human lung epithelial cells. Virus nonstructural 1 (NS1) glycoprotein was responsible for the effect. DENV-induced production of IFN-λ1 was dependent on signaling pathways involving toll-like receptor (TLR)-3, interferon regulation factor (IRF)-3, and nuclear factor-kappaB (NF-κB). Blocking interaction between IFN-λ1 and its receptor IFN-λR1 through siRNA interference reduced DENV-induced DC migration towards the chemoattractants CCL19 and CCL21, by inhibiting CCR7 expression. Furthermore, IFN-λ1 itself induced CCR7 expression and DC migration. Our study presents the first evidence of the mechanisms and effects of IFN-λ1 induction in DENV-infected DCs and highlights the role of this cytokine in the immunopathogenesis of DENV infection.
ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells
Authors: Wee Boyoung , Pietras Alexander , Ozawa Tatsuya , Bazzoli Elena , Podlaha Ondrej , Antczak Christophe , Westermark Bengt , Nelander Sven , Uhrbom Lene , Forsberg-Nilsson Karin , Djaballah Hakim , Michor Franziska , Holland Eric C.
Published: July 2016

Glioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 using the side population assay, and their characteristics include increased self-renewal, high stem cell marker expression and high tumorigenic capacity in vivo. Here, we show that ABCG2 can actively drive expression of stem cell markers and self-renewal in glioma cells. Stem cell markers and self-renewal was enriched in cells with high ABCG2 activity, and could be specifically inhibited by pharmacological and genetic ABCG2 inhibition. Importantly, despite regulating these key characteristics of stem-like tumor cells, ABCG2 activity did not affect radiation resistance or tumorigenicity in vivo. ABCG2 effects were Notch-independent and mediated by diverse mechanisms including the transcription factor Mef. Our data demonstrate that characteristics of tumor stem cells are separable, and highlight ABCG2 as a potential driver of glioma stemness.