The neurobiological basis of fear : a concise review

Anxiety disorders are amongst the most common psychiatric disorders affecting approximately 25% of all adults. Fear and anxiety have many shared neuroanatomical and neurochemical characteristics. In this paper we refer to a) fear conditioning, (i.e. after a harmless and an aversive stimulus have coincided, the harmless stimulus encountered on its own will cause fear), b) the fear response, including the effects on the hypothalamo-pituitary-adrenal (HPA) axis, c) sensitization, which refers to a general hyperresponsivity of the fear circuits, d) fear memory, and e) extinction, the new learning that the harmless stimulus no longer forecasts a threat. The role of the amygdala and long-term potentiation (LTP) are discussed. Possible anatomical correlates of anxiety disorders and different therapeutic modalities, including the novel drug D-cycloserine, are briefly discussed

Supportive neurodevelopmental evidence for ADHD as a developmental disorder

A baby is dependent on its primary caregiver (hereafter referred to as ‘mother’) for its emotional regulation. The development of emotional self-regulation is dependent on the growth and myelinisation of connections between cortical (control) and limbic (emotion) structures in the infant brain. The subcortical sympathetic limbic system is dominant from birth, and it is only at 14–18 months of age that the parasympathetic cortical inhibitory part develops. The maturation of specifically the right orbitofrontal cortex, which dominates both the sympathetic and parasympathetic limbic systems, is essential for the regulation of emotion for the rest of an individual’s life. Behavioral hyperactivity, impulsivity and inattention are considered normal for children in the early practising phase (10–14 months). This stage is characterised by sympathetic dominance stimulated by the ventral tegmental limbic circuit. We hypothesise that children with Attention Deficit Hyperactivity Disorder remain stuck in this phase, and accordingly do not enter the next stage of emotional development, i.e., the late practising period, in which the lateral tegmental limbic circuit, which stimulates the parasympathetic system develops. Parental reactions, which may contribute to this block in emotional development, include: largely ignoring their child, until the child does something the parent disapproves of, then scolding the child, without consoling the child again afterwards. This leads susceptible children to develop defensive hyperactivity and inattention in order to avoid a shame state they are unable to cope with. Implications for therapy are that caregivers should be taught firstly to give lots of positive attention to their child, and if necessary to scold, to console the child immediately afterwards. If this can be achieved consistently, the child will have the chance to develop their parasympathetic lateral limbic circuit, and eventually right orbitofrontal dominance over both limbic circuits, which translates into the ability to self-regulate their emotional states

Non-termination of sickness behavior as precipitating factor for mental disorders

Sickness behavior can be defined as a combination of coordinated behavioral and physiological changes that develop in response to any condition that elicits pro-inflammatory activity. It is an adaptational homeostasis initiated by the influence of pro-inflammatory cytokines on central nervous system neurohormonal functioning. This paper introduces the concept of non-termination of sickness behavior as a potential threat to mental health. In view of the similarities between the behavioral symptoms, the neuroendocrine and the cytokine profiles of sickness behavior and that of a number of mental disorders it is hypothesized that the inappropriate continuation of sickness behavior, (i.e., non-termination), after recovery from the initial disease, could form the basis for mental disturbances. This would be particularly relevant in individuals with alterations in stress vulnerability (altered activation threshold and impaired negative feedback), which may occur due to the combination of genetic disposition and priming by early life experiences

Dissociation: a developmental psychoneurobiological perspective: review article

Article includes commentary by Allan N. Schore. Dissociation can be defined as the failure to integrate experience. Dissociation is a common symptom of a spectrum of severe psychopathologies, from reactive attachment disorder of infants to dissociative identity disorders, psychotic experiences, borderline personality disorders and post-traumatic stress disorders of adults. The incidence of abuse in the childhood histories of adults with dissociative disorders is extremely high. The adaptational value of dissociation is that it allows survival in catastrophic events. The disadvantage is that when dissociation occurs frequently, the development of neural networks is impaired. Especially disadvantageous are problems which develop with a) higher circuit control over lower circuits, b) primitive parasympathetic regulation by the dorsal motor nucleus, c) memory, d) left hemisphere, e) integration of bodily sensations, f) sense of self, and g) affect and motivation. These aspects are discussed in more detail. The clinician's primary function is as an affect regulator and therapy should focus on integration. SA Psychiatry Rev. Vol.7(3) 2004: 11-12, 12, 16-1

The central noradrenergic system : an overview

The central noradrenergic system belongs to a group of brainstem neuromodulatory systems previously referred to as the ascending reticular activating system. In this article a heuristic model is presented of the central noradrenergic system depicting the major projections to other cerebral areas, its interactions with other neuromodulatory systems, mechanisms through which it can influence cerebral function, as well as the major functions and disorders associated with alterations in central noradrenergic activity. It is not the aim of this paper to provide fine detail on the various aspects, but rather to provide a concise overview where structure and function, as well as the interactions with other systems are brought together. The contents of the paper are summarized in a diagram.Mrs Sigi Dannheimer for assistance with Figure 1

Dissociation : a developmental psychoneurobiological perspective

Dissociation can be defined as the failure to integrate experience. Dissociation is a common symptom of a spectrum of severe psychopathologies, from reactive attachment disorder of infants to dissociative identity disorders, psychotic experiences, borderline personality disorders and post-traumatic stress disorders of adults. The incidence of abuse in the childhood histories of adults with dissociative disorders is extremely high. The adaptational value of dissociation is that it allows survival in catastrophic events. The disadvantage is that when dissociation occurs frequently, the development of neural networks is impaired. Especially disadvantageous are problems which develop with a) higher circuit control over lower circuits, b) primitive parasympathetic regulation by the dorsal motor nucleus, c) memory, d) left hemisphere, e) integration of bodily sensations, f) sense of self, and g) affect and motivation. These aspects are discussed in more detail. The clinician's primary function is as an affect regulator and therapy should focus on integration

The central noradrenergic system: an overview

The central noradrenergic system belongs to a group of brainstem neuromodulatory systems previously referred to as the ascending reticular activating system. In this article a heuristic model is presented of the central noradrenergic system depicting the major projections to other cerebral areas, its interactions with other neuromodulatory systems, mechanisms through which it can influence cerebral function, as well as the major functions and disorders associated with alterations in central noradrenergic activity. It is not the aim of this paper to provide fine detail on the various aspects, but rather to provide a concise overview where structure and function, as well as the interactions with other systems are brought together. The contents of the paper are summarized in a diagram.Mrs Sigi Dannheimer for assistance with Figure 1

Influence of chelidonine, an inhibitor of tubulin polymerisation on tyrosine kinase activity in normal, transformed and malignant cell lines

Chelidonine, a tertiary hexahydro-benzophenanthridine alkaloid is an inhibitor of tubulin polymerisation and has been revealed to arrest cells in G2/M. Since enhanced tyrosine kinase (TK) activity is linked to the transition from normal to the immortal malignant phenotype, the effect of 10 mM chelidonine was evaluated on TK activity in normal, transformed and malignant cell lines after 2 hours of exposure. Chelidonine caused a stimulation of TK activity in two normal cell lines (human foreskin fibroblast (Hs27) and normal monkey kidney (NMK)). In contrast, an inhibition of TK activity was observed in transformed human embryonic kidney (Graham 293) and transformed African green monkey kidney (Vero), as well as in human cervical carcinoma (HeLa) and squamous oesophageal carcinoma (WHCO5) cells. Hs27 cells exposed to chelidonine, revealed an increase in TK activity of 1.27-fold (P < 0.05). NMK cells showed a 1.15-fold increase in TK activity. A decrease in TK activity was observed in Graham 293 (0.91-fold) and Vero (0.45-fold) (P < 0.005) cells. In both HeLa and WHCO5 cells, the TK activity was reduced to 0.68-fold (P < 0.05) and 0.56-fold (P < 0.005) respectively. These data, including results from our previous studies, suggest a potential cross talk between the SAPK/JNK and TK signal transduction pathways and a possible differential effect of chelidonine on the phosphorylation status of role players involved in determining the length of G2 arrest in normal versus transformed and malignant cells

Hoekom skrik 'n mens vir koue pampoen?

Die onwillekeurige skrikreaksie vorm deel van die eerste vinnige vreesreaksies wat 'n organisme ervaar in respons tot 'n skielike bedreiging. Dit is voordelig in die sin dat dit 'n organisme toelaat om onmiddellik weg te beweeg van 'n voorwerp wat potensieel gevaarlik kan wees, terwyl die hoër breinsentra nog besig is om uit te werk of die voorwerp inderdaad gevaarlik is. Die skrikreaksie is daarop ingestel om die organisme te beskerm teen potensiële gevaar. Die onwillekeurige skrikreaksie onderlê wat in die omgangstaal bekend staan as "om te skrik vir koue pampoen", waar 'n individu skrik vir iets geheel en al onskadeliks, byvoorbeeld 'n tak wat aangesien word vir 'n slang - dus "eerder bang Jan as dooie Jan". Hierdie manuskrip poog om te verduidelik hoekom ons skrik, al besef ons 'n paar millisekondes later dat dit geheel en al onnodig was. Die onderliggende neuroanatomie, met verwysing na die direkte en indirekte (kortikale) bane waardeur sensoriese inligting die amigdala bereik, word hersien. Die fisiologie van die vreesreaksie word kortliks bespreek en die skrywe word afgesluit met 'n integrerende figuur

Probiotics diet supplements of live non-pathogenic micro-organisms

Meer as vier honderd spesies van verskillende kommensale mikroörganismes kom normaalweg op die mens se slymvliesoppervlaktes voor. Die verwantskap tussen hierdie mikroörganismes en die mens kan wissel van saprofities tot parasities tot simbioties. Twee van die belangrikste groepe van hierdie voordelige simbiotiese bakterieë ressorteer onder die genera Lactobacillus en Bifidobacterium wat onderskeidelik in die dunderm en kolon gevind word. Verlies of versteuring van die normale mukosale mikroflora kan bydra tot gesondheidsprobleme (soos diaree en voedselallergieë), en die terapeutiese of profilaktiese aanvulling van die normale flora is in sekere gastroïntestinale en immunologiese afwykings van waarde. Probiotika is dieet-aanvullende preparate wat bestaan uit lewende niepatogene mikroörganismes, wat natuurlik in die gastroïntestinale kanaal voorkom en wat die intestinale funksies, die mikrobiologiese balans, sowel as die algemene gesondheid verbeter wanneer dit in genoegsame hoeveelhede ingeneem word. Hierdie artikel bespreek meganismes waardeur probiotika die interne milieu kan bevoordeel, en gee 'n kort oorsig oor belangrike kliniese proewe op die profilaktiese en terapeutiese effekte van probiotika, sowel as moontlike newe effekte. Die geweldige toename in navorsing op die gebied van die natuurlike mikroflora en probiotika word gedeeltelik deur die kommersiële potensiaal van probiotiese preparate gedryf en talle hiervan is reeds in die handel beskikbaar. Die artikel sluit af met riglyne oor die beheer van die produksie en verspreiding van probiotiese preparate, soos gestel deur die Wêreld Gesondheidsorganisasie en aanbeveel in Suid-Afrika. More than four hundred species of different commensal micro-organisms exist on human mucosal surfaces. The relationship between these micro-organisms and their human host varies from saprophitic, to parasitic, to symbiotic. Two of the most important groups of the beneficial symbiotic bacteria resort under the genera Lactobacillus and Bifidobacterium, which are found in the small intestine and colon, respectively. Loss or disturbance of the normal mucosal microflora may contribute to health problems (e.g. diarrhoea and food allergies), and the therapeutic or prophylactic supplementation of the normal flora is of value in certain gastrointestinal and immunological disturbances. Probiotics are diet supplements which consist of live non-pathogenic micro-organisms, which occur naturally in the gastrointestinal tract and which improve intestinal functions, the microbiological balance, as well as general health when ingested in sufficient quantities. This article discusses mechanisms by which probiotics can enhance the internal milieu, and provides a short summary of important clinical trials on the prophylactic and therapeutic effects of probiotics, as well as possible side-effects. The tremendous increase in research on the topic of natural microflora and probiotics is prompted partially through the commercial potential of probiotics, of which many different types are already commercially available. The article concludes with guidelines for the control of the production and distribution of probiotics as stated by the World Health Organisation and as suggested in South Africa