Kc Kirkby

Inflammatory cytokines in general and central obesity and modulating effects of physical activity.

Context Chronic systemic inflammation in obesity originates from local immune responses in visceral adipose tissue. However, assessment of a broad range of inflammation-mediating cytokines and their relationship to physical activity and adipometrics has scarcely been reported to date. Objective To characterize the profile of a broad range of pro- and anti-inflammatory cytokines and the impact of physical activity and energy expenditure in individuals with general obesity, central obesity, and non-obese subjects. Design, Setting, and Participants A cross-sectional study comprising 117 obese patients (body mass index (BMI) ≥ 30) and 83 non-obese community-based volunteers. Main Outcomes Measures Serum levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α were measured. Physical activity and energy expenditure (MET) were assessed with actigraphy. Adipometrics comprised BMI, weight, abdominal-, waist- and hip-circumference, waist to hip ratio (WHR), and waist-to-height-ratio (WHtR). Results General obesity was associated with significantly elevated levels of IL-5, IL-10, IL-12, IL-13, IFN-γ and TNF-α, central obesity with significantly elevated IL-5, IL-10, IL-12, IL-13 and IFN-γ-levels. In participants with general obesity, levels of IL-4, IL-10 and IL-13 were significantly elevated in participants with low physical activity, even when controlled for BMI which was negatively associated with physical acitivity. Cytokines significantly correlated with adipometrics, particularly in obese participants. Conclusions Results confirm up-regulation of certain pro- and anti-inflammatory cytokines in obesity. In obese subjects, physical activity may lower levels and thus reduce pro-inflammatory effects of cytokines that may link obesity, insulin resistance and diabetes.

Attitudes toward psychiatry among students entering medical school

Objective:  To survey the attitudes of Australian medical students to determine their views about the relative attractiveness of psychiatry as a career compared with other specialities, and against findings from a North American study.

Cytokines as biomarkers in depressive disorder: current standing and prospects

Abstract The frequently observed co-occurrence of depressive disorders and inflammatory diseases suggests a close connection between the nervous and the immune systems. Increased pro-inflammatory and type 1 cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF)-α and interferon (IFN)-γ, appear to be an important link. Cytokines are synthesized by immune cells in the blood and peripheral tissues and by glial cells in the central nervous system (CNS). Evidence suggests that the blood–brain barrier (BBB) is permeable to cytokines and immune cells, and that afferent nerves, e.g. the vagus nerve, mediate the communication between peripheral inflammatory processes and CNS. Cytokines such as IL-1ß, TNF-α and IFN-γ seem to contribute to the pathophysiology of depression by activating monoamine reuptake, stimulating the hypothalamic–pituitary–adrenocortical (HPA) axis and decreasing production of serotonin due to increased activity of indolamine-2,3-dioxygenase (IDO). However, critical appraisal of these hypotheses is required, because cytokine elevation is not specific to depression. Moreover, several effective antidepressants such as amitriptyline and mirtazapine have been shown to increase cytokine production. When applying immunomodulatory therapies, these drugs may increase the risk of specific side effects such as infections or interact with antidepressant drugs on important functions of the body such as the coagulation system.

Controlled comparison of computer-aided vicarious exposure versus live exposure in the treatment of spider phobia

Forty-five participants diagnosed as having specific phobia of spiders were randomly assigned to one of three treatment groups: (a) computer-aided vicarious exposure; (b) therapist-delivered live exposure; (c) relaxation placebo. Each group received three 45-minute sessions. Phobic symptom severity was measured at pretreatment, post-treatment, and at a 3-month follow-up assessment with the Spider Questionnaire, Fear Questionnaire, Phobic Targets and Work Adjustment Ratings Scale, and a Behavioral Assessment Test with Subjective Units of Distress Rating Scale. The results showed that the computer-aided vicarious exposure was an effective treatment for spider phobia and comparable to live exposure therapy in significantly reducing phobic symptoms. Both the computer and live exposure treatments were more effective than the relaxation placebo treatment.

A pilot study of computer-aided vicarious exposure for obsessive-compulsive disorder

Objective: This study reports the use of an interactive computer program to instruct vicarious exposure and ritual prevention for obsessive-compulsive disorder (OCD). Method: Thirteen OCD volunteers and 10 non-OCD volunteers completed three 45-minute sessions at weekly intervals. Subjects with OCD completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Padua Inventory (PI) and the Beck Depression Inventory (BDI) 1 week prior to and 1 week after the three computer treatment sessions. Non-OCD subjects only completed these measures at baseline, allowing confirmation that they had no significant level of OCD symptomatology. Results: In the OCD subjects, scores fell significantly on the PI and BDI, and Y-BOCS scores fell non-significantly. Engagement in vicarious exposure with ritual prevention improved from sessions 1–3. Compared to the non-OCD participants, OCD subjects did less vicarious exposure in session 1 but not sessions 2 and 3. Performance of vicarious exposure by OCD subjects in session 1 correlated with pre-post improvement in PI and BDI scores. Conclusions: The vicarious exposure program may have a role to play as an adjunct in behaviour therapy.

Computer-aided vicarious exposure versus live graded exposure for spider phobia in children.

The efficacy of computer-aided vicarious exposure (CAVE) for the treatment of spider phobia in children was evaluated in a single blind, randomised, controlled trial. Twenty-eight participants, aged 10-17 years, received three 45-min sessions of either Live graded exposure (LGE), CAVE or were assigned to a Waitlist. Phobic symptomatology was measured at pre- and post-treatment, and at one month follow-up on a range of behavioural and subjective assessments. The results showed the superiority of the LGE treatment over the CAVE and Waitlist conditions. Effect sizes support CAVE treatment as being superior to the Waitlist and resulting in reductions of phobic symptomatology.

Consensus Paper: Cerebellum and Emotion

Over the past three decades, insights into the role of the cerebellum in emotional processing have substantially increased. Indeed, methodological refinements in cerebellar lesion studies and major technological advancements in the field of neuroscience are in particular responsible to an exponential growth of knowledge on the topic. It is timely to review the available data and to critically evaluate the current status of the role of the cerebellum in emotion and related domains. The main aim of this article is to present an overview of current facts and ongoing debates relating to clinical, neuroimaging, and neurophysiological findings on the role of the cerebellum in key aspects of emotion. Experts in the field of cerebellar research discuss the range of cerebellar contributions to emotion in nine topics. Topics include the role of the cerebellum in perception and recognition, forwarding and encoding of emotional information, and the experience and regulation of emotional states in relation to motor, cognitive, and social behaviors. In addition, perspectives including cerebellar involvement in emotional learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are briefly discussed. Results of this consensus paper illustrate how theory and empirical research have converged to produce a composite picture of brain topography, physiology, and function that establishes the role of the cerebellum in many aspects of emotional processing.

Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro

Changes within the immune system have been reported to contribute to the pathophysiology of bipolar disorder and epilepsy. Interestingly, overlapping results regarding the cytokine system have been found for both diseases, namely alterations of interleukins IL-1β, IL-2, IL-4, IL-6, and tumor necrosis factor-α (TNF-α). However, the effect of mood stabilizers and antiepileptic drugs (AEDs) on these cytokines has not been systematically evaluated, and their effect on IL-17 and IL-22, other immunologically important cytokines, has not been reported. Therefore, we systematically measured levels of IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in stimulated blood of 14 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as stimulant. Blood was supplemented with the mood stabilizers or antiepileptic drugs primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), valproic acid (VPA), oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), lithium, or no drug. IL-1β production was significantly decreased by PRM, CBZ, LEV, LTG, OXC, PB and lithium. IL-2 significantly decreased by PRM, CBZ, LEV, LTG, VPA, OXC, TPM and PB. IL-22 significantly increased by PRM, CBZ, LEV, OXC, TPM and lithium and decreased by VPA. TNF-α production significantly decreased under all applied drugs. The mechanism of action and side effects of mood stabilizers and AEDs may involve modulation of IL-1β, IL-2, IL-22 and TNF-α signaling pathways. IL-22 may be a research target for specific therapeutic effects of mood stabilizers and AEDs. These drugs might influence cytokine production by modulating ion channels and γ-aminobutyric acid (GABA) receptors of immune cells.

Comparison of the amnesic effects of midazolam and diazepam

Thirty patients undergoing gastroscopy received intravenous premedication with either midazolam or diazepam in a randomised double blind study. Mean dosages were similar for the midazolam (6.13 mg) and diazepam (6.4 mg) groups. Neuropsychological testing pre- and post-medication comprised the Wechsler Memory Scale, Complex Figure Test, Word Association Test, and a Tactile Memory Test. There was a significant impairment on post-medication tests requiring delayed recall of verbal, visual and tactile stimuli. Midazolam produced significantly greater anterograde amnesia than diazepam at similar mean dosages. With the exception of Digit Span and Associate Learning, cognitive tasks which do not require delayed recall were not affected. It is concluded that the amnesic deficit is discrete and not secondary to sedative effects.

Seasonal variation in hospital admission for bipolar disorder, depression and schizophrenia in Tasmania

Objective: Seasonal variation has been reported for both affective disorders and schizophrenia. The current study examines seasonal variation in admissions in schizophrenia, depression and bipolar disorder in Tasmania, the southernmost state of Australia.