Rates of treated schizophrenia and its clinical and cultural features in the population isolate of the Iban of Sarawak: a tri-diagnostic approach

BACKGROUND: We present results of a study of treated rates of schizophrenia among the Iban of Sarawak, Malaysia. Most Iban live in longhouses, each comprising a kindred group of up to 300 individuals. Cultural practices such as minimal intermarriage with members of adjacent ethnic groups and in-depth genealogical knowledge make them a population suitable for genetic investigation. Iban culture is conducive to a focus on symptoms and illness, and to patterns of treatment-seeking behaviour that are enthusiastic and persistent. METHOD: We identified all known cases of psychotic disorder within a defined catchment area based on an exhaustive survey of available medical records. From corresponding Malaysian census data (91,056 persons), we report rates of treated schizophrenia in the Iban population, using three diagnostic systems, as well as the demographic and clinical characteristics of these individuals. RESULTS: The most frequent presenting complaints were insomnia and aggression. We found higher treated rates for narrowly defined schizophrenia among males, but no significant gender difference for age of onset. Estimates of treated rates to age 55 years (per 10,000) for narrow schizophrenia were 41.9 (ICD-10), 56.5 (DSM-IV), and 83 (RDC), while the rates for broad schizophrenia were 105.5, 103.2, and 107.5 respectively. CONCLUSIONS: Treated rates of schizophrenia were higher than the reported prevalence for many populations at risk, including many small-scale societies, although different methodological approaches may partly explain these findings. Given the cultural patterns of Iban treatment-seeking behaviour, treated rates of schizophrenia reported here may closely approximate the population prevalence of this disorder.     

Sustained neural activity associated with cognitive control during temporally extended decision making

Decision making has both cognitive and affective components, but previous neuroimaging studies in this domain predominantly have focused on affect and reward. The current study examined a decision-making paradigm that placed strong demands on cognitive control processes by making reward payoffs contingent upon decision-making history. Payoffs were maximized by choosing the option that, paradoxically, was associated with a lower payoff on the immediate trial. Temporal integration requirements were manipulated by varying, across conditions, the window of previous trials over which the reward function was calculated. The cognitive demands of the task were hypothesized to engage neural systems responsible for integrating and actively maintaining actions and outcomes over time and the top-down biasing of response selection. Brain activation was monitored with functional magnetic resonance imaging (fMRI) using a mixed-blocked and event-related design to extract both transient and sustained neural responses. A network of brain regions commonly associated with cognitive control functions, including bilateral prefrontal cortex (PFC), bilateral parietal cortex, and medial frontal cortex, showed selectively sustained activation during the task. Increasing temporal integration demands led to a shift from transient to sustained activity in additional regions, including right hemisphere dorsolateral and frontopolar PFC. These results demonstrate the contribution of cognitive control mechanisms to temporally extended decision-making paradigms and highlight the benefits of decomposing activation responses into sustained and transient components.     

Effects of intermittent hypoxia on sympathetic activity and blood pressure in humans

Sympathetic nerve activity and arterial pressure are frequently elevated in patients with obstructive sleep apnea (OSA). The mechanisms responsible for chronic sympathetic activation and hypertension in OSA are unknown. To determine whether repetitive apneas raise sympathetic nerve activity and/or arterial pressure, awake and healthy young subjects performed voluntary end-expiratory apneas for 20 s per min for 30 min (room air apneas). To accentuate intermittent hypoxia, in a separate group of subjects, hypoxic gas (inspired O2 10%) was added to the inspiratory port for 20 s before each apnea (hypoxic apneas). Mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA, peroneal microneurography) were determined before and up to 30 min following the repetitive apneas. Following 30 hypoxic apneas (O2 saturation nadir 83.1+/-1.2%), MSNA increased from 17.4+/-2.7 to 23.4+/-2.5 bursts/min and from 164+/-28 to 240+/-35 arbitrary units respectively (P<0.01 for both; n=10) and remained elevated while MAP increased transiently from 80.5+/-3.7 to 83.1+/-3.9 mm Hg (P<0.05; n=11). In contrast, in the subjects who performed repetitive apneas during room air exposure (O2 saturation nadir 95.1+/-0.8%), MAP and MSNA did not change (n=8). End-tidal CO2 post-apnea, an index of apnea-induced hypercapnia, was similar in the 2 groups. In a separate control group, no effect of time on MAP or MSNA was noted (n=7). Thus, repetitive hypoxic apneas result in sustained sympathetic activation and a transient elevation of blood pressure. These effects appear to be due to intermittent hypoxia and may play a role in the sympathetic activation and hypertension in OSA.     

An Abeta sequestration approach using non-antibody Abeta binding agents

Amyloid beta (Abeta) has been considered as a primary cause of Alzheimer's disease (AD), and Abeta lowering approaches have been tested. Active immunization against Abeta is one of several promising Abeta-lowering approaches. Two mechanisms have been proposed: enhancement of microglial phagocytosis and Abeta sequestration (also called "peripheral sink"). We hypothesized that Abeta sequestration without immune modulation is sufficient to reduce the brain Abeta load and have demonstrated effective sequestration with Abeta binding agents that do not stimulate an immune reaction. Recent reports from other groups showed two other non-immune related Abeta binding agents, which have no structural relation to compounds we previously tested, reduced brain Abeta after peripheral administration. Congo red is a chemically synthesized small molecule that has binding affinity to Abeta. In the present study, we tested three Congo red derivatives in Abeta plaque-forming mice at an early pathological stage. Unfortunately, peripheral administration for three weeks did not substantially alter brain Abeta load. Optimized Abeta binding agents with high affinity to soluble Abeta are necessary for the sequestration approach.     

Primary hyperaldosteronism with normokalaemia secondary to an adrenal adenoma (Conn's syndrome) in a 12 year-old boy

A 12-1/2 year-old boy presented to the Accident Department following an episode of dizziness and was found to be hypertensive. Investigations revealed primary hyperaldosteronism secondary to an adrenal adenoma (Conn's syndrome). He had normal electrolytes during the period of investigation and potassium concentrations were > or = 4.2 mmol/l on all but one occasion. The hypertension resolved following excision of the adrenal tumour. Normokalaemia with potassium >4.0 mmol/l is very unusual in patients with Conn's syndrome and has not been described in childhood before. Primary hyperaldosteronism needs to be considered in hypertensive children even when potassium concentrations are well within the laboratory reference range.     

Stereological analysis of microvascular parameters in a double transgenic model of Alzheimer's disease

Morphological alterations in microvasculature occur as a common finding in the brains of non-demented aged persons and patients with Alzheimer's disease. Quantifying the extent of this vascular pathology, however, has been complicated by systematic error (bias) associated with the applications of assumption- and model-based morphometric techniques to human and animal tissues. The current study used novel assumption- and model-free stereological approaches to quantify capillary parameters in the corpus callosum of a double amyloid precursor protein/presenilin-1 transgenic murine model of Alzheimer's disease. The results revealed significant reductions in the total number of capillary segments in white matter of transgenic mice compared to non-transgenic littermates, with no differences in total capillary length. These findings support the view that the expression of mutant human genes for beta-amyloid peptides alters the normal architecture of cerebral capillary vessels in the white matter of mouse brain, which may model microvasculature changes reported in Alzheimer's disease.     

Factor structure and construct validity of the Anxiety Sensitivity Index among island Puerto Ricans

The factor structure and convergent and discriminant validity of the Anxiety Sensitivity Index (ASI) were examined among a sample of 275 island Puerto Ricans. Results from a confirmatory factor analysis (CFA) comparing our data to factor solutions commonly reported as representative of European American and Spanish populations indicated a poor fit. A subsequent exploratory factor analysis (EFA) indicated that a two-factor solution (Factor 1, Anxiety Sensitivity; Factor 2, Emotional Concerns) provided the best fit. Correlations between the ASI and anxiety measures were moderately high providing evidence of convergent validity, while correlations between the ASI and BDI were significantly lower providing evidence of discriminant validity. Scores on all measures were positively correlated with acculturation, suggesting that those who ascribe to more traditional Hispanic culture report elevated anxiety.