Miriam Garcia Brunstein

Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic implications.

Based on the neuromodulatory and homeostatic actions of adenosine, adenosine dysfunction may contribute to the neurobiological and clinical features of schizophrenia. The present model of adenosine dysfunction in schizophrenia takes into consideration the dopamine and glutamate hypotheses, since adenosine exerts neuromodulatory roles on these systems, and proposes that adenosine plays a role in the inhibitory deficit found in schizophrenia. Given the role of adenosine activation of adenosine A1 receptor (A1R) in mediating neurotoxicity in early stages of brain development, pre- and peri-natal complications leading to excessive adenosine release could induce primary brain changes (i.e., first hit). These events would lead to an adenosine inhibitory deficit through a partial loss of A1R that may emerge as reduced control of dopamine activity and increased vulnerability to excitotoxic glutamate action in the mature brain (i.e., second hit). Adenosine dysfunction is reasonably compatible with symptoms, gray and white matter abnormalities, progressive brain loss, pre- and peri-natal risk factors, age of onset, response to current treatments, impaired sensory gating and increased smoking in schizophrenia. Pharmacological treatments enhancing adenosine activity could be effective for symptom control and for alleviating deterioration in the course of the illness. Accordingly, allopurinol, which may indirectly increase adenosine, has been effective and well tolerated in the treatment of schizophrenia. Since much of the evidence for the adenosine hypothesis is preliminary and theoretical, further investigation in the field is warranted.

The Affective and Emotional Composite Temperament (AFECT) model and scale: A system-based integrative approach

UNLABELLED Based on many temperament frameworks, here we propose an integration of emotional and affective temperaments (the AFECT model), forming a common substrate for mood, behavior, personality and part of cognition. Temperament is conceived as a self-regulated system with six emotional dimensions: volition, anger, inhibition, sensitivity, coping and control. The different combinations of these emotional dimensions result in 12 affective temperament types, namely depressive, anxious, apathetic, obsessive, cyclothymic, dysphoric, irritable, volatile, disinhibited, hyperthymic and euphoric. We also developed and validated a self-report scale to evaluate this construct, the Affective and Emotional Composite Temperament Scale (AFECTS). METHODS Exploratory and confirmatory psychometric analyses were performed with the internet version of the AFECTS in 2947 subjects (72% females, 35±11years old). RESULTS The factors interpreted as volition, anger, inhibition, sensitivity, coping and control showed very good Cronbachs alphas for 5 dimensions (0.87-0.90) and acceptable alpha for inhibition (0.75). Confirmatory factor analysis corroborated this 6-factor structure when considering inhibition as a second-order factor with fear and caution as first-order factors (SRMR=0.061; RMSEA=0.053). In the Affective section, all 12 categorical affective temperaments were selected in the categorical choice, with 99% of volunteers identifying at least one adequate description of their affective temperament. LIMITATIONS Only the internet version was used in a general population sample. CONCLUSION The AFECT model provides an integrated framework of temperament as a self-regulated system, with implications for mental health, psychiatric disorders and their treatment. The AFECTS showed good psychometric properties to further study this model.