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A prospective study in treatment-resistant schizophrenic patients was performed over 10 years to evaluate the therapeutic response to clozapine and the variables related to this treatment. Eighty schizophrenic and schizoaffective patients (according to Diagnostic and Statistical Manual [DSM]-IIIR criteria), considered as refractory (previously resistant to at least two different typical neuroleptics), were studied. The average dose of clozapine was 267 mg/d. The clinical variables considered were: Brief Psychiatric Rating Scale (BPRS), number of admissions before and after clozapine treatment and the Strauss-Carpenter scale as measures of efficacy; Premorbid Adjustment Scale (PAS), to assess personal and social adjustment before illness; Karolinska Personality Scale (KPS) to assess stable traits of personality; and the Simpson-Angus scale as a measure of extrapyramidal symptoms. Sixty percent of patients showed a significant improvement after clozapine treatment. Side-effects were mild and well tolerated, with no cases of haematological disturbance and only five withdrawals because of adverse events. The severity of the episode, according to BPRS score and anxiety as a personal trait, are related to good prognosis. Other relationships between improvement and clinical and demographic variables are discussed.

Perinatal ethanol (EtOH) exposure is associated with high incidence of behavioral disorders such as depression and anxiety. The cerebral areas related with these consequences involve the corticolimbic system, in particular the prefrontal cortex, hippocampus, amygdala, and cingulate cortex, although the latter has not been thoroughly studied yet. Different animal models of prenatal or perinatal EtOH exposure have reported morphofunctional alterations in the central nervous system, which could explain behavioral disorders along life; these results focus on youth and adolescents and are still controversial. In the light of these inconclusive results, the aim of this work was to analyze adult behavior in CD1 mice perinatally exposed to low concentrations of EtOH (PEE) during gestation and lactation, and describe the morphology of the cingulate cortex and amygdala with a view to establishing structure/function/behavior correlations. Primiparous CD1 female mice were exposed to EtOH 6% v/v for 20 days prior to mating and continued drinking EtOH 6% v/v during pregnancy and lactation. After weaning, male pups were fed food and water ad libitum until 77 days of age, when behavioral and morphological studies were performed. Mouse behavior was analyzed through light-dark box and open field tests. Parameters related to anxious behavior and locomotor activity revealed anxiogenic behavior in PEE mice. After behavioral studies, mice were perfused and neurons, axons, serotonin transporter, 5HT, CB1 receptor (CB1R) and 5HT1A receptor (5HT1AR) were studied by immunofluorescence and immunohistochemistry in brain sections containing cingulate cortex and amygdala. Cingulate cortex and amygdala cytoarchitecture were preserved in adult PEE mice, although a smaller number of neurons was detected in the amygdala. Cingulate cortex axons demonstrated disorganized radial distribution and reduced area. Serotonergic and endocannabinoid systems, both involved in anxious behavior, showed differential expression. Serotonergic afferents were lower in both brain areas of PEE animals, while 5HT1AR expression was lower in the cingulate cortex and higher in the amygdala. The expression of CB1R was lower only in the amygdala. In

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The endocannabinoid system, which has been conserved evolutionarily from plants to vertebrates (Elphick & Egertová, 2005; Solymosi & Köfalvi, 2017), modulates synaptic transmission and consists of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), its endogenous ligands (anandamide and 2-arachidonoylglycerol) and enzymes involved in its metabolism (Lambert & Fowler, 2005). CB1R is widely expressed in the central nervous system in vertebrates, both in neurons and glial cells (Facchinetti, Del Giudice,

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