Differential relationship between neurological and cognitive dysfunction in first episode psychosis patients and in healthy individuals.

The minor neurological and cognitive deficits consistently reported in psychoses may reflect the same underlying brain dysfunction. Still, even in healthy individuals minor neurological abnormalities are associated with worse cognitive function. Therefore, establishing which neurological and cognitive deficits are specific to psychosis is essential to inform the pathophysiology of this disorder. We evaluated a large epidemiological sample of patients with first episode psychosis (n=242) and a population-based sample of healthy individuals (n=155), as part of the AESOP study. We examined neurological soft signs using the Neurological Evaluation Scale (Buchanan and Heinrichs, 1989), and generalized and specific cognitive deficits (memory; verbal abilities; attention, concentration and mental speed; executive functions and working memory; language; visual constructual/perceptual abilities). In patients, more neurological signs across all subscales were associated with worse general cognitive function, while in controls this was only present for sensory integration and sequencing signs. Furthermore, in patients, but not in healthy individuals, more sensory integrative signs were associated with deficits in specific cognitive domains, such as memory, verbal abilities, language, visual/perceptual, executive function (p ranging <0.001-0.002); sequencing signs with language, executive function, and attention (p<0.001-0.004); and motor signs with poorer verbal abilities (p=0.001). These findings indicate the presence of specific associations between neurological and cognitive deficits in psychosis that are distinct from those of healthy individuals.

Neurological abnormalities and cognitive ability in first-episode psychosis.

BACKGROUND: It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS: To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD: Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS: Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS: Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

Neurological abnormalities and cognitive ability in first-episode psychosis.

BACKGROUND: It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS: To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD: Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS: Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS: Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the Æsop First-Onset Psychosis Study

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naý¨ve), 26 werereceiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22percent , p=0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15 percent larger in antipsychotic-free patients (p¼0.028), 17 percent larger in patients receiving atypicals (p¼0.01), and 30 percent larger in patients receiving typicals (p=0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (11 percent, p¼0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24 percent larger in patients with schizophrenia/schizophreniform disorder (n¼40, p=0.001), 19 percent larger in depressed patients (n¼13, p¼0.022), 16 percent larger in bipolar patients (n¼16, p¼0.037), and 12 percent larger in those with other psychoses (n¼9, p¼0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presenceof antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effecton pituitary volume, likely to be related to activation of prolactin-secreting cells...

Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the AEsop first-onset psychosis study.

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22%, p< 0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p=0.028), 17% larger in patients receiving atypicals (p=0.01), and 30% larger in patients receiving typicals (p<0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (+11%, p=0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n=40, p<0.001), 19% larger in depressed patients (n=13, p=0.022), 16% larger in bipolar patients (n=16, p=0.037), and 12% larger in those with other psychoses (n=9, p=0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (’SOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.

Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study.

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.