Suckling as incentive to instrumental learning in preweanling rats.

Neonatal rats as young as 7 days of age learned, reversed, and retained a left-right discrimination with a nonlactating nipple as the incentive. These results have implications for the ontogeny of associative processes and for their neurological and neurochemical mediators.

Relationship between smooth pursuit eye-tracking and cognitive performance in schizophrenia.

The relationship between measures of smooth pursuit and neuropsychological performance was assessed in 20 unmedicated schizophrenics. Eye-tracking measures included gain, catch-up saccade parameters, and rate of saccadic intrusions. Neuropsychological measures included tests generally considered as "frontal": Wisconsin Card Sorting Test (WCST), Consonant Trigram Test (CTT), and Controlled Oral Word Association Test (COWAT). The Digit Symbol Test (DST), which is generally considered to be a measure of global functioning, was also included. Gain and other pursuit measures were significantly correlated with the DST and the COWAT, but were not correlated with the WCST or the CTT.

Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine.

Cognitive functions and psychopathology were assessed in 36 treatment-refractory schizophrenic patients before initiation of clozapine, and at 6 weeks and 6 months, thereafter. Before treatment, cognitive impairment was found in each measure of memory, attention, and executive function as compared with 26 normal controls. After both 6 weeks and 6 months of treatment, significant improvement occurred in the Controlled Oral Word Association Test, a measure of retrieval from reference memory. Improvement was also noted at 6 months in the Category Instance Generation Test, another measure of retrieval from reference memory, and in some, but not all, tests of executive function, attention, and recall memory. Clozapine treatment also resulted in significant improvement in Brief Psychiatric Rating Scale (BPRS) Total and Positive symptom scores at both 6-week and 6-month assessment points. There was some evidence for a relationship between improvement in psychopathology and cognitive function. The improvement in cognitive function during clozapine treatment could have consequences for capacity to work and social function.

An MRI study of adolescent patients with either schizophrenia or bipolar disorder as compared to healthy control subjects.

BACKGROUND: There are few imaging studies in adolescent patients with either schizophrenia or bipolar disorder. Such studies are of interest because adolescents may have a more severe illness and neurodevelopmental events may have a greater role in their pathophysiology. METHODS: We compared 20 patients with schizophrenia and 15 patients with bipolar disorder (10 to 18 years) to 16 normal adolescents on magnetic resonance imaging (MRI) measures of intracranial volume and ventricular and sulcal enlargement. Two planned comparison contrasts were employed, one comparing the two patient groups to each other (contrast 1), and one comparing both patient groups combined to control subjects (contrast 2). RESULTS: None of the contrast 1 comparisons (schizophrenia vs bipolar) were statistically significant. Contrast 2 comparisons (control subjects vs patients) were statistically significant for intracranial volume (reduced in patients) as well as frontal and temporal sulcal size (increased in patients). CONCLUSIONS: The patient groups were not statistically significantly different from each other on any measure. The combined patient groups were different from control subjects on intracranial volume and frontal and temporal sulcal size. Also, there was evidence for ventricular enlargement, after removal of a control subject with an extreme value. These findings indicate that the same abnormalities noted in adult populations are present in adolescents.

Cognitive impairment in adolescents with schizophrenia.

OBJECTIVE: The purpose of this study was to determine whether adolescent schizophrenia is characterized by neuropsychological deficits. METHOD: The performance on a battery of neuropsychological tests of 17 adolescents with schizophrenia (mean age = 15.71 years) was compared with that of 17 normal adolescents (mean age = 15.12 years). RESULTS: Compared with the normal subjects, the patients were impaired on 10 of the 13 measures; larger effect sizes were shown for measures involving working memory and attention than for those involving secondary memory, generative naming, and executive functions. CONCLUSIONS: Adolescents with schizophrenia have generalized cognitive dysfunction, which is most apparent on tests of attention and working memory.

Treatment and outcomes in adolescents with schizophrenia.

The pharmacologic treatment and assessment of outcomes in adolescents with schizophrenia have been inadequately addressed. Structural brain imaging and brain function studies both point to a continuity between adolescent and adult stages of schizophrenia. Because the teenage population seems to be less tolerant of physical side effects, the advent of atypical antipsychotic medications may offer increased safety and efficacy. Studies support the notion that adolescent illness is associated with a more severe form of schizophrenia and that length of illness before treatment is correlated with long-term outcome. As a consequence, the authors recommend assertive pharmacologic intervention in adolescents with schizophrenia and future research focused on the issues of treatment and outcome in teenagers suffering a psychotic disorder.

Schedule-induced polydipsia: the role of oral and plasma factors.

To appreciate the contribution of oral and post-absorptive factors in the control of schedule-induced polydipsia (SIP), body fluid balance was determined at various times into the 4 hr session. Although dehydrated at the start of the session, rats quickly returned to normal balance which was maintained, despite excessive intake, by a brisk water diuresis. Plasma, as measured via the T-1824 technique, was also normal. Gastric infusion of water following each pellet delivery failed to eliminate the polydipsia despite marked hemodilution, whereas, oral infusion of equivalent amounts of water completely abolished the phenomenon. Taken together, these results suggest that SIP is mediated by oropharyngeal rather than hydration controls.

Adolescent schizophrenia: a methodologic review of the current neuroimaging and neuropsychologic literature.

This paper reviews all relevant articles that reported structural neuroimaging or neuropsychological data in adolescent patients with schizophrenia. These papers were subsequently examined from a methodological perspective. Few papers have been written that have examined whether adolescent schizophrenia is associated with structural neuroimaging abnormalities or cognitive dysfunction. In these studies, major methodologic issues exist. Therefore, at present, firm conclusions cannot be made regarding the presence or absence of neuropsychologic dysfunction or structural neuroimaging abnormalities in this population. Attention to certain methodologic issues may improve future studies of this topic.

Brain activation during silent word generation evaluated with functional MRI.

This is a study of word generation during functional MRI (fMRI). Eleven normal healthy subjects were instructed to generate words covertly, (i.e., silently) that began with particular letters. Images were acquired on a conventional 1.5T scanner at three contiguous axial planes encompassing language-related areas of the temporal and frontal lobe. The data were analyzed at the level of a Talairach box, after individually fitting the proportional Talairach grid system to each slice. The main variable of interest was the number of activated pixels within a Talairach box. Boxes with a significant increase in the proportion of activated pixels were located in three regions of the left neocortex: (1) Brodmann areas 44 and 45 in the dorsolateral frontal cortex (Broca's area), (2) areas 21 and 37 in the temporal cortex, (3) and the striate/extrastriate cortex (areas 17 & 18). The results are discussed in terms of a cognitive model of word generation and are compared, in detail, with the results of prior relevant imaging studies.

Attention and higher cortical functions in schizophrenia.

The purpose of this study was to evaluate the role of attention in the cognitive abnormalities of schizophrenia. Controlling for attention by analysis of covariance (ANCOVA) had very little effect on the differences between 15 schizophrenic patients and 14 controls in regard to recently acquired, long-term episodic memory recall or remote semantic memory retrieval. Differences between the patients and controls on the percent perseverative response of the Wisconsin Card Sorting Test (WCST) were eliminated. These data suggest that deficits in attention may not underlie impaired recall of newly acquired information in schizophrenia or in the retrieval of information from remote, semantic memory, even under circumstances requiring more effortful processing. The data also suggest a contribution of attentional deficits to perseveration in schizophrenia.

The ontogeny of plasma osmolality and intravascular volume maintenance during short-term starvation in rats.

Body fluid deviations were examined in albino rats of both genders between 30 and 100 days of age during food deprivation. Plasma volume declined with age in free-feeding control groups. Hypovolemia induced by starvation (4 days) was more intense in 30- to 60-day-old animals than in 80- and 100-day groups. Plasma ismolality concentration of control groups indicated increases with age leveling off after 60 days. The initiation of drinking during fasting was accompanied by physiologically significant elevations in plasma osmolality over ad libitum concentrations at each age tested. In a second experiment, repeated exposure to short periods of food deprivation (2 days) during development resulted in the maintenance of intravascular fluid at control volumes. Longer periods (4 days) of deprivation did not result in savings of intravascular volume loss evidenced during starvation. These results suggest that rats compensate for hypovolemia induced by short-term starvation when provided experience with food restriction during development.

The use of clozapine in borderline-intellectual-functioning and mentally retarded schizophrenic patients.

The effect of clozapine, an atypical antipsychotic medication, in five patients with treatment-resistant schizophrenia or schizoaffective disorder and borderline intellectual functioning or mental retardation (MR) was studied. Four of the five patients responded favorably to clozapine with few side effects. Progressive improvement in psychopathology, social functioning, and ability to participate in daily activities were noted.