John T. Kenny

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.

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 (Brocas 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.

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.

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.

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.

209. An MRI study of adolescent psychiatric patients and healthy controls

voluntarysuppressionof tics in Tourette’ssyndromeis a potentially importantmodelof impulsecontrol.UsingfunctionalMRIwestudiedtic suppressionin 22 adult subjects who had a diagnosisof Tourette’s syndrome.Wecomparedimagesacquiredduringperiodsof voluntarytic suppressionwithimagesacquiredwhensubjectsallowedthespontaneous expressionof their tics. We then correlatedthe magnitudesof signal changein the imageswithmeasuresof the severityof tic symptoms.We observedsignificantchangesin signalintensityin the basal gangliaand thalarnusand in anatornicrdlyconnectedcortical regions believed to subserveattention-demanding tasks. The magnitudesof regionsJsignal change in the basal ganglia and thalamus correlated inversely with symptomseverity.Thesefindingssuggestthat the pathogenesisof tics involves an impaired modulationof neuronal activity in subcortical neural circuits. Similarstudies of childrenwho have tic disordersare underway.