Tuula Ilonen

Striatal Dopamine Synthesis in First-degree Relatives of Patients with Schizophrenia

BACKGROUND First degree relatives (FDR) of patients with schizophrenia have higher risk of developing schizophrenia than the general population. Previous positron emission tomography (PET) studies have shown that striatal presynaptic dopamine synthesis capacity is increased in schizophrenia. We investigated whether this same phenomenon is shared by individuals with increased genetic risk for schizophrenia. METHODS We used 6-[18F]-fluorodopa (FDOPA) PET imaging to measure striatal dopamine synthesis capacity. We studied 17 nonpsychotic subjects with an FDR with schizophrenia. This group was compared to 17 healthy subjects with no FDRs with schizophrenia. RESULTS A conventional region of interest (ROI)-analysis indicated that FDOPA uptake (K(i)) in the caudate-putamen was statistically significantly higher in the FDR group than in the control group. A voxel-level analysis confirmed these results. CONCLUSIONS These results suggest that the changes of striatal presynaptic dopamine synthesis seen previously in neuroleptic-naive schizophrenic patients is also present in FDRs of patients with schizophrenia. These findings have implications for the early detection of psychosis as well as for pharmacological interventions in individuals at risk for psychosis.

Axis-I disorders and vulnerability to psychosis

BACKGROUND The psychopathology that manifests during the prodromal phase of first-episode psychosis is varied. Little is known about the clinical diagnoses of subjects with so-called prodromal or psychotic-like symptoms. METHOD Samples of psychotic patients, first-degree relatives (FDRs) of psychotic, or severely ill patients, treatment-seeking patients, and a random community sample (in all 157 subjects) were assessed by the Structured Interview for Prodromal Symptoms (SIPS) and the SCID-I. Vulnerability to psychosis (VTP) was defined by severity of positive symptoms reported in the SIPS interview and associated with lifetime SCID-I diagnoses. RESULTS The number of lifetime diagnoses received increased linearly as the SIPS symptoms approached more psychotic-like phenomena. All VTP subjects received on average 2.5, and currently prodromal subjects 2.9 lifetime SCID-I diagnoses, while the corresponding figure for non-VTP subjects was 0.7 (p<0.0001). Mood disorders and comorbid anxiety disorders were particularly common. CONCLUSION Vulnerability to psychosis seems to be associated with a high number of lifetime Axis-I diagnoses. Occurrence of anxiety disorders is remarkable, and most VTP subjects can be diagnosed with a lifetime mood disorder. VTP subjects require careful assessment of mood and anxiety symptoms and adequate treatment for their multiple disorders.

Habituation of the blink reflex in first-episode schizophrenia, psychotic depression and non-psychotic depression

OBJECTIVE Electrophysiological recording of the electrically elicited blink reflex is the most reliable method of investigating habituation of the startle reflex. The purpose of this study was to compare the habituation and the late R3-component of the blink reflex between control subjects (N=19) and first-episode patients with schizophrenia (N=17), psychotic depression (N=23), and severe non-psychotic depression (N=25). METHODS The blink reflex was evoked by electrical stimulation of the supraorbital nerve, and the deficient habituation of the R2i-component was measured with a computer-assisted integral area measurement. Prefrontal executive function of the patients was assessed with the Wisconsin Card Sorting Test. Current psychiatric symptoms were assessed with the Brief Psychiatric Rating Scale, the Hamilton Depression Scale, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale. RESULTS Deficient habituation of the blink reflex and occurrence of the late R3 component were associated both with a previous diagnosis of psychotic disorder and with the presence of current psychosis. The sensitivity and specificity of the abnormal habituation of the blink reflex in detecting psychotic disorder were 0.50 and 0.80, respectively. The abnormalities of the blink reflex were not associated with psychotropic medication. In schizophrenic patients, defective habituation of the blink reflex was associated with negative and cognitive symptoms, and in depressive patients with the presence of delusions. CONCLUSIONS The deficient habituation of the blink reflex and occurrence of the late R3 component seem to be both trait and state markers of a psychotic disorder. The results suggest that schizophrenia and psychotic depression share some common neurobiological mechanisms involved in the modulation of the startle reflex.

Dopamine D2/D3 receptor binding in the anterior cingulate cortex and executive functioning ☆

The objective was to investigate the association between extrastriatal dopamine D(2)/D(3) receptor binding and performance on the Wisconsin Card Sorting Test (WCST), a measure of executive functioning. Thirty-two healthy volunteers performed the WCST and underwent positron emission tomography and a high-affinity D(2)/D(3) receptor tracer, [(11)C]FLB 457. All WCST error parameters, in particular nonperseverative errors, correlated positively with [(11)C]FLB 457 binding in the cognitive division of the right anterior cingulate cortex. An independent voxel-based receptor parametric mapping analysis confirmed these findings. The results indicate that executive functioning in healthy volunteers is modulated by D(2)/D(3) receptors in the anterior cingulate cortex.

Childhood trauma and premorbid adjustment among individuals at clinical high risk for psychosis and normal control subjects

Traumatic childhood experiences are associated with psychotic illness and are frequently reported in patients at clinical high risk (CHR) for psychosis. Moreover, deteriorating premorbid functioning from childhood, and through adolescence, is related to greater severity of overall symptomatology and poorer outcomes in patients with psychosis. We studied the prevalence of traumatic childhood experiences and premorbid adjustment and their association with each other in patients at CHR for psychosis and normal control subjects (NCSs).

Diagnostic efficiency of the Rorschach schizophrenia and depression indices in identifying first-episode schizophrenia and severe depression

We studied the diagnostic efficiency of the Rorschach schizophrenia (SCZI) and depression (DEPI) indices for detecting first-episode schizophrenia and severe depression with and without psychotic features using DSM-IV as a gold standard measure. Twenty-seven patients with first-episode schizophrenia, 13 with bipolar I disorder, 28 with psychotic depression, 29 with non-psychotic depression, and 60 healthy controls were recruited for the study. The SCZI was highly specific with a very low false positive rate. The lowest positive value of 4, however, may yield false positives, especially among manic patients. The DEPI identified severe non-psychotic depression but not psychotic depression, suggesting that these patient groups invoke different perceptual-cognitive processes in formulating and articulating their Rorschach responses. Anyway, both the SCZI and the DEPI based on the psychological organization and functioning that are known to play a clearly formulated role in schizophrenia and depression, respectively, provide a valuable addition for diagnostics characterized by overt symptoms.

Effects of fluoxetine on dopamine D2 receptors in the human brain: a positron emission tomography study with [11C]raclopride

We have previously reported that repeated dosing with the selective serotonin reuptake inhibitor (SSRI) citalopram decreases striatal [11C]raclopride binding in healthy volunteers. As the SSRI-class antidepressant drugs are believed to have a similar mechanism of action, we wanted to explore whether the prototype SSRI drug, fluoxetine, shares the effects of citalopram on subcortical dopamine neurotransmission. Eight healthy male volunteers were studied using a randomized double-blind placebo-controlled study design. Striatal and thalamic D2-receptor binding was measured at baseline, after a single oral dose (20 mg) of fluoxetine, and after repeated dosing (2 wk, 20 mg/d). The D2-receptor binding potential (BP) was assessed using [11C]raclopride and 3D positron emission tomography. Repeated dosing of fluoxetine decreased BP in the right medial thalamus (p=0.022). Fluoxetine did not decrease striatal BP, but there was a trend (p=0.090) towards increased BP in the left putamen after repeated dosing. A single dose of fluoxetine did not affect BP in the thalamus or striatum. Fluoxetine appears to have a regionally selective effect on the dopaminergic neurotransmission in various areas of the brain. The current results after fluoxetine together with our previous data on citalopram suggest that the modulatory effects of these drugs on striatal dopaminergic neurotransmission are different upon repeated dosing and further substantiates pharmacological differences between SSRI-class drugs.

Impaired Wisconsin Card Sorting Test performance in first-episode severe depression

An important issue in the practice of clinical neuropsychology is to define the degree to which impaired executive functions associated with severe depression are a result of organic dysfunction or of only current depressive experience, reflecting clinical state. Twenty-eight patients with psychotic depression, 29 with nonpsychotic depression and 30 healthy controls, matched for age and education were tested on WCST, WAIS-R, and the Rorschach according to the Comprehensive System, providing indices of depression (DEPI) and coping deficit (CDI). Patients were impaired in WCST performance. The stepwise regression for WCST scores yielded two significant predictor variables: the DEPI and Digit Symbol as a measure of complex attention and response speed. Within the groups, Picture Completion in patients with nonpsychotic depression and the CDI in patients with psychotic depression emerged as the significant predictors of WCST scores. Patients with severe major depressive disorder have profound executive impair...An important issue in the practice of clinical neuropsychology is to define the degree to which impaired executive functions associated with severe depression are a result of organic dysfunction or of only current depressive experience, reflecting clinical state. Twenty-eight patients with psychotic depression, 29 with nonpsychotic depression and 30 healthy controls, matched for age and education were tested on WCST, WAIS-R, and the Rorschach according to the Comprehensive System, providing indices of depression (DEPI) and coping deficit (CDI). Patients were impaired in WCST performance. The stepwise regression for WCST scores yielded two significant predictor variables: the DEPI and Digit Symbol as a measure of complex attention and response speed. Within the groups, Picture Completion in patients with nonpsychotic depression and the CDI in patients with psychotic depression emerged as the significant predictors of WCST scores. Patients with severe major depressive disorder have profound executive impairments as assessed by the WCST at early stages of the illness. Intense emotional distress and psychomotor retardation seem to contribute to impaired performance. The depression groups revealed different response patterns, reflecting more severe deterioration and signs of possible organic dysfunction in patients with psychotic depression.

Self-image of adolescents with diabetes mellitus type-I and rheumatoid arthritis.

The purpose of this research was to determine possible differences in the self-concept of chronically ill and healthy adolescents. A group of adolescents with diabetes mellitus type-I (DM) and a group with rheumatoid arthritis (RA) were chosen for the study, together with a control group without any chronic illness. The groups were matched for gender, age (DM 17.8, RA 17.9, control group 17.6 years) and social class. The Offer Self-Image Questionnaire (OSIQ) was used to estimate differences between the groups of 23 DM adolescents, 25 RA adolescents and 26 control group adolescents. The scores are reversed; thus the higher the score, the better the self-image. The results indicate that Body Image, and Vocational and Educational Goals were lower in the groups of chronically ill adolescents than in the control group; however, no statistically significant differences were found between the groups on the OSIQ scales. The self-image of adolescents with DM with good metabolic control and moderate and long-lasting RA is relatively well developed.

Different vulnerability indicators for psychosis and their neuropsychological characteristics in the Northern Finland 1986 Birth Cohort.

This study is one of very few that has investigated the neuropsychological functioning of both familial and clinical high risk subjects for psychosis. Participants (N = 164) were members of the Northern Finland 1986 Birth Cohort in the following four groups: familial risk for psychosis (n = 62), clinical risk for psychosis (n = 20), psychosis (n = 13), and control subjects (n = 69). The neurocognitive performance of these groups was compared across 19 cognitive variables. The two risk groups did not differ significantly from controls, but differed from the psychosis group in fine motor function. Neuropsychological impairments were not evident in a non-help-seeking high-risk sample.