Laterality patterns in relation to schizophrenia patients' age at onset.

Based on numerous findings of an abnormal laterality in schizophrenia disorder, we hypothesized that handedness and lateral preferences may affect the age at onset in schizophrenia patients. Two samples of schizophrenia patients, the first a sample of 34 right-handers and 42 left-handers and a replication set of 84 right-handers, were examined with regard to age at onset considering handedness and the four Luria's signs (arm folding, hand clasping, familial sinistrality and eye dominance) as well as gender. The association between these parameters and age at onset was investigated by means of multiple regression analysis. Our analyses revealed that right-handers with right arm folding and left-handers with left arm folding showed an early age at onset, while in the late age at onset the opposite preferences prevailed. Apart from arm folding, signs of ambilaterality, i.e., left eye dominance in right-handers and familial sinistrality in left-handers were additional predictors for an early age at onset. Remarkably, all observations found in the first right-handed sample were confirmed in the right-handed replication set. We conclude that among the many different factors specific lateral preferences should also be considered in assessing patients who are at risk of psychosis.

Effects of eye dominance (left vs. right) and cannabis use on intermanual coordination and negative symptoms in schizophrenia patients.

Based on the previous findings, it has been assumed that in schizophrenia patients, eye dominance and cannabis use will affect negative symptoms and intermanual coordination (IMC), an index of interhemispheric communication. But eye dominance, specifically the clinical findings for it, has been neglected in schizophrenia research. We therefore investigated its effects in 52 right-handed (36 right-eyed and 16 left-eyed) and 51 left-handed (35 left-eyed and 16 right-eyed) schizophrenia in-patients without and with drug use. Eye dominance affected IMC in all schizophrenia patients. When comparing right- and left-handers, we found that this result was only significant in the right-handed patients and in the smaller subgroup without drug use. In the right-handers, left eye dominance-like left-handedness-was associated with higher values in IMC and less pronounced manifestation of negative symptoms, right eye dominance was not. Thus, left-eyed right-handers may be more closely related to left-handers than to right-handers. In accordance with the results from the literature, we suggest that these findings are due to better interhemispheric connections and less impairment of white matter structures, especially in right-hemispheric regions. Moreover, cannabis use was related to higher scores in IMC and less pronounced negative symptoms, but only in the right-eyed and not in the left-eyed right-handers or in the left-handers. Hence, differences in eye dominance and handedness may be partially responsible for different results in interhemispheric connections among cannabis users. In conclusion, both eye dominance and use of cannabis should be taken into account when assessing clinical symptoms in schizophrenia patients.

Effects of handedness (left vs right) and cannabis abuse on intermanual coordination and negative symptoms in schizophrenic patients of the paranoid type.

Intermanual coordination as an index of interhemispheric transfer and negative symptoms were investigated in 50 left- and 42 right-handed schizophrenic inpatients of the paranoid type, also including drug abusers. The primary objective was to show that there were higher values in intermanual coordination and fewer manifestations of negative symptoms in the left-handed compared to the right-handed patients. This assumption was based on previous studies. Most importantly, right- and left-handed patients showed a different behaviour in intermanual coordination, when the duration of illness was taken into consideration. Thus, long-term left-handed paranoid patients performed better in intermanual coordination and showed fewer manifestations of negative symptoms than did long-term right-handed patients. These results were true for the large group of all patients, and among them for the subgroup of patients without drug abuse. Consequently, higher scores in intermanual coordination in left-handed patients may be related to a better interhemispheric crosstalk resulting in less pronounced negative symptoms. Secondary objectives assessed by explorative data analysis included the effects of cannabis abuse. While cannabis abuse may be more prevalent in left-handed patients, its effects may be more pronounced in right-handed patients, scoring higher in intermanual coordination and lower in manifestations of negative symptoms.

Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

Reduction of auditory event-related P300 amplitude in subjects with at-risk mental state for schizophrenia.

Neurophysiological methods allow the examination of cognitive-cortical functioning in patients with schizophrenia in its prodromal states. As revealed by previous studies, event-related potential components such as auditory evoked P300 associated with cognitive processes, such as attention and orientation, are known to be reduced in amplitude in acute and chronic as well as in medicated and unmedicated patients. It is, however, unclear whether a P300 amplitude reduction occurs before the schizophrenic psychosis is fully manifested. We studied patients in the prodromal phase of the schizophrenic disorder (i.e. subjects with an at-risk mental state showing attenuated psychotic symptoms or brief limited intermittent symptoms) as well as first-episode patients and chronic patients with schizophrenia and compared these groups to healthy subjects. The event-related P300 was recorded during an auditory oddball paradigm. Groups differed significantly from each other in the P300 amplitude at Pz (F(3/149)=2.532, p=0.02). Post-hoc tests revealed significantly lower P300 amplitudes of non-medicated prodromal (p=.03), first-episode (p=.01) and chronic patients (p=.001) compared to the healthy controls. The study revealed that there are neurophysiological changes as the reduction in P300 amplitudes begins early in schizophrenia at the prodromal phase, i.e. before a manifestation of full-blown psychosis, and that these changes seem to have a progressive course from prodromal to chronic state of schizophrenia as assumed in this cross-sectional study.

Is the loudness dependence of auditory evoked potentials modulated by the selective serotonin reuptake inhibitor citalopram in healthy subjects?

The loudness dependence of auditory evoked potentials (LDAEP) has been discussed as a non-invasive in vivo marker of central serotonergic function. Evidence for this has been found in animal studies, but studies in humans provide less consistent results. In this study, the relationship between LDAEP and directly modulated central serotonergic activity in healthy subjects was investigated. In a single-blind cross-over design, the LDAEP of female participants (age: 24.0 +/- 2.3 years) was measured under two conditions: (1) infusion of 20 mg citalopram diluted in 250 ml 0.9% saline and (2) infusion of 250 ml 0.9% saline as placebo. LDAEP was measured at five different time points before, during and up to 60 min after drug/placebo administration and dipole source analysis was performed. The increase of the central serotonin activity in response to citalopram was not accompanied by a significant change of the LDAEP compared to the placebo condition. The result underlines that the acceptance of LDAEP as a marker of central serotonergic function still needs further discussion.

Hand skill and hand-eye preference in relation to verbal ability in healthy adult male and female right-handers.

Verbal as well as non-verbal performances were investigated in relation to both hand skill assessed by finger-tapping performances and hand-eye preference in 83 healthy adult right-handers, most of them students. The primary objective of this study was to show better finger-tapping performances in right-handed participants with best verbal IQ values. We found that it was not the non-verbal but the verbal abilities that were related to finger-tapping performances. This was proven, especially as to the left-hand taps. Faster left-hand taps in participants with higher verbal IQ values may be due to a closer cooperation of right-hemispheric regions in information processing and an intimate relationship between language and finger-motor functions. Secondary objectives assessed by explorative data analyses included gender differences and hand-eye preference. While in the females left-hand taps correlated somewhat more with verbal IQ values, in the males this effect was seen in selected variables of the right-hand taps. Moreover, laterality assessed in finger-tapping performances may not be in accordance with laterality found in the handedness questionnaire. In addition to this, congruent hand-eye dominance was found to be slightly more prevalent in participants with best verbal IQ values. However, these findings will have to be confirmed in further experiments.

Intermanual coordination in relation to different clinical subgroups in right-handed patients with schizophrenic and other psychotic disorders.

BACKGROUND: Interhemispheric transfer in psychotic patients is still a controversial issue. Based on the fact that intermanual coordination is associated with interhemispheric transfer, scores in intermanual coordination were investigated in patients with psychotic disorders. METHOD: Intermanual coordination was assessed by alternating finger-tapping in 73 adult right-handed in-patients with schizophrenic and other psychotic disorders and was compared with that of 75 healthy right-handed controls. Five clinical subgroups of patients whose diagnoses were based on the DSM-IV classification were specified. RESULTS: Scores in intermanual coordination in the patients as a whole did not differ from those of the controls. When, however, different clinical subgroups and various manifestations of symptoms were taken into consideration, the scores among those subgroups differed significantly. For instance, patients with residual schizophrenia and chronic symptoms showed lower values in intermanual coordination than did patients with schizoaffective disorders and prevailing acute symptoms. CONCLUSIONS: The assessment of intermanual coordination may provide new insights into the functional coupling of both hemispheres in schizophrenic and other psychotic disorders and may be of a certain prognostic value. Because of its non-invasive, fast and simple application, this approach is thought to be especially suited for investigating acute psychiatric in-patients.