Navigated and individual α-peak-frequency-guided transcranial magnetic stimulation in male patients with treatment-refractory schizophrenia.

BACKGROUND: Previous electroencephalography (EEG) studies have indicated altered brain oscillatory α-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized α-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual α-peak-frequency-guided rTMS (αTMS) on treatment-refractory schizophrenia. METHODS: We recruited medication-refractory male patients with schizophrenia or schizoaffective disorder in this doubleblind, sham-controlled study. We randomized patients to a 3-week course of either active αTMS or sham stimulation applied to the left dorsolateral prefrontal cortex (DLPFC). We assessed participants with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) at baseline and after treatment. We conducted a follow-up assessment with the PANSS 3 months after intervention. RESULTS: We included 44 patients. After treatment, we observed a significantly higher PANSS total score (p = 0.029), PANSS general psychopathology score (p = 0.027) and PANSS 5-factor model cognitive-disorganized factor score (p = 0.011) in the αTMS group than the sham group. In addition, the CGI-Improvement score was significantly higher among those who received αTMS compared with sham stimulation (p = 0.048). LIMITATIONS: The limited number of study participants included only male patients. Depression was not formally evaluated. CONCLUSION: Navigated αTMS to the left DLPFC reduced total, general psychopathological, and cognitive-disorganized symptoms of schizophrenia. These results provide evidence for the therapeutic efficacy of individual α-peak-frequency-guided rTMS in treatment-refractory schizophrenia. CLINICAL TRIAL REGISTRATION: NCT01941251; ClinicalTrials.gov.

[Restrictions during psychiatric hospitalization]. / Potilaan rajoittaminen psykiatrisessa sairaalahoidossa.

The Finnish Constitution affirms that everyone has the right to remain private and undisturbed. During the course of involuntary psychiatric treatment, only the exemptions stipulated in the Mental Health Act are allowed. The Act on the Status and Rights of Patients states that cooperation with the patient must also be attempted during involuntary treatment. The orders for restraints are different in psychiatric hospitals. For decades, restrictions were derived from early 19th century regulations, when all mentally ill individuals were considered to be incompetent. Nowadays, a patient's mental competence is based on functional disabilities, which should also apply to psychiatric treatment.

Extrapyramidal side-effects and dopamine D(2/3) receptor binding in substantia nigra.

BACKGROUND: The exact mechanisms for antipsychotic-induced extrapyramidal side-effects have remained obscure despite intensive research. Previous studies have highlighted a central role for nigral dopamine D(2) receptors in the control of motor functions. AIMS: The aim of the present study was to examine relationships between dopamine D(2) receptor binding in both substantia nigra and temporal cortex with extrapyramidal symptoms among antipsychotic-treated patients with schizophrenia. METHODS: Single-photon emission-computed tomography (SPECT) ligand [(123)I]epidepride was used to determine dopamine D(2/3) apparent binding potential in 13 antipsychotic-treated (seven with clozapine, four with olanzapine and two with haloperidol) patients with schizophrenia. Extrapyramidal symptoms were assessed with the Simpson and Angus Scale (SAS). RESULTS: A statistically significant correlation was observed between dopamine D(2/3) receptor apparent binding potential in the substantia nigra and extrapyramidal side-effects (r = -0.62, P = 0.024). No correlations were detected in the temporal cortex between dopamine D(2/3) receptor binding and extrapyramidal side-effects. CONCLUSIONS: These findings support the role of dopamine D(2) autoreceptors in substantia nigra regarding drug-induced movement disorders.

Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine.

AIMS: Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second-generation antipsychotics in dopamine D(2) receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D(2/3) receptor apparent binding potential (BP(app)) and occupancy in midbrain and temporal cortex among clozapine-, olanzapine- and haloperidol-treated schizophrenia patients. METHODS: Dopamine D(2/3) binding was studied on single-photon emission computed tomography ligand [(123)I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug-naïve patients and seven healthy controls. RESULTS: Statistically significant differences in midbrain dopamine D(2/3) receptor BP(app) (P = 0.015) and occupancy (P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine-treated patients (5%), followed by olanzapine-treated patients (28%), compared to haloperidol-treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug-naïve vs healthy controls) in the examined brain areas (P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used. CONCLUSION: Both typical and second-generation antipsychotics occupy cortical dopamine D(2/3) receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D(2/3) occupancy between classical antipsychotics and second-generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.

Midbrain dopamine D2/3 receptor binding in schizophrenia.

Several studies suggest that dysregulation of dopaminergic transmission in the midbrain and thalamus may contribute to the symptomatology of schizophrenia. The objective of this study was to examine the putative alteration of dopamine D(2/3 )receptor densities in the thalamus and midbrain of drug-naïve schizophrenic patients. We used the high-affinity single-photon emission tomography ligand [(123)I]epidepride for imaging D(2/3 )receptor binding sites in six neuroleptic-naïve schizophrenic patients, and seven healthy controls. Schizophrenic symptoms were evaluated by the Positive and Negative Syndrome Scale. Significantly lower D(2/3 )values were observed in the midbrain of patients with schizophrenia compared to controls (P = 0.02). No statistically significant difference was observed in the thalamus between two groups. Negative correlations were found between thalamic D(2/3 )receptor binding and general psychopathological schizophrenic symptoms (r from -0.78 to -0.92). These observations implicate altered dopaminergic activity in the midbrain of schizophrenic patients.