Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia.

BACKGROUND: Schizophrenia has been associated with disturbances of thalamic functioning. In light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether modulation of the glutamatergic system via blockage of the N-methyl-D-aspartate (NMDA)-receptor might lead to changes of thalamic functional connectivity. METHODS: Based on the ketamine model of psychosis, we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55-minute resting-state scan. Thirty healthy volunteers were measured with pharmacological functional magnetic resonance imaging using a double-blind, randomized, placebo-controlled, crossover design. RESULTS: Functional connectivity analysis revealed significant ketamine-specific changes within the thalamus hub network, more precisely, an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex. CONCLUSIONS: Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behavior during the application of NMDA-receptor antagonists.

A randomized trial of short psychotherapy versus sustained-release bupropion for smoking cessation.

AIMS: To compare the efficacy and safety of a novel psychological intervention for smoking cessation called psychodynamic model (PDM) training to an active control condition of sustained-release bupropion. DESIGN: Randomized controlled clinical trial with allocation concealment. SETTING: Private psychiatric practice. PARTICIPANTS: Seven hundred and seventy-nine adult smokers recruited by advertising. INTERVENTIONS: PDM training (n = 366 participants) consisted of a very brief (1.5 days) psychoeducation and a supervised training in autosuggestion techniques (guided imageries) aimed at enhancing self-management, decidedness, assertiveness, security and competence in relationships, natural functions of organs and awareness of bodily functions. Bupropion SR (n = 413) was increased to 150 mg twice daily over 1 week and given over a 8-week period. MEASUREMENTS: Twelve-month continuous abstinence confirmed by exhaled carbon monoxide (CO) of 9 parts per million (p.p.m.) or less at all interviews conducted at 3, 6 and 12 months. FINDINGS: Intention-to-treat analysis revealed Russell standard 12-month continuous abstinence rates of 39.1% in the psychotherapy group versus 12.3% in the bupropion SR group (P < 0.001) with a relative benefit (RB) of 3.16 (2.38-4.26). Completer analysis revealed 12-month continuous abstinence rates of 39.9% in the psychotherapy group versus 22.5% in the bupropion group [P < 0.001; RB 1.78 (1.35-2.34)]. Of note, bupropion abstinence rates were comparable to previous medications/placebo-only comparisons in geographically different samples. CONCLUSIONS: The 1.5-day psychotherapy exceeded bupropion's efficacy, presenting an alternative to pharmacological smoking cessation aids, especially for smokers who reject drugs to treat their substance dependence, at a similar cost (Euro 350) as the bupropion treatment (Euro 355).

St. John's wort (Hypericum perforatum) and breastfeeding: plasma and breast milk concentrations of hyperforin for 5 mothers and 2 infants.

BACKGROUND: Herbal preparations for depression, such as St. John's wort, are often preferred over pharmaceutical preparations by mothers and midwives after childbirth because these preparations are available to patients as over-the-counter "natural" treatments and are popularly assumed to be safe. The only existing report on St. John's wort excretion into human milk showed that only 1 active component (hyperforin) was detectable in breast milk, but was not detectable in the infants' plasma. Another report found more cases of minor problems in infants breast-fed by women taking St. John's wort. However, significance was reached only in comparison with disease-matched women (p<.01), not healthy controls (p=.20). METHOD: Five mothers who were taking 300 mg of St. John's wort 3 times daily (LI 160 [Jarsin], Lichtwer Pharma GmbH; Berlin, Germany) and their breastfed infants were assessed. Thirty-six breast milk samples (foremilk and hindmilk collected during an 18-hour period) and 5 mothers' and 2 infants' plasma samples were analyzed for hyperforin levels by tandem mass spectrometry (LC/MS/MS; limit of quantification=0.1 ng/mL). Data were gathered from January 2001 to February 2002. RESULTS: Hyperforin is excreted into breast milk at low levels. However, the compound was at the limit of quantification in the 2 infants' plasma samples (0.1 ng/mL). Milk/plasma ratios ranged from 0.04 to 0.13. The relative infant doses of 0.9% to 2.5% indicate that infant exposure to hyperforin through milk is comparable to levels reported in most studies assessing anti-depressants or neuroleptics. No side effects were seen in the mothers or infants. CONCLUSION: These results add to the evidence of the relative safety of St. John's wort while breast-feeding found in previous observational studies.