Person: Wojcik, Joanne
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Wojcik
First Name
Joanne
Name
Wojcik, Joanne
5 results
Search Results
Now showing 1 - 5 of 5
Publication N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis(Oxford University Press, 2017) Conus, Philippe; Seidman, Larry J; Fournier, Margot; Xin, Lijing; Cleusix, Martine; Baumann, Philipp S; Ferrari, Carina; Cousins, Ann; Alameda, Luis; Gholam-Rezaee, Mehdi; Golay, Philippe; Jenni, Raoul; Woo, T -U Wilson; Keshavan, Matcheri; Eap, Chin B; Wojcik, Joanne; Cuenod, Michel; Buclin, Thierry; Gruetter, Rolf; Do, Kim QAbstract Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC’s impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment.Publication Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia(Proceedings of the National Academy of Sciences, 2009) Whitfield-Gabrieli, S.; Thermenos, Heidi; Milanovic, Snezana M.; Tsuang, Ming; Faraone, Stephen; McCarley, Robert William; Shenton, Martha; Green, Alan; Nieto-Castanon, A.; LaViolette, P.; Wojcik, Joanne; Gabrieli, John; Seidman, Larry JoelWe examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.Publication Frequency and pattern of childhood symptom onset reported by first episode schizophrenia and clinical high risk youth(Elsevier BV, 2014) Woodberry, Kristen; Serur, Rachael A.; Hallinan, Sean B.; Mesholam-Gately, Raquelle; Giuliano, Anthony J.; Wojcik, Joanne; Keshavan, Matcheri; Frazier, Jean A.; Goldstein, Jill; Shenton, Martha; McCarley, Robert William; Seidman, Larry JoelBackground—Psychosis prevention and early intervention efforts in schizophrenia have focused increasingly on sub-threshold psychotic symptoms in adolescents and young adults. Although many youth report symptom onset prior to adolescence, the childhood incidence of prodromal level symptoms in those with schizophrenia or related psychoses is largely unknown. Methods—This study reports on the retrospective recall of prodromal-level symptoms from 40 participants in a first-episode of schizophrenia (FES) and 40 participants at “clinical high risk” (CHR) for psychosis. Onset of positive and non-specific symptoms was captured using the Structured Interview for Prodromal Syndromes. Frequencies are reported according to onset during childhood (prior to age 13), adolescence (13–17), or adulthood (18 +). Results—Childhood-onset of attenuated psychotic symptoms was not rare. At least 11% of FES and 23% of CHR reported specific recall of childhood-onset of unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most recalled experiencing non-specific symptoms prior to positive symptoms. CHR and FES did not differ significantly in the timing of positive and non-specific symptom onset. Other than being younger at assessment, those with childhood onset did not differ demographically from those with later onset. Conclusion—Childhood-onset of initial psychotic-like symptoms may be more common than previous research has suggested. Improved characterization of these symptoms and a focus on their predictive value for subsequent schizophrenia and other major psychoses are needed to facilitate screening of children presenting with attenuated psychotic symptoms. Accurate detection of prodromal symptoms in children might facilitate even earlier intervention and the potential to alter pre-illness trajectories.Publication F43. POTENTIATION OF INHIBITORY NEUROTRANSMISSION IN THE TREATMENT OF RECENT-ONSET SCHIZOPHRENIA BY MODIFICATION OF DEVELOPMENTAL PRUNING OF PREFRONTAL CIRCUITRY(Oxford University Press, 2018) Burke, Erin; Wojcik, Joanne; Seidman, Larry J; Green, Alan; Woo, Tsung-UngAbstract Background: The overt symptoms and deficits of schizophrenia (SZ) typically emerge during late adolescence and early adulthood, followed by a period of post-onset functional deterioration. This peri-onset period temporally coincides with the final maturation of the prefrontal cortex (PFC), which is characterized by a process of extensive pruning of synaptic connectivities. Developmental maturation of inhibitory neurotransmission may play a key role in regulating the onset and duration of peri-adolescent synaptic pruning. We hypothesize that a deficit in the developmental increase in inhibitory neurotransmission may disturb the PFC synaptic pruning process and hence contribute to the onset and the functional deterioration that is characteristic of the early course of SZ. Enhancement of inhibitory neurotransmission may therefore restore the integrity of PFC neural circuitry, which may then lead to lasting improvements in cognitive deficits and clinical symptoms. Methods: Here, we report preliminary data on the possible efficacy of tiagabine (Gabitril), which is a selective uptake inhibitor of the GABA (gamma-aminobutyric acid) transporter GAT-1, in the treatment of recent-onset schizophrenia. Subjects were randomized to receive either tiagabine or placebo added on to their antipsychotic regimen. Results: Our data suggest that treatment with tiagabine during the early course of the illness can modulate PFC activation, as demonstrated by functional magnetic resonance imaging during working memory, and improve negative symptoms. Discussion Taken together, the proposed treatment strategy represents an effort to actively translate preclinical findings in SZ research into clinically testable hypotheses. This kind of translational approach, we believe, will ultimately lead to breakthrough in the treatment and possible prevention of SZ.Publication F44. AN ADD-ON TRIAL WITH N-ACETYL-CYSTEINE (NAC) IN EARLY PSYCHOSIS PATIENTS: TOWARDS BIOMARKER GUIDED TREATMENT(Oxford University Press, 2018) Conus, Philippe; Fournier, Margot; Xin, Lijing; Cleusix, Martine; Baumann, Philipp S; Ferrari, Carina; Cousins, Ann; Alameda, Luis; Gholam-Razaee, Mehdi; Golay, Philippe; Jenni, Raoul; Woo, Tsung-Ung; Keshavan, Matcheri; Eap, Chin B; Wojcik, Joanne; Cuenod, Michel; Buclin, Thierry; Gruetter, Rolf; Seidman, Larry; Do, KimAbstract Background: Oxidative stress, coupled with dysregulation of inflammation, NMDAR and dopamine, is involved in schizophrenia (SZ) pathophysiology. Earlier add-on clinical trials showed in chronic SZ patients that NAC, a precursor of glutathione (GSH), an important cerebral antioxidant, improved negative symptoms, mismatch negativity and local synchronization. We hypothesized that NAC at an earlier stage of illness would have a greater impact. Methods: Early psychosis patients (EP, less than 5 years of illness, N=63; NAC=32, placebo=31) were supplemented with NAC (2.7g/day, 6 months) in a double-blind randomized placebo-controlled trial. Outcome measures: PANSS and neurocognition (MATRICS Consensus Cognitive Battery; n=36); quantification of medial prefronfal cortex glutathione (GSHmPFC) by 1H-magnetic-resonance-spectroscopy, of white matter diffusion properties estimated by generalized fractional anisotropy (gFA) computed from diffusion spectrum imaging (DSI), of blood cells GSH (GSHBC) and GSH peroxidase activity (GPxBC) at start and end of trial Results: While PANSS negative and positive were not affected by NAC, NAC improved Processing Speed (NAC > Placebo; F(1, 30)=5.849, p=.022), favoring 2 of 3 processing speed tasks (Trail Making A, F(1, 30)=4.279, p=.048 & Verbal Fluency, F(1, 30)=5.749, p=.023). GSHmPFC (+23%, p=0.005) and GSHBC (+19%, p=0.05) were increased following NAC treatment. In patients with high-baseline GPxBC (>22.3U/gHb), subgroup explorations revealed an improvement of PANSS positive compared to placebo (p=0.02). The change of PANSS positive correlated negatively with that of GPxBC activity, showing that the improvement paralleled the restoration of redox status. NAC group showed 11% increase in fornix white matter integrity as measured by gFA, correlating with an increase in GSHmPFC over the 6-months period. Discussion This is the first clinical trial assessing the impact of NAC treatment in a sample of EP and the potential predictive role of peripheral biomarkers of redox dysregulation. The hypothesis that NAC would be beneficial to negative symptoms in EP was not confirmed in this small sample, most likely in reason of their very low level at baseline. The NAC induced GSHmPFC increase demonstrates its target engagement. NAC improved Processing Speed showing a therapeutic enhancement of cognitive functions. Most importantly, NAC improved fornix integrity, in association with brain GSH elevation, demonstrating for the first time that a redox regulator can enhance structural connectivity. Peripheral redox status allows identifying a subgroup of patients with improved positive symptoms. Future biomarker guided antioxidant interventions in larger EP samples should replicate these findings.