Dominique Arion, PhD; David A. Lewis, MD
free access
Arch Gen Psychiatry. 2011;68(1):21-31. doi:10.1001/archgenpsychiatry.2010.114
ContextDisturbances in markers of cortical 纬-aminobutyric acid neurotransmission are a common finding in schizophrenia. The nature of 纬-aminobutyric acid neurotransmission (hyperpolarizing or depolarizing) depends on the local intracellular chloride concentration. In the central nervous system, the intracellular chloride level is determined by the activity of 2 cation-chloride transporters, NKCC1 and KCC2. The activities of these transporters are in turn regulated by a network of serine-threonine kinases that includes OXSR1, STK39, and the WNK kinases WNK1, WNK3, and WNK4.ObjectiveTo compare the levels of NKCC1, KCC2, OXSR1, STK39, WNK1, WNK3, and WNK4 transcripts in prefrontal cortex area 9 between subjects with schizophrenia and healthy comparison subjects.DesignReal-time quantitative polymerase chain reaction technique was used to measure transcript levels in the prefrontal cortex.SettingHuman brain specimens were obtained from autopsies conducted at the Allegheny County Medical Examiner's Office, Pittsburgh, Pennsylvania.ParticipantsPostmortem brain specimens from 42 subjects with schizophrenia and 42 matched healthy comparison subjects. Brain specimens from 18 macaque monkeys exposed to haloperidol, olanzapine, or sham long-term.Main Outcome MeasuresRelative expression levels for NKCC1, KCC2, OXSR1, STK39, WNK1, WNK3, and WNK4 transcripts compared with the mean expression level of 3 housekeeping transcripts.ResultsOXSR1 and WNK3 transcripts were substantially overexpressed in subjects with schizophrenia relative to comparison subjects. In contrast, NKCC1, KCC2, STK39, WNK1, and WNK4 transcript levels did not differ between subject groups. OXSR1 and WNK3 transcript expression levels were not changed in antipsychotic-exposed monkeys and were not affected by potential confounding factors in the subjects with schizophrenia.ConclusionIn schizophrenia, increased expression levels, and possibly increased kinase activities, of OXSR1 and WNK3 may shift the balance of chloride transport by NKCC1 and KCC2 and alter the nature of 纬-aminobutyric acid neurotransmission in the prefrontal cortex.
George S. Alexopoulos, MD; Patrick J. Raue, PhD; Dimitris N. Kiosses, PhD; et al.
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Arch Gen Psychiatry. 2011;68(1):33-41. doi:10.1001/archgenpsychiatry.2010.177
An Pan, PhD; Michel Lucas, PhD; Qi Sun, MD, ScD; et al.
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Arch Gen Psychiatry. 2011;68(1):42-50. doi:10.1001/archgenpsychiatry.2010.176
Charles F. Reynolds III, MD; Meryl A. Butters, PhD; Oscar Lopez, MD; et al.
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Arch Gen Psychiatry. 2011;68(1):51-60. doi:10.1001/archgenpsychiatry.2010.184
Ritsaert Lieverse, MD; Eus J. W. Van Someren, PhD; Marjan M. A. Nielen, PhD; et al.
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Arch Gen Psychiatry. 2011;68(1):61-70. doi:10.1001/archgenpsychiatry.2010.183
Charles S. Grob, MD; Alicia L. Danforth, MA; Gurpreet S. Chopra, MD; et al.
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Arch Gen Psychiatry. 2011;68(1):71-78. doi:10.1001/archgenpsychiatry.2010.116
ContextResearchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer.ObjectiveTo explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety.DesignA double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin.SettingA clinical research unit within a large public sector academic medical center.ParticipantsTwelve adults with advanced-stage cancer and anxiety.Main Outcome MeasuresIn addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment.ResultsSafe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance.ConclusionsThis study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field.Trial Registrationclinicaltrials.gov Identifier:
Melissa A. Polusny, PhD; Shannon M. Kehle, PhD; Nathaniel W. Nelson, PhD; et al.
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Arch Gen Psychiatry. 2011;68(1):79-89. doi:10.1001/archgenpsychiatry.2010.172
Ronald C. Kessler, PhD; Johan Ormel, PhD; Maria Petukhova, PhD; et al.
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Arch Gen Psychiatry. 2011;68(1):90-100. doi:10.1001/archgenpsychiatry.2010.180
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Editorial
A Dimensional-Spectrum Model of Psychopathology: Progress and Opportunities
Robert F. Krueger, PhD; Kristian E. Markon, PhD
Arch Gen Psychiatry
Karen Pierce, PhD; David Conant; Roxana Hazin, BS; et al.
free access
Arch Gen Psychiatry. 2011;68(1):101-109. doi:10.1001/archgenpsychiatry.2010.113
ContextEarly identification efforts are essential for the early treatment of the symptoms of autism but can only occur if robust risk factors are found. Children with autism often engage in repetitive behaviors and anecdotally prefer to visually examine geometric repetition, such as the moving blade of a fan or the spinning of a car wheel. The extent to which a preference for looking at geometric repetition is an early risk factor for autism has yet to be examined.ObjectivesTo determine if toddlers with an autism spectrum disorder (ASD) aged 14 to 42 months prefer to visually examine dynamic geometric images more than social images and to determine if visual fixation patterns can correctly classify a toddler as having an ASD.DesignToddlers were presented with a 1-minute movie depicting moving geometric patterns on 1 side of a video monitor and children in high action, such as dancing or doing yoga, on the other. Using this preferential looking paradigm, total fixation duration and the number of saccades within each movie type were examined using eye tracking technology.SettingUniversity of California, San Diego Autism Center of Excellence.ParticipantsOne hundred ten toddlers participated in final analyses (37 with an ASD, 22 with developmental delay, and 51 typical developing toddlers).Main Outcome MeasureTotal fixation time within the geometric patterns or social images and the number of saccades were compared between diagnostic groups.ResultsOverall, toddlers with an ASD as young as 14 months spent significantly more time fixating on dynamic geometric images than other diagnostic groups. If a toddler spent more than 69% of his or her time fixating on geometric patterns, then the positive predictive value for accurately classifying that toddler as having an ASD was 100%.ConclusionA preference for geometric patterns early in life may be a novel and easily detectable early signature of infants and toddlers at risk for autism.