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Objective: This report summarizes findings from a 2020 survey of US child and adolescent psychiatry training programs that explored the impact of the COVID-19 pandemic on pediatric telepsychiatry training. The authors hypothesized that telepsychiatry training significantly increased during the pandemic, in part due to legal and regulatory waivers during the COVID-19 public health emergency., Methods: In August 2020, an anonymous, 28-question online survey was emailed to all (138) accredited child psychiatry fellowships on the Accreditation Council for Graduate Medical Education website. Forty-nine programs responded (36%). This analysis focuses on three of the 28 questions relevant to the hypotheses: characteristics of the program's training in telepsychiatry; perceived impediments to clinical training; and perceived impediments to didactic training pre-COVID onset vs. post-COVID onset, respectively. Total scores were created to investigate differences in training programs and impediments to including telepsychiatry pre- and post-COVID onset. Paired sample t-tests were used to compare means pre- and post-COVID onset., Results: Results provided support for significant differences between training components related to telepsychiatry pre- and post-COVID onset, with participants reporting more training components post-COVID onset (M = 5.69) than pre-COVID onset (M = 1.80); t(48) = 9.33, p < .001. Participants also reported significantly fewer barriers to providing clinical experiences in pediatric telepsychiatry post-COVID onset (M = 2.65) than pre-COVID onset (M = 4.90); t(48) =  - 4.20, p < .001., Conclusions: During the COVID-19 pandemic, pediatric telepsychiatry training in child psychiatry fellowships increased significantly. Perceived barriers to providing clinical, but not didactic, training decreased significantly., (© 2021. Academic Psychiatry.)

Objectives: Our goal was to develop an open access nationally disseminated online curriculum for use in graduate and continuing medical education on the topic of pediatric telepsychiatry to enhance the uptake of telepsychiatry among child psychiatry training programs and improve access to mental health care for youth and families. Methods: Following Kern's 6-stage model of curriculum development, we identified a core problem, conducted a needs assessment, developed broad goals and measurable objectives in a competency-based model, and developed educational content and methods. The curriculum was reviewed by experts and feedback incorporated. Given the urgent need for such a curriculum due to the COVID-19 pandemic, the curriculum was immediately posted on the American Academy of Child and Adolescent Psychiatry and American Association of Directors of Psychiatric Residency Training websites. Further evaluation will be conducted over the next year. Results: The curriculum covers the six areas of core competence adapted for pediatric telepsychiatry and includes teaching content and resources, evaluation tools, and information about other resources. Conclusion: This online curriculum is available online and provides an important resource and set of standards for pediatric telepsychiatry training. Its online format allows for ongoing revision as the telepsychiatry landscape changes.

Mental health continues to be a significant concern both globally and locally in Hawai'i, with nearly half of all mental illness beginning in childhood or adolescence. A shortage of mental health providers has led to less than a third of patients receiving appropriate and timely care. Primary care providers are often the first-line responders to untreated mental health conditions, but they are often underprepared to address these conditions. To help provide guidance to primary care providers and other first-line responders, a child and adolescent mental health resource manual was developed, that is tailored to Hawai'i. This manual was presented at several pediatric didactic sessions and general conferences to describe its evolution, utility, to elicit feedback, as well as for an initial distribution. While feedback was overall positive, future manual development and strategic updates will be made to insure its suitability and timeliness, while continuing circulation efforts to primary care providers will ultimately benefit a greater proportion of children in need., Competing Interests: None of the authors identify any conflict of interest., (©Copyright 2020 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

HIV-infected individuals (HIV+) has 2-3 times the rate of tobacco smoking than the general population, and whether smoking may lead to greater psychiatric symptoms or cognitive deficits remains unclear. We evaluated the independent and combined effects of being HIV+ and chronic tobacco-smoking on impulsivity, psychopathological symptoms and cognition. 104 participants [27 seronegative (SN)-non-Smokers, 26 SN-Smokers, 29 HIV+ non-Smokers, 22 HIV+ Smokers] were assessed for psychopathology symptoms (Symptom Checklist-90, SCL-90), depressive symptoms (Center for Epidemiologic Studies-Depression Scale, CES-D), impulsivity (Barratt Impulsiveness Scale, BIS), decision-making (The Iowa Gambling Task, IGT, and Wisconsin Card Sorting Test, WCST), and cognition (seven neurocognitive domains). Both HIV+ and Smoker groups had higher SCL-90 and CES-D scores, with highest scores in HIV+ Smokers. On BIS, both HIV+ and Smokers had higher Total Impulsiveness scores, with higher behavioral impulsivity in Smokers, highest in HIV+ Smokers. Furthermore, across the four groups, HIV+ Smokers lost most money and made fewest advantageous choices on the IGT, and had highest percent errors on WCST. Lastly, HIV+ had lower z-scores on all cognitive domains, with the lowest scores in HIV+ Smokers. These findings suggest that HIV-infection and chronic tobacco smoking may lead to additive deleterious effects on impulsivity, psychopathological (especially depressive) symptoms and cognitive dysfunction. Although greater impulsivity may be premorbid in HIV+ and Smokers, the lack of benefits of nicotine in chronic Smokers on attention and psychopathology, especially those with HIV-infection, may be due to the negative effects of chronic smoking on dopaminergic and cardio-neurovascular systems. Tobacco smoking may contribute to psychopathology and neurocognitive disorders in HIV+ individuals.

Methamphetamine (METH) is an addictive stimulant, and METH users have abnormal brain structures and function. The aims of this study were to investigate the relationships between impulsivity, brain structures, and possible sex-specific differences between METH users and non-drug using Controls. Structural MRI and the Barratt Impulsiveness Scale (BIS) questionnaire were completed in 124 subjects: 62 METH (ages 41.2 ± 1.4 years, 34 males) and 62 Controls (ages 43.3 ± 2.3 years, 36 males). Independent and interactive effects of METH use status and sex were evaluated. Relationships between METH usage characteristics, brain morphometry, and impulsivity scores were examined. METH users had higher impulsivity scores, on both the Cognitive and Behavioral Factors from the BIS (p < 0.0001-0.0001). Compared with same-sex Controls, male METH users had larger, while female METH users had smaller, right superior frontal cortex (interaction-p = 0.0005). The male METH users with larger frontal volumes and female METH users with smaller or thinner frontal cortices had greater Cognitive impulsivity (interaction-p ≤ 0.05). Only female METH users showed relatively larger nucleus accumbens (interaction-p = 0.03). Greater impulsivity and thinner frontal cortices in METH users are validated. Larger superior frontal cortex in male METH users with greater cognitive impulsivity suggest decreased dendritic pruning during adolescence might have contributed to their impulsive and drug use behaviors. In the female METH users, smaller frontal cortices and the associated greater impulsivity suggest greater neurotoxicity to these brain regions, while their relatively larger nucleus accumbens suggest an estrogen-mediated neuroprotective glial response. Men and women may be affected differently by METH use., Competing Interests: The authors declare that they have no conflict of interest.

Importance: Methamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development., Objective: To investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences., Design, Setting, and Participants: A prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community., Exposures: Prenatal methamphetamine and/or tobacco exposure., Main Outcomes and Measures: Quantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method., Results: Of the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher diffusivities in superior (SCR) and posterior corona radiatae (PCR) (group × age × sex, P = .002; group × age × sex, P = .01) at baseline that normalized by age 3 months. Only methamphetamine/tobacco- and tobacco-exposed girls showed persistently lower FA in anterior corona radiata (ACR) (group, P = .04; group × age × sex, P = .01). Tobacco-exposed infants showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02)., Conclusions and Relevance: Prenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.

Objective: The goal of the University of Hawaii (UH) child and adolescent psychiatry telemental health (TMH) program is to train child and adolescent psychiatry fellows to provide behavioral health services for the children of Hawaii and the Pacific Islands in the cultural context of their rural communities using interactive videoteleconferencing (IVTC). The training experience balances learning objectives with community service. Learning objectives include: Understanding mental health disparities in rural communities, leveraging community resources in ongoing treatment, providing culturally effective care, and improving health care access and delivery through TMH service research and evaluation., Methods: We describe the UH experience. Several UH faculty are experienced with IVTC technology. They are triple-board trained, are recognized for their research in program evaluation and mental health disparities, and are committed to serving Hawaii's rural communities. We demonstrate the role of TMH in linking children and their families living in rural communities with multiple mental health treatment providers. The service-learning curriculum and a unique collaboration with Mayo Clinic provide the opportunity to examine the role of TMH in global service, and training, education, and research., Results: TMH provides direct services to patients and consultation on Hawaii Island and Maui County. The collaboration with the Mayo Clinic brings further consultation in complex diagnostics, pharmacogenomics, and cross-cultural psychiatry. A curriculum provides trainees experience with IVTC with the goal of potential recruitment to underserved rural communities. The TMH program at UH is unique in its team building and workforce development by joining multiple entities through IVTC and translating expertise from the Mayo Clinic to rural communities, and strengthening collaboration with local child and adolescent psychiatrists, and primary care and other mental health providers., Conclusions: The UH psychiatry program is a model program to develop an expert mental health workforce in cultural context for children living in rural communities.

Diffusion tensor imaging (DTI) has been widely used to investigate the development of the neonatal and infant brain, and deviations related to various diseases or medical conditions like preterm birth. In this study, we created a probabilistic map of fiber pathways with known associated functions, on a published neonatal multimodal atlas. The pathways-of-interest include the superficial white matter (SWM) fibers just beneath the specific cytoarchitectonically defined cortical areas, which were difficult to evaluate with existing DTI analysis methods. The Jülich cytoarchitectonic atlas was applied to define cortical areas related to specific brain functions, and the Dynamic Programming (DP) method was applied to delineate the white matter pathways traversing through the SWM. Probabilistic maps were created for pathways related to motor, somatosensory, auditory, visual, and limbic functions, as well as major white matter tracts, such as the corpus callosum, the inferior fronto-occipital fasciculus, and the middle cerebellar peduncle, by delineating these structures in eleven healthy term-born neonates. In order to characterize maturation-related changes in diffusivity measures of these pathways, the probabilistic maps were then applied to DTIs of 49 healthy infants who were longitudinally scanned at three time-points, approximately five weeks apart. First, we investigated the normal developmental pattern based on 19 term-born infants. Next, we analyzed 30 preterm-born infants to identify developmental patterns related to preterm birth. Last, we investigated the difference in diffusion measures between these groups to evaluate the effects of preterm birth on the development of these functional pathways. Term-born and preterm-born infants both demonstrated a time-dependent decrease in diffusivity, indicating postnatal maturation in these pathways, with laterality seen in the corticospinal tract and the optic radiation. The comparison between term- and preterm-born infants indicated higher diffusivity in the preterm-born infants than in the term-born infants in three of these pathways: the body of the corpus callosum; the left inferior longitudinal fasciculus; and the pathway connecting the left primary/secondary visual cortices and the motion-sensitive area in the occipitotemporal visual cortex (V5/MT+). Probabilistic maps provided an opportunity to investigate developmental changes of each white matter pathway. Whether alterations in white matter pathways can predict functional outcomes will be further investigated in a follow-up study., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Probabilistic maps of white matter pathways related to motor, somatosensory, auditory, visual, and limbic functions, and major white matter tracts (the corpus callosum, the inferior fronto-occipital fasciculus, and the middle cerebellar peduncle) were applied to evaluate the developmental trajectories of these tracts, using longitudinal diffusion tensor imaging (DTI) obtained in term-born and preterm-born healthy infants. Nineteen term-born and 30 preterm-born infants completed MR scans at three time points: Time-point 1, 41.6±2.7 postmenstrual weeks; Time-point 2, 46.0±2.9 postmenstrual weeks; and Time-point 3, 50.8±3.7 postmenstrual weeks. The DTI-derived scalar values (fractional anisotropy, eigenvalues, and radial diffusivity) of the three time points are available in this Data article.

Psychological maturation continues into young adulthood when substance abuse and several psychiatric disorders often emerge. Marijuana is the most common illicit drug abused by youths, typically preceding other illicit substances. We aimed to evaluate the complex and poorly studied relationships between marijuana use, psychiatric symptoms, and cortisol levels in young marijuana users. Psychiatric symptoms and salivary cortisol were measured in 122 youths (13-23 years old) with and without marijuana use. Psychiatric symptoms were evaluated using the Symptom-Checklist-90-R and Brief Psychiatric Rating Scale. Mid-day salivary cortisol levels were measured. Additionally, salivary cytokine levels were measured in a subset of participants. Although the cortisol levels and salivary cytokine levels were similar, the young marijuana users had more self-reported and clinician rated psychiatric symptoms than controls, especially anxiety-associated symptoms. Moreover, marijuana users with earlier age of first use had more symptoms, while those with longer abstinence had fewer symptoms. Greater cumulative lifetime marijuana use was also associated with greater psychiatric symptoms. The discordant anxiety (feeling stressed or anxious despite normal cortisol) in the marijuana users, as well as symptom exacerbations with early and continued marijuana use in young marijuana users suggest that marijuana use may contribute to an aberrant relationship between stress response and psychiatric symptoms. The greater symptomatology, especially in those with earlier initiation and greater marijuana usage, emphasize the need to intervene for substance use and perceived anxiety in this population.

Importance: The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders., Objective: To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth., Design, Setting, and Participants: Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013., Main Outcomes and Measures: We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms., Results: Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10-13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development., Conclusions and Relevance: Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.

Background and Aims: No effective pharmacotherapy for methamphetamine (MA) use disorder has yet been found. This study evaluated sustained-release methylphenidate (MPH-SR) compared with placebo (PLA) for treatment of MA use disorder in people also undergoing behavioral support and motivational incentives., Design: This was a randomized, double-blind, placebo-controlled design with MPH-SR or PLA provided for 10 weeks (active phase) followed by 4 weeks of single-blind PLA. Twice-weekly clinic visits, weekly group counseling (CBT) and motivational incentives (MI) for MA-negative urine drug screens (UDS) were included., Setting: Treatment sites were in Los Angeles, California (LA) and Honolulu, Hawaii (HH), USA., Participants: A total of 110 MA-dependent (via DSM-IV) participants (LA = 90; HH = 20)., Measurements: The primary outcome measure is self-reported days of MA use during the last 30 days of the active phase. Included in the current analyses are drug use (UDS and self-report), retention, craving, compliance (dosing, CBT, MI), adverse events and treatment satisfaction., Findings: No difference was found between treatment groups in self-reported days of MA use during the last 30 days of the active phase (P = 0.22). In planned secondary outcomes analyses, however, the MPH group had fewer self-reported MA use days from baseline through the active phase compared with the PLA group (P = 0.05). The MPH group also had lower craving scores and fewer marijuana-positive UDS than the PLA group in the last 30 days of the active phase. The two groups had similar retention, other drug use, adverse events and treatment satisfaction., Conclusions: Methylphenidate may lead to a reduction in concurrent methamphetamine use when provided as treatment for patients undergoing behavioral support for moderate to severe methamphetamine use disorder, but this requires confirmation., (© 2014 Society for the Study of Addiction.)

In Hawai'i, rural residents suffer disproportionately from poor health and mental health outcomes. Hawai'i's island geography makes rural health service disparities especially compelling. Physician workforce shortages are projected to increase, despite 30 years of programs aimed at recruiting physicians to rural areas. Telepsychiatry has been shown to be a feasible way to provide a variety of health services to individuals living in rural areas with limited access to healthcare. The University of Hawai'i Rural Health Collaboration (UHRHC) was established by the Department of Psychiatry to address the need for workforce development and rural access to mental health services across the State of Hawai'i by using telepsychiatry. Partnerships with community health clinics have been formed to provide patient care and consultation-liaison services through telepsychiatry technology. In addition, UHRHC focuses on workforce development in its residency training curriculum by utilizing a service-learning approach to rural mental health. Evaluation of these efforts is currently underway, with preliminary evidence suggesting that UHRHC is a promising strategy to increase access to critical mental health services and reduce health disparities in rural Hawai'i.

Background: Methamphetamine can be neurotoxic to the adult brain; however, many individuals first use methamphetamine during adolescence, and the drug's impact on this period of brain development is unknown. Therefore, we evaluated young methamphetamine users for possible abnormalities in brain metabolite concentrations., Methods: Anterior cingulate cortex (ACC), frontal white matter (FWM), basal ganglia, and thalamus were studied with localized proton magnetic resonance spectroscopy in 54 periadolescent (ages 13-23 years) methamphetamine users and 53 comparison subjects. The concentrations of major brain metabolites and their associations with age, sex and cognition were assessed., Results: FWM total-creatine correlated with age in methamphetamine-using males and comparison females, but not comparison males or methamphetamine-using females, leading to a drug by sex by age interaction (p=0.003) and ACC choline-containing compounds (CHO) correlated with age only in comparison males leading to a drug by sex by age interaction (p=0.03). Higher ACC CHO was associated with faster performance on the Stroop Interference task in the control males. Male methamphetamine users had slowest performance on the Stroop Interference task and did not show age-appropriate levels of ACC CHO., Conclusions: The altered age-appropriate levels of ACC CHO and poorer executive function in male methamphetamine users suggest methamphetamine abuse may interfere with brain maturation. These periadolescents did not have the abnormal neuronal markers previously reported in adult methamphetamine users, suggesting that neuronal abnormalities may be the result of long-term use or interference in normal cortical maturation, emphasizing the need for early intervention for young methamphetamine users., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Methamphetamine (METH) is a widely abused drug. However, little is known about the effects of chronic METH consumption on HPA axis function and psychiatric symptomatology in adolescent METH users. The current study evaluated psychiatric symptoms and changes in the stress response of adolescent METH users. Forty-one adolescent METH users and 75 comparison subjects in the same age range (ages 12-23 years) were recruited. Each subject completed the Symptom Checklist-90R (SCL-90) and was evaluated using the Brief Psychiatric Rating Scale. In addition, the subjects completed the Trier Social Stress Test (TSST) and had salivary cortisol levels measured 30 min before, immediately after, and 60 min after the TSST. Adolescent METH users showed greater severity of symptoms across all measures of the SCL-90. Younger female METH users had the most symptoms. Furthermore, the METH users exhibited significantly enhanced cortisol levels immediately following the TSST (+31%, p = 0.03). Adolescent METH use is associated with greater psychiatric symptoms and enhanced cortisol secretion following a social stressor, particularly in younger female METH users. The psychiatric symptoms may reflect altered prefrontal cortical function resulting from chronic stress/drug use and the resulting glucocorticoid exposure. The results further suggest that treatment approaches should focus on stress-coping strategies to decrease the probability of relapse.

Background: Methamphetamine (METH) is a widely abused psychostimulant that is associated with neurotoxicity and neurocognitive impairments in adults. However, the effects of METH use on neurocognitive performance of adolescents are unclear., Methods: Fifty-four adolescent METH users and 74 age-matched comparison subjects (ages 12 to 23 years) were evaluated with a battery of neuropsychological tests. The cognitive domains evaluated include psychomotor (Symbol Digit, Trail Making), executive function (Stroop Interference task, Wisconsin Card Sort task), fine-motor speed (Grooved Pegboard), memory (Digit span and Auditory Verbal Learning Task), as well as attention and working memory (California Computerized Assessment package)., Results: METH users were slower on the Stroop Interference task than the comparison subjects (F(1,114) = 4.33, p = 0.03). METH subjects also performed worse than controls on the Wechsler Adult Intelligence Scale III/Wechsler Intelligence Scale for Children IV (WAIS/WISC) Matrices task (F(1,114) = 4.37, p = 0.04) and performed significantly worse on the Peg Board task than the comparison subjects for both the dominant (F(1,114) = 7.56, p = 0.01) and non-dominant (F(1,114) = 6.75, p = 0.01). Lastly, length of abstinence was associated with improved performance on the Peg Board test with the dominant had (r = -0.34), as well as the WAIS/WISC Forward Digit Span task (r = 0.38), Conclusions: METH use is associated with impaired executive functions in adolescent users.

Methamphetamine (METH) users showed structural and chemical abnormalities on magnetic resonance (MRI) studies, particularly in the frontal and basal ganglia brain regions. Diffusion tensor imaging (DTI) may provide further insights regarding the microstructural changes in METH users. We investigated diffusion tensor measures in frontal white matter and basal ganglia of 30 adult METH users and 30 control subjects using a 3 T MR scanner. Compared with healthy control subjects, METH users showed lower fractional anisotropy (FA) in right frontal white matter, and higher apparent diffusion coefficient (ADC) in left caudate and bilateral putamen. Higher left putamen ADC was associated with earlier initiation of METH use, greater daily amounts, and a higher cumulative lifetime dose. Similarly, higher right putamen ADC was associated with greater daily amounts and a higher cumulative lifetime dose. The lower FA in the right frontal white matter suggests axonal injury in these METH users. The higher ADC in the basal ganglia suggests greater inflammation or less myelination in these brain regions of those with younger age of first METH use and greater METH usage.

This study examined the differences in psychiatric symptoms between adult methamphetamine users (n = 46) and control subjects (n = 31), the relationship between psychiatric symptoms and the intensity of methamphetamine craving, and whether psychiatric symptoms were correlated to methamphetamine drug-usage variables (ie, length of abstinence, frequency, duration, and lifetime grams). We found that depressive symptoms on the Center for Epidemiology Studies-Depression (CES-D) and many other psychiatric symptoms on the Symptom Checklist-90 (SCL-90) significantly correlated with craving methamphetamine on the visual analog scale (VAS) for craving. Methamphetamine users had significantly more depressive symptoms (on CES-D) and psychotic symptoms (on SCL-90) compared to controls. There were no significant correlations between psychiatric symptoms and methamphetamine-usage variables. This study provides the first evidence to suggest that depressive symptoms (on CES-D) and psychiatric symptoms (on SCL-90) are strongly associated with the intensity of craving (on VAS) for the drug in methamphetamine users. However, the methamphetamine usage variables had no relationship with psychiatric symptoms. Therefore, methamphetamine users, regardless of their usage patterns, may benefit from treatment of their psychiatric symptoms in order to minimize craving and subsequent relapse to drug use.

Aims: To review structural, chemical and metabolic brain changes, particularly those in the basal ganglia, in individuals who used methamphetamine, as well as in children with prenatal methamphetamine exposure., Methods: Magnetic resonance imaging (MRI) and positron emission tomography (PET) studies that evaluated brain structural, chemical and metabolite changes in methamphetamine subjects, or children with prenatal methamphetamine exposure, were reviewed and summarized. Relevant pre-clinical studies that provided insights to the interpretations of these imaging studies were also reviewed., Results: In adults who used methamphetamine, MRI demonstrates enlarged striatal volumes, while MR spectroscopy shows reduced concentrations of the neuronal marker N-acetylasparate and total creatine in the basal ganglia. In contrast, children with prenatal methamphetamine exposure show smaller striatal structures and elevated total creatine. Furthermore, PET studies consistently showed reduced dopamine transporter (DAT) density and reduced dopamine D(2) receptors in the striatum of methamphetamine subjects. PET studies also found lower levels of serotonergic transporter density and vesicular monoamine transporter (VMAT2) across striatal subregions, as well as altered brain glucose metabolism that correlated with severity of psychiatric symptoms in the limbic and orbitofrontal regions., Conclusion: Neuroimaging studies demonstrate abnormalities in brain structure and chemistry convincingly in individuals who used methamphetamine and in children with prenatal methamphetamine exposure, especially in the striatum. However, many important questions remain and larger sample sizes are needed to validate these preliminary observations. Furthermore, longitudinal studies are needed to evaluate the effects of treatment and abstinence on these brain changes and to determine whether imaging, and possibly genetic, markers can be used to predict treatment outcome or relapse.

Objective: Many schizophrenia patients remain undiagnosed and untreated for long periods of time. It has been suggested that untreated psychosis may have deleterious neurotoxic effects. However, studies examining the correlates of untreated initial psychosis duration have been mixed. Previous MRI studies have reported no significant correlations between duration of untreated initial psychosis and brain volumes but have not examined specific brain regions that may be most susceptible to neuronal damage., Method: The authors investigated the relationship between duration of untreated initial psychosis and hippocampus morphology in 105 patients with first-episode DSM-IV schizophrenia spectrum disorders. High-resolution MRI-based hippocampal volume measurements were obtained by using a semiautomated artificial neural network method., Results: There were no significant associations between hippocampal volumes and duration of untreated initial psychosis. When the patient group was split around the median duration of untreated initial psychosis (13 weeks), there were again no significant differences in left, right, or total hippocampal volume between groups., Conclusions: These findings do not support the hypothesis that psychosis is neurotoxic or that delaying antipsychotic drug treatment results in reduced hippocampal volumes.

Objective: Studies of patients experiencing their first episode of psychosis have demonstrated that they typically remain undiagnosed and untreated for 1-2 years. It has been postulated that prolonged untreated psychosis may have serious effects: poor response to neuroleptic medications, poor clinical outcomes, and direct neurotoxicity. This study investigated the relationships between duration of untreated initial psychosis and neurocognitive functioning and high-resolution imaging brain measurements., Method: A total of 156 subjects with DSM-IV schizophrenia, schizophreniform disorder, or schizoaffective disorder were evaluated during their first episode of psychosis. Measurements included nine domains of neurocognitive functioning, volumetric measures of total brain tissue, gray and white matter, and CSF, and measures of brain surface anatomy., Results: The mean duration of untreated initial psychosis was 74.3 weeks. Correlations between neurocognitive functioning, brain volumetric measurements, and surface anatomy measurements with duration of untreated initial psychosis were weak; none reached statistical significance. When the group was divided on the basis of median duration of untreated initial psychosis, there were again no significant differences between the groups with long and short duration of untreated initial psychosis except on two measures (verbal memory and cortical sulcal depth)., Conclusions: The absence of strong correlations suggests that untreated initial psychosis has no direct toxic neural effects. These results suggest that large-scale initiatives designed to prevent neural injury through early intervention in the prepsychotic or early psychosis phase may be based on incorrect assumptions that neurotoxicity or cognitive deterioration may be avoided. Nevertheless, early treatment is justified because it reduces suffering.

Previous structural and functional imaging studies suggest that the corticocerebellar-thalamic-cortical circuit is dysfunctional in schizophrenia. Accurate identification and volumetric measurement of cerebellar subregions are essential to the assessment of the cerebellum's role in healthy and disease states. Manual parcellation of the cerebellum on MR images was performed with the use of guide traces. Guide traces identified relevant fissures and borders in several planes, and their intersections with the primary tracing plane were used to maintain consistency and accuracy during the parcellation. The cerebellum was parcellated into right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. A systematic review of the final traces ensured their accuracy. An artificial neural network was trained using a novel landmark-warped method to help account for wide variability in structure size and location. Overlaps of the manually traced lobes (intersection/union) ranged from 0.78 to 0.85 and intraclass correlations (r2) ranged from 0.82 to 0.94. In a comparison of the semiautomated method with the manual method overlaps ranged from 0.83 to 0.88 and intraclass correlations ranged from 0.92 to 0.97. For two raters using the semiautomated method overlaps ranged from 0.83 to 0.88 and intraclass correlations ranged from 0.97 to 0.99. The semiautomated method was built on the groundwork of the manual method to produce more reliable results in a fraction of the time, making valid measurements possible on a large number of subjects.

Kinetic effects of osmotic stress on sodium ionic and gating currents have been studied in crayfish giant axons after removal of fast inactivation with chloramine-T. Internal perfusion with media made hyperosmolar by addition of formamide or sucrose, reduces peak sodium current (before and after removal of fast inactivation with chloramine-T), increases the half-time for activation, but has no effect on tail current deactivation rate(s). Kinetics of ON and OFF gating currents are not affected by osmotic stress. These results confirm (and extend to sodium channels) the separation of channel gating mechanisms into voltage-sensitive and solvent-sensitive processes recently proposed by Zimmerberg J., F. Bezanilla, and V. A. Parsegian. (1990. Biophys. J. 57:1049-1064) for potassium delayed rectifier channels. Additionally, the kinetic effects produced by hyperosmolar media seem qualitatively similar to the kinetic effects of heavy water substitution in crayfish axons (Alicata, D. A., M. D. Rayner, and J. G. Starkus. 1990. Biophys. J. 57:745-758). However, our observations are incompatible with models in which voltage-sensitive and solvent-sensitive gating processes are presumed to be either (a) strictly sequential or, (b) parallel and independent. We introduce a variant of the parallel model which includes explicit coupling between voltage-sensitive and solvent-sensitive processes. Simulations of this model, in which the total coupling energy is as small as 1/10th of kT, demonstrate the characteristic kinetic changes noted in our data.

Schauf and Bullock (1979. Biophys. J. 27:193-208; 1982. Biophys. J. 37:441-452), using Myxicola giant axons, demonstrated that solvent substitution with deuterium oxide (D2O) significantly affects both sodium channel activation and inactivation kinetics without corresponding changes in gating current or tail current rates. They concluded that (a) no significant component of gating current derives from the final channel opening step, and (b) channels must deactivate (during tail currents) by a different pathway from that used in channel opening. By contrast, Oxford (1981. J. Gen. Physiol. 77:1-22) found in squid axons that when a depolarizing pulse is interrupted by a brief (approximately 100 microseconds) return to holding potential, subsequent reactivation (secondary activation) is very rapid and shows almost monoexponential kinetics. Increasing the interpulse interval resulted in secondary activation rate returning towards control, sigmoid (primary activation) kinetics. He concluded that channels open and close (deactivate) via the same pathway. We have repeated both sets of observations in crayfish axons, confirming the results obtained in both previous studies, despite the apparently contradictory conclusions reached by these authors. On the other hand, we find that secondary activation after a brief interpulse interval (50 microseconds) is insensitive to D2O, although reactivation after longer interpulse intervals (approximately 400 microseconds) returns towards a D2O sensitivity similar to that of primary activation. We conclude that D2O-sensitive primary activation and D2O-insensitive tail current deactivation involve separate pathways. However, D2O-insensitive secondary activation involves reversal of the D2O-insensitive deactivation step. These conclusions are consistent with "parallel gate" models, provided that one gating particle has a substantially reduced effective valence.

Internal perfusion with solutions made hyperosmolar by 10% formamide selectively reduces the initial fast component of ON gating current (fast Ig) in crayfish axons. This result parallels the effects of formamide perfusion seen in Myxicola giant axons (Schauf, C. L., and M. A. Chuman. 1986. Neural Membranes. Alan R. Liss, Inc., New York. 3-23). However, our findings do not confirm their conclusion that internal formamide has a specific pharmacological effect on fast Ig. Formamide-induced suppression of fast Ig is always associated with changes in linear capacity current, indicating a reduction in the rate of rise of the voltage clamp. Furthermore, this suppression of fast Ig can be reversed when clamp rise time is returned to its control rate by increasing compensation for series resistance (Rs) during formamide perfusion. Increases in Rs during 10% formamide perfusion of up to 5 omega.cm2 were measured by evaluating the increase in Rs compensation required to return the following parameters to their control levels: (a) peak capacity current, (b) peak gating current, (c) the voltage maximum of the /Na-V curve, and (d) "tau h". We conclude that hyperosmolar internal formamide increases Rs, reduces clamp speed, and thus selectively suppresses fast Ig. On the other hand, the reversible block of sodium ionic current by internal formamide, reported by Schauf and Chuman, is not eliminated by correcting for series resistance changes during formamide perfusion.