Nitrous Oxide Inhalant Use Disorder Preceding Symptoms Concerning for Primary Psychotic Illness.

BACKGROUND AND OBJECTIVE: Nitrous oxide has long been used recreationally for its ability to induce euphoria and other deliriant effects. In modern times, it remains a popular, legal, and widely available option for those seeking altered states. Though substance-induced psychotic symptoms have been mentioned in the literature, the potential long-term negative neuropsychiatric effects related to its use have not been well established. METHODS AND RESULTS: This is a patient case report of a young man (N = 1) who initially presented with acute neurological symptoms requiring hospitalization due to heavy nitrous oxide inhalant use, and went on to present with symptoms concerning for a primary psychotic illness over multiple inpatient admissions. He provided both verbal and written consent to share his story for this case report. DISCUSSION AND CONCLUSIONS: It is important to consider nitrous oxide use as a possible contributing factor to the development of primary psychotic illness. SCIENTIFIC SIGNIFICANCE: Current literature suggests that psychosis associated with nitrous oxide use is transient and resolves upon cessation and treatment of vitamin B12 deficiency. Here, we present a patient with risk factors for psychotic illness developing psychotic illness following extensive nitrous oxide use. This report offers a unique perspective of longitudinal follow-up (often not provided with reports on this topic), and illustrates the importance of healthcare providers inquiring about nitrous oxide abuse in patients presenting with early psychotic symptoms. (Am J Addict 2020;29:525-527).

COVID 19 and the Opioid Epidemic: An Analysis of Clinical Outcomes During COVID 19.

Background and Objectives: Here we aimed to characterize clinical outcomes in those receiving treatment at a Veterans Health Administration (VHA) methadone maintenance treatment program (MMT) during the COVID 19 pandemic in which SAMSHA regulations for MMTs were changed to provide a greater number of methadone allotments and decreased clinic-visit frequency. Methods: We report results of a single-site, pre-post cohort study of urine drug screen data 3 months before and after an increase in allotments of take-home medication from the methadone clinic. One hundred twenty-nine patients met inclusion criteria for this study. The study was reviewed by the NYHHS IRB committee and granted final approval by the Research and Development Committee. Results: The sample was predominately male, average age 66years and average years in most recent treatment is 4.1 years. No statistical significance was found between period 1 and period 2 in the positive test detection for nonprescribed opiates, methadone and illicit substances (P > .05), number of new medical illnesses or overdoses. We controlled for participant age, substance use disorder diagnosis, psychiatric disorder diagnosis, and number of years in treatment. Discussion/Conclusions: The results of the study illustrate the relative safety of the changes made at this particular MMT during the pandemic. Additionally, there was continued adherence to methadone treatment with minimal change in illicit substance use during period 1 and period 2. Scientific Significance: To these authors' knowledge this paper is one of the first to examine clinical outcomes in those with opioid addiction prescribed methadone from MMTs during the COVID 19 pandemic.

Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study.

BACKGROUND: In vivo magnetic resonance studies have found that cocaine dependence is associated with T2 signal hyperintensities and metabolite abnormalities in cerebral white matter (WM). Functional neuroimaging studies have suggested that chronic cocaine use is primarily associated with frontal lobe deficits in regional cerebral blood flow and brain glucose metabolism levels; however, the effects of cocaine dependence, if any, on frontal WM microstructure are unknown. Thus, we sought to examine the effects of cocaine dependence on frontal WM integrity. METHODS: Diffusion tensor imaging was employed to examine the WM integrity of frontal regions at four levels: 10 mm above, 5 mm above, 0 mm above, and 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. The fractional anisotropy (FA) of 12 cocaine-dependent patients and 13 age-similar control subjects was compared. RESULTS: The cocaine-dependent patients had significantly reduced FA in the frontal WM at the AC-PC plane and a trend toward reduced FA at 5 mm below the AC-PC plane, suggestive of reduced WM integrity in these regions. CONCLUSIONS: These findings were consistent with the hypothesis that cocaine dependence involves alterations in orbitofrontal connectivity, which may be involved in the decision-making deficits seen in this disorder.

Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study.

OBJECTIVE: The purpose of this study was test the hypothesis that abnormalities of inferior frontal white matter are related to the negative symptoms of schizophrenia. METHOD: Fractional anisotropy of white matter tracts in the prefrontal area of 10 schizophrenic patients was determined by diffusion tensor imaging. Patients were also assessed for severity of negative symptoms by using the Schedule for the Assessment of Negative Symptoms (SANS). RESULTS: Inferior frontal white matter fractional anisotropy was significantly inversely correlated with the SANS global ratings of negative symptoms. CONCLUSIONS: These data, while preliminary, suggest that impaired white matter integrity in the inferior frontal region may be associated with the severity of negative symptoms in schizophrenia.

Cognitive performance in schizophrenia: relationship to regional brain volumes and psychiatric symptoms.

In an all-male sample of schizophrenic patients stabilized by medication (n=62) and normal controls (n=27), we obtained neuropsychological test data and high-resolution whole brain magnetic resonance scans, as well as detailed psychiatric rating scales on a subset of the patients (n=47). Schizophrenic patients had significantly worse overall age-adjusted cognitive performance than normal controls (average z-score=-0.90, range=-0.60 to -1.81), which included relatively more severe deficits with different types of memory, psychomotor speed, verbal fluency and verbal abstraction. Schizophrenic patients also had significantly smaller bilateral volumes in gray but not white matter in the prefrontal region, superior temporal gyrus and whole temporal lobe, but no group differences were observed in the hippocampus and parahippocampus. Correlations between the brain regions and cognitive performance revealed different sets of significant relationships for the two groups, particularly in the prefrontal and hippocampal regions. In addition, inverse correlations were observed between certain cognitive abilities (psychomotor speed, cognitive flexibility and verbal fluency) and patients' psychiatric ratings, especially with measures of negative symptoms. The convergence of findings for schizophrenic patients regarding the prefrontal region, negative symptoms, psychomotor speed and cognitive flexibility suggests that schizophrenic negative symptoms may involve disruption of frontal-subcortical connections.

FDG-PET and MRI imaging of the effects of sertindole and haloperidol in the prefrontal lobe in schizophrenia.

Sertindole, a 2nd generation antipsychotic with low movement disorder side effects, was compared with haloperidol in a 6-week crossover study. Fifteen patients with schizophrenia (mean age=42.6, range=22-59, 11 men and 4 women) received sertindole (12-24 mg) or haloperidol (4-16 mg) for 6 weeks and then received a FDG-PET scan and an anatomical MRI. Patients were then crossed to the other treatment and received a second set of scans at week 12. Dose was adjusted by a physician blind to the medication type. Brodmann areas were identified stereotaxically using individual MRI templates applied to the coregistered FDG-PET image. Sertindole administration was associated with higher dorsolateral prefrontal cortex metabolic rates than haloperidol and lower orbitofrontal metabolic rates than haloperidol. This effect was greatest for gray matter of the dorsolateral Brodmann areas 8, 9, 10, 44, 45, and 46. Patients were further contrasted with an approximately age and sex-matched group of 33 unmedicated patients with schizophrenia and with a group of 55 normal volunteers. Sertindole administration was associated with greater change toward normal values and away from the values found in the unmedicated comparison group for dorsolateral prefrontal cortex gray matter and white matter underlying medial prefrontal and cingulate cortex. These results are consistent with the low motor side-effect profile of sertindole, greater improvement on prefrontal cognitive tasks with sertindole than haloperidol, and with the tendency of 2nd generation antipsychotic drugs to have greater frontal activation than haloperidol.