Quantifying abnormal emotion processing: A novel computational assessment method and application in schizophrenia.

Abnormal emotion processing is a core feature of schizophrenia spectrum disorders (SSDs) that encompasses multiple operations. While deficits in some areas have been well-characterized, we understand less about abnormalities in the emotion processing that happens through language, which is highly relevant for social life. Here, we introduce a novel method using deep learning to estimate emotion processing rapidly from spoken language, testing this approach in male-identified patients with SSDs (n = 37) and healthy controls (n = 51). Using free responses to evocative stimuli, we derived a measure of appropriateness, or "emotional alignment" (EA). We examined psychometric characteristics of EA and its sensitivity to a single-dose challenge of oxytocin, a neuropeptide shown to enhance the salience of socioemotional information in SSDs. Patients showed impaired EA relative to controls, and impairment correlated with poorer social cognitive skill and more severe motivation and pleasure deficits. Adding EA to a logistic regression model with language-based measures of formal thought disorder (FTD) improved classification of patients versus controls. Lastly, oxytocin administration improved EA but not FTD among patients. While additional validation work is needed, these initial results suggest that an automated assay using spoken language may be a promising approach to assess emotion processing in SSDs.

Effects of Ayahuasca on Gratitude and Relationships with Nature: A Prospective, Naturalistic Study.

Qualitative studies and anecdotal reports suggest that experiences with ayahuasca, a psychedelic brew found in Central and South America, may be followed by individuals enduringly feeling more grateful and connected to nature. Yet, to date, these changes have been understudied. Here, participants (N = 54) completed validated surveys related to gratitude, nature relatedness, and nature appreciation one-week before, one-week after, and one-month after attending an ayahuasca retreat center. Compared to baseline, there was a significant increase in gratitude, nature relatedness, and nature appreciation at the one-week and one-month follow-ups. Ratings of mystical-type experiences and awe, but not ego dissolution, during participants' ayahuasca sessions were weakly-to-moderately correlated with these increases. The number of ayahuasca ceremonies attended at the retreat was not related to change in outcomes, underscoring the importance of the quality rather than the quantity of the experiences in post-acute change. Lastly, participant age was negatively related to the occurrence of mystical-type experiences and awe, supporting literature indicating blunted psychedelic effects with increased age. In the context of study limitations, the results suggest that mystical-type experiences and awe occasioned by ayahuasca may be linked to prosocial changes in gratitude and relationships with nature that may be beneficial to mental health.

Risks and benefits of psilocybin use in people with bipolar disorder: An international web-based survey on experiences of 'magic mushroom' consumption.

BACKGROUND: Psilocybin, the primary psychoactive component of psychedelic 'magic mushrooms', may have potential for treating depressive symptoms, and consequent applications for bipolar disorder (BD). Knowledge of the risks and benefits of psilocybin in BD is limited to case studies. AIM: To support the design of clinical trials, we surveyed experiences of psilocybin use in people with BD. METHODS: An international web-based survey was used to explore experiences of psilocybin use in people with a self-reported diagnosis of BD. Quantitative findings were summarised using descriptive statistics. Qualitative content analysis was used to investigate free-text responses, with a focus on positive experiences of psilocybin use. RESULTS: A total of 541 people completed the survey (46.4% female, mean 34.1 years old). One-third (32.2%; n = 174) of respondents described new/increasing symptoms after psilocybin trips, prominently manic symptoms, difficulties sleeping and anxiety. No differences in rates of adverse events overall were observed between individuals with BD I compared to BD II. Use of emergency medical services was rare (n = 18; 3.3%), and respondents (even those who experienced adverse effects) indicated that psilocybin use was more helpful than harmful. Quantitative findings elaborated on perceived benefits, as well as the potential for psilocybin trips to contain both positively and negatively received elements. CONCLUSIONS: The subjective benefits of psilocybin use for mental health symptoms reported by survey participants encourage further investigation of psilocybin-based treatments for BD. Clinical trials should incorporate careful monitoring of symptoms, as data suggest that BD symptoms may emerge or intensify following psilocybin use.

"A sense of the bigger picture:" A qualitative analysis of follow-up interviews with people with bipolar disorder who self-reported psilocybin use.

OBJECTIVES: People with bipolar disorder (BD) spend more time depressed than manic/hypomanic, and depression is associated with greater impairments in psychosocial functioning and quality of life than mania/hypomania. Emerging evidence suggests psilocybin, the psychoactive compound in "magic mushrooms," is a promising treatment for unipolar depression. Clinical trials of psilocybin therapy have excluded people with BD as a precaution against possible adverse effects (e.g., mania). Our study centered the experiences of adults living with BD who consumed psilocybin-containing mushrooms, and aimed to (1) understand its subjective impacts on BD symptoms, (2) deepen understanding of Phase I survey results, and (3) elucidate specific contextual factors associated with adverse reactions in naturalistic settings. METHODS: Following an international survey (Phase I), follow-up interviews were conducted with 15 respondents (Phase II) to further understand psilocybin use among adults with BD. As part of a larger mixed-methods explanatory sequential design study, reflexive thematic analysis was used to elaborate findings. RESULTS: Three major themes containing sub-themes were developed. (1) Mental Health Improvements: (1.1) decreased impact and severity of depression, (1.2) increased emotion processing, (1.3) development of new perspectives, and (1.4) greater relaxation and sleep. (2) Undesired Mental Health Impacts: (2.1) changes in sleep, (2.2) increased mania severity, (2.3) hospitalization, and (2.4) distressing sensory experiences. (3) Salient Contextual Factors for psilocybin use included: (3.1) poly-substance use and psilocybin dose, (3.2) solo versus social experiences, and (3.3) pre-psilocybin sleep deprivation. CONCLUSION: Our findings demonstrate both benefits and risks of psilocybin use in this population. Carefully designed clinical trials focused on safety and preliminary efficacy are warranted.

Automatic Imitation in Comorbid PTSD & Alcohol Use Disorder and Controls: an RCT of Intranasal Oxytocin.

INTRODUCTION: Mimicking movements of others makes both the imitating and imitated partners feel closer. Oxytocin may increase focus on others and has been shown to increase automatic imitation in healthy controls (HC). However, this has not been replicated, and oxytocin's effects on automatic imitation have not been demonstrated in clinical populations. This study attempts to replicate effects on HC and examine effects on people with comorbid posttraumatic stress disorder and alcohol use disorder (PTSD-AUD). METHODS: Fifty-four males with PTSD-AUD and 43 male HC received three intranasal treatment conditions (placebo, oxytocin 20 International Units (IU), and oxytocin 40 IU) in a randomized order, across three separate testing days, as part of a double-blind, crossover parent study. At 135 min post-administration, each performed the imitation-inhibition task, which quantifies automatic imitation as the congruency effect (CE). After exclusions, the final analyzed data set included 49 participants with PTSD-AUD and 38 HC. RESULTS: In HC, oxytocin 20 IU demonstrated a statistically significant increase in CE, and 40 IU showed a trend-level increase. In PTSD-AUD, oxytocin did not significantly increase CE. Post-hoc analysis showed the PTSD-AUD group had higher CE than HC on placebo visits. DISCUSSION: Our data suggest PTSD-AUD is associated with higher automatic imitation than HC in the absence of oxytocin administration. We successfully replicated findings that oxytocin increases automatic imitation in HC. This demonstrates an unconscious motor effect induced by oxytocin, likely relevant to more complex forms of imitative movements, which have the potential to improve social connection. We did not find a significant effect of oxytocin on automatic imitation in PTSD-AUD. Future research should examine imitation in both sexes, at peak oxytocin levels, and on increasingly complex forms of imitation.

Six month durability of targeted cognitive training supplemented with social cognition exercises in schizophrenia.

BACKGROUND: Deficits in cognition, social cognition, and motivation are significant predictors of poor functional outcomes in schizophrenia. Evidence of durable benefit following social cognitive training is limited. We previously reported the effects of 70 h of targeted cognitive training supplemented with social cognitive exercises (TCT + SCT) verses targeted cognitive training alone (TCT). Here, we report the effects six months after training. METHODS: 111 participants with schizophrenia spectrum disorders were randomly assigned to TCT + SCT or TCT-only. Six months after training, thirty-four subjects (18 TCT + SCT, 16 TCT-only) were assessed on cognition, social cognition, reward processing, symptoms, and functioning. Intent to treat analyses was used to test the durability of gains, and the association of gains with improvements in functioning and reward processing were tested. RESULTS: Both groups showed durable improvements in multiple cognitive domains, symptoms, and functional capacity. Gains in global cognition were significantly associated with gains in functional capacity. In the TCT + SCT group, participants showed durable improvements in prosody identification and reward processing, relative to the TCT-only group. Gains in reward processing in the TCT + SCT group were significantly associated with improvements in social functioning. CONCLUSIONS: Both TCT + SCT and TCT-only result in durable improvements in cognition, symptoms, and functional capacity six months post-intervention. Supplementing TCT with social cognitive training offers greater and enduring benefits in prosody identification and reward processing. These results suggest that novel cognitive training approaches that integrate social cognitive exercises may lead to greater improvements in reward processing and functioning in individuals with schizophrenia.

Intranasal Oxytocin May Improve High-Level Social Cognition in Schizophrenia, But Not Social Cognition or Neurocognition in General: A Multilevel Bayesian Meta-analysis.

While there is growing interest in the potential for intranasal oxytocin (IN-OT) to improve social cognition and neurocognition (ie, nonsocial cognition) in schizophrenia, the extant literature has been mixed. Here, we perform a Bayesian meta-analysis of the efficacy of IN-OT to improve areas of social and neurocognition in schizophrenia. A systematic search of original research publications identified randomized controlled trials (RCTs) of IN-OT as a treatment for social and neurocognitive deficits in schizophrenia for inclusion. Standardized mean differences (SMD) and corresponding variances were used in multilevel Bayesian models to obtain meta-analytic effect-size estimates. Across a total of 12 studies (N = 273), IN-OT did not improve social cognition (SMD = 0.07, 95% credible interval [CI] = [-0.06, 0.17]) or neurocognition (SMD = 0.12, 95% CI = [-0.12, 0.34]). There was moderate between study heterogeneity for social cognition outcomes (τs= 0.12). Moderator analyses revealed that IN-OT had a significantly larger effect on high-level social cognition (ie, mentalizing and theory of mind) compared to low-level social cognition (ie, social cue perception) (b = 0.19, 95% CI = [0.05, 0.33]). When restricting our analysis to outcomes for high-level social cognition, there was a significant effect of IN-OT (SMD = 0.20, 95 % CI = [0.05, 0.33]) but the effect was not robust to sensitivity analyses. The present analysis indicates that IN-OT may have selective effects on high-level social cognition, which provides a more focused target for future studies of IN-OT.

Creating Live Interactions to Mitigate Barriers (CLIMB): A Mobile Intervention to Improve Social Functioning in People With Chronic Psychotic Disorders.

BACKGROUND: Numerous psychosocial interventions for individuals with chronic psychotic disorders (CPD) have shown positive effects on social cognitive and functional outcome measures. However, access to and engagement with these interventions remains limited. This is partly because these interventions require specially trained therapists, are not available in all clinical settings, and have a high scheduling burden for participants, usually requiring a commitment of several weeks. Delivering interventions remotely via mobile devices may facilitate access, improve scheduling flexibility, and decrease participant burden, thus improving adherence to intervention requirements. To address these needs, we designed the Creating Live Interactions to Mitigate Barriers (CLIMB) digital intervention, which aims to enhance social functioning in people with CPD. CLIMB consists of two treatment components: a computerized social cognition training (SCT) program and optimized remote group therapy (ORGT). ORGT is an innovative treatment that combines remote group therapy with group texting (short message service, SMS). OBJECTIVES: The objectives of this single-arm study were to investigate the feasibility of delivering 6 weeks of CLIMB to people with CPD and explore the initial effects on outcomes. METHODS: Participants were recruited, screened and enrolled via the Internet, and delivered assessments and interventions remotely using provided tablets (iPads). Participants were asked to complete 18 hours of SCT and to attend 6 remote group therapy sessions. To assess feasibility, adherence to study procedures, attrition rates, engagement metrics, and acceptability of the intervention were evaluated. Changes on measures of social cognition, quality of life, and symptoms were also explored. RESULTS: In total, 27 participants were enrolled over 12 months. Remote assessments were completed successfully on 96% (26/27) of the enrolled participants. Retention in the 6-week trial was 78% (21/27). Of all the iPads used, 95% (22/23) were returned undamaged at the end of the intervention. Participants on average attended 84% of the group therapy sessions, completed a median of 9.5 hours of SCT, and posted a median of 5.2 messages per week on the group text chat. Participants rated CLIMB in the medium range in usability, acceptability, enjoyment, and perceived benefit. Participants showed significant improvements in emotion identification abilities for prosodic happiness (P=.001), prosodic happiness intensity (P=.04), and facial anger (P=.04), with large within-group effect sizes (d=.60 to d=.86). Trend-level improvements were observed on aspects of quality of life (P values less than .09). No improvements were observed for symptoms. CONCLUSIONS: It is feasible and acceptable to remotely deliver an intervention aimed at enhancing social functioning in people with CPD using mobile devices. This approach may represent a scalable method to increase treatment access and adherence. Our pilot data also demonstrate within-group gains in some aspects of social cognition after 6 weeks of CLIMB. Future randomized controlled studies in larger samples should evaluate the extent to which CLIMB significantly improves social cognition, symptoms, and quality of life in CPD.

Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder.

OBJECTIVES: A pharmacotherapy that both improves social abilities and promotes abstinence may be particularly helpful for the treatment of alcohol use disorder. Recent clinical and preclinical evidence suggests that oxytocin has prosocial and antiaddiction effects. We performed a pilot, laboratory-based, preclinical trial of oxytocin in subjects with alcohol abuse (as per Diagnostic and Statistical Manual of Mental Disorders, 4 Edition criteria) to evaluate therapeutic potential and assess tolerability. METHODS: Social perceptual ability, cue-induced craving, and approach bias for alcohol and appetitive imagery were quantified after intranasal oxytocin and placebo administration to 32 nontreatment-seeking individuals with alcohol abuse in a double-blind, crossover study. Because attachment style can moderate the effects of oxytocin, we also explored whether attachment style moderated oxytocin's effects on our behavioral measures. RESULTS: Oxytocin significantly improved recognition of easier items on a social perception task, but had no significant group-level effect on cue-induced craving. However, oxytocin effects on craving were moderated by attachment anxiety, with oxytocin reducing craving in more anxiously attached individuals and increasing craving in less anxiously attached individuals. Subjects did not display an approach bias to alcohol images on the placebo day, preventing meaningful analysis of this measure. Subjects did display an approach bias to appetitive images on the placebo day, which was significantly reduced by oxytocin administration. No adverse reactions were observed. CONCLUSIONS: Intranasal oxytocin has potential to improve social perception, reduce cue-induced alcohol cravings, and reduce appetitive approach bias in subjects with alcohol abuse, and can be safely tolerated in this population. The effects of oxytocin are complex, however, and require further investigation.

The effects of intranasal oxytocin in opioid-dependent individuals and healthy control subjects: a pilot study.

RATIONALE: There has been an explosion of research on the potential benefits of the social neuropeptide oxytocin for a number of mental disorders including substance use disorders. Recent evidence suggests that intranasal oxytocin has both direct anti-addiction effects and pro-social effects that may facilitate engagement in psychosocial treatment for substance use disorders. OBJECTIVES: We aimed to assess the tolerability of intranasal oxytocin and its effects on heroin craving, implicit association with heroin and social perceptual ability in opioid-dependent patients receiving opioid replacement therapy (ORT) and healthy control participants. METHODS: We performed a randomized, double-blind, placebo-controlled, within- and between-subjects, crossover, proof-of-concept trial to examine the effects of oxytocin (40 international units) on a cue-induced craving task (ORT patients only), an Implicit Association Task (IAT), and two social perception tasks: the Reading the Mind in the Eyes Task (RMET) and The Awareness of Social Inference Test (TASIT). RESULTS: Oxytocin was well tolerated by patients receiving ORT but had no significant effects on craving or IAT scores. There was a significant reduction in RMET performance after oxytocin administration versus placebo in the patient group only, and a significant reduction in TASIT performance after oxytocin in both the patient and healthy control groups. CONCLUSIONS: A single dose of intranasal oxytocin is well tolerated by patients receiving ORT, paving the way for future investigations. Despite no significant improvement in craving or IAT scores after a single dose of oxytocin and some evidence that social perception was worsened, further investigation is required to determine the role oxytocin may play in the treatment of opioid use disorder. CLINICAL TRIAL REGISTRATION: Methadone Oxytocin Option. ClinicalTrials.gov identifier: NCT01728909.

Impaired Recognition and Regulation of Disgust Is Associated with Distinct but Partially Overlapping Patterns of Decreased Gray Matter Volume in the Ventroanterior Insula.

BACKGROUND: The ventroanterior insula is implicated in the experience, expression, and recognition of disgust; however, whether this brain region is required for recognizing disgust or regulating disgusting behaviors remains unknown. METHODS: We examined the brain correlates of the presence of disgusting behavior and impaired recognition of disgust using voxel-based morphometry in a sample of 305 patients with heterogeneous patterns of neurodegeneration. Permutation-based analyses were used to determine regions of decreased gray matter volume at a significance level p <= .05 corrected for family-wise error across the whole brain and within the insula. RESULTS: Patients with behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia were most likely to exhibit disgusting behaviors and were, on average, the most impaired at recognizing disgust in others. Imaging analysis revealed that patients who exhibited disgusting behaviors had significantly less gray matter volume bilaterally in the ventral anterior insula. A region of interest analysis restricted to behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia patients alone confirmed this result. Moreover, impaired recognition of disgust was associated with decreased gray matter volume in the bilateral ventroanterior and ventral middle regions of the insula. There was an area of overlap in the bilateral anterior insula where decreased gray matter volume was associated with both the presence of disgusting behavior and impairments in recognizing disgust. CONCLUSIONS: These findings suggest that regulating disgusting behaviors and recognizing disgust in others involve two partially overlapping neural systems within the insula. Moreover, the ventral anterior insula is required for both processes.

Satiety-related hormonal dysregulation in behavioral variant frontotemporal dementia.

OBJECTIVE: To investigate whether patients with behavioral variant frontotemporal dementia (bvFTD) have dysregulation in satiety-related hormonal signaling using a laboratory-based case-control study. METHODS: Fifty-four participants (19 patients with bvFTD, 17 patients with Alzheimer disease dementia, and 18 healthy normal controls [NCs]) were recruited from a tertiary-care dementia clinic. During a standardized breakfast, blood was drawn before, during, and after the breakfast protocol to quantify levels of peripheral satiety-related hormones (ghrelin, cortisol, insulin, leptin, and peptide YY) and glucose. To further explore the role of patients' feeding abnormalities on hormone levels, patients were classified into overeating and nonovereating subgroups based on feeding behavior during separate laboratory-based standardized lunch feeding sessions. RESULTS: Irrespective of their feeding behavior in the laboratory, patients with bvFTD, but not patients with Alzheimer disease dementia, have significantly lower levels of ghrelin and cortisol and higher levels of insulin compared with NCs. Furthermore, while laboratory feeding behavior did not predict alterations in levels of ghrelin, cortisol, and insulin, only patients with bvFTD who significantly overate in the laboratory demonstrated significantly higher levels of leptin compared with NCs, suggesting that leptin may be sensitive to particularly severe feeding abnormalities in bvFTD. CONCLUSIONS: Despite a tendency to overeat, patients with bvFTD have a hormonal profile that should decrease food intake. Aberrant hormone levels may represent a compensatory response to the behavioral or neuroanatomical abnormalities of bvFTD.

A new biomarker of hedonic eating? A preliminary investigation of cortisol and nausea responses to acute opioid blockade.

Overweight and obese individuals differ in their degree of hedonic eating. This may reflect adaptations in reward-related neural circuits, regulated in part by opioidergic activity. We examined an indirect, functional measure of central opioidergic activity by assessing cortisol and nausea responses to acute opioid blockade using the opioid antagonist naltrexone in overweight/obese women (mean BMI=31.1±4.8) prior to the start of a mindfulness-based intervention to reduce stress eating. In addition, we assessed indices of hedonic-related eating, including eating behaviors (binge eating, emotional eating, external eating, restraint) and intake of sweets/desserts and carbohydrates (Block Food Frequency); interoceptive awareness (which is associated with dysregulated eating behavior); and level of adiposity at baseline. Naltrexone-induced increases in cortisol were associated with greater emotional and restrained eating and lower interoceptive awareness. Naltrexone-induced nausea was associated with binge eating and higher adiposity. Furthermore, in a small exploratory analysis, naltrexone-induced nausea predicted treatment response to the mindfulness intervention, as participants with more severe nausea at baseline maintained weight whereas those with little or no nausea responses tended to gain weight. These preliminary data suggest that naltrexone-induced cortisol release and nausea may help identify individuals who have greater underlying food reward dependence, which leads to an excessive drive to eat. Future research is needed to confirm this finding and to test if these markers of opioidergic tone might help predict success in certain types of weight management programs.

BDNF serum concentrations show no relationship with diagnostic group or medication status in neurodegenerative disease.

Brain-derived neurotrophic factor (BDNF) is a growth factor implicated in neuronal survival. Studies have reported altered BDNF serum concentrations in patients with Alzheimer's disease (AD). However, these studies have been inconsistent. Few studies have investigated BDNF concentrations across multiple neurodegenerative diseases, and no studies have investigated BDNF concentrations in patients with frontotemporal dementia. To examine BDNF concentrations in different neurodegenerative diseases, we measured serum concentrations of BDNF using enzyme-linked immunoassay in subjects with behavioral-variant frontotemporal dementia (bvFTD, n=20), semantic dementia (SemD, n=16), AD (n=34), and mild cognitive impairment (MCI, n=30), as well as healthy older subjects (HS, n=38). BDNF serum concentrations were compared across diagnoses and correlated with cognitive tests and patterns of brain atrophy using voxelbased morphometry. We found small negative correlations between BDNF serum concentrations and some of the cognitive tests assessing learning, information processing speed and cognitive control in complex situations, however, BDNF did not predict disease group membership despite adequate power. These findings suggest that BDNF serum concentration may not be a reliable diagnostic biomarker to distinguish among neurodegenerative diseases.

The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease.

OBJECTIVE: To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease. METHOD: Systematic, retrospective, blinded chart review was performed of 252 patients with a neurodegenerative disease diagnosis seen in our specialty clinic between 1999 and 2008. Neurodegenerative disease diagnoses included behavioral-variant frontotemporal dementia (n = 69), semantic dementia (n = 41), and progressive nonfluent aphasia (n = 17) (all meeting Neary research criteria); Alzheimer's disease (n = 65) (National Institute of Neurologic and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association research criteria); corticobasal degeneration (n = 25) (Boxer research criteria); progressive supranuclear palsy (n = 15) (Litvan research criteria); and amyotrophic lateral sclerosis (n = 20) (El Escorial research criteria). Reviewers remained blinded to each patient's final neurodegenerative disease diagnosis while reviewing charts. Extensive caregiver interviews were conducted to ensure accurate and reliable diagnostic histories. For each patient, we recorded history of psychiatric diagnosis, family psychiatric and neurologic history, age at symptom onset, and demographic information. RESULTS: A total of 28.2% of patients with a neurodegenerative disease received a prior psychiatric diagnosis. Depression was the most common psychiatric diagnosis in all groups. Behavioral-variant frontotemporal dementia patients received a prior psychiatric diagnosis significantly more often (50.7%; P < .001) than patients with Alzheimer's disease (23.1%), semantic dementia (24.4%), or progressive nonfluent aphasia (11.8%) and were more likely to receive diagnoses of bipolar disorder or schizophrenia than were patients with other neurodegenerative diseases (P < .001). Younger age (P < .001), higher education (P < .05), and a family history of psychiatric illness (P < .05) increased the rate of prior psychiatric diagnosis in patients with behavioral-variant frontotemporal dementia. Cognitive, behavioral, and emotional characteristics did not distinguish patients who did or did not receive a prior psychiatric diagnosis. CONCLUSIONS: Neurodegenerative disease is often misclassified as psychiatric disease, with behavioral-variant frontotemporal dementia patients at highest risk. While this study cannot rule out the possibility that psychiatric disease is an independent risk factor for neurodegenerative disease, when patients with neurodegenerative disease are initially classified with psychiatric disease, the patient may receive delayed, inappropriate treatment and be subject to increased distress. Physicians should consider referring mid- to late-life patients with new-onset neuropsychiatric symptoms for neurodegenerative disease evaluation.

Neuromyelitis optica, psychiatric symptoms and primary polydipsia: a case report.

Neuromyelitis optica (NMO) is an aggressive demyelinating disease that typically affects the optic nerves and spinal cord. While it is increasingly recognized that cerebral lesions are common in NMO, there have been no reported cases of NMO presenting with psychiatric symptoms and polydipsia. We describe a patient with classic signs and symptoms of NMO who also demonstrated prominent psychiatric symptoms and polydipsia that were tied to his flares and resolved with treatment of his NMO. This case expands our understanding of possible presentations of NMO.