Resting-state fMRI is associated with trauma experiences, mood and psychosis in Afro-descendants with bipolar disorder and schizophrenia.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SCZ) may exhibit functional abnormalities in several brain areas, including the medial temporal and prefrontal cortex and hippocampus; however, a less explored topic is how brain connectivity is linked to premorbid trauma experiences and clinical features in non-Caucasian samples of SCZ and BD. METHODS: Sixty-two individuals with SCZ (n = 20), BD (n = 21), and healthy controls (HC, n = 21) from indigenous and African ethnicity were submitted to clinical screening (Di-PAD), traumata experiences (ETISR-SF), cognitive and functional MRI assessment. The item psychosis/hallucinations in SCZ patients showed a negative correlation with the global efficiency (GE) in the right dorsal attention network. The items mania, irritable mood, and racing thoughts in the Di-PAD scale had a significant negative correlation with the GE in the parietal right default mode network. CONCLUSIONS: Differences in the activation of specific networks were associated with earlier disease onset, history of physical abuse, and more severe psychotic and mood symptoms in SCZ and BD subjects of indigenous and black ethnicity. Findings provide further evidence on SZ and BD's brain connectivity disturbances, and their clinical significance, in non-Caucasian samples.

Co-developing a health promotion programme for indigenous youths in Brazil: A concept mapping report.

BACKGROUND: Latin America and the Caribbean Region are home to about 42 million Indigenous people, with about 900,000 living in Brazil. The little routinely collected population-level data from Indigenous communities in the region available shows stark inequities in health and well-being. There are 305 Indigenous ethnic groups, speaking 274 languages, spread across the remote national territory, who have endured long-lasting inequities related to poverty, poor health, and limited access to health care. Malnutrition and mental health are key concerns for young people. Building on our Indigenous communities-academic partnerships over the last two decades, we collaborated with young people from the Terena Indigenous ethnic group, village leaders, teachers, parents, and local health practitioners from the Polo Base (community health centres) to obtain their perspectives on important and feasible actions for a youth health promotion programme. METHODS: The report was conducted in the Tereré Village in Mato Grosso do Sul. Concept mapping, a participatory mixed method approach, was conducted in 7 workshops, 15 adults and 40 youths aged 9-17 years. Art-based concept mapping was used with 9 to 11 years old children (N = 20). Concept systems software was used to create concept maps, which were finalised during the workshops. Focused prompts related to factors that may influence the health and happiness of youths. The participatory method gave Terena youths a significant voice in shaping an agenda that can improve their health. RESULTS: Terena youths identified priority actions that clustered under 'Family', 'School', 'Education', 'Socio-economic circumstances', 'Respect' and 'Sport' in response to protecting happiness; and 'Nutrition pattern', 'Physical activity', 'Local environment', and 'Well-being' in response to having a healthy body. Through the participatory lens of concept mapping, youths articulated the interconnectedness of priority actions across these clusters such that behaviours (e.g. Nutrition pattern, drinking water, physical activity) and aspirations (being able to read, to have a good job) were recognised to be dependent on a wider ecology of factors (e.g. loss of eco-systems, parent-child relationships, student- teacher relationships, parental unemployment). In response to developing youth health, Terena adults suggested priority actions that clustered under 'Relationships', 'Health issues', 'Prevention at Polo Base', 'Access to health care', 'Communication with young people', 'Community life', 'Raising awareness' and 'School support'. Their priorities reflected the need for structural transformative actions (e.g. Polo Base and school staff working together) and for embedding actions to protect Indigenous culture (e.g. integrating their cultural knowledge into training programmes). CONCLUSIONS: Concept maps of Indigenous youths emphasised the need for a health promotion programme that engages with the structural and social determinants of health to protect their happiness and health, whilst those of adults emphasised the need to address specific health issues through preventative care via a school-Polo Base collaboration. Investment in a co-developed school-Polo-Base health promotion programme, with intersectoral engagement, has potential for making Indigenous health systems responsive to the inequalities of youth health, to yield dividends for healthy ageing trajectories as well as for the health of the next generation.

Neural correlates of negative and disease-specific emotional stimuli in panic disorder: a functional magnetic resonance imaging study.

OBJECTIVE: Decades of research have highlighted the involvement of the prefrontal cortex, anterior cingulated cortex, and limbic areas (amygdala) in panic disorder (PD). However, little attention has been given specifically to the inferior frontal gyrus. The current study aimed to investigate the neural substrates, including the inferior frontal gyrus, of both panic-related and negative conditions among individuals with PD and healthy controls. METHODS: We examined 13 medication-free PD patients and 14 healthy controls with functional magnetic resonance imaging (fMRI) during exposure to negative and neutral pictures and a set of specific panic-related pictures. RESULTS: Subtraction between the conditions indicated activation of the left amygdala region and the right inferior frontal gyrus in PD patients during the specific panic-related condition, whereas the left amygdalar region and left inferior frontal gyrus were activated during the negative condition in controls. CONCLUSION: These results suggest that in patients with PD, a prominent bottom-up process is involved in specific panic-related conditions, which might be associated with weak modulation of the left frontal area. These data add to our current understanding of the neural correlates of PD and can contribute to future clinical interventions targeting the functional reestablishment of these regions.

Polygenic risk for anxiety influences anxiety comorbidity and suicidal behavior in bipolar disorder.

Bipolar disorder is often comorbid with anxiety, which is itself associated with poorer clinical outcomes, including suicide. A better etiologic understanding of this comorbidity could inform diagnosis and treatment. The present study aims to test whether comorbid anxiety in bipolar disorder reflects shared genetic risk factors. We also sought to assess the contribution of genetic risk for anxiety to suicide attempts in bipolar disorder. Polygenic risk scores (PRS) were calculated from published genome-wide association studies of samples of controls and cases with anxiety (n = 83,566) or bipolar disorder (n = 51,710), then scored in independent target samples (total n = 3369) of individuals with bipolar disorder who reported or denied lifetime anxiety disorders or suicidal attempts in research interviews. Participants were recruited from clinical and nonclinical settings and genotyped for common genetic variants. The results show that polygenic risk for anxiety was associated with comorbid anxiety disorders and suicide attempts in bipolar disorder, while polygenic risk for bipolar disorder was not associated with any of these variables. Our findings point out that comorbid anxiety disorders in bipolar disorder reflect a dual burden of bipolar and anxiety-related genes; the latter may also contribute to suicide attempts. Clinical care that recognizes and addresses this dual burden may help improve outcomes in people living with comorbid bipolar and anxiety disorders.

Corrigendum: Early Trauma and Cognitive Functions of Patients With Schizophrenia.

[This corrects the article DOI: 10.3389/fpsyt.2019.00261.].

Early Trauma and Cognitive Functions of Patients With Schizophrenia.

Aim: The following work aims to investigate the putative correlation between early trauma and cognitive functions, as well as psychotic symptoms and cognitive functions, in individuals diagnosed with schizophrenia. Methods: A quantitative assessment was performed with 20 individuals diagnosed with schizophrenia according to the 5th edition of the Diagnostic and Statistical Manual (DSM-5) criteria and who were in ongoing outpatient treatment in Psychosocial Care Centres in Brazil. Clinical measurements comprised a semistructured clinical interview, a screening questionnaire for common mental disorders, the Positive and Negative Syndrome Scale (PANSS), and the Early Trauma Inventory Self-Report-Short Form (ETISR-SF). Cognitive assessment included Beta III test, Concentrated Attention (CA) test, Color Trails Test (CTT), and Visual Face Memory (VFM) test. Results: Age-adjusted analysis showed a negative correlation between early trauma and visual memory performance (r = -0.585, p = 0.007) and negative symptoms and attention performance (r = -0.715, p = 0.000). Conclusion: Although a cause-effect relationship cannot be firmly stated, an association between early trauma experience and cognitive impairment such as visual memory, as well as a relationship between negative symptoms and attention domains, is suggested by our preliminary findings. Future studies with larger sample sizes and prospective design will clarify the long-term effects of early exposure to trauma and its clinical meaning in terms of developing psychotic-related illness.

Breves considerações sobre a atenção à pessoa com transtorno do espectro autista na rede pública de saúde / Brief considerations regarding the attention to individuals with autism spectrum disorder in the public health system / Breves consideraciones sobre la atención a la persona con trastorno del espectro autista en la red pública de salud

O Transtorno do Espectro Autista (TEA) é uma desordem do neurodesenvolvimento, caracterizada por déficits na comunicação social e presença de padrões de comportamento repetitivos. Como uma condição usualmente crônica, o TEA normalmente requer atenção de equipes interdisciplinares por afetar o desenvolvimento de forma global. Recentemente, o Ministério da Saúde publicou dois documentos que estabelecem a linha de cuidado e as diretrizes para sua reabilitação na rede pública de saúde brasileira. O presente artigo caracteriza e analisa a linha de cuidado proposta e as abordagens terapêuticas recomendadas. A análise permitiu verificar que os documentos reafirmam que pessoas com TEA são indivíduos com os mesmos direitos de pessoas com deficiência, seu cuidado deve ocorrer de maneira multidisciplinar pela Rede de Atenção Psicossocial, mas faltou clareza quanto aos critérios de escolha das abordagens terapêuticas e o local em que estas seriam oferecidas. Algumas implicações para o tratamento do TEA são discutidas.

Autism Spectrum Disorder (TEA) is a neurodevelopmental disorder, characterized by deficits in social communication and by the presence of repetitive patterns of behavior. As a chronic condition, TEAD usually requires attention from interdisciplinary teams as it affects development in many areas. Recently, the Brazilian Ministry of Health (MS) published two documents establishing the guidelines for attention and rehabilitation of people with TEA in the national public health system. This article aims to characterize and analyze these guidelines and the recommended therapeutic approaches. The analysis showed the recognition of the TEA as a condition with the same rights as people with disabilities. The care approach is essentially multidisciplinary and supported by the Psychosocial Attention Network, but the criteria for recommending the therapeutic approaches and the place where therapies would be offered are not clear. Some implications for TEA treatment are discussed.

El Trastorno del Espectro Autista (TEA) es un desorden del neurodesarrollo, caracterizado por déficits en la comunicación social y presencia de patrones de comportamiento repetitivo. Como una condición usualmente crónica, el TEA normalmente requiere atención de equipos interdisciplinares pues afecta el desarrollo de manera global. Recientemente, el Ministerio de Salud publicó dos documentos que establecen la línea de cuidado y las directrices para su rehabilitación en la red pública de salud brasileña. El presente artículo caracteriza y analiza la línea de cuidado propuesta y las intervenciones terapéuticas recomendadas. El análisis permitió verificar que los documentos reafirman que personas con TEA son individuos con los mismos derechos que personas con discapacidad, y su cuidado debe realizarse de manera multidisciplinar por la Red de Atención Psicosocial, pero faltó aclarar en lo que se refiere a los criterios de elección de las intervenciones terapéuticas y el local donde dichos tratamientos serían ofrecidos. También se discuten algunas implicaciones para el tratamiento del TEA.

Traumatic experiences and cognitive profiles of schizophrenia cases influenced by the BDNF Val66met polymorphism.

The association of early trauma exposure with current cognition was examined in a research series of 56 schizophrenia cases with respect to the BDNF Val66Met polymorphism (rs6265, Val66Val, Val66Met, Met66Met), as met allele carriers have reduced neurotrophic activity. The Perceptual Organization Index had a significant negative correlation with trauma exposures only in met carriers, including early physical abuse, general trauma after age 18 years, and physical abuse. Within the Val66Val subgroup, there were no significant correlations between WAIS indices and traumatic experiences.

Early trauma, attachment experiences and comorbidities in schizophrenia / Relação entre traumas precoces, experiências de apego e comorbidades na esquizofrenia

Abstract Objective To evaluate attachment patterns in subjects with schizophrenia and their relationships to early traumatic events, psychotic symptoms and comorbidities. Methods Twenty patients diagnosed with schizophrenia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) underwent retrospective symptom assessment and careful assessment of the number and manner of childhood caregiver changes. The Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD) was used to assess symptoms related to schizophrenia (positive and negative symptoms), depression and mania. Anxiety disorder comorbidities were assessed by the Liebowitz Social Anxiety Scale (LSAS), Yale-Brown Obsessions and Compulsions Scale (Y-BOCS) and Panic and Schizophrenia Interview (PaSI). Experience in Close Relationships - Relationship Structures (ECR-RS) and Early Trauma Inventory Self Report-Short Form (ETISR-SF) were used to assess attachment patterns and traumatic history, respectively. Results Moderate and significant correlations between attachment patterns and early trauma showed that greater severity of anxious attachment was predicted by a higher frequency of total early traumas (Spearman ρ = 0.446, p = 0.04), mainly general traumas (ρ = 0.526, p = 0.017; including parental illness and separation, as well as natural disaster and serious accidents). Among the correlations between early trauma and comorbid symptoms, panic attacks occurring before the onset of schizophrenia showed significant and positive correlations with ETISR-SF total scores and the sexual trauma subscale. Conclusion Children with an unstable early emotional life are more vulnerable to the development of psychopathology, such as panic anxiety symptoms. Traumatic events may also predict later schizophrenia.

Resumo Objetivos Avaliar o padrão de apego em portadores de esquizofrenia e discutir a relação que tais padrões apresentam com a sintomatologia psicótica e as comorbidades dos pacientes investigados. Métodos Vinte pacientes diagnosticados com esquizofrenia de acordo com os critérios do Manual Diagnóstico e Estatístico de Transtornos Mentais, 5ª edição (DSM-5) foram submetidos a avaliação de sintomas retrospectivos e avaliação cuidadosa do número e modo de mudança de cuidador da infância. A Entrevista Diagnóstica para Psicoses e Transtornos Afetivos (DI-PAD) foi utilizada para avaliar sintomas relacionados à esquizofrenia (sintomas positivos e negativos), depressão e mania. As comorbidades de transtorno de ansiedade foram avaliadas pela Escala de Ansiedade Social de Liebowitz (LSAS), Escala de Sintomas Obsessivo-Compulsivos de Yale-Brown (Y-BOCS) e Entrevista de Pânico e Esquizofrenia (PaSI). Os instrumentos Questionário das Experiências nas Relações Próximas-Estruturas Relacionais (ECR-RS) e Inventário de Autorrelato de Trauma Precoce - Forma Curta (ETISR-SF) foram utilizados para avaliar padrões de apego e histórico traumático, respectivamente. Resultados Foram identificadas correlações significativas entre a ocorrência de traumas precoces e o apego do tipo ansioso. Também foi verificada a relação entre traumas gerais e sintomas de pânico, constatando-se que as crises de pânico antecipam surtos quando predominam sintomas ansiosos, somáticos, alucinações e ideias delirantes. Foi observado que a ocorrência de traumas precoces contribui para o pânico, elevando o risco de episódios psicóticos. Conclusão . Os resultados indicam que as adversidades ambientais na infância estão associadas com o risco de desenvolvimento de esquizofrenia e de outras psicoses mais tarde na vida.

Early trauma, attachment experiences and comorbidities in schizophrenia.

OBJECTIVE: To evaluate attachment patterns in subjects with schizophrenia and their relationships to early traumatic events, psychotic symptoms and comorbidities. METHODS: Twenty patients diagnosed with schizophrenia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) underwent retrospective symptom assessment and careful assessment of the number and manner of childhood caregiver changes. The Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD) was used to assess symptoms related to schizophrenia (positive and negative symptoms), depression and mania. Anxiety disorder comorbidities were assessed by the Liebowitz Social Anxiety Scale (LSAS), Yale-Brown Obsessions and Compulsions Scale (Y-BOCS) and Panic and Schizophrenia Interview (PaSI). Experience in Close Relationships - Relationship Structures (ECR-RS) and Early Trauma Inventory Self Report-Short Form (ETISR-SF) were used to assess attachment patterns and traumatic history, respectively. RESULTS: Moderate and significant correlations between attachment patterns and early trauma showed that greater severity of anxious attachment was predicted by a higher frequency of total early traumas (Spearman ρ = 0.446, p = 0.04), mainly general traumas (ρ = 0.526, p = 0.017; including parental illness and separation, as well as natural disaster and serious accidents). Among the correlations between early trauma and comorbid symptoms, panic attacks occurring before the onset of schizophrenia showed significant and positive correlations with ETISR-SF total scores and the sexual trauma subscale. CONCLUSION: Children with an unstable early emotional life are more vulnerable to the development of psychopathology, such as panic anxiety symptoms. Traumatic events may also predict later schizophrenia.

Rare missense coding variants in oxytocin receptor (OXTR) in schizophrenia cases are associated with early trauma exposure, cognition and emotional processing.

BACKGROUND: Oxytocin is a peptide hormone that influences the integration of social cognition with behavior and affect regulation. Oxytocin also prominently directs the transition of neuronal GABA neurotransmission from excitatory to inhibitory after birth. The oxytocin receptor (OXTR) is linked to schizophrenia, a heterogeneous syndrome. Relationships of OXTR polymorphisms with specific clinical features could aid in evaluating any role of oxytocin in the pathogenesis of schizophrenia. METHOD: Schizophrenia cases with rare missense coding OXTR single nucleotide variants (SNVs) were identified from a well-characterized sample of cases and controls who were assessed for symptoms, cognition and early life trauma. RESULTS: Five of 48 cases showed rare OXTR variants. Compared to the other cases they had less severe negative symptoms (deficits in emotional expression and motivation) and less severe general psychopathology scores (depression and anxiety). They demonstrated lower nonverbal (performance) than verbal intelligence due to deficient perceptual organization and slow processing speed. They also reported greater early trauma exposure (physical and sexual abuse and emotional trauma). CONCLUSION: Cases carrying rare OXTR SNVs had less negative and affective symptoms than other cases, but similar psychotic symptoms, along with specific cognitive deficits. The clinical characterization of these cases occurred in association with environmental exposure to early trauma, especially sexual abuse, which may have influenced the expression of schizophrenia in subjects harboring specific SNVs in the OXTR.

Schizophrenia dissection by five anxiety and depressive subtype comorbidities: Clinical implications and evolutionary perspective.

Twenty patients with DSM5 schizophrenia were comprehensively and formally assessed by an experienced psychiatrist. All subjects were assessed for: positive and negative psychotic symptoms; social anxiety; panic anxiety; obsessive compulsive disorder, atypical depression; major depression; suicide risk; and global assessment of functioning. Different profiles of clinical presentation and symptom evolution emerged for patients with schizophrenia who had co-morbid depression (15%), OCD (15%), panic or limited symptom attacks (55%) and social anxiety (5%). At least eighty percent of the sample had one or more of these co-morbidities. Summing up, the data support our previous finding that panic is highly prevalent in Schizophrenia with Auditory Hallucinations (>73% here, versus 100% before), and panic was paroxysmally concurrent with voice onset. Moreover, characteristic clinical findings may help point clinicians to five specific co-morbidity psychosis subtypes. Moreover, co-morbidity dissection of psychotic diagnoses recalls and parallels the historical psychopharmacologic dissection of non-psychotic anxiety and depressive subtypes diagnoses. Larger studies should further test and explore these preliminary findings.

Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation.

The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB1 and CB2), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep-wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N-arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents.

Effect of Heteropterys aphrodisiaca on Anxiety and Male Exposure of Female Mice with Advanced Age.

BACKGROUND: Effect of Heteropterys aphrodisiaca (dog-node) on anxiety and function of adult female wistar mice. The project is an experiment with the use of H. aphrodisiac root extract, in order to observe the frequency of sexual exposure of females exposed to the extract, quantify the effect of the extract on the concentration of total testosterone and observe the anxiety levels of the animals exposed. Results will be measured with the laboratory testosterone test and LCE and CA tests. METHODS: In preparation of the extract, the root was oven dried at 40°C and diluted in alcohol extract (100g of root for 1 liter of alcohol) and lyophilized. 40 adult female mice were enrolled, separated in control group (placebo) and treatment group (50 mg/kg/day) for 15, 30, 45 and 60 days. At each period, hormonal testosterone and anxiety levels by the Elevated-Cross Labyrinth (ECL) tests and Open Camp (CA) were measured in 10 animals that were later euthanized (SBNeC). RESULTS: The results showed an improvement in the decrease of anxiety, as shown in the variables of number of open arm entries, time on the same side of the field, less avoidance and leakage. However, it appears that the time of exposure to the extract does not result in increased benefit, with possible decline of effect after 45 days of use. CONCLUSION: With this performed experiment with the "no-de-cachorro" extract, it was possible to understand a little more how this root can act in relation to anxiety, as predicted by the pharmacology that validates the animal models; anxiolytic components decrease anxiety-related behaviors, as shown in the variables of entry numbers in the open arm, time on the same side of the field, less avoidance and escape. However, it seems that the time of exposure to the extract does not modify the performance in the tests, observing until an apparent exhaustion of the anxiolytic action, which evidences the need for more specific studies on the possible effects of the extract.

Paranoid delusional disorder follows social anxiety disorder in a long-term case series: evolutionary perspective.

Social anxiety disorder (SAD) patients may have self-referential ideas and share other cognitive processes with paranoid delusional disorder (PDD) patients. From an evolutionary perspective, SAD may derive from biologically instinctive social hierarchy ranking, thus causing an assumption of inferior social rank, and thus prompting concerns about mistreatment from those of perceived higher rank. This naturalistic longitudinal study followed four patients with initial SAD and later onset of PDD. These four patients show the same sequence of diagnosed SAD followed by diagnosed PDD, as is often retrospectively described by other PDD patients. Although antipsychotic medication improved psychotic symptoms in all patients, those who also had adjunctive serotonin-specific reuptake inhibitors for SAD had much more improvement in both psychosis and social functioning. From an evolutionary perspective, it can be conjectured that when conscious modulation of the SAD social rank instinct is diminished due to hypofrontality (common to many psychotic disorders), then unmodulated SAD can lead to paranoid delusional disorder, with prominent ideas of reference. Non-psychotic SAD may be prodromal or causal for PDD.

Attachment and self-consciousness: a dynamic connection between schizophrenia and panic.

INTRODUCTION: Attachment theory offers an evolutionary explanation for the occurrence of panic states. The distance between a mother and child causes the sensation of fear. The experience of feared annihilation, an intense fear reaction (panic), is presented as a threat to the individual's cohesiveness, disrupting the mental representation of self-consciousness, specifically self-unity. Alterations in self-consciousness in schizophrenia are so important that they are mostly included among Kurt Schneider's first-ranked symptoms. HYPOTHESES: Based on clinical trials, case reports, and brain imaging and pharmacological studies, a paradigm is proposed to explain the relationship between panic anxiety and psychosis. CONCLUSION: The psychosis-anxiety pathophysiology explanation needs further investigation into the brain areas that integrate self-monitoring with fear areas, but it seems possible to note the importance of the anterior cingulate cortex.

A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine.

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.