Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity

New advances in the understanding of schizophrenia etiology, course, and treatment have increased interest on the part of patients, families, advocates, and professionals in the development of consensus-defined standards for clinical status and improvement, including illness remission and recovery As demonstrated in the area of mood disorders, such standards provide greater clarity around treatment goals, as well as an improved framework for the design and comparison of investigational trials and the subsequent evaluation of the effectiveness of interventions Unlike the approach to mood disorders, however, the novel application of the concept of standard outcome criteria to schizophrenia must reflect the wide heterogeneity of its long-term course and outcome, as well as the variable effects of different treatments on schizophrenia symptoms As an initial step in developing operational criteria, an expert working group reviewed available definitions and assessment instruments to provide a conceptual framework for symptomatic, functional, and cognitive domains in schizophrenia as they relate to remission of illness The first consensus-based operational criteria for symptomatic remission in schizophrenia are based on distinct thresholds for reaching and maintaining improvement, as opposed to change criteria, allowing for alignment with traditional concepts of remission in both psychiatric and nonpsychiatric illness This innovative approach for standardizing the definition for outcome in schizophrenia will require further examination of its validity and utility, as well as future refinement, particularly in relation to psychosocial and cognitive function and dysfunction These criteria should facilitate research and support a positive, longer-term approach to studying outcome in patients with schizophrenia

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Remission in Schizophrenia: Proposed Criteria and Rationale for Consensus

A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.

A rating scale for drug-induced akathisia

https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2051-5545.2011.tb00014.x

Physical illness in patients with severe mental disorders.I. Prevalence, impact of medications and disparities in health care

This report builds on a highly valued predecessor, the 1994 Institute of Medicine (IOM) report entitled Reducing Risks for Mental Disorders: Frontiers for Preventive Intervention Research. That report provided the basis for understanding prevention science, elucidating its then-existing research base, and contemplating where it should go in the future. This report documents that an increasing number of mental, emotional, and behavioral problems in young people are in fact preventable. The proverbial ounce of prevention will indeed be worth a pound of cure: effectively applying the evidence-based prevention interventions at hand could potentially save billions of dollars in associated costs by avoiding or tempering these disorders in many individuals. Furthermore, devoting significantly greater resources to research on even more effective prevention and promotion efforts, and then reliably implementing the findings of such research, could substantially diminish the human and economic toll.

Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities

Objective; This study was undertaken to assess the potential effect ofduration of untreated illness on outcome in a group offirst-episode schizophrenic patients. Method: Seventy patients with schizophrenia diagnosed according to the Research Diagnostic Criteria entered the study and were followed for up to 3 years. All patients received standardized treatment and uniform assessments both during the acute phase of their illness and throughout the follow-up period. Outcome was measured in terms of time to remission ofacute psychotic symptoms as well as degree ofsymptom remission. Results: The mean duration ofpsychotic symptoms before initial treatment was 52 weeks, preceded by a substantial prepsychotic period. According to survival analysis, duration of illness before treatment was found to be significantly associated with time to remission as well as with level ofremission. The effect ofduration ofillness on outcome remained significant when diagnosis and gender variables, themselves associated with outcome, were controlled in a regression analysis. Duration ofiliness was not correlated with age at onset, mode of onset, premorbid adjustment, or severity of illness at entry into the study. Conclusions: Duration ofpsychosis before treatment may be an important predictor of outcome in first-episode schizophrenia. Acute psychotic symptoms could reflect an active morbid process which, if not ameliorated by neuroleptic drug treatment, may result in lasting morbidity. Further implications of these findings are discussed. (AmJ Psychiatry 1992; 149:1183-1188) C onsiderable attention has been focused on clinical factors that may influence the outcome of patients

Duration of psychosis and outcome in first-episode schizophrenia.

Objective: To examine the course and potential predictors of treatment response in the early phase of schizophrenia. Design: Prospective study of an inception cohort. Setting: Psychiatric division of an academic medical center with a suburban metropolitan catchment area. Patients and Intervention: Seventy first-episode patients who had undergone four biologic assessment procedures (brain magnetic resonance imaging, behavioral response to methylphenidate hydrochloride, growth hormone levels, eye tracking) were treated with a standardized antipsychotic drug protocol until recovery. Response was measured in terms of psychopathology and degree of remission. Results: Using survival analysis, the proportion of pa- tients remitting by 1 year was estimated at 83%. Mean and median times to remission were 35.7 weeks and 11 weeks, respectively. No baseline demographic or psychopathologic measure significantly predicted time to or level of remission. However, males tended to be nonresponders to treatment and have diagnoses of schizophrenia rather than schizoaffective disorder. Brain pathomorphology and abnormal basal growth hormone significantly predicted time to remission. Conclusions: These results indicate that the antipsychotic treatment response of first-episode schizophrenics is better than chronic multiepisode patients and suggest that specific pathobiologic markers reflect pathophysiologic processes that mediate antipsychotic treatment response.

Time Course and Biologic Correlates of Treatment Response in First-Episode Schizophrenia

Objective: Gender differences in onset ofillness, response to treatment, course, and biologic measures have been consistently reported in patients with chronic schizophrenia. Patients with f irst-episode schizophrenia were examined to determine whether gender differences also occur in these patients. Method: Fifty-four neuroleptic-naive schizophrenic patients (29 men and 25 women) were studied beginning in an initial stage of the first hospitalization for psychosis while undergoing treatment with a standardized medication regimen. Before antipsychotic drug treatment and during I year of follow-up each patient was rated on the Schedule for Affective Disorders and Schizophrenia-Change Version (psychosis and disorganization items), Scale for the Assessment of Negative Symptoms, Clinical Global Impression, modified Simpson Tardive Dyskinesia Scale, and Simpson-Angus Rating Scale for extrapyramidal side effects. Methylphenidate challenge testing was done at study entry. Plasma neuroleptic, homovanillic acid (HVA), and prolactin levels were determined weekly for the first 6 weeks. Results: The female schizophrenic patients had a later onset and better treatment response than the men. Plasma HVA levels at baseline and week 1 and changes in prolactin levels from baseline to weeks 1 through 6 were greater among the women. Conclusions: Gender differences in onset and degree oftreatment response in first-episode schizophrenic patients are similar to those of chronic patients and are apparent at early stages of the illness. The greater pharmacologic responsivity of the female patients, as indicated by the neuroendocrine results, is consistent with the gender difference in degree ofsymptom improvement with medication. (AmJ Psychiatry 1995; 152:698-703)

Gender differences in onset of illness, treatment response, course, and biologic indexes in first-episode schizophrenic patients

Stimulant drugs such as cocaine and amphetamine are among the most commonly abused substances by schizophrenic patients. This may be due in part to aspects of the illness and treatment side effects that impel patients to use dopamine agonist drugs. Dopaminergic neural systems have been shown to mediate both stimulant drug effects and schizophrenia. Because of the hypothesized overlap in the pathophysiology of schizophrenia and the neurobiological effects of chronic stimulant use, the potential for serious complication of the primary disease by substance abuse exists. This article reviews the neurobiological mechanisms of behavioral sensitization and neurotoxicity associated with chronic stimulant administration in the context of pathophysiological theories of schizophrenia. Discussion focuses on the potential impact of stimulant use on the disease process as well as the manifest phenomenology and course of schizophrenia.

Dopaminergic Mechanisms in Idiopathic and Drug-induced Psychoses

In July 2013, the Food and Drug Administration approved lurasidone for the treatment of bipolar I depression. Two studies discussing its monotherapy and adjunctive use that were pivotal in obtaining this approval are featured in this issue.

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Antony Loebel

Papers

Duration of psychosis and outcome in first-episode schizophrenia.

Time Course and Biologic Correlates of Treatment Response in First-Episode Schizophrenia

Gender differences in onset of illness, treatment response, course, and biologic indexes in first-episode schizophrenic patients

Dopaminergic Mechanisms in Idiopathic and Drug-induced Psychoses

Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study.