A pilot double-blind sham-controlled trial of repetitive transcranial magnetic stimulation for patients with refractory schizophrenia treated with clozapine.

Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory verbal hallucinations occur in 50-70% of patients with schizophrenia and are associated with significant distress, decreased quality of life and impaired social functioning. This study aimed to investigate the effects of active compared with sham 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal-parietal cortex in patients with schizophrenia treated with clozapine. Symptom dimensions that were evaluated included general psychopathology, severity of auditory hallucinations, quality of life and functionality. Seventeen right-handed patients with refractory schizophrenia experiencing auditory verbal hallucinations and treated with clozapine were randomly allocated to receive either active rTMS or sham stimulation. A total of 384 min of rTMS was administered over 20 days using a double-masked, sham-controlled, parallel design. There was a significant reduction in Brief Psychiatric Rating Scale (BPRS) scores in the active group compared with the sham group. There was no significant difference between active and sham rTMS on Quality of Life Scale (QLS), Auditory Hallucinations Rating Scale (AHRS), Clinical Global Impressions (CGI) and functional assessment staging (FAST) scores. Compared with sham stimulation, active rTMS of the left temporoparietal cortex in clozapine-treated patients showed a positive effect on general psychopathology. However, there was no effect on refractory auditory hallucinations. Further studies with larger sample sizes are needed to confirm these findings.

Effects of repetitive transcranial magnetic stimulation over supplementary motor area in patients with schizophrenia with obsessive-compulsive-symptoms: A pilot study.

In patients with schizophrenia, obsessive-compulsive symptoms (OCS) are associated with lower rates of quality of life and polypharmacy. No previous controlled studies have tested the efficacy of repetitive transcranial magnetic stimulation (rTMS) on the treatment of OCS in this population. The present study examined the therapeutic effects of rTMS applied to the supplementary motor area (1Hz, 20min, 20 sessions) on OCS and general symptoms in patients with schizophrenia or schizoaffective disorder, and whether this intervention can produce changes in plasma levels of brain derived neurotrophic factor (BDNF). A double-blind randomized controlled trial was conducted. Active and sham rTMS were delivered to 12 patients (6 on each group). Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Brief Psychiatric Rating Scale (BPRS) scores, as well as BDNF levels, were assessed before, after, and 4 weeks after treatment. rTMS did not significantly change the outcomes after treatment and on the follow-up (Y-BOCS: Wald's X(2)=3.172; p=0.205; BPRS: X(2)=1.629; p=0.443; BDNF: X(2)=2.930; p=0.231). There seemed to be a trend towards improvement of BPRS scores 4 weeks after rTMS treatment comparing with sham (Cohen's d=0.875, with 32.9% statistical power). No side effects were reported. Future studies with larger sample sizes are needed.

Recognition of bipolar disorder type I before the first manic episode: challenges and developments.

Bipolar disorder (BD) usually follows a neurobiological progression pathway, but a relatively long interval between the first symptoms of the disorder and the correct diagnosis and treatment takes place in most patients. Strategies used to recognize BD at an early stage and even prior to the first manic episode could help identify the risk and modifying factors that influence the onset and course of disease, and improve outcomes. Drawing on current research results, this article presents considerations on risk factors for the development of BD, including genetic/familial risk, endophenotypes and clinical characteristics. Taken together, this article provides a framework and tools for research on the BD prodrome, as well as for the early recognition and timely treatment of patients prior to and immediately after the emergence of BD.

The association of child abuse and neglect with adult disability in schizophrenia and the prominent role of physical neglect.

OBJECTIVE: To assess long-lasting effects of childhood trauma on the functional outcome of adult patients diagnosed with schizophrenia. METHOD: Ninety-nine stable patients with schizophrenia followed in an outpatient program at a public university hospital in Porto Alegre, southern Brazil, were investigated for childhood traumatic experiences by the Childhood Trauma Questionnaire (CTQ) and for functional impairment by the World Health Organization Disability Assessment Schedule (WHO/DAS). The schizophrenia diagnosis was assessed by ICD-10 and DSM-IV criteria according to the Operational Criteria Checklist for Psychotic Illness (OPCRIT). RESULTS: Childhood trauma in general was associated with increased disability in adulthood, reflected by impaired Overall Behavior (p=.023) and Global Evaluation (p=.032). Analysis of specific traumatic domains revealed that increased childhood physical neglect was associated with functional impairment in Overall Behavior (p<.000), Social Role Performance (p=.037) and Global Evaluation (p=.014). Higher emotional abuse was associated with impaired Overall Behavior (p=.026), and higher emotional neglect with poor Global Evaluation (p=.047). Additionally, earlier onset of illness was associated with lower level of functioning evidenced by impairment in Overall Behavior (p=.042). Linear regression using WHO/DAS sections (Overall Behavior, Social Role Performance and Global Evaluation) as dependent variables and CTQ subscales indicated that only physical neglect had an effect on adult functionality. CONCLUSIONS: Childhood trauma was associated with functional and social impairment in adult patients with schizophrenia. Specific types of abuse and neglect, such as physical neglect and emotional abuse and neglect, influenced disability, and the most robust association was physical neglect. Studies involving more patients, with normal controls and additional measurements of biological liability, should be conducted to confirm this association and to increase the understanding of gene-environment relationship in schizophrenia and pathways to disability. PRACTICE IMPLICATIONS: Further investigation is warranted to clarify the association between childhood trauma and disability in schizophrenia, as well as to develop standardized instruments for the assessment of trauma and earlier detection of risk along with education of patients and families about adequate care, in an effort to reduce the incidence of disability in schizophrenia.