OBJECTIVE: Given the ability of mood stabilizers and antipsychotics to promote cell proliferation, we wanted to determine the effects of these drugs on neuronal markers previously reported to be altered in subjects with psychiatric disorders. METHODS: Male Sprauge-Dawley rats were treated with vehicle (ethanol), lithium (25.5 mg per day), haloperidol (0.1 mg/kg), olanzapine (1.0 mg/kg) or a combination of lithium and either of the antipsychotic drugs for 28 days. Levels of cortical synaptic (synaptosomal associated protein-25, synaptophysin, vesicle associated protein and syntaxin) and structural (neural cell adhesion molecule and alpha-synuclein) proteins were determined in each treatment group using Western blots. RESULTS: Compared to the vehicle treated group; animals treated with haloperidol had greater levels of synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.05), those treated with olanzapine had greater levels of synaptophysin (p<0.01) and syntaxin (p<0.01). Treatment with lithium alone did not affect the levels of any of the proteins. Combining lithium and haloperidol resulted in greater levels of synaptophysin (p<0.01), synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.01). The combination of lithium and olanzapine produced greater levels of synaptophysin (p<0.01) and alpha-synuclein (p<0.05). CONCLUSION: Lithium alone had no effect on the neuronal markers. However, haloperidol and olanzapine affected different presynaptic markers. Combining lithium with olanzapine additionally increased alpha-synuclein. These drug effects need to be taken into account by future studies examining presynaptic and neuronal markers in tissue from subjects with psychiatric disorders.
alpha-Synuclein ; Animals ; Antipsychotic Agents ; Benzodiazepines ; Cell Adhesion ; Cell Proliferation ; Haloperidol ; Humans ; Lithium ; Male ; Nerve Tissue Proteins ; Neural Cell Adhesion Molecules ; Neurons ; Neurotransmitter Agents ; Proteins ; Qa-SNARE Proteins ; Rats ; SNARE Proteins ; Synaptophysin

Earlier structural magnetic resonance imaging in schizophrenia have noted smaller white matter volumes in diverse brain regions and recent diffusion tensor imaging (DTI) studies have allowed better elucidation of changes in brain white matter integrity within the illness. As white matter abnormalities have been reported to occur early in the course of schizophrenia, we systematically review extant DTI studies of anomalies of white matter integrity in first episode schizophrenia (FES) up till October 2011. Overall, disruptions of white matter integrity were found in the cortical, subcortical brain regions and white matter associative and commissural tracts, suggesting that changes of cortical-subcortical white matter integrity were found at an early stage of the disorder. These changes in white matter integrity were correlated with specific cognitive deficits (verbal and spatial working memory) as well as psychopathology (positive more than negative symptoms) in patients with FES. The correlation of these white matter integrity changes with cognitive and phenomenological factors may shed light on neurobiological substrates underlying these clinical manifestations. Future studies need to validate these findings in larger samples of subjects and in different populations as well as chart the progress of these cerebral white matter changes over time so as to better appreciate their trajectory with illness course, treatment and chronicity.
Anisotropy ; Brain ; Diffusion ; Diffusion Tensor Imaging ; Humans ; Light ; Magnetic Resonance Imaging ; Psychopathology ; Schizophrenia

Schizophrenia is a psychiatric disorder that includes symptoms such as hallucinations, disordered thoughts, disorganized or catatonic behaviour, cognitive dysfunction and sleep-wake disturbance. In addition to these symptoms, cardiometabolic dysfunction is common in patients with schizophrenia. While previously it has been thought that cardiometabolic symptoms in patients with schizophrenia were associated with medications used to manage this disorder, more recently it has been demonstrated that these symptoms are present in drug naive and unmedicated patients. Sleep-wake disturbance, resulting in chronic sleep loss has also been demonstrated to induce changes in cardiometabolic function. Chronic sleep loss has been associated with an increased risk for weight gain, obesity and cardiac and metabolic disorders, independent of other potentially contributing factors, such as smoking and body mass index. We hypothesise that the sleep-wake disturbance comorbid with schizophrenia may play a significant role in the high prevalence of cardiometabolic dysfunction observed in this patient population. Here we present a critical review of the evidence that supports this hypothesis.
Body Mass Index ; Hallucinations ; Humans ; Obesity ; Prevalence ; Schizophrenia ; Smoke ; Smoking ; Weight Gain

The Figure 1A was given incorrectly.

Post-traumatic stress disorder (PTSD) is a pathological response to trauma characterized by frequent recollections, recurrent nightmares, and flashbacks of the traumatic event(s). To date, the precise mechanisms underlying the development of PTSD remain unknown. Several studies have suggested that antiepileptic drugs, such as gabapentin and lamotrigine, may be effective in the treatment of PTSD symptoms. We report on a 15-year-old Japanese female junior high school student who developed PTSD symptoms following repeated teasing from male classmates. Additionally, we underscore the beneficial effects of treatment with gabapentin and lamotrigine on flashbacks and nightmares. This patient developed PTSD symptoms after repeated teasing from male classmates at school. Her flashbacks and nightmares were treated with a combination of gabapentin and lamotrigine. After recovery, treatment with lamotrigine alone controlled her symptoms. Our observations suggest that a process of sensitization may be involved in the development of PTSD symptoms. Additionally, gabapentin and/or lamotrigine were effective in the treatment of flashbacks and nightmares in this patient. Thus, doctors should consider using these anti-epileptic drugs as an alternative approach to treating PTSD symptoms.
Adolescent ; Anticonvulsants ; Asian Continental Ancestry Group ; Dreams ; Female ; Humans ; Male ; Stress Disorders, Post-Traumatic*

Tourette syndrome consists of multiple motor tics and one or more vocal tics. Psychopathology occurs in approximately 90% of Tourette syndrome patients, with attention-deficit/hyperactivity, mood, and obsessive-compulsive disorders being common. Additionally, Tourette syndrome and bipolar disorder may be related in some individuals. However, it is unclear why bipolar disorder may be overrepresented in Tourette syndrome patients, and more research is needed. Herein, we report the case of a 15-year-old boy diagnosed with both Tourette syndrome and bipolar disorder, whose symptoms improved with aripiprazole, atomoxetine, and valproate. The patient was diagnosed with Tourette syndrome at 8 years of age when he developed tics and experienced his first depressive episode. The patient had a poor response to a variety of antidepressants and anti-tic medications. A combination of valproate and aripiprazole stabilized both the patient's tics and mood symptoms. It is important to assess individuals with Tourette syndrome for other disorders, including bipolar disorder. The treatment of children and adolescents with both Tourette syndrome and bipolar disorder is an important clinical issue.
Adolescent* ; Antidepressive Agents ; Bipolar Disorder* ; Child ; Humans ; Male ; Obsessive-Compulsive Disorder ; Psychopathology ; Tics ; Tourette Syndrome* ; Valproic Acid ; Aripiprazole ; Atomoxetine Hydrochloride

OBJECTIVE: Many studies suggest an association between the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and anxiety-related personality traits (e.g., neuroticism) in healthy subjects. This study investigated the interaction of 5-HTTLPR genotype on body dissatisfaction by neuroticism and to evaluate the interaction of 5-HTTLPR genotype on self-esteem by body dissatisfaction in a young adult Korean population. METHODS: Two hundred and eighty three subjects were included in this study. The Eysenck Personality Questionnaire-Korean version was used to evaluate neuroticism, the Body Dysmorphic Disorder Examination-Self Report (BDDE-SR)-Korean version was used to evaluate body dissatisfaction, and the Self-Esteem Scale (SES)-Korean version was used to evaluate self-esteem. The 5-HTTLPR genotype by neuroticism (high : low) interaction was assessed according to the total BDDE-SR score, and 5-HTTLPR genotype by BDDE-SR (high : low) interaction was assessed according to the total SES score. RESULTS: The analysis of 5-HTTLPR genotype and neuroticism (high : low) with respect to body dissatisfaction showed no main effects of genotype whereas neuroticism did influence the BDDE-SR score and no interaction of the genotype with neuroticism. The analysis of 5-HTTLPR genotype and BDDE-SR (high : low) with respect to self-esteem score showed no main effects of genotype whereas BDDE-SR did influence the self-esteem score and no interaction of the genotype with body dissatisfaction. CONCLUSION: These results suggest that an interaction between 5-HTTPLR genotype and neuroticism does not affect body dissatisfaction and an interaction between 5-HTTPLR genotype and body dissatisfaction does not affect self-esteem in a young adult Korean population.
Body Dysmorphic Disorders ; Genotype* ; Humans ; Serotonin Plasma Membrane Transport Proteins ; Young Adult*

OBJECTIVE: A randomized double-blind cross-over trial was conducted in patients with persistent auditory hallucinations (AHs) to investigate whether bilateral repetitive transcranial magnetic stimulation (rTMS) at the temporoparietal area or Broca's area is more effective at high- or low-frequencies compared to a sham condition. METHODS: Twenty three patients with persistent AHs who remained stable on the same medication for 2 months were enrolled. They were randomized to one of four conditions: low-frequency (1 Hz)-rTMS to the temporoparietal area (L-TP), high-frequency (20 Hz)-rTMS to the temporoparietal area (H-TP), high-frequency (20 Hz)-rTMS to Broca's area (H-B), or sham. RESULTS: All the four rTMS conditions resulted in significant decrease in the scores under the auditory hallucination rating scale and hallucination change scale over time. However, there were no significant treatment effects or interaction between time and treatment, suggesting no superior effects of the new paradigms over the sham condition. CONCLUSION: Our findings suggest that bilateral rTMS at the temporoparietal area or Broca's area with high- or low-frequency does not produce superior effects in reducing AHs compared to sham stimulation.
Cross-Over Studies* ; Frontal Lobe ; Hallucinations* ; Humans ; Schizophrenia* ; Transcranial Magnetic Stimulation*

OBJECTIVE: The relationship between paranoia symptoms and underlying prefrontal cortex mechanisms among healthy subjects was analyzed using near-infrared spectroscopy. METHODS: Seventy-eight healthy subjects were assessed for paranoia symptoms using the Japanese version of the Paranoia Checklist. Changes in hemoglobin concentrations were assessed using 2-channel near-infrared spectroscopy on the surface of the prefrontal cortex while subjects performed a verbal fluency test. RESULTS: Changes in the concentration of oxygenated hemoglobin in the prefrontal cortex during a verbal fluency test did not correlate with the Japanese version of the Paranoia Checklist. CONCLUSION: Our findings show that the symptoms of paranoia do not negatively affect the prefrontal cortex function among healthy subjects.
Asian Continental Ancestry Group ; Checklist ; Humans ; Oxygen ; Paranoid Disorders* ; Prefrontal Cortex ; Spectroscopy, Near-Infrared

OBJECTIVE: This open-label study examined the effects of ramelteon on cognitive functions in 10 outpatients with schizophrenia. METHODS: Ramelteon (8 mg/day) was administered to 10 patients with schizophrenia for six months. The verbal fluency test, Trail-Making Test, the Wisconsin Card Sorting Test, the Stroop Test, the Digit Span Distraction Test, Iowa Gambling Task, the Rey Auditory Verbal Learning Test were evaluated at baseline and 6 months after treatment with ramelteon. RESULTS: Ramelteon improved significantly the scores of Rey Auditory Verbal Learning Test. Additionally, ramelteon exerted improvements in the verbal fluency and Iowa Gambling Task in 4 patients. CONCLUSION: Ramelteon could be a potential therapeutic drug, in adjunctive treatment of learning and memory deficits seen in patients with schizophrenia.
Gambling ; Humans ; Iowa ; Learning ; Memory Disorders ; Outpatients ; Schizophrenia* ; Stroop Test ; Verbal Learning ; Wisconsin