The Curse of the Dolphins: Cognitive Decline and Psychosis.

CASE: Isela is an 11-year-old Mexican-American girl with mild intellectual disability. During a vacation with her family, she went swimming with dolphins. A few days later, Isela awoke at night with laughing spells; during the day, she was pacing, aggressive, and had a decline in self-care and communication skills. Her parents attributed the symptoms to the dolphins. She was evaluated by a pediatric neurologist. The sleep-deprived electroencephalogram, brain magnetic resonance imaging, lumbar puncture, and thyroid function tests were normal. A genomic microarray was sent. The neurologist initiated empirical therapy for seizures with lamotrigine, which caused a rash. It was discontinued. She was then treated with oxcarbazepine followed by topiramate for several months without any change in symptoms. Comparative genomic hybridization revealed a small deletion at 14q13.1, which includes the NPAS3 gene. Psychiatry was consulted after several months of persistent symptoms. Isela seemed to be laughing in response to internal stimuli. Owing to the decline in communication and her apparent preoccupation with visual and auditory internal stimuli, Isela could not be interviewed adequately to confirm that she was experiencing hallucinations, but her laughter seemed to be in response to hallucinations. Isela was diagnosed with disorganized schizophrenia with psychosis. Risperidone was prescribed. A psychology evaluation was completed a few months later. Parents noted significant improvement after starting risperidone with reduced inappropriate laughing spells, reduced pacing, as well as improved eating, sleeping, communication, and self-care. Cognitive assessment with the Wechsler Abbreviated Scale of Intelligence-II indicated the following: verbal estimated intelligence quotient (IQ) = 70, perceptual estimated IQ = 71, and full-scale estimated IQ = 68. There was no cognitive decline compared with testing at school 4 years previously. Although psychotic symptoms were significantly improved on antipsychotic medication and function appeared to have been restored to her previous level, her parents continued to perceive a significant decline of functioning, and they continued to attribute the psychosis to swimming with the dolphins.

[The use of acatinol in the treatment of stable patients with schizophrenia with predominance of behaviour disorganization and subcatatonic features].

Our study was based on the hypothesis that a non competitive antagonist of NMDA receptors can improve clinical effects of antipsychotic therapy in a subgroup of patients with schizophrenia with clinical signs of glutamatergic hyperfunction such as catatonic symptoms and disorganization. The study design was open and non-comparative. The duration of the study for each patient was 6 months, the target dosage of acatinol was 20 mg. Forty stable patients with schizophrenia with predominance of signs of disorganization and subcatatonic symptoms were included. The following instruments were used: PANSS, NSA, CGI, BACS, UKU. Adding of acatinol to the antipsychotic treatment improved clinical symptoms, cognitive functioning and social functioning and decreased the number of side effects. The drug was well-tolerated.

Do patients with paranoid and disorganized schizophrenia respond differently to antipsychotic drugs?

OBJECTIVE: The aim of this study was to compare the differential response to amisulpride in patients with paranoid versus disorganized schizophrenia. METHOD: We reanalyzed the original data from five different randomized drug trials comparing Brief Psychiatric Rating Scale (BPRS) scores in a database containing 427 paranoid and 296 disorganized patients with schizophrenia. RESULTS: Both the disorganized and the paranoid group showed a substantial improvement of the BPRS total score within the first 4 weeks. In the paranoid group, mean (±SD) BPRS reduction was 16.9 (±14.6) (t = 24.06, df = 426, P < 0.001) and in the disorganized group 17.0 (±15.9) (t = 18.49, df = 295, P < 0.001). An analysis of covariance (ancova) controlling for BPRS at baseline and the influence of different trial protocols showed significant differences between diagnostic groups (F = 13.47, df = 1, P < 0.001), Cohen's D 0.31 (CI = 0.16-0.46). Paranoid patients improved by 4.8 BPRS points more than disorganized patients (adjusted means 18.90 (CI = 17.33-20.37) for the paranoid and 14.1 (CI = 12.04 - 16.11) for the disorganized group. CONCLUSION: We conclude that amisulpride is effective in disorganized as well as in paranoid schizophrenia, but that symptom reduction in the disorganized subtype is less pronounced.

Is disorganized schizophrenia a predictor of treatment resistance? Evidence from an observational study

Objective: To investigate whether inpatients with disorganized schizophrenia are more resistant to treatment. Method: Eighty-five inpatients were assessed at admission and at discharge for schizophrenia subtype, symptom severity, and treatment resistance criteria. Results: Disorganized patients were significantly more treatment-resistant than paranoid patients (60%, p = 0.001), and presented worse scores on the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI-S), and the Global Assessment of Functioning Scale (GAF) (p < 0.001). Although the difference was not significant, 80% of treatment-resistant patients with disorganized schizophrenia responded to clozapine. Conclusion: Patients with the disorganized subtype of schizophrenia should benefit from clozapine as a second-line agent. .

Is disorganized schizophrenia a predictor of treatment resistance? Evidence from an observational study.

OBJECTIVE: To investigate whether inpatients with disorganized schizophrenia are more resistant to treatment. METHOD: Eighty-five inpatients were assessed at admission and at discharge for schizophrenia subtype, symptom severity, and treatment resistance criteria. RESULTS: Disorganized patients were significantly more treatment-resistant than paranoid patients (60%, p = 0.001), and presented worse scores on the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI-S), and the Global Assessment of Functioning Scale (GAF) (p < 0.001). Although the difference was not significant, 80% of treatment-resistant patients with disorganized schizophrenia responded to clozapine. CONCLUSION: Patients with the disorganized subtype of schizophrenia should benefit from clozapine as a second-line agent.

Interaction of St John's wort (Hypericum perforatum) with clozapine.

St John's wort (Hypericum perforatum) is notorious for its ability to induce the enzymes of the P450 system. Especially, it induces CYP1A2 and CYP3A4, enzymes that are closely involved in the metabolism of clozapine. We present a patient with schizophrenia, who was stable on a fixed dose with stable plasma level of clozapine, and who deteriorated after she started self-medicating with St John's wort. The reduced plasma clozapine level and the psychiatric condition normalized after the withdrawal of St John's wort. It is possible that, beside the induction of P450-enzymes, the induction of P-glycoprotein by St John's wort aggravated psychiatric deterioration of the patient. Physicians should be alert to patients self-medicating with over-the-counter medicines, especially when these medicines can lower clozapine concentrations below the therapeutic range.

Quantitative motor activity differentiates schizophrenia subtypes.

BACKGROUND: Motor symptoms are frequent in schizophrenia and relevant to the diagnosis of subtypes. However, the assessment has been limited to observations recorded in scales and experimental designs. The aim of this study was to use wrist actigraphy to obtain motor activity data in 3 schizophrenia subtypes. METHODS: In total, 60 patients with schizophrenia (35 paranoid, 12 catatonic, 13 disorganized) were investigated using continuous wrist actigraphy over 24 h in an inpatient setting on average 38 days after admission. Data of the wakeful hours of the day were analyzed. RESULTS: The activity level was predicted by schizophrenia subtype and by the type of antipsychotic medication. The movement index and mean duration of uninterrupted immobility were found to be predicted only by the schizophrenia subtype. Age, gender, duration of illness and chlorpromazine equivalents did not contribute to the variance of the activity data. A MANOVA demonstrated the significant differences in the 3 parameters between schizophrenia subtypes (p = 0.001). Patients with catatonic schizophrenia had lower activity levels, a lower movement index and a longer duration of immobility than those with paranoid schizophrenia. CONCLUSIONS: Schizophrenia subtypes can be differentiated using objective measures of quantitative motor activity. The increased duration of immobility appears to be the special feature of catatonic schizophrenia.

Preattentional processes and disorganization in schizophrenia: Influence of a 6-week risperidone treatment.

INTRODUCTION: Visual orientation and attention are impaired in schizophrenia. Engagement and disengagement of attention and the ability to prompt responses to a stimulus in patients before and after six weeks of risperidone were compared to controls. METHODS: Ten unmedicated (nine naïve) schizophrenic patients, and eleven controls performed 1) A visual orienting task, the Cued Target Detection task (CTD), with the detection of a visual stimulus in valid, invalid, no cue and double cue trials, two conditions for fixation offset for a modulation of visual fixation: Gap: 200 ms before target; No Gap: simultaneous with target, 2) Choice Reaction Time (CRT 0.5 and 2 s delays). RESULTS: At baseline, patients showed longer RT than controls in CRT, but not in CTD, with in CTD, no facilitation of RT with the gap procedure. The alertness index was almost null in CTD-Gap and comparable to controls in CTD-No Gap. Efficiency to detect attended stimuli (CTD-No Gap) and warning effect (CRT 0.5 s) were negatively correlated to disorganization. After treatment, readiness to act in CRT had decreased. In CTD-No Gap, change in PANSS disorganization was correlated to an increased validity index, change in negative sub-score was correlated to decreased attention cost. CONCLUSION: Untreated patients displayed a deficit of Gap effect and a slowing in sustained attention. Disorganization interfered with warning and visual detection. After treatment, its improvement and negative symptoms improvement were associated with better visual detection. These alterations in visual orienting provide new evidence for an oculomotor dysregulation of attentional engagement in schizophrenia.

The clinical dilemma--prescribing in pregnancy.

Antipsychotic prescription in pregnancy is a complex topic and raises a great deal of anxiety in professionals. There is limited data about atypical antipsychotic prescription in pregnancy and its possible teratogenicity. There are no randomised controlled studies of atypical antipsychotic use in pregnancy due to obvious reasons of ethical issues. We present two cases where a choice had to be made as to whether to prescribe Olanzapine during pregnancy, with different results.

Three cases of schizophrenia for which olanzapine was effective after early acute phase.

AIMS: It clarifies a difference between early acute phase and late acute phase in medication. METHODS: The present report describes three patients with schizophrenia who presented with restlessness and excitement requiring hospitalization. RESULTS: Treatment with risperidone solution orally or parenteral haloperidol until the day after admission, followed by olanzapine, successfully improved the clinical condition of the patients. In the early stage of hospitalization, selection of fast-acting drugs that can be administered to uncooperative patients is considered preferable, focusing on rapid control of symptoms and behavioral disorders, whereas after this early stage, olanzapine is preferable for improving patient compliance in addition to stabilizing symptoms. CONCLUSIONS: Because the target symptoms differ between the early and late acute phases, the term 'acute phase' used in the broad sense should be divided into two units, each requiring a different therapeutic strategy, and independent clinical approaches should be considered in order to provide more suitable treatment.

[Recurrent dysregulation of body temperature during antipsychotic pharmacotherapy]. / Rezidivierende Temperaturregulationsstörung unter Therapie mit Neuroleptika.

OBJECTIVE: This case report presents a rare, potentially life-threatening vegetative disturbance, which can occur during pharmacotherapy of schizophrenia. METHOD: A retrospective descriptive transversal and longitudinal section consideration of in-patient treatments of one female was performed. RESULTS: A 50-years old woman suffering from oligophrenia and disorganized psychosis (ICD-10: F71, F20.1; DSM-IV: 318, 295.10) successively evolved hypothermias up to 32.0 degrees C rectal, between them fever up to 40.0 degrees C rectal, hypothermia-accompanied bradycardias up to 32/min, recurrent subclinical hypoglycaemias up to 55 mg/dl and somnolence until coma under benperidol with levomepromazine or melperone, pipamperone with and without amisulpride, promethazine as well as zuclopenthixole. Within hours the hypothermias responded to antipsychotic drug holiday. No pathbreaking finding could be ensured on levels of internal medicine, toxicology, neurology as well as neurophysiology including a transient aetiologically uncertain partial insufficiency of the adenohypophysis. CONCLUSIONS: During long-term treatment with antipsychotics especially in higher dosage unpredictable vegetative crises may occur. Antipsychotics having pronounced 5HT2- and D2-antagonism seem to be rather associated with hypothermia. We recommend in case of hypothermia below 35,5 degrees C immediate antipsychotic or anticholinergic drug discontinuation, usage of benzodiazepines like lorazepam for a few days and a following trial with ziprasidone, aripiprazole or clozapine. These atypical neuroleptics show receptor binding profiles potentially advantageous in hypothermia.

Delay of gratification and executive performance in individuals with schizophrenia: putative role for eating behavior and body weight regulation.

OBJECTIVE: Impairment in executive functions and disturbed weight regulation are common features in individuals with schizophrenia on antipsychotics. Still, the clinical management of weight gain, including educational programs, is insufficient. Therefore, we hypothesized that distinct executive impairment is associated with the inability to self-control food intake. METHOD: In the present study we investigated the performance in a paradigm analyzing the executive subfunction "delay of gratification" in individuals with schizophrenia (n=29) compared with controls (n=23) and the interrelationship between delay of gratification, overall executive functioning, reported eating behavior and the BMI. We applied a board-game paradigm to operationalize delay of gratification: on designated fields individuals need to decide about a small amount of immediate reinforcement versus double the amount in the end. Appetite and eating behavior were assessed by self-report scales, executive functioning by BADS. RESULTS: We found that the patients performed significantly worse in our paradigm and that this is associated with lower executive functioning. However, the interrelationship between all parameters is complex: there is a significant positive correlation between the reported perceived appetite and executive functioning whereas the reported restrained eating behavior, significantly more frequent in patients, is correlated with low executive functioning and high disinhibition in eating situations. CONCLUSIONS: We conclude that executive functions are necessary to successfully manage eating behavior. Thus, better understanding of the cognitive mechanisms might help to support the patients more efficiently in their tough job to keep control.

[The cardiovascular risk of schizophrenic patients]. / Das kardiovaskuläre Risiko schizophrener Patienten.

OBJECTIVE: Schizophrenia is associated with increased cardiovascular mortality. The deceleration capacity of heart rate is discussed to be a predictor of mortality, more powerful than conventional measures of heart rate variability (HRV) or the left ventricular ejection fraction. The aim of this study was to determine whether patients with schizophrenia, receiving antipsychotic medication have a reduced HRV indicating an elevated mortality risk. METHODS: We quantified HRV and the deceleration capacity in 24-hour electrocardiogram recordings from 28 medicated patients with schizophrenia and 28 matched controls. In addition to the evaluation of the 24-hour recording, 4-hour periods of "sleep" and "wake" recordings were evaluated separately, as activity has a major influence on HRV. Actigraphy was used to identify coherent sleep and wake phases and to ensure comparable levels of activity in patients and controls. RESULTS: Medicated patients showed a significant reduction of the HRV. The HRV was reduced significantly according to the time domain and frequency domain measures. The deceleration capacity of medicated patients was 5.36 compared with 8.26 for the controls (p < .05). CONCLUSIONS: Heart rate deceleration capacity is significantly reduced in schizophrenic patients treated with antipsychotics and may serve as an indicator of increased cardiovascular mortality risk.

Amoxapine as an antipsychotic: comparative study versus haloperidol.

It has been proposed that the lack of extrapyramidal side effects of atypical antipsychotic drugs is caused by their fast dissociation or low affinity for the D2 receptor or their concomitant high affinity for other receptors, for example, 5HT2 and D4. We noted that amoxapine, an established antidepressant, has affinity for 5HT2 and D2 receptors, and its effects in preclinical model are very similar to atypical antipsychotics. The objective of this study was to examine the antipsychotic effect and side effect profile of amoxapine versus haloperidol in a double-blind study for 6 weeks in patients with schizophrenia. A total of 54 patients with schizophrenia were titrated to the starting dose of 150 mg/d of amoxapine or 5 mg/d of haloperidol within 3 days. Clinical efficacy and side effects were monitored at baseline, and Weeks 2, 4, and 6.Forty-one patients completed 5 weeks, and 36 patients completed the 6 weeks of follow-up. Both treatment groups showed significant improvement in Positive and Negative Syndrome Scale positive (30%) and total scores (20%), without significant differences between the groups. In addition, in the amoxapine group, significant improvement was seen in the negative symptoms and the Clinical Global Impression. No significant changes were seen on Calgary Depression Scale for Schizophrenia, side effect checklists, and prolactin levels in both groups. The results suggest that amoxapine may be as effective an antipsychotic as haloperidol as predicted by its affinity for D2 and 5HT2 receptors, supporting earlier studies. However, it did not prove to have fewer extrapyramidal side effects than haloperidol, possibly because the baseline scores were very low.

Characteristics and use patterns of patients taking first-generation depot antipsychotics or oral antipsychotics for schizophrenia.

OBJECTIVE: Investigators compared patient characteristics and antipsychotic use patterns between individuals with schizophrenia treated in usual care with first-generation depot antipsychotics and those treated with oral antipsychotics (first- or second-generation or both). METHODS: Analyses used data from the U.S. Schizophrenia Care and Assessment Program, a large, prospective study of treatment for schizophrenia conducted July 1997 through September 2003. Participants were assessed at enrollment and every six months thereafter with patient self-report, validated psychiatric measures, and systematic extraction of medical records. Individuals treated with a first-generation depot antipsychotic at any time during the three-year study (N=569) were compared with those treated with only oral antipsychotics (N=1,617) on characteristics at enrollment and medication use pattern during the year after enrollment. RESULTS: Compared with patients receiving only oral antipsychotics, participants treated with depot medications (haloperidol or fluphenazine decanoate) were more likely to be African American (p<.001); less likely to be a veteran (p=.005); had more psychiatric hospitalizations in the year before enrollment (p<.001); and were more likely to have been arrested (p<.001), to use alcohol and illicit substances (p<.001), and to show higher psychopathology, particularly psychotic symptoms and disorganized thinking (p<.01 for both). In the year after enrollment, participants treated with depot medications had a high mean medication possession ratio (91%), and most of the medication regimens (68%) were augmented with oral antipsychotics for prolonged durations (median of 144 days). CONCLUSIONS: Patients with schizophrenia treated with first-generation depot antipsychotics differed from those treated with only oral antipsychotics. Findings suggest that first-generation depot antipsychotics might address some unmet needs of a unique subgroup of patients with schizophrenia.

Severe hypernatraemia due to nephrogenic diabetes insipidus - a life-threatening side effect of chronic lithium therapy.

Renal toxicity of long-term lithium therapy is a common problem. Nephrogenic diabetes insipidus is the most frequently encountered complication, but often remains unrecognised because of the rather benign symptoms. We present a patient with long-term lithium therapy who developed life-threatening hypernatraemia due to insufficient oral fluid intake after elective spinal surgery. Careful daily substitution of up to 25 l of hypotonic fluids led to full recovery within 9 days. Nephrogenic diabetes insipidus should always be considered in lithium-treated patients undergoing elective surgery in order to avoid severe hypernatraemia.