Comorbid substance abuse in first-episode schizophrenia: effects on cognition and psychopathology in the EUFEST study.

UNLABELLED: Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients. METHOD: In a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N=119, consisting of N=88 patients with persisting SUD at baseline and N=31 patients with previous SUD) and without SUD (FE-non-SUD, N=204) were compared at baseline and 6 months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding. RESULTS: In total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p=0.033, Cohen's d=0.26) in patients with SUD at 6 months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p=0.008, Cohen's d=0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16 years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption. CONCLUSIONS: FE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6 months of antipsychotic treatment.

Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia.

OBJECTIVE: Toxoplasmosis is a lifelong parasitic disease that appears to be associated to schizophrenia. However, no distinguishing attributes in Toxoplasma-infected schizophrenia patients have been described as yet. METHOD: We searched for differences in symptom profile, cognitive performance and treatment response between 194 Toxoplasma-free and 57 (22.7%) Toxoplasma-infected schizophrenia patients treated in Prague Psychiatric Centre between 2000 and 2010. RESULTS: Infected and non-infected patients differed in severity of symptoms (P = 0.032) measured with the Positive and Negative Symptom Scale (PANSS). Infected patients scored higher in positive subscale of PANSS, but not in the general and negative subscales. Infected men scored higher also in Total PANSS score, and negative, reality distortion, disorganisation and cognitive scores. Higher PANSS scores of positive, negative and disorganised psychopathology were associated with the lower titres of anti-Toxoplasma antibodies suggesting that psychopathology deteriorates with duration of parasitic infection. Infected patients remained about 33 days longer in hospital during their last admission than uninfected ones (P = 0.003). Schizophrenia started approximately 1 year earlier in infected men and about 3 years later in infected women, no such difference was observed in uninfected subjects. CONCLUSION: Latent toxoplasmosis in schizophrenia may lead to more severe positive psychopathology and perhaps less favourable course of schizophrenia.

Familial sinistrality and handedness in patients with first episode schizophrenia: the EUFEST study.

The population with schizophrenia is characterised by a leftward shift in handedness-sinistrality. However, findings are inconsistent in chronic patients, and familial sinistrality (FS), defined as the presence of left-handed close relatives, might contribute to the discrepancies. Therefore the aim of this study was to investigate the strength of manual lateralisation in patients with first episode schizophrenia, taking into account familial sinistrality. The Edinburgh Inventory (EI) allowed us to categorise 179 patients from the EUFEST study and 189 controls presenting "strong handedness" (SH: EI absolute value between ∣81∣ and ∣100∣) or "weak-handedness" (WH: EI value between -80 and +80). The nominal logistic regression did not show an FS effect, but a nearly significant interaction between illness and FS (p =.07). There were fewer participants without FS presenting SH among patients (99/151: 65.6%) than among controls (134/164: 81.7%, p =.001). In contrast, the number of participants with FS presenting SH was similar between controls (68%) and patients (75%, p =.57). The presence of left-handed relatives (FS + ) tended to reduce manual lateralisation, but only in controls. This supports the notion that reduced manual lateralisation in schizophrenia is related to the illness rather than to familial left-handedness.

Unmet needs in patients with first-episode schizophrenia: a longitudinal perspective.

BACKGROUND: This study aimed to identify the course of unmet needs by patients with a first episode of schizophrenia and to determine associated variables. METHOD: We investigated baseline assessments in the European First Episode Schizophrenia Trial (EUFEST) and also follow-up interviews at 6 and 12 months. Latent class growth analysis was used to identify patient groups based on individual differences in the development of unmet needs. Multinomial logistic regression determined the predictors of group membership. RESULTS: Four classes were identified. Three differed in their baseline levels of unmet needs whereas the fourth had a marked decrease in such needs. Main predictors of class membership were prognosis and depression at baseline, and the quality of life and psychosocial intervention at follow-up. Depression at follow-up did not vary among classes. CONCLUSIONS: We identified subtypes of patients with different courses of unmet needs. Prognosis of clinical improvement was a better predictor for the decline in unmet needs than was psychopathology. Needs concerning social relationships were particularly persistent in patients who remained high in their unmet needs and who lacked additional psychosocial treatment.

Clinical and demographic characteristics of psychiatric patients seropositive for Borrelia burgdorferi.

PURPOSE: Borrelia burgdorferi (Bb) infection can affect the central nervous system and possibly lead to psychiatric disorders. We compared clinical and demographic variables in Bb seropositive and seronegative psychiatric patients and healthy controls. METHOD: Nine hundred and twenty-six consecutive psychiatric patients were screened for antibodies to Bb and compared with 884 simultaneously recruited healthy subjects. RESULTS: Contrary to healthy controls, seropositive psychiatric patients were significantly younger than seronegative ones. None of the studied psychiatric diagnostic categories exhibited stronger association with seropositivity. There were no differences between seropositive and seronegative psychiatric patients in hospitalization length, proportion of previously hospitalized patients and proportion of subjects with family history of psychiatric disorders. CONCLUSION: These findings elaborate on potential association between Bb infection and psychiatric morbidity, but fail to identify any specific clinical 'signature' of Bb infection.

Comorbidity of parkinsonism and schizophrenia in a patient treated with clozapine.

Clozapine is the least likely anti-psychotic to induce extrapyramidal symptoms (EPS). We present a surprising case of a woman schizophrenic patient treated with clozapine suffering from EPS. Single photon emission computed tomography (SPECT) revealed a low density of presynaptic dopamine transporters in our patient's brain. A comorbid diagnosis of Parkinson's disease in schizophrenia was confirmed in this way. This helped us to find a proper therapeutic strategy for our patient.

Antiepileptic drugs in schizophrenia: a review.

The first choice group of psychotropic agents in schizophrenia is neuroleptics. However, this treatment is not effective in all patients and with every symptom. We summarize papers published on the role of antiepileptic drugs in treatment-resistant schizophrenia. We have searched the computer database system MEDLINE for relevant articles including reviews, reports of drug studies and case histories. Antiepileptic drugs can change symptoms of schizophrenia by their action on GABA-ergic neurotransmission or via anti-glutamatergic mechanisms. High doses of adjunctive benzodiazepines reduce positive symptoms, anxiety, and agitation. Carbamazepine is effective in affective symptoms of schizophrenia and influences violent behavior in psychotic patients. Its anti-kindling action may represent a promising treatment strategy for some patients with chronic course of schizophrenia. Valproate treatment leads to a decrease in positive symptoms as well as hostility. Lamotrigine is expected to influence the positive, negative, affective, and cognitive symptoms of schizophrenia. New antiepileptics (e.g., gabapentin, oxcarbazepine, topiramate, vigabatrin) present a promise as potential adjuncts to neuroleptic treatment in resistant symptoms of schizophrenia.

Rights and responsibilities of the psychiatric profession.

Psychiatry as a medical discipline relies on the authority of medicine that is associated with the help to a suffering and deserving individual. If this source of authority is obscured, the discipline will be blamed for serving as a social tool for controlling undesirable phenomena and practices. Psychiatry as a medical science accumulates knowledge on the relationship of biology and psychopathology. It can provide an explanation of the extent to which mental illness participates in socially undesirable behaviour and phenomena. But it cannot explain undesirable social phenomena as a mental illness of sorts, let alone offer an effective treatment for them. We should carefully guard the boundaries of psychiatry to prevent its abuse in the future.

Effects of haloperidol treatment on prolactin response to D-fenfluramine challenge in acute schizophrenia.

We have previously described an association between higher serotonin (5-HT) responsivity, indexed by prolactin response to D-fenfluramine challenge, and poorer treatment response to haloperidol in non-medicated schizophrenics. The aim of the present study was to investigate the effects of antidopaminergic treatment on the prolactin response in the repeated challenge test. D-Fenfluramine was administered to 22 young, acutely ill schizophrenics (11 females and 11 males) after 4 weeks of haloperidol treatment. Whereas neuroleptic administration significantly raised basal prolactin levels (P < 0.0001), subsequent D-fenfluramine challenge produced an additional significant increase (P < 0.001). Moreover, the magnitude of this increase was not different from the pretreatment response. Our results demonstrate that prolactin response to the challenge is mediated through the 5-HT system. An observed negative association between posttreatment prolactin response and therapeutic response to haloperidol did not reach statistical significance.

Prolactin response to D-fenfluramine challenge test as a predictor of treatment response to haloperidol in acute schizophrenia.

D-fenfluramine has been identified as a highly selective serotonin (5-HT) releaser and re-uptake inhibitor. The objective of our study was to investigate prolactin response to D-fenfluramine challenge in non-medicated, first episode schizophrenics. We hypothesized that 5-HT reactivity can predict a response to the neuroleptic treatment. Twenty-three inpatients, 11 males and 12 females, at the Prague Psychiatric Center participated in the study. Inclusion criteria were: ICD-10 diagnosis of schizophrenia, first episode or duration of illness shorter than 36 months. D-fenfluramine challenge test was performed before 4 weeks of the haloperidol treatment. During the test, prolactin plasma levels were measured. The Brief Psychiatric Rating Scale (BPRS) was administered before and after the treatment. A statistically significant negative correlation was found between prolactin response to the D-fenfluramine challenge and improvement of psychopathology measured by the change in total BPRS score (p = 0.0004), in positive (p = 0.0403), negative (p = 0.0267), and anxiety-depression symptoms of BPRS (p = 0.0014). Our data support the original hypothesis that there is a relationship between 5-HT system activity and treatment response. The higher responsiveness of the 5-HT system in first episode, non-medicated schizophrenics, was associated with a poorer treatment response to haloperidol, an antidopaminergic neuroleptic.

Community violence and inpatient assaults: neurobiological deficits.

The goals of this study were to examine the relationship between community violence and inpatient assaults and to identify neurological and neuropsychological deficits underlying violent behavior. Thirty-three inpatients with a history of community violence were compared with 69 patients who did not have such a history. Inpatient assaults were recorded for 4 weeks; a neurological/neuropsychological battery was then administered. Patients without community violence were more likely to show transient or no violence while in the hospital. Patients with community violence performed more poorly on the Wisconsin Card Sorting Test and on psychomotor tasks, impairments that are consistent with frontal lobe dysfunction. Inpatient assaults were not associated with these neuropsychological impairments. They were related, however, to impairment on frontal motor programming tasks and a history of community violence.

[Pharmacotherapy in resistance depression]. / Farmakoterapie rezistentní deprese.

This article reviews pharmacological approaches used to overcome treatment resistance in patients with serious unipolar depressive disorders. Resistant depression is defined as depression the symptoms of which persist despite adequate treatment. Main causes of unsuccessful treatment are incorrect diagnosis, inadequate duration of treatment or inadequate dosage. Other reasons for resistance are also discussed in the article. There are three basic strategies in treatment of resistance: optimization of treatment, substitution-replacement of the current treatment with a different one, combination-concurrent use of several treatments to enhance the effect. Treatment recommendations related to these strategies are discussed.

Does the change of psychopathology during the placebo period predict the response to subsequent treatment with active medication.

We examined whether deterioration in psychiatric symptoms during the placebo period predicted short-term response to subsequent treatment. Acutely exacerbated chronic schizophrenic or schizoaffective patients (n = 123) received placebo for 6.2 days on average. Afterwards, fixed haloperidol plasma levels were maintained for 6 weeks. Psychopathology was evaluated on the basis of the Brief Psychiatric Rating Scale (BPRS), which was administered weekly by trained raters. The global BPRS score at the beginning of the active treatment accounted for 11% of the end-point variance of the global BPRS score (p < 0.0002) and the change of psychopathology during the preceding placebo period explained additional 3.1% (p < 0.053) of it. The change in most of the BPRS factor scores contributed significantly to the prediction of the end-point BPRS score. The patients who had low scores on admission to the study and high scores at the end of the placebo period showed the greatest improvement. The results suggest that in addition to the baseline severity of psychopathology, the change of psychopathology that occurs during the pretreatment placebo period can partially account for treatment response.

[Evoked visual responses in schizophrenic patients]. / Vyvolané zrakové odpovedi u schizofrenních pacientu.

The authors investigated during prolonged ambulatory treatment with the neuroleptic preparation isofloxythepine (IFT) changes of visually induced responses in 24 psychotic patients. The reference group was formed by 10 healthy volunteers examined before and after administration of a single dose of IFT by the oral route. In addition to the visually induced responses the authors investigated also plasma prolactin levels (PRL). It was found that the latency of the P1 peak and amplitude between peaks A1 are in psychotic patients altered, as compared with healthy subjects. The latency of the P1 peak is after a single dose of IFT in healthy subjects longer and the amplitude A1 higher than in the sick group. In healthy subjects after administration of IFT a negative correlation was observed between the amplitude and the basal PRL level. In patients no relationship was found between PRL levels and parameters of the visually induced response.

Clozapine in the treatment of schizophrenic patients: an international multicenter trial.

One hundred twenty schizophrenic patients were treated with clozapine for two months in accordance with a standard trial protocol at ten research centers in the USSR, Czechoslovakia, Hungary, Poland, Bulgaria, and in the GDR. The daily dose ranged from 50 mg to 550 mg (mean: 272.1 mg for responders; 298 mg for nonresponders). In 94 patients (78%) the disease was clearly progressive; in 57 (47.5%) it was continuous; in 63 (52.5%) it was episodic. Before the start of clozapine treatment, 95 of the patients (79%) had been receiving other neuroleptics. There was a positive therapeutic response in 80% of the responding patients. The effect of clozapine was closely related to the dominant syndrome structure of the psychosis: a positive response was noted in 89% of patients with delusional, hallucinatory-delusional, and catatonic states and in 60% of patients with affective-delusional syndromes. Moderate side effects were noted in 87 patients (73%). The incidence of side effects reached a peak during the first four weeks of treatment and then declined despite maintenance of or even an increase in the daily clozapine dose. Hematological changes (moderate leukocytosis and thrombocytopenia) were noted in eight patients (6.7%).