Neuropsychological deficits in the prodromal phase and course of an early-onset schizophrenia. A case report.

OBJECTIVES: Although clear advances have been achieved in the study of early-onset schizophrenia (EOS), little is known to date about premorbid and prodromal neuropsychological functioning in EOS. METHOD: Here, we report on a case of an adolescent male with EOS who underwent neuropsychological testing before and after illness onset. RESULTS: Marked cognitive deficits in the domains of attention, set-shifting, and verbal memory were present both pre-onset and during the course of schizophrenia, though only deficits in verbal memory persisted after illness-onset and antipsychotic treatment. CONCLUSION: The findings of this case study suggest that impairments in the verbal memory domain are particularly prominent symptoms of cognitive impairment in prodromal EOS and persist in the course of the disorder, which further demonstrates the difficult clinical situation of adequate schooling opportunities for adolescent patients with EOS.

[Cognitive deficits in first episode psychosis patients and people at risk for psychosis: from diagnosis to treatment]. / Troubles cognitifs des sujets présentant un premier épisode psychotique et à haut risque de transition vers la psychose: du repérage à la prise en charge.

BACKGROUND: Up to now, studies have not demonstrated significant efficacy of antipsychotics on cognitive impairments in patients with psychotic disorders. These cognitive deficits are of particular interest since they traditionally start early before the diagnosis of psychosis. They are observed during premorbid and prodromal stages, and during the first episode of psychosis. Moreover, cognitive impairments may be detected without any psychotic symptoms (such as positive symptoms) suggesting their development independently of the psychotic symptoms. Cognitive disturbances consist of impairments of episodic and working memories, intellectual functioning, executive functions (planning, inhibition, and cognitive flexibility), selective and sustained attentions and social cognition (emotion, recognition, theory of mind). The altered cognitive functions observed in schizophrenia are the same as in earlier stages but at a lower level of severity. LITERATURE FINDINGS: Data suggest that cognitive deficits can be considered as vulnerability markers of psychosis since they have been described in healthy relatives of psychotic patients with high genetic risk. Cognitive deficits might also be considered as predictive of the occurrence of the disease after the first episode of psychosis. Indeed, retrospective studies suggest cognitive impairments in patients with schizophrenia during premorbid and prodromal phases but not in bipolar patients. Cognitive assessment might be of particular interest in people at risk for psychosis, in order to differentiate diagnostic outcomes. Cognitive functioning impairs until the diagnosis of first episode psychosis, even though cognitive profiles are quite heterogeneous in these patients. Once the diagnosis of schizophrenia is considered, cognitive deficits may be stable, although the literature is still controversial. Several factors such as symptoms and gender can contribute in diversifying the cognitive profiles. Moreover, age of onset might worsen the prognosis because of a disruption of the cognitive development and the disturbance of scholarship in young individuals. DISCUSSION: Considering these results, the treatment of cognitive deficits should be initiated as soon as possible, e.g. in people at risk for psychosis in order to reinforce the normal cognitive development, prevent cognitive decline and to preserve the educational, professional and social status. Since antipsychotic medications do not impact on cognitive functioning, alternative therapeutics should be developed such as cognitive remediation. Several studies and meta-analyses have shown that cognitive remediation programs are particularly efficient in patients with schizophrenia or bipolar disorders. Contrary to antipsychotics, these techniques should be used in patients with a first psychotic episode, but also in individuals with subpsychotic symptoms, subthreshold to the diagnosis of schizophrenia.

[Teraligen in the complex treatment of anxiety-phobic, behavioral and depressive syndromes in children and adolescents with schizotypal disorder]. / Teralidzhen v kompleksnoi terapii trevozhno-fobicheskikh, povedencheskikh i depressivnykh narushenii u detei i podrostkov s shizotipicheskim rasstroistvom.

OBJECTIVE: To determine the frequency of prescribing and the main therapeutic targets of Teraligen in the treatment of Schizotypal disorder (STD) in childhood and adolescence. MATERIAL AND METHODS: The sample consisted of 151 patients aged 7 to 16 years with a diagnosis of STD (F 21), of which 31.1% (n=47) of female patients and 68.9% (n=104) of male patients who received inpatient or outpatient treatment at the FSBI NCPZ from 2008 to 2020. The study was conducted by clinical-psychopathological, clinical-catamnestic, and statistical methods. RESULTS: Teraligen was prescribed by psychiatrists to patients with STD in 74.2% of cases, of which in 46.4% of cases patients received Teraligen even before the diagnosis of STD in connection with complaints of neurotic disorders (anxiety, fears and sleep disorders) (n=30), as well as in connection with autistic-like behavior (n=22). At the time of follow-up, 55% (n=83) of patients received Teraligen, of which 63.9% (n=53) of patients were prescribed it for the first time. The applied schemes of prescribing Teraligen for the treatment of anxiety-phobic, depressive and behavioral syndromes within the framework of the STD in a relatively age-related aspect are presented. CONCLUSION: The high frequency of prescribing Teraligen by psychiatrists and neurologists to children and adolescents with STD at different stages of observation is shown, which reflects the confidence of specialists in this drug. Teraligen has demonstrated a multidimensional pharmacological effect, including a mild antipsychotic effect, providing reduction of a wide range of psychopathological symptoms, with good tolerability and drug interaction. The study of the possibilities of Teraligen, both for monotherapy and for augmentation of the treatment of mental pathology in childhood, remains relevant.

Psychedelic drug use and schizotypy in young adults.

Despite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented. Here, we studied an adult population (n = 1032) with a special focus on young (18-35 years) and healthy individuals (n = 701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders. Experimental behavioural testing was performed in a subsample of the subjects (n = 39). We observed higher schizotypy scores in psychedelic users in the total sample. However, the effect size was notably small and only marginally significant when considering young and healthy subjects (Cohen's d = 0.13). Controlling for concomitant drug use, none of our analyses found significant associations between psychedelic use and schizotypal traits. Results from experimental testing showed that total exposure to psychedelics (frequency and temporal proximity of use) was associated with better evidence integration (Cohen's d = 0.13) and a higher sensitivity of fear responses (Cohen's d = 1.05) to the effects instructed knowledge in a reversal aversive learning task modelled computationally with skin conductance response and pupillometry. This effect was present even when controlling for demographics and concomitant drug use. On a group level, however, only difference in sensitivity of fear responses to instructed knowledge reached statistical significance. Taken together, our findings suggest that psychedelic drug use is only weakly associated with psychosis-like symptoms, which, in turn, is to a large extent explained by psychiatric comorbidities and use of other psychoactive substances. Our results also suggest that psychedelics may have an effect on flexibility of evidence integration and aversive learning processes, that may be linked to recently suggested therapeutic effects of psychedelic drugs in non-psychotic psychiatric populations.

Antipsychotic side-effect - potential risk of patients rejecting their treatments.

Antipsychotics side-effects pose an enormous problem in psychiatric treatment. The choice of antipsychotics is a crucial issue in the treatment as both patients' cooperation and compliance often depend upon it. Severe side-effects might sometimes cause the treatment interruption, to which each patient is entitled. Schizotypal personality disorder (SPD) features include social and interpersonal deficits, discomfort with close relationships, as well as cognitive and perceptual distortions and eccentricities of behaviour. Dominant symptoms often determine psycho pharmacotherapy and therefore antipsychotic treatment is possible. A 23 year-old man was treated for 4 months due to disturbances typical for SPD. Since the patient did not respond well to haloperidol, zuclopenthixol was advised. The latter medication produced severe, life-threatening side-effects which caused urgent hospitalisation. Althouth zuclopenthixol was instantly retracted from the therapy, the patient and his family rejected any further psychiatric treatment. In spite the fact that hetero-data obtained from his mother a few months later, revealed disturbances which greatly affected the patient's live, the patient showed resistance to further psychiatric treatment because of his negative experience with this medication.

Is oestrogen neuroprotective?

Neuro-protection in this context is an important concept in the treatment of patients in the early, prodromal phase of psychosis, otherwise known as the 'At Ultra High Risk Mental State'. Neuro-protection as described here refers to the use of agents to control the process of apoptosis, which occurs more rapidly in the earliest phases of schizophrenia. There is a need to identify medications with fewer side effects than anti-psychotics in order to treat at risk mental states, or prodromal psychosis. Studies have shown that schizophrenia occurs in males at an earlier age than females. Later, at about the time of the menopause, there is a second peak in the incidence of psychosis (schizophrenia) in women. Hence it has been suggested that Oestrogen may be neuroprotective. Studies have shown that the addition of oestradiol to anti-psychotics in the treatment of schizophrenia in females increased the efficacy of the treatment, which suggests that oestrogen does indeed have a neuroprotective action. However oestrogen has never been used in 'at ultra high risk mental states', perhaps because of concern regarding side effects.

The use of antipsychotic medication in child and adolescent psychiatric treatment in Denmark. A cross-sectional survey.

The number of children and adolescents with psychiatric disorders being treated with antipsychotic medication is increasing significantly; however, only a limited evidence-base is available on this topic, especially when children are concerned. This study reports and discusses the use of antipsychotic medication in children and adolescents below 19 years of age in Denmark. A national cross-sectional survey registered the use of antipsychotic drugs on a given date. A questionnaire was sent to all child and adolescent psychiatric departments and all consultants in child and adolescent psychiatry throughout the country. All children and adolescents, aged 0-18 years, registered in treatment with antipsychotic medication, were included. Sixty-seven per cent of clinics and 63% of consultants participated. The total number of subjects registered in examination or treatment in the participating units was 3854. Antipsychotic medication was used in n=244 (6.4%) of these cases. Eighty-eight patients received additional medication, of which 24% received antidepressants, 8% sedative medication and 4% psychostimulants. The age of the patients was 4-18 years, and 63% was male. The most frequent diagnoses for patients in antipsychotic treatment were: schizophrenia, schizotypal disorder, autism spectrum disorders and personality disorders. Monotherapy was used in 87% of cases. Sixty-four per cent of patients treated with antipsychotics, received a second-generation antipsychotic as the main treatment. All 244 patients received one or more additional treatment modalities other than medication. Antipsychotic medication has a definite role in the treatment of children and adolescents with psychiatric disorders. Second-generation antipsychotics used as monotherapy prevail.

Toward a better identification and treatment of schizophrenia prodrome.

The prodromal period leading to schizophrenia has been the focus of significant interest in recent years. This is due not only to the possibility of identification of preschizophrenic states but also to the potential for improving prognosis as a result of early intervention. There are many approaches to the identification of the schizophrenia prodrome. Interventions in the prodromal period have met with various degrees of success. In this article, the authors present an overview of the literature reflecting the development of the prodromal concept and its implications for early identification. They also discuss various interventions proposed for this period and some ethical considerations related to these interventions. Despite the growing body of knowledge in this field, there is a need for more research data to support the establishment of treatment guidelines. Future directions of research are also discussed.

Predictors of falls and fractures leading to hospitalization in people with schizophrenia spectrum disorder: A large representative cohort study.

AIM: To investigate predictors of falls/fractures leading to hospitalisation in people with schizophrenia-spectrum disorders. METHODS: A historical cohort of people with schizophrenia-spectrum disorders (ICD F20-29) from 01/2006-12/2012 was assembled using data from the South London and Maudsley NHS Biomedical Research Centre Case Register. Falls/fractures were ascertained from a linkage to national hospitalisation data. Separate multivariate Cox regression analyses were employed to identify predictors of falls and fractures. RESULTS: Of 11,567 people with schizophrenia-spectrum disorders (mean age 42.6 years, 43% female), 579 (incidence rate 12.79 per 1000 person-years) and 528 (11.65 per 1000 person-years) had at least one reported hospital admission due to a fall or fracture respectively and 822 patients had at least either a recorded fall or a fracture during this period (i.e. 7.1% of sample). Overall, 6.69 and 10.74 years of inpatient hospital stay per 1000-person years of follow-up occurred due to a fall and fracture respectively. 14(0.12%) and 28(0.24%) died due to a fall and fracture respectively. In Multivariable analysis, increasing age, white ethnicity, analgesics, cardiovascular disease, hypertension, diseases of the genitourinary system, visual disturbance and syncope were significant risk factor for both falls and fractures. A previous fracture (HR 2.05, 95% CI 1.53-2.73) and osteoporosis (HR 6.79, 95% CI 4.71-9.78) were strong risk factors for consequent fractures. CONCLUSION: Comorbid physical health conditions and analgesic medication prescription were associated with higher risk of falls and fractures. Osteoporosis and previous fracture were strong predictors for subsequent fractures. Interventions targeting bone health and falls/fractures need to be developed and evaluated in these populations.

The effects of guanfacine on context processing abnormalities in schizotypal personality disorder.

BACKGROUND: The signature of impaired cognition in people with schizotypal personality disorder (SPD) may be centrally related to working memory impairments. Guanfacine, an alpha2A agonist that acts post-synaptically in the prefrontal cortex (PFC), has shown potential for reducing working memory limitations in other populations. This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD. METHODS: 29 individuals with SPD entered into a 4-week, randomized parallel-design, double-blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week open-label extension. A modified version of the AX-Continuous Performance Test (AX-CPT) was administered. On this task, evidence of intact context processing includes few BX errors (false cue, correct probe) and higher levels of AY errors (correct cue, false probe). RESULTS: At the end of double-blind treatment, participants treated with guanfacine demonstrated a significant reduction in BX errors and a small but significant increase in AY errors, a pattern that was not seen in the participants treated with placebo. CONCLUSIONS: SPD participants improved in their context processing toward a normal response bias, making fewer BX and more AY errors, after being treated with guanfacine.

Orienting of attention in unmedicated patients with schizophrenia, prodromal subjects and healthy relatives.

In typical orienting of attention tasks subjects have to respond as fast as possible to targets which appear in the periphery of the visual field and are preceded by spatial cues (e.g. brightening of a peripheral box where the target may subsequently appear). Reaction times (RT) are facilitated when cue and target appear at the same location (valid cueing) and the cue target interval is short (<250 ms). However, RTs slow down again when the target follows a valid cue after an interval of 250 ms and longer. This latter phenomenon is called Inhibition of Return (IOR) and is thought to reflect an automatic, inhibitory mechanism to protect the organism from redundant and distracting stimuli. Deficits of IOR were repeatedly reported in patients with schizophrenia. However, the role of medications and the nature of the deficit (trait or vulnerability indicator?) were unclear. In the present study we examined 15 unmedicated patients with schizophrenia (age: 31.2+/-11.1, m/f: 11/4, global scores SAPS: 48.33+/-33.09, SANS: 19.22+/-26.16), 29 subjects who were putatively in a prodromal state of psychosis, 30 first-degree relatives, another 8 first-degree relatives who had one child and at least one more relative with schizophrenia, and 50 healthy controls. We found an impairment of IOR only in the unmedicated patient group. In conclusion, blunted IOR in schizophrenia is not secondary to medications. According to this and previous studies blunted IOR may be most probably viewed as a trait cognitive feature of the schizophrenic disorder.

Predictors of acute treatment response in patients with a first episode of non-affective psychosis: sociodemographics, premorbid and clinical variables.

Approximately 60% of patients with a first episode of psychosis will significantly reduce the severity of their positive symptomatology with antipsychotic drugs. The aim of this study was to investigate predictors of response to antipsychotic treatment during the first episode of non-affective psychosis. 172 patients (107 male) with a diagnosis of schizophreniform, schizophrenia, schizoaffective, brief reactive psychosis, schizotypal personality disorder or psychosis non-otherwise specified entered the study. Sociodemographic, premorbid and clinical data at baseline were evaluated. Unpaired t-test for continuous and chi2 for categorical data, respectively, were used to compare responders and non-responders selected variables. Multivariate logistic regression was used to establish a prediction model. 57.6% of study subjects (99 of 172) responded to antipsychotic treatment. The following variables were significantly associated with less likelihood of response: 1.--lower severity of general psychopathology, positive symptoms and disorganized symptoms at baseline; 2.--earlier age of onset; 3.--diagnosis of schizophrenia; 4.--longer DUP; 5.--poorer premorbid adjustment during adolescence, and 6.--hospitalization. Multivariate logistic regression demonstrated that differences between responders and non-responders were largely accounted for by BPRS total score, age of onset, premorbid adjustment at early adolescence, and diagnosis. Patients with an early age of onset of schizophrenia, a poor premorbid adolescent functioning, and with a lower severity of psychopathology at intake seem to have a decrease likelihood of responding to antipsychotic treatment. Helping clinicians to identify non-responders is meant as a first step to optimise therapeutic effort to benefit individuals in this vulnerable group.

Neuroprotection: a therapeutic strategy to prevent deterioration associated with schizophrenia.

Schizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases. The illness begins with genetic susceptibility and generally expresses itself after puberty through subtle changes that begin during the prodromal stage. Symptoms get progressively worse and tend to become more resistant to treatment with each relapse. Evidence for a neuroprotective effect of some forms of early treatment is beginning to emerge. While the underlying mechanisms remain uncertain, atypical antipsychotics may counteract some of the progressive deteriorative effects by enhancing synaptic plasticity and cellular resilience. However, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in at-risk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia. In this expert roundtable supplement, Jeffrey A. Lieberman, MD, reviews the historical context of progressive deterioration in schizophrenia. Next, Diana O. Perkins, MD, MPH, reviews some of the challenges to early identification of illness as well as the impact of early versus delayed treatment. Finally, L. Fredrik Jarskog, MD, focuses on the neurobiology of functional progression in schizophrenia as well as pharmacology and the potential for neuroprotection.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of personality disorders.

These practical guidelines for the biological treatment of personality disorders in primary care settings were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). They embody the results of a systematic review of all available clinical and scientific evidence pertaining to the biological treatment of three specific personality disorders, namely borderline, schizotypal and anxious/avoidant personality disorder in addition to some general recommendations for the whole field. The guidelines cover disease definition, classification, epidemiology, course and current knowledge on biological underpinnings, and provide a detailed overview on the state of the art of clinical management. They deal primarily with biological treatment (including antidepressants, neuroleptics, mood stabilizers and some further pharmacological agents) and discuss the relative significance of medication within the spectrum of treatment strategies that have been tested for patients with personality disorders, up to now. The recommendations should help the clinician to evaluate the efficacy spectrum of psychotropic drugs and therefore to select the drug best suited to the specific psychopathology of an individual patient diagnosed for a personality disorder.

Aripiprazole: effectiveness and safety under naturalistic conditions.

A retrospective study was conducted to examine aripiprazole's effectiveness and safety in a naturalistic treatment setting in both inpatients and outpatients affected by schizophrenia and other psychotic disorders. All patients with schizophrenia, schizoaffective and delusional disorders, and schizoid and schizotypal personality disorders treated with aripiprazole from March 1, 2005, to March 1, 2006, in the authors' community mental health service were divided into outpatient (n=26) and inpatient (n=17) groups; the average treatment periods were 204 days and 25 days, respectively. Effectiveness was evaluated by improvement of symptoms (a 25% reduction of Brief Psychiatric Rating Scale [BPRS] score from baseline) and functioning level (a 50% increase of Global Assessment of Functioning [GAF] scale score from baseline), as well as dropout rate. Adverse effects and their impact on treatment course were also evaluated. The final scores of the 2 scales showed a statistically significant difference from baseline (BPRS: p<.001 in the 2 groups; GAF: p<.005 in inpatients, p<.001 in outpatients). The average improvements in BPRS and GAF were 54% and 35%, respectively, in outpatients and 71% and 71% in inpatients. Side effects included anxiety, psychomotor agitation, insomnia, and psychotic symptom worsening. The dropout rate was 24% in inpatients and 23% in outpatients, largely because of the aforementioned side effects. The data, though limited by the small sample and naturalistic methodology, suggest that aripiprazole may be effective for both long- and short-term treatment, with a greater improvement among inpatients and a similar dropout rate between groups.

Acute effects of treatment for prodromal symptoms for people putatively in a late initial prodromal state of psychosis.

BACKGROUND: People in a putatively late prodromal state not only have an enhanced risk for psychosis but already suffer from mental and functional disturbances. AIMS: To evaluate the acute effects of a combined supportive and antipsychotic treatment on prodromal symptoms. METHOD: Putatively prodromal individuals were randomly assigned to a needs-focused intervention without (n=59) or with amisulpride (n=65). Outcome measures at 12-weeks effects were prodromal symptoms, global functioning and extrapyramidal side-effects. RESULTS: Amisulpride plus the needs-focused intervention produced superior effects on attenuated and full-blown psychotic symptoms, basic, depressive and negative symptoms, and global functioning. Main side-effects were prolactin associated. CONCLUSIONS: Coadministration of amisulpride yielded a marked symptomatic benefit. Effects require confirmation by a placebo-controlled study.

Aripiprazole in the treatment of the psychosis prodrome: an open-label pilot study.

BACKGROUND: Research studies for the treatment of the putative prodromal phase of psychotic disorders have begun to appear. AIMS: To obtain preliminary evidence of the short-term efficacy and safety of aripiprazole treatment in people with the psychosis prodrome. METHOD: Fifteen participants meeting prodrome criteria (mean age 17.1 years, s.d.=5.5) enrolled in an open-label, single-site trial with fixed-flexible dosing of aripiprazole (5-30 mg/day) for 8 weeks. RESULTS: In the mixed-effects repeated-measures analysis, improvement from baseline on the Scale of Prodromal Symptoms total score was statistically significant by the first week. No participant converted to psychosis and 13 completed treatment. Neuropsychological measures showed no consistent improvement; mean weight gain was 1.2 kg. Akathisia emerged in 8 participants, but the mean Barnes Akathisia Scale score fell to baseline levels by the final visit. Adverse events were otherwise minimal. CONCLUSIONS: Aripiprazole shows a promising efficacy and safety profile for the psychosis prodrome. Placebo-controlled studies are indicated.

[Early detection of psychotic disorders]. / Früherkennung psychotischer Störungen.

UNLABELLED: Over the last decade there has been considerable interest in early intervention in schizophrenia and other psychotic disorders, driven by observations that early intervention might favorably alter the course of illness. New clinical and research programs have been established around the globe aiming to reduce treatment delays in psychosis and, more recently, to identify and possibly treat individuals in the pre-psychotic phase who are at imminent risk of developing psychosis. Since May 2004, a service for individuals at high risk (HR) for psychosis has been established at Vienna General Hospital. Individuals are offered comprehensive assessment and treatment which includes participation in a RCT investigating the effects of Omega-3 fatty acids versus placebo in addition to standard care. The aim of this article is to describe (1) classification of psychotic symptoms in incipient psychosis and (2) findings of the screening process as well as baseline characteristics in individuals with and without transition to psychosis. INCLUSION CRITERIA: 1. Age 13 to 24 years 2. High Risk (HR) as classified by Yung et al. (1998) HR criteria: one or more of following characteristics occurred within the last 12 months: 1. Frank psychotic symptoms < 1 week 2. Attenuated psychotic symptoms > 1 week, several times per week 3. Drop in GAF of > 30% (>1 months) plus family history of psychosis or individual has schizotypal personality disorder Other psychiatric measures: SCID for DSM-IV, PANSS, MADRS, and the UKU side effect rating scale. Between May 2004 and June 2005, 140 individuals were referred to our service for suspected psychosis. 69 individuals (49,3%) met HR criteria, 21 (15%) were detected with first-episode psychosis at initial presentation; 50 (35,7%) individuals did not meet criteria for HR or DSM-IV psychotic disorder. 42 (60,9%) of 69 individuals with HR agreed to participate in the proposed EPA/DHA treatment trial. Co-morbidity of axis-I disorders was high in the HR group: 54,3% affective disorders, 40% anxiety/obsessive-compulsive disorders, 14,3 substance related disorders, 11,4% eating disorders and 2,9% somatoform disorders. To date 6 (14,3%) individuals have made a transition to psychotic disorder. These subjects scored significantly higher at the negative and at the general psychopathology scale ofPANSS and at the MADRS at time of randomization. Early detection and intervention in psychotic disorders seems to be a feasible goal which can be achieved in an outpatient setting. Individuals with HR can be detected and already show a substantial loss of functioning. In the process of screening for individuals with HR a high number of undiscovered cases of psychosis can be found. Given their high prevalence, treatment of comorbid axis-I conditions should be carefully addressed in HR and studied in relation to the risk of progression to psychosis. In contrast to antipsychotics, Omega-3 fatty acids have a high acceptance among youth and parents. At this stage the role of Omega-3 fatty acids remains unclear because the trial is not finished yet.

Ethics of the early intervention in the treatment of schizophrenia.

When second generation antipsychotics were introduced in the mid 1990-s they offered the possibility of early psychopharmacological interventions in the treatment of schizophrenia. The idea applying antipsychotics in the prodromal phase of schizophrenia today is an realistic option. However ethical dilemmas about offering antipsychotics to the adolescents with at risk mental states, of whom only a few are real prodromes of schizophrenia remain for clinicians. In the literature about the ethics of the early interventions in psychiatry there are still many ethical questions which call for caution because of the low predictive value of at risk mental states, of which only 40% turn out to be a real prodrome of schizophrenia. These ethical questions can be addressed in three categories: - how to best identify who should receive early pharmacological intervention? - what this intervention should consist of? - how to evaluate treatment efficacy in the absence of illness base rates in the adolescents with a real prodrome of schizophrenia? Besides, arguing against the concept of early psychopharmacological interventions in the adolescent population are the fact of the unknown effect of antipsychotics on the developing brain as well as negative effects of stigma on those adolescents who receive them. The authors in the article analyse these ethical questions and take the side of those clinicians who think that caution and careful ethical judgment are needed before the prescribing of antipsychotics to adolescents with at risk mental states.

Antipsychotic treatment of schizotypy and schizotypal personality disorder: a systematic review.

Schizotypal personality disorder (SPD) is characterised by thought disorders, experiences of illusions, obsessive ruminations, bizarre or eccentric behaviour, cognitive problems and deficits in social functioning - symptoms that SPD shares with schizophrenia. Efforts have been undertaken to investigate the relationship between these conditions regarding genetics, pathophysiology, and phenomenology. However, treatment of SPD with antipsychotics has received less scientific attention. Embase and PubMed databases were searched using all known generic names of antipsychotics as search terms in combination with the following diagnostic terms: latent schizophrenia, schizotypal disorder, latent type schizophrenia, or SPD. Studies were categorised according to evidence level on the basis of their methodology from A, being the best, to E, being the worst. Five hundred and nine studies were retrieved and scrutinised. Sixteen studies, from the period 1972 to 2012, on antipsychotic treatment of SPD were extracted. Four studies were categorised as evidence level A, two as level B, six as level C and three as level D, with one study level E. Only four randomised, double-blind, placebo-controlled trials, on subjects with well-defined diagnoses, exists. Only amisulpride, risperidone and thiothixene have been studied according to evidence level A. This result warrants further high quality studies of the effects of antipsychotic treatment of SPD.