Patients suffering from schizophrenia display an impairment of memory performance among other cognitive deficits. Long term memory impairment can arise from disturbed encoding and/or retrieval processes subserved by mediotemporal, mesencephalic as well as prefrontal brain regions. We assessed functional and structural integrity of these regions in schizophrenia, specifically during cognitive processes of memory encoding and retrieval.

We assessed in a set of 3 fMRI studies in a total of 50 schizophrenia patients and an equal number of matched controls whether

1. 1) hippocampal/parahippocampal activity during encoding into long term memory is impaired,

2. 2) this impairment is related to the memory deficit,

3. 3) impaired memory retrieval is associated to mediotemporal/prefrontal dysfunction,

4. 4) hippocampal dysfunction is related to symptoms in schizophrenia,

5. 5) mesolimbic novelty detection is defective.

Functional alterations were related to structural brain changes as detected by voxel-based morphometry.

Patients with schizophrenia displayed a markedly impaired memory performance in our studies. It was related to dysfunction of hippocampal areas during memory encoding as well as novelty detection. During novelty detection, patients had a significantly impaired activity in the mesolimbic loop (hippocampus-ventral tegmental area). Prefrontral and mediotemporal hypofunction was evident during memory retrieval. Positive symptoms were related to a more dysregulated hippocampus activity during memory encoding.

Evident memory dysfunction in schizophrenia is related to severely altered neuronal processes subserving memory encoding and retrieval which importantly include defective mesolimbic novelty detection. Dysregulated hippocampal activity is related to positive symptoms in schizophrenia and importantly provides a neurobiological link to cognitive deficits.

To explore changes in functioning with flexible doses of paliperidone ER in a large international study in patients with schizophrenia previously unsuccessfully treated with other oral antipsychotics.

Prospective 6-month open-label study. Functioning was assessed using the Personal and Social Performance Scale (PSP), including four domains:

1. (1) personal and social relationships,

2. (2) socially useful activities including work and study,

3. (3) self care and

4. (4) disturbing and aggressive behavior.

1812 patients were included (59.9% male, mean age 40.1±12.6 years, 75.8% paranoid schizophrenia); most were enrolled because of lack of efficacy (n=1026) or lack of tolerability (n=490) with prior antipsychotic treatment. The median mode dose of paliperidone ER was 6 mg/day. 70.7% of patients completed the study. Most frequent reasons for early discontinuation were patient choice (8.8%), lack of efficacy or adverse event (5.1% each). AEs reported in >= 5% of patients were insomnia (9.2%) and anxiety (7.2%). Mean total baseline PSP score was 57.7±14.5, which improved to 64.1±15.6 at endpoint (mean change +6.4±13.5; 95% confidence interval 5.8;7.0, p< 0.0001); 49.0% of patients improved by at least one 10-point category in PSP. At baseline, 84.3% of patients had moderate to severe functional impairment, mostly driven by at least marked difficulties in socially useful activities (46.4.%) and personal and social relationships (36.4%). These percentages decreased to 30.6% and 22.9%, respectively.

In this large prospective flexible-dose study, results from recent randomized controlled studies are supported that paliperidone ER is associated with a clinically meaningful improvement of functioning in patients with schizophrenia.

To explore tolerability, safety and treatment response of flexible doses of paliperidone ER in adult non-acute patients with schizophrenia previously unsuccessfully treated with oral antipsychotics.

International prospective 6-month open-label study. Endpoints were the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity Scale (CGI-S), patient satisfaction, adverse events (AEs), extrapyramidal symptoms (Extrapyramidal Symptom Rating Scale; ESRS) and weight change.

1812 patients were included (59.9% male, mean age 40.1±12.6 years, 75.8% paranoid schizophrenia); most were enrolled because of lack of efficacy (n=1026) or lack of tolerability (n=490) with prior antipsychotic treatment. The median mode dose of paliperidone ER was 6 mg/day. 70.7% of patients completed the 6-month study. Most frequent reasons for early discontinuation were patient choice (8.8%), lack of efficacy or adverse event (5.1% each) independent of the reason for switching. Mean total PANSS decreased significantly from 79.4±20.4 at baseline to 66.1±21.5 at endpoint (mean change -13.3±19.7; 95% confidence interval -14.2;-12.3, p< 0.0001). The percentage of patients rated mildly ill or less in CGI-S increased from 27.0% to 52.2% at endpoint, and the rate of patients with mild functional impairment increased from 15.8% to 34.9%. AEs reported in greater-than-or-equal-to 5% of patients were insomnia (9.2%) and anxiety (7.2%). Extrapyramidal symptoms in ESRS decreased significantly from 3.5±5.8 to 2.1±4.6 (p< 0.0001). Mean weight gain from baseline to endpoint was 0.3±4.8kg.

These data support results from recent randomized controlled studies that paliperidone ER is safe, well tolerated and effective in patients previously unsuccessfully treated with other oral antipsychotics.

To explore tolerability, safety and treatment response of flexible doses of paliperidone ER in adult non-acute patients with schizophrenia previously unsuccessfully treated with oral risperidone.

International prospective 6-month open-label study. Endpoints were the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity Scale (CGI-S), adverse events (AEs), extrapyramidal symptoms (Extrapyramidal Symptom Rating Scale; ESRS) and weight change.

694 patients were included (59.2% male, mean age 40.0±12.8 years, 74.8% paranoid schizophrenia); most were enrolled because of lack of efficacy (n=366) or lack of tolerability (n=178) with prior oral risperidone treatment. 74.1% of patients (n=514) completed the 6-month study. Most frequent reasons for early discontinuation were patient choice (7.3%) and lack of efficacy (5.2%). The median mode dose of paliperidone ER was 6 mg/day, independent of the reason for switching. For all patients, mean total PANSS decreased significantly from 78.6±20.5 at baseline to 65.6±22.5 at endpoint (mean change -13.0±19.4; 95% confidence interval -14.5;-11.5, p< 0.0001). The percentage of patients rated mildly ill or less in CGI-S increased from 28.3% to 52.5% at endpoint, and the rate of patients with mild functional impairment increased from 16.5% to 36.6%. AEs reported in greater-than-or-equal-to 5% of patients were insomnia (8.8%) and anxiety (7.3%). Extrapyramidal symptoms in ESRS decreased significantly from 3.8±6.1 to 2.3±5.1 (p< 0.0001). Mean weight gain from baseline to endpoint was 0.4±4.3kg.

These data support results from recent randomized controlled studies that paliperidone ER is safe, well tolerated and effective in patients previously unsuccessfully treated with oral risperidone.

To compare the longer-term metabolic effects and efficacy of paliperidone ER and olanzapine in patients with schizophrenia.

Prospective 6-month randomized study evaluating flexible doses of paliperidone ER and oral olanzapine (OLA). Primary endpoint was the change in triglyceride to high-density lipoprotein (TG:HDL) ratio, a sensitive measure of insulin resistance. Additional endpoints were the Positive and Negative Syndrome Scale (PANSS), body weight, lipids, homoeostasis model of insulin resistance (HOMA-IR) and adverse events (AEs).

239 patients were randomized to paliperidone ER, 220 to olanzapine. Demographics and baseline characteristics were comparable. Mean doses were 6.9±1.3 mg/day for paliperidone ER and 11.6±2.3 mg/day for olanzapine. The TG:HDL ratio for olanzapine significantly worsened from baseline to endpoint (0.42±1.19;p< 0.0001); it remained unchanged for paliperidone ER (-0.08±1.10;p=0.4718; between-group difference p< 0.0001). PANSS total scores at endpoint significantly improved (olanzapine -16.6±15.0; paliperidone ER -13.5±15.9; both p< 0.0001 vs. baseline); the between-group difference met prespecified non-inferiority criteria. Endpoint weight change was 3.8±5.9kg for olanzapine and 1.2±4.6kg for paliperidone ER (p< 0.0001). Insulin resistance in HOMA-IR did not change with paliperidone ER (p=0.1507) but significantly worsened with olanzapine (p=0.003 vs. baseline). The most frequently reported treatment-emergent AEs (>=5%) were weight increase (OLA 18.2%;Pali ER 9.6%), insomnia (OLA 1.4%;Pali ER 9.6%), somnolence (OLA 9.5%;Pali ER 3.3%) and schizophrenia (OLA 1.8%;Pali ER 5.0%).

In this randomized controlled study paliperidone ER was superior to olanzapine with regards to insulin resistance, weight gain, lipid changes and other relevant metabolic endpoints. Efficacy was non-inferior between paliperidone ER and olanzapine.

To develop a toolkit (QuIRC) for assessing the living conditions, care and human rights of people with long term mental illness in psychiatric and social care facilities.

The QuIRC was developed by research partners across ten countries: UK; Germany; Spain; Czech Republic; Bulgaria; Italy; Netherlands; Poland; Greece and Portugal. Its content was informed by triangulation of the evidence on critical components of care collated from: a review of care standards in each country; an international literature review; and Delphi exercises. Its final format was agreed by an international panel of rehabilitation and recovery experts. QuIRC scores were compared against service users’ quality of life, autonomy, experiences of care and markers of recovery to assess whether the QuIRc could provide a proxy-assessment of the unit’s promotion of service users’ autonomy and Recovery.

The finalised tool was used to interview managers from 21 units throughout Germany. One hundred and eighty-eight service users were also interviewed. QuIRC domain ratings were compared by facility type and with service user assessments. The QuIRC’s ability to deliver assessments relevant to Germany’s established systems of change at local, regional and national level will be discussed.

Antipsychotics are mainstay treatment in schizophrenia; atypicals including clozapine were widely used. Clozapine was considered different due to its distinct effectiveness. We report the clinical profile of these groups.

In Nithsdale, South-west Scotland, the schizophrenia population was identified by ‘key informant’ method in 2006. The clinical variables were determined and compared between the groups.

The study identified 205 people with schizophrenia (point prevalence: 3.7/1000 general population) of which 131(64%) took part in the study. 22(17%) were receiving typicals, 63(48%) atypicals excluding clozapine, 29(22%) clozapine, 8(6%) combination of typical and atypicals, and 9(7%) were on no antipsychotic medications.

Comparison between atypicals excluding clozapine, typicals and clozapine groups showed: clozapine group were younger than atypicals and typicals (Mean years: 43,54 and 62, p=< 0.001). The length of illness was longer in typicals than atypicals and clozapine (Mean years: 35,24 and 18,p=0.002).

With mental state, clozapine group had higher score in positive subscore of PANSS than that of atypicals and typicals (Mean: 1.83,1.52 and 1.21, p=< 0.001); while there were no significant differences in the negative subscore (Mean: 2.11,2.01 and 1.77, p=0.24).

Tardive dyskinesia was more prevalent in typicals and clozapine groups than atypicals as assessed by AIMS scale (Mean: 41,41 and 18, p=0.02); while there were no significant differences between the three groups in the severity of parkinsonism as assessed by Simpson & Angus scale (Mean: 0.34,0.36 and 0.25, p=0.37).

Atypicals including clozapine were no better than typicals in symptom control or in the neurological side effect profile.

There is a significant incidence of psychiatric symptoms in patients with multiple sclerosis, the most common after receiving the diagnosis. We describe a man who was admitted for a first episode psychosis and a diagnosis of multiple sclerosis was made moreover.

A 24-year-old man was admitted with a paranoid delusion, auditory hallucinations with emotional response and the believe that their thoughts were being interfered. Blood test and cranial CT were normal. Risperidone was started. He developed ataxia and sensitive disturbances on the right arm. A cranial and spinal cord MRI revealed multiple T2 and FLAIR hyperintense lesions located in supra and infratentorial white matter, lesions in C3, and one lesion in right basal ganglia that enhanced with gadolinium. CSF analysis showed oligoclonals bands. Three years ago the patient had had transient sensitive symtoms. A diagnosis of relapsing-remitting multiple sclerosis was made and was started methyl-prednisolone intravenously. Risperidone was changed for amisulpride 800 mg/day because lack of response. He was discharged after 25 days. Six months later he has attenuated psychotic symptoms without news lesions in MRI. Glatiramer acetate has been started.

The most frequent disorder associated to multiple sclerosis is depression (prevalence of 20%). Psychosis is unusual, transient, sometimes as the onset relapse followed by remission. There's evidence of correlation between psychosis in multiple sclerosis and multiple lesions in temporal periventricular area. We suggest that in our case these two disorders are two separated entities since the enhanced lesion does not correpond with clinical findings.

Tobacco smoking is considered as one of leading preventable causes of death. High prevalence of tobacco smoking was reported among individuals with mental illnesses, and it is extremely high among patients with Schizophrenia. It is possible that antipsychotic drugs side effects are contributing to this negative trend. Objective of this paper was to establish frequency of cigarette smoking among patients with Schizophrenia hospitalized at the psychiatry clinic and to determinate the difference in frequencies of cigarette smoking among patients with Schizophrenia treated with first or second generation antipsychotics.

Study included 60 patients with Schizophrenia treated with antipsychotics for period of six months or longer. Experimental group included 30 patients treated with second generation antipsychotics, and control group included 30 patients treated with first generation antipsychotics. Descriptive statistical methods are used. The levels of statistical significance between parametric data were determined by t- test, and between nonparametric data by chi square test. Level of significance was established at P < .05.

In this sample was 75% smokers, and out of this 46.6% consume up to 20 cigarettes per day, 40% consume 20 to 40 cigarettes, 8.8% between 40-60 cigarettes, and 4.4% consume over 60 cigarettes per day. There was no significant differences between groups of patients treated with first and second generation antipsychotics.

Tobacco smoking is very frequent among patients with Schizophrenia. In this study we did not found significant difference in frequency of tobacco smoking between groups of patients treated with first or second generation antipsychotics.

Spectral delta and gamma activity were recorded in 17 schizophrenia patients and 17 matched controls to study brain dysfunction/inhibition and functional linguistic impairment in different phases of written word processing.

Most of patients were suffering from paranoid schizophrenia and obtained relatively high rating in Delusions (P1) and Conceptual disorganization (P2) of the PANSS. Delta and gamma amplitudes were measured while participants performed three linguistic tasks, i.e., visuo-perceptual, rhyming and semantic judgment.

Compared with healthy controls, patients showed no overall delta and gamma differences, revealing a lack of pharmacological-dependent impairment. However, ANOVAs revealed bilateral delta and gamma distributions in patients and, compared with controls, significant greater delta and lower gamma levels in left anterior sites. Healthy participants showed higher delta amplitude in right vs. left anterior sites and a reversed pattern for gamma amplitude: delta and gamma provided complementary results which suggested that controls, but not patients, activated left anterior regions during the linguistic processing. Patients’ hypofrontality was functionally correlated to their lack of left hemispheric specialization for language: the higher delta amplitude in left anterior sites, the higher levels of P1 and P2 positive symptoms; the higher gamma percentage in right anterior sites, the higher levels of N4 (i.e. Passive/apathetic social withdrawal).

Delta and gamma rhythms are quantitative indices of the amount of neurons engaged in specific cognitive processes and they represent complementary physiological indices of neural inhibition/activation able to measure both the hypofrontality and the functional deficit of language lateralization in schizophrenia patients.

To create an image of therapeutic options available for the first episode psychsis and the way these options influence the evolution of patients.

The present study is part of a larger follow-up study on a number of 121 patients with a diagnostic of first episode psychosis admitted in the Timisoara Psychiatric Clinic and The Day Clinic in the Timisoara Mental Health Center between 2003-2006 and prospectively monitored from the moment of their first contact with psychiatric services.

The average calculated duration of prodrome period and average Duration of Untreated Psychosis (DUP) are similar to the results indicated by most other studies. The results of statistical tests show that: the longest the prodrome, the worse the improvement of illness during course; a longer prodrome is correlated with a higher number of relapses during the patient's illness course and a longer Duration of Untreated Psychosis is likely to lead to an increased severity of illness. Patients’ adherence to treatment is influenced both by the traits of the first psychotic episode and the way the patients perceive the side effects and the general utility of the administered medication.

Psychiatrists have to dedicate more time and interest to establishing a therapeutic alliance with their patients with first episode psychosis; an individualized strategy is required to establish the adequate means and ways of intervention before initiating any type of therapy.

Cognitive deficits in schizophrenia consist of deficits in attention, concentration, fluency, and executive function. Especially the working memory deficits influence everyday function and rehabilitation.

The ame of the study was to investigate a potential of a neurocognitive intervention in schizophrenia (CS) and multiple sclerosis (MS) by application of a computerised working memory training.

So far, 30 ms patients and 14 cs patients were investigated. Patients are allocated to a treatment group or to a control design. At baseline, all participants underwent a comprehensive neuropsychological examination including memory, working memory, attention, concentration, information processing speed, mental flexibility and intelligence. The treatment group performed a computer program (Brainstim®) four times a week over a period of four weeks. After 16 training sessions all participants were evaluated again neuropsychologically.

In both patient groups a significant increase in cognitive performance within the training procedure could be shown. This increase was expressed by an initial exponential function with a steep increase and an asymptotic slope. Pre-post-test-comparisons revealed significant improvement for shortterm and working memory on the neuropsychological outcomes. The program was well accepted by the patients.

This preliminary results show, that working memory might be trained in schizophrenia and thus it might interfere positively the cognitive und rehabilitative outcome.

Estimation of acoustic startle response (ASR) and its prepulse modification in Russian population of patients with schizophrenia and healthy controls.

All subjects were males 25-50 years old. ASR was measured bilaterally by orbicularis oculi electromyographic response to 50 ms 110 dB white band noise. Prepulse at lead intervals of 60, 120 and 2500 ms were delivered according to protocol, recommended by Consortium on the genetics of schizophrenia.

ASR magnitude to pulse alone trials in initial block and habituation didn’t differ significantly between patients and controls. Patients compared to controls displayed reduced magnitude prepulse inhibition that was significant at 60 ms lead interval and reduction was more pronounced at the left eye. Startle latency prepulse facilitation at 60 ms lead interval was observed in patients but not in controls whereas prepulse inhibition of startle latency at 120 ms lead interval was seen in controls but not in patients. ASR amplitude prepulse facilitation (PPF) at 2500 ms lead interval was impaired in patients and this deficit was observed only in drug-naïve subjects. Effects of head trauma and experience of psychoactive drugs intake on ASR prepulse modification were revealed only in controls. High initial amplitude and short ASR latency in patients correlated with excitation level (PANSS scale P4). At the same time, PPF reduction correlated with scales P2, P4, P5, P7 and sum of positive PANSS scales.

Results of present study testify the possibility of ASR prepulse modification use for schizophrenia endophenotyping in Russia.

Study of psychophysiological candidate schizophrenia endophenotypes in relation with neurotransmitters blood level and mental disorders.

23 patients with schizophrenia and 24 healthy subjects performed horizontal antisaccades. Acoustic startle response (ASR) prepulse modification was studied according to protocol, recommended by Consortium on the genetics of schizophrenia. Neurotransmitters blood plasma level was estimated using HPLC.

Significant increase of errors and saccade latencies was revealed in patients compared to controls. ASR prepulse inhibition (PPI) at 60 ms lead interval and ASR prepulse facilitation (PPF) at 2500 ms lead interval were impaired in patients. Analysis didn’t reveal any correlations between ASR and antisaccades measures in patients while in healthy controls high initial ASR amplitude correlated with incorrect antisaccades number and PPF level correlated with antisaccades latencies. Significantly higher individual variability of plasma serotonin, glutamate and taurine content was found in patients compared to controls. Positive correlations of PPI with glutamate and taurine content were observed in patients but not in controls. At the same time, correlation between PPI and serotonine turnover ratio was positive in control group and negative in patients. Antisaccade latencies in controls displayed negative correlation with DOPAC and taurine level while in patients they positively correlated with dopamine and negatively with serotonine turnover ratio. It was also found that antisaccades parameters and ASR measures displayed correlations with different PANSS scales.

These data support the hypothesis that PPI and antisaccades are associated with different neural networks and have different genetic aetiology.

Schizophrenia is a chronic and potentially devastating disease. Patients with schizophrenia have severe and persistent sleep disturbance. Sleep deprivation may foster poor functioning and high levels of thought disorder, hostility, and excitement. Sleep deprivation in patients with schizophrenia have a negative impact on HRQoL. This study was done, as definitive study, to determine the sleep quality and quality of life in schizophrenia.

72 schizophrenic inpatients treated in a mental health care centre with the diagnosis of schizophrenia between March 1st and May 31st, 2009 were included to the study. The data was gathered through personal data forms, PSQI and WHOQOL-Brief Turkish Version.

It was found that there was a meaningful relationship between the age, sleep quality and quality of life of the patients (p< 0.05), it was also defined that sleep quality decreased as the age increased and quality of life decreased since the quality of sleep was decreased. The life quality points, except physical field, of the patients who live alone, hospitalized more than three times a year, do not use their medicine regularly were defined low.

There is a close relationship between the sleep quality and quality of life of the schizophrenia. As the sleep quality diminished, their quality of life decreases. The quality of life of the schizophrenia may be increased by regulating their sleep pattern and supporting their adoption to the illness.

Finally recognized as a powerful co-therapeutic factor, family caregivers of persons suffering from schizophrenia play an important role in the treatment process.

The aim of our study was to examine the family caregivers’ perceptions of antipsychotic medications.

In this study, the European Federation of Associations of Families of people with mental illness self-completion questionnaire was used. Data were collected from 40 family members, the key caregivers of 40 schizophrenic patients.

Average age of a carer was 56, 97 (±11, 48) and 65% of them were females. Parents were dominant, caring for an ill son (37, 5%) or daughter (42, 5%). Family caregivers spent every day caring for the ill relative (100%); mean time of caring was 15, 2 years. Lack of education about condition and treatment side effects were seen as main reasons for drug discontinuation. Nearly half of caregivers (45%) stated forgetfulness as an important factor of treatment non-adherence. Every 6th family member had complains about complicated drug routine and too many medications prescribed. At the same time, they considered that keep taking the medication as recommended is very important for the remission achievement and that reaching remission is a long process which usually requires multiple changes of antipsychotic medications (4 changes on average).

Family caregivers of schizophrenia sufferers share almost the same considerations about antipsychotic medications with professional caregivers. Further closer collaborations between formal and informal caregivers may help to go beyond some obstacles and to get a better treatment adherence.

This was an observational, uncontrolled, 4 week inpatient study, conducted at Unit VII, Clinical Hospital of Psychiatry Prof Dr. Alexandru Obregia, Bucharest. We included in the study 31 inpatients that suited the criteria admitted between January and March 2008. Patients received aripriprazol oral for four weeks. The patients received initially 15 mg aripiprazol. When the symptomatically hadn’t responded in 5 to 7 days we added 15 more mg aripiprazol. The group was divided in 2 parts: in one of them the patients received 15 mg in the morning, and in the other 15 mg in the morning and 15 more at noon.

Treatment efficacy was assessed using PANSS at baseline and at the end of weeks 2 and 4.

The CGI-S was performed at baseline and at the end of weeks 1,4. CGI-I assessments were conducted at the end of weeks 1, 2 and 4.

Clinically important change were not noted with regard vital signs measurements and physical examinations.

At the end of the study a persons gain weight.

The results of the study suggest that aripriprazole was efficacious safe and well tolerated for patients with acute psychosis - Aripriprazol 30mg/day was. Adverse events were generally mild and not treatment limiting. The majority of patients remain on the 30mg/day dose during the study.

Kartagener's Syndrome is a rare congenital malformation and characterized by the triad of bronchiectasis, sinusitis, and situs inversus. We presented a case diagnosed as Kartagener's syndrome and psychotic disorder not elsewhere specified.

The case was a male patient, 32 years old, high school educated, married, with two children. He had a history with increasing psychotic symptoms and two times of suicide attempts for the last two months needed hospitalisation. In the psychiatric examination affect was blunted, there were anxiety, fear due to auditive hallusinations and referance delusions, anhedonia, suicidal thoughts and attempts, secondary depression. Psychiatric disorder predominently with auditive hallusinations and social withdrawal had a duration of three years. He was diagnosed as Kartagener's Syndrome when he was nine years old. The patient was treated with haloperidol 20 mg/day, biperiden 5 mg/day, klorpromazin 100 mg/day during hospitalisation. The psychotic symptoms were reduced within third day. On radiography his heart was seen at the right side of his body, there was bronchial dilatation in the medial and inferior lobes of left lung, thickness of walls of bronches and increased peribronchial density.

We assume that the biochemical disorder that is the cause of the development of Kartegener Syndrome is related with the genetic location which facilitates the development of psychosis or risk of psychosis.