The contribution of fast growing, psychrotrophic microorganisms on biodiversity of refrigerated raw cow's milk with high bacterial counts and their food spoilage potential.

Storage of raw milk in the bulk tank creates an environment which selects for psychrotrophic bacteria. Results from earlier studies suggested that the microbiota of bulk tank milk with high bacterial counts is dominated by single, cold-adapted species with high growth rates at low temperatures. We checked this assumption in more detail and analyzed the microbial diversity of 48 samples from bulk tank raw cow's milk with bacterial counts >100,000 cfu/mL from different geographic regions by culture-dependent and -independent methods. Contrary to presumptions from earlier studies, only the minority (24%) of samples was dominated by a single bacterial species and diversity was not correlated with bacterial counts. The dominating species in this group of samples were identified as psychrotrophic Acinetobacter and Pseudomonas species, related to poor hygiene and spoilage, or mesophilic, mastitis-related Streptococcus species and Escherichia coli. This shows that storage of raw milk under refrigeration does not always lead to a selection of cold-adapted bacteria. Approximately half of the raw milk isolates showed either lipolytic or proteolytic activity at 10 °C or 4 °C. Consistent or increased enzymatic activity at cold temperatures was detected for Acinetobacter spp. and Pseudomonas spp., but also for genera with minor abundance, e.g. Carnobacterium and Arthrobacter.

Predictors of treatment response to psychological interventions in people at clinical high risk of first-episode psychosis.

AIM: Psychological interventions, such as cognitive behavioural therapy (CBT) and supportive counselling (SC), are used to treat people with schizophrenia and people at clinical high risk (CHR) of psychosis. However, little information is available on predictors of treatment response. This study aims to identify such predictors of psychological interventions in CHR. METHODS: A total of 128 help-seeking CHR outpatients were randomized into two groups-integrated psychological intervention (IPI), including CBT, and SC-for 12 months. Multiple regression analysis was used to identify demographic, symptomatic and functional variables that predict improvement in positive (PANSS Positive), negative (PANSS Negative) and basic symptoms (Basic symptom total score) and improvement in functioning (GAF) at 1-year follow up. RESULTS: In the merged group (IPI + SC), people who lived independently, were younger and presented with higher baseline functioning showed more improvement in symptomatic outcomes at follow up. Negative symptoms at baseline predicted less improvement in positive and basic symptoms. Being married or cohabiting and living in the primary family were found to correlate with good functioning at 1-year follow up. CONCLUSIONS: Younger CHR individuals and those who are functioning well may particularly benefit from early intervention. Treatment might need to be modified for low-functioning CHR and those who already display higher scores of negative symptoms. Registration number: NCT00204087.

Coping as a predictor of treatment outcome in people at clinical high risk of psychosis.

AIM: The concept of coping is relevant to recent models of psychosis, and people with established psychotic disorders have been found to predominately use maladaptive coping strategies. This study aimed to examine the general coping patterns of people at clinical high risk of psychosis (CHR) and to investigate whether pre-therapy coping behaviour plays a role in predicting responsiveness to early interventions. METHODS: One hundred twenty-eight help-seeking CHR outpatients were randomized into two treatment groups: either receiving integrated psychological intervention (IPI), including cognitive behaviour therapy, or supportive counselling (SC) for 12 months. Of those, 91 persons completed a Stress Coping Questionnaire (SCQ) at intake: 45 in the IPI group and 46 in the SC group. General coping behaviour in this sample was analysed and several regressions were conducted separately for each treatment group to examine coping as a predictor of outcome after 12 months of different forms of treatment. RESULTS: Participants relied significantly more on negative than on positive coping strategies, t(90) = -7.185, P < 0.001, and within the positive strategies, stress control was the most preferred one, t(90) = 10.979, P < 0.001. Several pre-therapy coping strategies significantly predicted improvement in symptomatic outcome in both treatment groups, explaining between 16% and 25% of variance. The predictive value of coping was higher in the SC group. CONCLUSIONS: Maladaptive coping behaviours were found to emerge in the early stages of psychosis and coping behaviour contributed significantly to the prediction of post-treatment symptom improvement. These findings indicate a need for psychosocial support and coping strategy enhancement in people at risk of psychosis.

[Neuropsychological Functioning as a Predictor of Treatment Response to Psychoeducational, Cognitive Behavioral Therapy in People at Clinical High Risk of First Episode Psychosis]. / Neuropsychologische Funktionen als Prädiktoren des Therapieerfolgs von psychoedukativer, kognitiv verhaltenstherapeutischer Therapie bei Personen mit erhöhtem Psychoserisiko.

OBJECTIVE: Investigate whether treatment response in people at clinical high risk of psychosis (CHR) is predicted by their cognitive performance. METHOD: 128 CHR outpatients were randomized into two treatment groups, one receiving integrated psychological intervention (IPI), including psychoeducation, the other receiving supportive counselling (SC) for 12 months. Multiple regression analysis was used to identify neurocognitive predictors of treatment response in a subgroup of n = 105, measured by symptomatic and functional improvement at 1-year follow-up. RESULTS: In the IPI, treatment response was associated with performance of executive control and processing speed (R²â€Š= 0.27, p = 0.002). In both treatment groups, performance of working memory/attention was a significant predictor (IPI: R²â€Š= 0.15, p = 0.039, SC: R²â€Š= 0.19, p = 0.012). CONCLUSION: Cognitive performance is associated with treatment response in CHR people. The enhancement of cognitive performance is a useful target of early intervention.

A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis.

Mutations in postsynaptic scaffolding genes contribute to autism, thus suggesting a role in pathological processes in neurodevelopment. Recently, two de novo mutations in SHANK3 were described in schizophrenia patients. In most cases, abnormal SHANK3 genotype was also accompanied by cognitive disruptions. The present study queries whether common SHANK variants may also contribute to neuropsychological dysfunctions in schizophrenia. We genotyped five common coding or promoter variants located in SHANK1, SHANK2 and SHANK3. A comprehensive test battery was used to assess neuropsychological functions in 199 schizophrenia patients and 206 healthy control subjects. In addition, an independent sample of 77 subjects at risk for psychosis was analyzed for replication of significant findings. We found the T allele of the SHANK1 promoter variant rs3810280 to lead to significantly impaired auditory working memory as assessed with digit span (12.5 ± 3.6 vs. 14.8 ± 4.1, P < .001) in schizophrenia cases, applying strict Bonferroni correction for multiple testing. This finding was replicated for forward digit span in the at-risk sample (7.1 ± 2.0 vs. 8.3 ± 2.0, P = .044). Previously, altered memory functions and reduced dendritic spines and postsynaptic density of excitatory synapses were reported in SHANK1 knock-out mice. Moreover, the atypical neuroleptic clozapine was found to increase SHANK1 density in rats. Our findings suggest a role of SHANK1 in working memory deficits in schizophrenia, which may arise from neurodevelopmental changes to prefrontal cortical areas.

Neuropsychological profiles in different at-risk states of psychosis: executive control impairment in the early--and additional memory dysfunction in the late--prodromal state.

Impairments in neuropsychological functioning have been described in subjects clinically at high risk for psychosis, but the specific cognitive deficits in different clinical high-risk groups remain to be elucidated. The German Research Network on Schizophrenia employs a heuristic 2-stage model: a putatively late prodromal state (LPS), characterized by the onset of attenuated positive or brief psychotic symptoms, and an early prodromal state (EPS), mainly characterized by the presence of basic symptoms, which are predictive for psychosis within the next 10 years. A total of 205 subjects met the criteria for either an EPS or an LPS of psychosis and were assessed with a comprehensive neuropsychological test battery. Neurocognitive profiles of high-risk groups were compared with data of 87 healthy controls comparable with regard to gender, age, and premorbid verbal IQ. Patients in the LPS were impaired in all neurocognitive domains (memory/learning, executive control/processing speed, and working memory) examined, with memory being the worst. Deficits were less pronounced in patients in the EPS, with a specific deficit in the executive control/processing speed domain. Consistent with a progressive neurodevelopmental disorder, some cognitive abilities were already impaired in patients in the EPS, followed by further deterioration in the LPS. Specifically, deficits in executive control functioning were related to the presence of basic symptoms, indicating a vulnerability for psychosis. Memory deficits were associated with the onset of psychotic symptoms indicating further disease progression in the trajectory to psychosis and, thus, may be useful in predicting psychosis and targeting early intervention.

Basic symptoms and ultrahigh risk criteria: symptom development in the initial prodromal state.

Symptom development during the prodromal phase of psychosis was explored retrospectively in first-episode psychosis patients with special emphasis on the assumed time-related syndromic sequence of "unspecific symptoms (UN)-predictive basic symptoms (BS)-attenuated psychotic symptoms (APS)-(transient) psychotic symptoms (PS)." Onset of syndromes was defined by first occurrence of any of their respective symptoms. Group means were inspected for time differences between syndromes and influence of sociodemographic and clinical characteristics on the recalled sequence. The sequence of "UN-BS/APS-PS" was clearly supported, and both BS and, though slightly less, APS were highly sensitive. However, onset of BS and APS did not show significant time difference in the whole sample (N = 126; 90% schizophrenia), although when each symptom is considered independently, APS tended to occur later than first predictive BS. On descriptive level, about one-third each recalled an earlier, equal and later onset of BS compared with APS. Level of education showed the greatest impact on the recall of the hypothesized sequence. Thereby, those with a higher school-leaving certificate supported the assumed sequence, whereas those of low educational background retrospectively dated APS before BS. These findings rather point out recognition and recall bias inherent to the retrospective design than true group characteristics. Future long-term prospective studies will have to explore this conclusively. However, as regards the criteria, the results support the notion of BS as at least a complementary approach to the ultrahigh risk criteria, which may also allow for an earlier detection of psychosis.

Impaired sensorimotor gating of the acoustic startle response in the prodrome of schizophrenia.

BACKGROUND: Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), which is commonly interpreted as a sensorimotor gating deficit. To date, it is unclear when these gating deficits arise. Results of animal studies and some human data suggest that PPI deficits are in part genetically determined, such that gating deficits could be present before the onset of a full-blown psychosis. To test this assumption, we investigated PPI of ASR in individuals with prodromal symptoms of schizophrenia and patients with first-episode schizophrenia. METHODS: Startle reactivity, habituation, and PPI of ASR, as well as a neuropsychological test battery, were assessed in 54 subjects with prodromal symptoms of schizophrenia (35 early and 19 late prodromal subjects), 31 first-episode schizophrenia patients (14 unmedicated, 17 medicated), and 28 healthy control subjects. Patients were also examined with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale. RESULTS: Prodromal subjects and unmedicated patients with first-episode schizophrenia showed significant PPI deficits, whereas schizophrenia patients treated with risperidone had almost normal PPI. Startle reactivity decreased with greater severity of symptoms (control subjects, early prodromal group > late prodromal group > unmedicated first-episode patients) but was almost normal in the medicated patients. With respect to habituation, prodromal subjects and schizophrenia patients did not differ from healthy control subjects. CONCLUSIONS: PPI disruption is already present in a prodromal state of schizophrenia, but startle reactivity deficits seem to emerge with the onset of acute psychosis.

5-HT2A receptor density is decreased in the at-risk mental state.

RATIONALE: Current perspectives on the pathophysiology of schizophrenia direct attention to serotonergic (serotonin, 5-HT) dysregulation in the prodrome or at-risk mental state (ARMS). OBJECTIVE: To study the cerebral 5-HT(2A) receptor (5-HT(2A)R) in the ARMS with [(18)F]altanserin positron emission tomography (PET) and a bolus-infusion paradigm. MATERIALS AND METHODS: We quantified the spatial distribution of 5-HT(2A)R binding potential (BP(1)') in never-medicated subjects assigned to early (n = 6) and late (n = 8) prodromal states of schizophrenia relative to healthy controls (n = 21). Five single nucleotide polymorphisms (SNPs) in the 5-HT(2A)R-encoding gene (HTR2A; 13q14-21) were genotyped to control for a potential bias in BP(1)' due to between-group differences in genotype distributions. RESULTS: Group comparisons of partial-volume corrected PET data by statistical parametric mapping and confirmatory volume of interest analysis yielded a dissemination of BP(1)' decreases consistent with increasing levels of risk. An additional decrease in caudate BP(1)' was present in subjects who subsequently converted to first-episode psychosis (n = 5), but absent in non-converters (n = 9). Between-group differences were not confounded by a differential distribution of SNP genotypes. CONCLUSION: These results suggest a progressive reduction of cortical 5-HT(2A)R density as a surrogate biological measure of increased risk for schizophrenia, irrespective of conversion. Progressive reductions of subcortical 5-HT(2A)R density could provide an indicator of illness activity and help to predict imminent conversion to schizophrenia. Moreover, our findings substantiate the rationale for establishing a phase-specific psychopharmacological intervention in the ARMS that addresses the serotonergic component of vulnerability to schizophrenia.

Randomized controlled multicentre trial of cognitive behaviour therapy in the early initial prodromal state: effects on social adjustment post treatment.

AIM: Improvement of social adjustment is a major aim of indicated prevention in young people at risk of developing psychosis. The present study explores the effect of specific cognitive behaviour therapy (CBT) as compared with supportive counselling (SC) on social adjustment in people in a potential early initial prodromal state of psychosis (EIPS) primarily defined by self-experienced cognitive thought and perception deficits (basic symptoms). METHODS: A total of 128 help-seeking outpatients in the EIPS were randomized to receive either specific CBT or SC for 12 months. Social adjustment was assessed with the Social Adjustment Scale II (SAS II) at baseline, time of transition or post treatment RESULTS: From 113 patients, who completed the SAS II at intake, 67 (59.3%) completed the SAS assessments at time of transition or post treatment. Both specific CBT and SC resulted in improvements in scales of SAS II, with no significant between-group differences post treatment. CONCLUSIONS: Although treatment in specially designed early detection and intervention centres improves functioning of people in the EIPS, specific CBT was not superior to SC. One could hypothesize that additional vocational rehabilitation, case management and involvement of multidisciplinary teams are needed to further improve short-term outcome of specific interventions on this dimension.

Proton magnetic resonance spectroscopy in subjects at risk for schizophrenia.

We used proton magnetic resonance spectroscopy (1H MRS) to examine biochemical characteristics of the brain tissue in subjects at risk for schizophrenia. Nineteen participants fulfilling research criteria for an early (n=10) or a late (n=9) at-risk syndrome, 21 patients with full disease according to DSM IV and 31 healthy control subjects were included in the study. Single-voxel 1H MRS was performed in the left frontal lobe, the anterior cingulate gyrus and the left superior temporal lobe. Subjects were followed longitudinally to detect conversion to schizophrenia. We observed a significant reduction of the metabolic ratios NAA/Cr and NAA/Cho in the left frontal lobe and of NAA/Cr in the anterior cingulate gyrus in both at-risk groups and in the schizophrenic patients compared with healthy controls. Those at-risk subjects, who converted to schizophrenia within the observation period, had a higher Cho/Cr and a lower NAA/Cho ratio in the anterior cingulate gyrus compared with non-converters. NAA/Cr did not differ between converters and non-converters. Six at-risk subjects were taking antidepressants, two were taking antipsychotics. There was no difference in any metabolic ratio in any region between at-risk subjects with and without medication. We conclude that the reduction of the neuronal marker NAA in the left prefrontal lobe and the anterior cingulate gyrus may represent a vulnerability indicator for schizophrenia in at-risk subjects, while elevated Cho in the anterior cingulate gyrus may be a predictor for conversion from the prodromal state to the full disease.

Cognitive-behavioral therapy in the pre-psychotic phase: an exploratory study.

Although the efficacy of cognitive-behavioral therapy (CBT) in schizophrenia has been established for persistent psychotic symptoms, little information is available on the effects of CBT in the pre-psychotic phase. We developed a comprehensive CBT program for clients in the early initial prodromal state that showed good feasibility and promising treatment effects in an uncontrolled prospective study. The specificity of these effects needs to be explored in a controlled trial.

[Pathways to care: help-seeking behavior in first-episode psychosis]. / Wege in die Behandlung: Hilfesuchverhalten schizophrener Ersterkrankter.

Several studies on first episode schizophrenia suggest that a longer duration of untreated psychosis (DUP) results in poorer clinical outcome. The same is expected for the duration of untreated illness (DUI). It is therefore important to expose people at risk of schizophrenia to adequate treatment early on. The improvement of pathways to adequate treatment within the health care system might well be helpful. Therefore, an analysis of the pathways to care is necessary. Thus, in this present study 80 in-patients with first episode psychosis were investigated using the semi-structured interview IRAOS ("Interview for the Retrospective Assessment of the Onset of Schizophrenia") and data about the pathways to care before psychiatric admission were collected. The results indicate that patients contact on average three carers. Contact to a psychiatrist or a psychotherapist was only made two and a half years after onset of illness; general practitioners were only contacted after more than five years. However, there was a significant time lapse between first contact to psychiatrist/ psychotherapist and psychiatric admission. Only 31 % of patients sought help in the prodromal phase of the illness. Two strategies for a public campaign can be derived from these results: firstly, a public awareness campaign has to be implemented to shorten the interval from onset of illness to first help-seeking behaviour and secondly, professionals need to have more knowledge and better awareness of prodromal signs in order to reduce the time between diagnosis and adequate treatment.