Sustained specialized and family treatment in first-episode schizophrenia or related disorders: a 5-year randomized controlled trial.

BACKGROUND: The long-term outcome of first-episode schizophrenia needs improvement. Here, we evaluate the effectiveness of 5 years sustained specialist treatment (ST), ST including Parent groups (ST + P) or treatment as usual (TAU) on psychotic relapse and social functioning. METHODS: A three condition randomized, parallel assigned, single-blind efficacy trial, in which 198 first-episode psychosis (FEP) patients aged 15-28 years were included. The effect on time to first relapse, first relapse rates, mean number of relapses per patient, and time to the improvement of social functioning were analyzed using Cox regression or ANOVA. RESULTS: We found no significant differences between treatment conditions in the ITT analysis concerning time to first relapse, nor first relapse rate. Mean number of relapses per patient differed at a trend level between ST, ST + P or TAU conditions, respectively: 0.72; 0.62 or 1.02 (p = 0.069). No evidence was found for differential effect of treatment conditions on social functioning. CONCLUSION: Five years sustained ST of FEP nor addition of parent groups increased time to first relapse or reduced first relapse rate, compared to sustained TAU. Indications for favorable effects of parent groups were found on relapses per patient.

Depression predicts persistence of paranoia in clinical high-risk patients to psychosis: results of the EPOS project.

BACKGROUND: The link between depression and paranoia has long been discussed in psychiatric literature. Because the causality of this association is difficult to study in patients with full-blown psychosis, we aimed to investigate how clinical depression relates to the presence and occurrence of paranoid symptoms in clinical high-risk (CHR) patients. METHODS: In all, 245 young help-seeking CHR patients were assessed for suspiciousness and paranoid symptoms with the structured interview for prodromal syndromes at baseline, 9- and 18-month follow-up. At baseline, clinical diagnoses were assessed by the Structured Clinical Interview for DSM-IV, childhood adversities by the Trauma and Distress Scale, trait-like suspiciousness by the Schizotypal Personality Questionnaire, and anxiety and depressiveness by the Positive and Negative Syndrome Scale. RESULTS: At baseline, 54.3% of CHR patients reported at least moderate paranoid symptoms. At 9- and 18-month follow-ups, the corresponding figures were 28.3 and 24.4%. Depressive, obsessive-compulsive and somatoform disorders, emotional and sexual abuse, and anxiety and suspiciousness associated with paranoid symptoms. In multivariate modelling, depressive and obsessive-compulsive disorders, sexual abuse, and anxiety predicted persistence of paranoid symptoms. CONCLUSION: Depressive disorder was one of the major clinical factors predicting persistence of paranoid symptoms in CHR patients. In addition, obsessive-compulsive disorder, childhood sexual abuse, and anxiety associated with paranoia. Effective pharmacological and psychotherapeutic treatment of these disorders and anxiety may reduce paranoid symptoms in CHR patients.

The distribution of self-reported psychotic-like experiences in non-psychotic help-seeking mental health patients in the general population; a factor mixture analysis.

PURPOSE: Factor mixture analysis (FMA) and item response mixture models in the general population have shown that the psychosis phenotype has four classes. This study attempted to replicate this finding in help-seeking people accessing mental health services for symptoms of non-psychotic mental disorders. METHODS: All patients (18-35 years old) referred for non-psychotic mental health problems to the secondary mental healthcare service in The Hague between February 2008 to February 2010 (N = 3,694), were included. Patients completed the Prodromal Questionnaire (PQ). Hybrid latent class analysis was applied to explore the number, size and symptom profiles of the classes. RESULTS: The FMA resulted in four classes. Class 1 (N = 1,039, 28.1%) scored high on conceptual disorganization, inattention and mood disorder. Patients in Class 2 (N = 619, 16.8%) endorsed almost all PQ-items, were more often screened as being psychotic or at high risk of developing psychosis, without care takers noticing. In Class 3 (N = 1,747, 47.3%) perplexity, paranoia and negative symptoms were more prevalent. Patients were more often at high risk of developing psychosis. Class 4 (N = 286, 7.7%) represented the 'normative' group with low probabilities for all items. DISCUSSION: The results support the hypothesis that a representation in four classes of psychotic-like experiences can also be applied in a help-seeking population.

Psychosocial outcome in patients at clinical high risk of psychosis: a prospective follow-up.

PURPOSE: In patients at clinical high risk (CHR) of psychosis, transition to psychosis has been the focus of recent studies. Their broader outcome has received less attention. We studied psychosocial state and outcome in CHR patients. METHODS: In the European Prediction of Psychosis Study, 244 young help-seeking CHR patients were assessed with the Strauss and Carpenter Prognostic Scale (SCPS) at baseline, and 149 (61.1%) of them were assessed for the second time at the 18-month follow-up. The followed patients were classified into poor and good outcome groups. RESULTS: Female gender, ever-married/cohabitating relationship, and good working/studying situation were associated with good baseline SCPS scores. During follow-up, patients' SCPS scores improved significantly. Good follow-up SCPS scores were predicted by higher level of education, good working/studying status at baseline, and white ethnicity. One-third of the followed CHR patients had poor global outcome. Poor working/studying situation and lower level of education were associated with poor global outcome. Transition to psychosis was associated with baseline, but not with follow-up SCPS scores or with global outcome. CONCLUSION: The majority of CHR patients experience good short-term recovery, but one-third have poor psychosocial outcome. Good working situation is the major indicator of good outcome, while low level of education and non-white ethnicity seem to be associated with poor outcome. Transition to psychosis has little effect on psychosocial outcome in CHR patients. In treating CHR patients, clinicians should focus their attention on a broader outcome, and not only on preventing transition to psychosis.

COMT Val(158) met genotype and striatal D(2/3) receptor binding in adults with 22q11 deletion syndrome.

Although catechol-O-methyltransferase (COMT) activity evidently affects dopamine function in prefrontal cortex, the contribution is assumed less significant in striatum. We studied whether a functional polymorphism in the COMT gene (Val(158) Met) influences striatal D(2/3) R binding ratios (D(2/3) R BP(ND) ) in 15 adults with 22q11 deletion syndrome and hemizygous for this gene, using single photon emission computed tomography and the selective D(2/3) radioligand [(123) I]IBZM. Met hemizygotes had significantly lower mean D(2/3) R BPND than Val hemizygotes. These preliminary data suggest that low COMT activity may affect dopamine levels in striatum in humans and this may have implications for understanding the contribution of COMT activity to psychiatric disorders.

Semantic fluency deficits and reduced grey matter before transition to psychosis: a voxelwise correlational analysis.

Early identification of subjects with an increased risk of psychosis is necessary to develop interventions to delay or prevent disease onset. We recently reported that decreased semantic verbal fluency performance in ultra high risk (UHR) subjects predicts the development of psychosis (Becker et al., 2010). The present study investigated whether semantic and verbal fluency scores correlate with grey matter density in UHR subjects. Thirty-seven UHR subjects underwent structural MRI scanning and verbal fluency assessment after which they were followed up for 2 years. Using voxel-based morphometry, we investigated whether grey matter density correlated with verbal fluency scores in 10 UHR subjects who developed psychosis during follow-up and 27 UHR subjects who did not develop psychosis. In UHR subjects developing psychosis, lower semantic fluency scores correlated significantly with reduced grey matter density in the right superior and middle temporal gyrus, the right insula, and the left anterior cingulate cortex. This study shows that a correlation between semantic fluency performance and grey matter density in task-related areas can differentiate between UHR subjects who subsequently will develop psychosis and those who will not. Combining these two measures could improve psychosis prediction in UHR subjects.

Social disability at admission for a first psychosis does not predict clinical outcome at 5-year follow-up.

Although it has often been reported that premorbid social deficits are associated with clinical outcome in schizophrenia, the association between clinical outcome and social disabilities during admission for a first psychosis is still unclear. We examined whether a detailed assessment of social disability (assessed using the Groninger Social Disabilities Schedule-II) in the month before admission for a first psychotic episode contributed to the prediction of disease outcome in terms of psychopathology in 82 patients with schizophrenia. After controlling for the Positive and Negative Syndrome Scale sum score at baseline, none of the social disability domains significantly predicted the number of relapses or the severity of clinical symptoms at a 5-year follow-up. Our results suggest that poor social functioning at admission does not necessarily predict poor disease outcome. Following Di Michele and Bolino (Psychopathology 37:98-104, 2004), we hypothesize that, to reliably predict the course of schizophrenia, it may be necessary to assess social functioning during clinical stabilization.

Obsessive-compulsive symptoms in first episode psychosis and in subjects at ultra high risk for developing psychosis; onset and relationship to psychotic symptoms.

OBJECTIVE: To determine the prevalence of obsessive-compulsive symptoms and obsessive-compulsive disorder in patients with schizophrenia or related disorders or subjects at ultra high risk for development of psychosis. Secondly, to determine the time of occurrence of obsessive-compulsive symptoms related to the onset of first psychosis. METHOD: We collected data on all patients who were referred consecutively to our specialized clinic for first episode psychosis patients and ultra high risk subjects in Amsterdam between 1 July 2006 and 1 July 2008. Diagnosis of psychotic disorders was established using the Comprehensive Assessment of Symptoms and History schedule. Obsessions and compulsions were defined in accordance with DSM-III-R criteria and assessed by clinicians. We analyzed the onset of obsessive-compulsive symptoms and its relation to the onset of first episode psychosis. RESULTS: When a strict definition of obsessive-compulsive symptoms is used, 9.3% (n = 18) of patients with schizophrenia or a related disorder exhibited obsessive-compulsive symptoms and 1.5% also met criteria for obsessive-compulsive disorder. The onset of obsessive-compulsive symptoms occurred before, concurrent with and after onset of first episode psychosis in the following proportion of patients: 7/18, 3/18, 8/18. We found a prevalence of 20.7% of obsessive-compulsive symptoms in ultra high risk subjects. CONCLUSION: Using a strict definition of obsessive-compulsive symptoms, we found relatively low prevalence rates of obsessive-compulsive symptoms and obsessive-compulsive disorder in patients with schizophrenia or related disorders; the rates are even lower than known rates of obsessive-compulsive symptoms and obsessive-compulsive disorder in the general population. Obsessive-compulsive symptoms rates in ultra high risk subjects are comparable to those in the general population. Further investigation of the predictive validity of obsessive-compulsive symptoms in ultra high risk subjects for developing psychosis is needed. Obsessive-compulsive symptoms either develop prior, during or after the onset of first episode psychosis.

Factor analysis of the scale of prodromal symptoms: differentiating between negative and depression symptoms.

BACKGROUND: This study examines the ability of the Scale of Prodromal Symptoms (SOPS) to differentiate between negative and depression symptoms in a young help-seeking ultrahigh risk (UHR) group. METHODS: SOPS data of 77 help-seeking patients at UHR for psychosis were analyzed with an exploratory factor analysis. The extracted Depression factor was validated with the Beck Depression Inventory (BDI). The extracted SOPS Negative symptoms factor was validated with the Negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS). RESULTS: Four factors were extracted from the SOPS: a negative, depression, disorganized and positive factor. The Negative symptom factor consisted of three items (N1: social anhedonia and withdrawal, N3: decreased expression of emotion; N4: decreased experience of emotions and self), and could be validated with the PANSS Negative symptoms subscale. The Depression factor was also made up of three items (G2: dysphoric mood, G4: impaired tolerance to normal stress, and D4: personal hygiene/social attentiveness), and could be validated with the BDI. CONCLUSIONS: Our results suggest that 3 items of the Negative symptoms subscale of the SOPS, 2 items of the General and 1 item of the Disorganization subscale differentiate validly between negative and depression symptoms in an UHR population.

Disability in people clinically at high risk of psychosis.

BACKGROUND: Decline in social functioning occurs in individuals who later develop psychosis. AIMS: To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition. METHOD: Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS-II). RESULTS: At baseline, the transition group displayed significantly greater difficulties in making new friends (z = -3.40, P = 0.001), maintaining a friendship (z =-3.00, P = 0.003), dealing with people they do not know (z =-2.28, P = 0.023) and joining community activities (z =-2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (ß = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238-2.550). CONCLUSIONS: Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

Cannabis use and callosal white matter structure and integrity in recent-onset schizophrenia.

Adolescent-onset cannabis use, compared with adult-onset use, has been associated with a higher risk for developing symptoms of schizophrenia-like psychotic disorders. To test the hypothesis that onset of cannabis use in early adolescence in male schizophrenia patients is associated with abnormalities in white matter structure and integrity, we used high resolution structural and diffusion tensor brain images to compare three groups of patients: those who started regular use of cannabis (1) before the age of 15 years (early-onset cannabis users, n = 10) or (2) at the age of 17 years or later (late-onset cannabis users, n = 8), and (3) those who were cannabis naïve (n = 8). To verify patient findings, we also compared white matter integrity of the three patient groups with that of a healthy control group (n = 10). Cannabis naïve patients showed reduced white matter density and reduced fractional anisotropy, an indicator for white matter integrity, in the splenium of the corpus callosum compared with patients with early-onset cannabis use. In the same brain area, cannabis naïve patients showed reduced fractional anisotropy compared with healthy controls. Our results suggest that the age of onset of cannabis use is not an identifying characteristic for white matter abnormalities in schizophrenia patients; however, our results might indicate a more vulnerable brain structure in cannabis naïve schizophrenia patients.

White matter connectivity and psychosis in ultra-high-risk subjects: a diffusion tensor fiber tracking study.

This study assessed with diffusion tensor imaging (DTI) whether ultra-high-risk subjects who later develop a psychotic disorder (UHR-P) show abnormalities in association white matter fiber tracts as compared to UHR subjects who do not convert to psychosis (UHR-NP) and healthy controls. Participants comprised 17 male UHR subjects and 10 male healthy controls, who received baseline DTI scans before clinical follow-up. The uncinate and arcuate fasciculi, anterior and dorsal cingulate, and subdivisions of the corpus callosum were calculated and visualized, and tract-specific measurements were performed. At 24-month follow-up seven UHR subjects had developed a first psychotic episode. Fractional anisotropy in baseline DTI scans, including left-right asymmetry measures, did not differ between the groups. Thus, DTI measures of these association white matter tracts were not biological markers of psychosis in our UHR sample. Abnormalities of these fiber tracts may develop around or after onset of psychosis. However, further DTI studies in UHR subjects are needed in larger samples.

Age of onset of cannabis use is associated with age of onset of high-risk symptoms for psychosis.

OBJECTIVE: Increasing interest in the prodromal stage of schizophrenia over the past decade led us to perform our study to monitor people at high risk for developing a psychosis. We hypothesized that cannabis use or a cannabis use disorder at a younger age relates to high-risk symptoms at a younger age. METHOD: People referred to the Academic Medical Centre in Amsterdam, the Netherlands, with an ultra-high risk (UHR) for psychosis were interviewed with the Composite International Diagnostic Interview to assess their cannabis consumption. The Interview for the Retrospective Assessment of the Onset of Schizophrenia was used to collect data about age of onset of high-risk or prodromal symptoms. Nine high-risk symptoms were selected and clustered because of their known relation with cannabis use. RESULTS: Among the 68 included participants, 35 had used cannabis (51.5%), of whom 15 had used recently. Twenty-two participants had been cannabis abusers or cannabis-dependent (32.4%) in the past. Younger age at onset of cannabis use was related to younger age of onset of the cluster of symptoms (rho = 0.48, P = 0.003) and also to 6 symptoms individually (rho = 0.47 to 0.90, P < 0.001 to 0.04). Younger age at onset of a cannabis use disorder was related to younger age of onset of the cluster of symptoms (rho = 0.67, P = 0.001) and also to 6 symptoms individually (rho = 0.50 to 0.93, P = 0.007 to 0.03). CONCLUSION: Cannabis use or a cannabis use disorder at a younger age in a group with an UHR for transition to psychosis is related to onset of high-risk symptoms for psychosis at a younger age.

Symptomatology and neuropsychological functioning in cannabis using subjects at ultra-high risk for developing psychosis and healthy controls.

OBJECTIVE: The relationship between cannabis use and psychosis has been studied intensively. Few data, however, are available on the relationship between cannabis use, ultra-high risk for developing psychosis and neurocognition. The aim of the present cross-sectional study was therefore to investigate the relationship between cannabis use, ultra-high-risk (UHR) symptoms and cognitive functioning in UHR patients and healthy controls. METHODS: A total of 63 ultra-high-risk patients (34 cannabis users) and 58 control subjects (28 cannabis users) were assessed with clinical measures and a neuropsychological test battery. Patients were eligible for the study if they were between the ages of 12 and 35 years and if they fell into one or more of the following inclusion groups: familial risk and reduced functioning, attenuated psychotic symptoms, brief limited intermittent psychotic symptoms and basic symptoms. Control subjects were eligible for the study if they were between the ages 12 and 35, had no present or past psychiatric illness, no family history of psychiatric illness, no drug use in the non-cannabis-using group, and use of at least four joints per week in the cannabis-using control group. RESULTS: In the UHR and the control group, cannabis users experienced more basic symptoms and UHR symptoms than the non-cannabis users. Moreover, cannabis users in the control group performed at the level of the UHR subjects on a test of verbal memory and verbal fluency. Frequency of cannabis use correlated with severity of several UHR symptoms. CONCLUSIONS: Cannabis-using UHR patients have more basic symptoms than non-using patients. In addition, healthy cannabis users have more subclinical UHR and basic symptoms and more neuropsychological dysfunctions than non-cannabis users. More frequent cannabis use was related to increased severity of certain UHR symptoms.

Baseline differences in clinical symptomatology between ultra high risk subjects with and without a transition to psychosis.

BACKGROUND: The chance of transition to psychosis in patients at Ultra High Risk for developing psychosis (UHR) is 10-15%. The aim of present study was to investigate differences in baseline clinical symptomatology, general level of functioning (GAF-score) and genetic risk between UHR patients who did (UHR+T) or did not (UHR+NT) make a transition to psychosis. Sharpening UHR inclusion criteria may aid in improving prediction of transition to psychosis. METHOD: The study sample was taken from 285 patients who were examined within the Dutch Prediction of Psychosis Study (DUPS) at the Academic Medical Center of the University of Amsterdam, the Netherlands. Out of 73 included UHR subjects, 18 made a transition to psychosis. Psychopathology was investigated with the Structured Interview for Prodromal Syndromes, Bonn Scale for the Assessment of Basic Symptoms and GAF-score. The follow-up period of the study was three years. RESULTS: The UHR+T group showed more social anhedonia and withdrawal, more bizarre thinking and a lower GAF score at baseline than the UHR+NT group. CONCLUSIONS: In agreement with the results of Cannon et al. [Cannon, T.D., Cadenhead, K., Cornblatt, B., Woods, S.W., Addington, J., Walker, E., Seidman, L.J., Perkins, D., Tsuang, M., McGlashan, T., Heinssen, R., 2008. Prediction of Psychosis in Youth at High Clinical Risk: A Multisite Longitudinal Study in North America. Arch. Gen. Psychiat. 65 (1) 28-37.], our study indicates that severity of specific symptoms at baseline is related to transition to psychosis in UHR subjects. These findings may contribute to a more accurate prediction of a first psychotic episode. Furthermore, symptoms that are increased at baseline in the UHR+T group could be a focus of cognitive behavioural therapy in the UHR period.

Subjective effects of cannabis before the first psychotic episode.

OBJECTIVE: The aim of the present study was to gain more insight into the positive and negative effects of cannabis in the prodromal phase of schizophrenia and in the ultra-high-risk (UHR) state for psychosis. METHOD: A theory-driven questionnaire was used to examine subjective effects in the prodromal phase in male subjects with a recent onset of schizophrenia or related disorder (n = 52) and in the UHR state in help-seeking male subjects screened for being at UHR for psychosis (n = 17); both groups were compared to cannabis-using controls from the general population (n=52). RESULTS: Recent-onset patients and UHR subjects reported feeling more anxious, depressed and suspicious immediately after cannabis use. Some patients also reported feeling less depressed after cannabis use. Recent-onset patients reported increased visual and acoustic hallucinations, and confusion after cannabis use. Of the recent-onset patients 37% reported that their very first psychotic symptoms occurred during cannabis intoxication. Long-term effects of cannabis reported more often by both patient groups were depression, less control over thoughts and social problems. CONCLUSIONS: These results suggest that schizophrenia patients in the prodromal phase and subjects at UHR for psychosis are more sensitive to some negative effects of cannabis, in particular psychotic effects, compared to cannabis users from the general population. Although limited by the retrospective design in the recent-onset patients, the present study adds qualitative evidence to longitudinal studies that suggest that cannabis is a component cause in the onset of the first psychotic episode. Further studies are needed on the objective and subjective effects of cannabis in UHR subjects.

Perceived negative attitude of others as an early sign of psychosis.

AIM: Risk of psychosis is defined by the presence of positive psychotic-like symptoms, by subtle self-perceived cognitive and perceptual deficiencies, or by decreased functioning with familial risk of psychosis. We studied the associations of psychiatric outpatients' self-reported functioning and interpersonal relationships with vulnerability to and risk of psychosis. METHODS: A total of 790 young patients attending psychiatric outpatient care completed the PROD screen [Heinimaa M, Salokangas RKR, Ristkari T, Plathin M, Huttunen J, Ilonen T, et al. PROD-screen - a screen for prodromal symptoms of psychosis. Int J Meth Psychiatr Res 2003;12:92-04.], including questions on functioning, interpersonal relationships and subtle specific (psychotic-like) and non-specific symptoms. Vulnerability to psychosis was assessed employing the patient's written descriptions of specific symptoms. Of the patients vulnerable to psychosis, those at current risk of psychosis were assessed using the Bonn Scale for Assessment of Basic Symptoms [Schultze-Lutter F, Klosterkötter J. Bonn scale for assessment of basic symptoms - prediction list, BSABS-P. Cologne: University of Cologne; 2002] and the Structured Interview for Positive symptoms [Miller TJ, McGlashan TH, Rosen JL, Somjee L, Markovich PJ, Stein K, et al. Prospective diagnosis of the initial prodrome for schizophrenia based on the structured interview for prodromal syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 2002;159:863-65.]. RESULTS: In all, 219 patients vulnerable to and 55 patients at current risk of psychosis were identified. Vulnerability to psychosis was associated with all items of functioning and interpersonal relationships. Current risk of psychosis, however, was associated only with the subjectively reported negative attitude of others. Negative attitude of others was also associated with feelings of reference at both vulnerability and risk levels. CONCLUSION: The subjective experience of negative attitude of others towards oneself may be an early indicator of psychotic development.

Childhood adversity predicts persistence of suicidal thoughts differently in females and males at clinical high-risk patients of psychosis. Results of the EPOS project.

AIM: Depression and suicidal ideation (SUI) and behaviour are more prevalent in females than males, and common in clinical high-risk (CHR) patients. Childhood adversities and trauma (CAT) are associated with adult depression and SUI. The role of gender as a moderator and depression as a mediator for the effect of CAT on SUI has not been explored in CHR patients. METHODS: In all, 245 young help-seeking CHR patients were assessed for SUI (thoughts of killing themselves) with the Beck Depression Inventory at baseline, 9-month and 18-month follow-ups. At baseline, clinical depression was assessed by the Structured Clinical Interview for DSM-IV (SCID-I), and CAT by the Trauma and Distress Scale (TADS) which includes the five domains of emotional, physical and sexual abuse, emotional and physical neglect. RESULTS: CAT total and all domains except physical neglect predicted SUI over the study period. The effect of CAT on SUI was mediated via clinical depression and concurrent depression symptoms differently for females and males. In females, the effect of emotional abuse and neglect on SUI was mediated via baseline depression. In males, emotional and physical abuse had a direct effect on SUI, and the effect of sexual abuse and emotional neglect was partly mediated via concurrent depression symptoms. CONCLUSIONS: For CHR females, the effect of CAT on adult SUI is mediated via depression, while for males, CAT and its domains have mainly direct effects in maintaining SUI. These gender differences should be taken into account when treating CHR patients with SUI.

Disrupted dopaminergic neurotransmission in 22q11 deletion syndrome.

22q11 Deletion syndrome (22q11DS) is associated with chromosome 22q11 microdeletions and high rates of psychiatric disorders. Susceptibility for these disorders could be explained by haploinsufficiency of the catechol-O-methyltransferase gene, which encodes an enzyme involved in dopamine (DA) breakdown. It is unknown how dopaminergic neurotransmission is affected in people with 22q11DS. To date, there have been no controlled studies investigating dopaminergic neurotransmission in people with 22q11DS. We report the results of a challenge study in high-functioning adults with 22q11DS and age- and gender-matched controls using neuro-endocrine and peripheral dopaminergic markers. At baseline, 22q11DS subjects compared to controls had higher urine DA levels and lower plasma levels of the predominant DA metabolite homovanillic acid (HVA). Following DA depletion, 22q11DS subjects showed lower urine and plasma HVA levels and a lower prolactin response than controls. The ratio of DA/HVA, a rough index of DA turnover, was significantly higher in the 22q11DS subjects at baseline and after DA depletion. Our results suggest that adults with 22q11DS have disrupted dopaminergic neurotransmission, which might explain their susceptibility for psychiatric disorders.

White matter fibertracking in first-episode schizophrenia, schizoaffective patients and subjects at ultra-high risk of psychosis.

There is increasing evidence of white matter pathology in schizophrenia. The aim of this study was to examine whether white matter abnormalities found with diffusion tensor imaging (DTI) in previous schizophrenia studies are present in the early phase of the illness. DTI was performed at 3 T on 10 male patients with a first (n = 8) or second (n = 2) psychotic episode of schizophrenia or schizoaffective disorder, 10 male patients at ultra-high risk of psychosis with (pre)psychotic symptoms and 10 healthy controls. Fibertracts found to be abnormal in other DTI studies (uncinate and arcuate fasciculus, anterior and dorsal cingulum, subdivisions of the corpus callosum) were calculated and visualized; tract-specific measurements (fractional anisotropy and trace) were performed. No differences were found between the healthy subjects and the 2 patient groups. These preliminary findings suggest that there is no white matter pathology of these association tracts detectable with DTI in the early stages of schizophrenic illness in males. Our findings are in contrast with DTI abnormalities found in some other first-episode studies. This discrepancy in findings may be related to differences in subject characteristics and DTI methodology. Possible effects of age, gender, level of education and illicit substance use on DTI findings in schizophrenia are discussed.