First-episode Non-affective Psychosis Research Articles

Diagnosis and neurocognitive profiles in first-episode non-affective psychosis patients.

This study explored whether there are distinguishable neurocognitive profiles in diagnostic subgroups of first-episode non-affective psychosis (FEP) patients. Four hundred and eighty-seven individuals with diagnoses of non-affective psychosis disorders were evaluated 6months after first contact with psychiatric services. Individuals with schizophrenia (n=257), schizophreniform (n=141), brief psychotic disorder (n=54), and psychosis not otherwise specified (n=35) were compared on baseline neuropsychological variables using analyses of variance and covariance with potential clinical, premorbid, and sociodemographic confounders. The brief psychotic disorder subgroup was the least impaired on global cognitive function, in particular when compared to the schizophrenia subgroup, and specifically on executive function, processing speed, and motor dexterity domains. However, with the exception of the processing speed domain, profile differences could be explained by sex, age, psychotic and negative symptoms, years of education, and premorbid IQ. These results suggest processing speed as a diagnostic marker for brief psychotic disorder in FEP patients. Further, there are quantitative and qualitative differences across the schizophrenia spectrum disorders subgroups, indicating different profiles with varying degrees of deficit.

Important first encounter: Service user experience of pathways to care and early detection in first-episode psychosis.

Long duration of untreated psychosis is associated with poor clinical and functional outcomes. However, few systematic attempts have been made to reduce this delay and little is known of service users' experience of early detection efforts. We explored service users' experience of an early detection service and transition to specialized treatment service, including pathway to care, understanding of illness and barriers to adequate assessment and treatment. In-depth interviews were conducted with 10 service users (median age 21, range 18-27, five males and five females) who were diagnosed with a first-episode non-affective psychosis and who were seen by an early detection team (TOP) and currently enrolled in a specialized early intervention service for this disorder (OPUS). Stigma and fear of the 'psychiatric system' were reported as significant barriers to help seeking, while family members were seen as a crucial support. Moreover, the impact of traumatic events on the experience and development of psychosis was highlighted. Finally, participants were relieved by the prospect of receiving help and the early detection team seemed to create a trusting relationship by offering a friendly, 'anti-stigmatized' space, where long-term symptomatology could be disclosed through accurate and validating questioning. Early detection services have two important functions. One is to make accurate assessments and referrals. The other is to instil hope and trust, and to facilitate further treatment by forming an early therapeutic alliance. The findings in this study provide important insights into the way in which early detection efforts and pathways to care are experienced by service users, with direct implications for improving psychiatric services.

Early Predictors of Ten-Year Course in First-Episode Psychosis.

Identifying patients at risk of poor outcome at an early stage of illness can aid in treatment planning. This study sought to create a best-fit statistical model of known baseline and early-course risk factors to predict time in psychosis during a ten-year follow-up period after a first psychotic episode. Between 1997 and 2000, 301 patients with DSM-IV nonorganic, nonaffective first-episode psychosis were recruited consecutively from catchment area-based sectors in Norway and Denmark. Specialized mental health personnel evaluated patients at baseline, three months, and one, two, five, and ten years (N=186 at ten years). Time in psychosis was defined as time with scores ≥4 on any of the Positive and Negative Syndrome Scale items P1, P3, P5, P6, and G9. Evaluations were retrospective, based on clinical interviews and all available clinical information. During the first two years, patients were also evaluated by their clinicians at least biweekly. Baseline and early-course predictors of long-term course were identified with linear mixed-model analyses. Four variables provided significant, additive predictions of longer time in psychosis during the ten-year follow-up: deterioration in premorbid social functioning, duration of untreated psychosis (DUP) of ≥26 weeks, core schizophrenia spectrum disorder, and no remission within three months. First-episode psychosis patients should be followed carefully after the start of treatment. If symptoms do not remit within three months with adequate treatment, there is a considerable risk of a poor long-term outcome, particularly for patients with a deterioration in premorbid social functioning, a DUP of at least half a year, and a diagnosis within the core schizophrenia spectrum.

Suicidal behaviour in first-episode non-affective psychosis: Specific risk periods and stage-related factors

Suicide is a major cause of premature death in psychosis. Earlier stages have been associated with higher risk. However, such risk periods have not been specifically determined and risk factors for suicidal behaviour may change over those periods, which may have crucial implications for suicide prevention. The aim of this study was to determine and characterize the highest risk period for suicide in a representative sample of first-episode psychosis (FEP) patients. Suicidal behaviour prior to first presentation of psychosis and during a 3-year follow-up was examined in a sample of 397 individuals. Risk factors for suicidal behaviour during specific time periods were investigated and compared. The greatest suicide risk was found during the month before and 2 months after first contact with psychiatric services (i.e., ‘early’ attempts). Severity of depressive symptoms and cannabis use emerged as predominant risk factors across time. ‘Early’ attempters were characterized as being male, living in urban areas, having poor premorbid adjustment, requiring hospitalization, scoring higher on anxiety measures and unusual thought content than non-attempters. Greater suspiciousness and more severe depressive symptoms distinguished the ‘late’ attempters. In conclusion, there is a specific high risk period for suicide in FEP around the time of the first presentation. Early intervention programmes targeting phase-specific risk factors, particularly psychotic symptoms management and secondary depression prevention strategies may be useful for suicide prevention in psychosis.

Effect of DISC1 polymorphisms on the long-term course of neurocognitive deficits in non-affective psychosis

Neurocognitive deficits are core symptoms of schizophrenia that determine a poorer outcome. High variability in the progression of neuropsychological deficits in schizophrenia has been described. It is still unknown whether genetic variations can affect the course of cognitive deficits. Variations in the Disrupted in Schizophrenia 1 (DISC1) gene have previously been associated with neurocognitive deficits. This study investigated the association between 3 DISC1 polymorphisms (rs6675281 (Leu607Phe), rs1000731, and rs821616 (Ser704Cys)) and long-term (3 years) cognitive performance. One-hundred-thirty-three Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped. Cognitive function was assessed at baseline and after 3 years of initiating treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects. Patients carrying the A allele of rs1000731 exhibited a significant improvement in Working Memory and Attention domains, and the homozygosity of the A allele of rs821616 showed a significant improvement in Motor Dexterity performance over 3 years of follow-up. In conclusion, DISC1 gene variations may affect the course of cognitive deficits found in patients suffering from the first episode of non-affective psychosis.

The role of obsessive-compulsive symptoms in the perception of insincere speech in first-episode psychosis

Objectives. The aim of the present study was to investigate the effects of comorbid obsessive-compulsive symptoms (OCS) on the perception of insincere speech (e.g., sarcasm and white lies) in patients with first-episode psychosis. Design and method. Participants were 65 patients with nonaffective first-episode psychosis (FEP) and 47 healthy controls. The patient group was divided into two subgroups, those with (FEP+; n= 38) and those without OCS (FEP–; n = 27). The ability to process sarcasm and lie was assessed with the Perception of Social Inference Test (PESIT). Severity of psychotic symptoms and OCS was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), respectively. Results. Deficits in the perception of sarcasm and lie were confirmed in patients with nonaffective first-episode psychosis compared to healthy controls. In patients, comorbidity with OCS was associated with worse performance on certain aspects of insincere speech (i.e., lie) compared to FEP– patients. Y-BOCS scores correlated significantly with the perception of lying. The cognitive factor of the PANSS predicted accuracy on the perception of sincere speech, paradoxical sarcasm, and white lies, while the presence of OCS predicted accuracy on the perception of sincere speech and white lies. Conclusions. Our finding of impaired counterfactual information processing in patients with first-episode psychosis suggests that these deficits are already present at illness onset. Presence of OCS appears to have additional deleterious effects on the successful interpretation of intentional lying, further supporting that these patients are characterized by more extensive cognitive impairment.

Rate and risk factors of depressive symptoms in Chinese patients presenting with first-episode non-affective psychosis in Hong Kong

BackgroundDepressive symptoms are a distinct symptom dimension in psychotic disorders and are associated with elevated suicide risk, and poorer clinical and functional outcomes. Previous research on depressive symptoms mainly focused on chronic patients and few studies were conducted to investigate factors associated with depression in the early illness course. We aimed to examine the prevalence and risk factors of depressive symptoms, and their impacts on functioning, subjective quality of life (QoL) and self-efficacy in first-episode non-affective psychosis. MethodThree hundred fifty-one Hong Kong Chinese aged 26-55years presenting with first-episode non-affective psychosis to early intervention service were recruited. Assessments encompassing sociodemographics, premorbid adjustment, clinical and treatment profiles, functioning, QoL and perceived self-efficacy were conducted. Patients who had Calgary Depression Scale for Schizophrenia (CDSS) total score ≥6 were classified as having depressive symptoms. ResultsFifty-three (15.1%) patients exhibited depressive symptoms at entry. Depressed patients had worse functioning, poorer QoL and lower level of self-efficacy than non-depressed counterparts. Multivariate regression analysis showed that previous exposure to stressful life events, unemployment, being married, more severe positive symptoms, higher level of antipsychotic-induced Parkinsonism and negative attitude towards medication treatment were independently associated with depression status. ConclusionsDepressive symptoms were frequently observed in adult patients with first-episode nonaffective psychosis, and were linked to poor functioning and QoL. Our findings indicated that, aside from social and clinical risk factors, presence of drug-induced Parkinsonism and negative treatment attitude may render patients more vulnerable to developing depression in the early stage of psychotic illness.

Variations in Disrupted-in-Schizophrenia 1 gene modulate long-term longitudinal differences in cortical thickness in patients with a first-episode of psychosis.

Schizophrenia patients typically present a widespread bilateral cortical thinning from the early stages of the illness. However, there is controversy whether this reduction in cortical thickness (CT) is static or progressive over the evolution of the disorder. Disrupted-in-Schizophrenia 1 (DISC1) is one of the main candidates genes for schizophrenia, as it has been found associated to the illness, and to several endophenotypes of the disorder including structural brain differences. This gene is known to be involved in neurodevelopment and brain maturation processes. We therefore hypothesized that variations in this gene modulate different progressions of CT in psychosis. Seventy-nine Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs6675281 (Leu607Phe) and rs821616 (Ser704Cys) SNPs of the DISC1 gene. Brain MRIs were carried out at baseline and 3years after initiating the treatment. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects. Patients homozygous for the Leu allele of the rs6675281 SNP had a significant (p < 0.05) descend in CT over the 3-years period, while those carrying the Phe allele presented an increase in CT. When combining the two SNPs we found a synergic effect on CT progression, presenting those patients homozygous for Leu607 +Ser704 a more pronounced cortical thinning. In conclusion, DISC1 gene variations may modulate the longitudinal changes in cortical thickness in patients suffering from a first episode of non-affective psychosis.

Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis

BackgroundReviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk of psychosis have not been consistently found. The current study aimed to explore adversity specificity and dose-response effects of adversities on risk of psychosis. MethodParticipants were 101 persons with first-episode psychosis (FEP) diagnosed with ICD-10 F20 – F29 (except F21) and 101 non-clinical control persons matched by gender, age and parents' socio-economic status. Assessment included the Childhood Trauma Questionnaire and parts of the Childhood Experience of Care and Abuse Questionnaire. ResultsEighty-nine percent of the FEP group reported one or more adversities compared to 37% of the control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all p<0.01). The risk of psychosis increased two and a half times for each additional adversity. All associations between specific adversities and psychosis decreased when they were adjusted for other adversities. ConclusionOur findings suggest that there is a large shared effect of adversities on the risk of psychosis. Contrary to the call for further research into specific adversities, we suggest a search for mechanisms in the shared effects of traumatization. Clinical implications are thorough assessment of adversities and their possible effects.

Progressive Structural Brain Changes and NRG1 Gene Variants in First-Episode Nonaffective Psychosis

Background: Structural brain abnormalities are already present during the early phases of psychosis, but factors underlying brain volume changes are still not well understood. The neuregulin 1 gene (NRG1), influencing neurodevelopment and neuroplasticity, has been associated with schizophrenia. Our aim was to examine whether variations in the NRG1 gene (SNP8NRG221132, SNP8NRG6221533 and SNP8NRG243177 polymorphisms) influence longitudinal changes in the brain during a first episode of psychosis (FEP). Methods: A 3-year follow-up magnetic resonance imaging (MRI) study was performed. Fifty-nine minimally medicated patients who were experiencing FEP and 14 healthy control individuals underwent genotyping and structural brain MRI at baseline and at 1- and 3-year follow-up. A comparison of brain volumes, gray matter, white matter (WM), lateral ventricles (LV), cortical cerebrospinal fluid, and thalamus and caudate was made between the groups according to their genotype. Results: In patients, the SNP8NRG6221533 risk C allele was significantly associated with increased LV volume across time. C allele carriers had significantly less WM compared with subjects homozygous for the T allele after the follow-up. No other significant differences were observed among subgroups. No significant changes according to the genotypes were found in healthy individuals. Conclusion: Our findings suggest that variations of neurodevelopment-related genes, such as the NRG1 gene, can contribute to brain abnormalities described in early phases of schizophrenia and progressive changes during the initial years of the illness. To our knowledge, it is the first time that a relation between NRG1 polymorphisms and longitudinal brain changes is reported.

Dysbindin gene variability is associated with cognitive abnormalities in first-episode non-affective psychosis

Introduction. Dystrobrevin-binding protein 1 gene (dysbindin or DTNBP1) has been associated with schizophrenia and cognitive performance. Its expression in areas implicated in cognition such as the dorsolateral prefrontal cortex, as well as its role in dopaminergic and glutamatergic system, has been replicated by several studies. The main aim of this study was to examine the association between DTNBP1 variability and cognitive performance in a sample of 238 patients with a first episode of a non-affective psychosis.Methods. Patients, and a comparison sample of 47 healthy subjects, completed an extensive neuropsychological battery. Five single nucleotide polymorphisms (SNPs) within DTNBP1 (rs2619528, rs2619538, rs3213207, rs2619539 and rs760761) and three haplotypes (GACAC, GAGAC and GTGAC) were analysed.Results. In the group of patients, we found a significant association between two of the DTNBP1 SNPs and one of the haplotypes (rs2619539, rs3213207 and GACAC) and a measure of premorbid IQ [Wechsler Adult Intelligence Scale-3rd Edition (WAIS-III) Vocabulary subtest]. Moreover, one of these SNPs, rs2619539, was also associated with our measure of working memory (WAIS-III Backward digits subtest) and two haplotypes, GAGAC and GTGAC, with our measure of verbal memory (Rey Auditory Verbal Learning Test), of visual memory (Rey Complex Figure Test) in the case of GAGAC, and of speed of processing (WAIS-III Digit Symbol-coding) in the case of GTGAC.Conclusions. Our findings add further evidence suggesting an association between dysbindin gene variability and cognitive abnormalities in schizophrenia, providing preliminary evidence of this association since the time of illness onset among minimally medicated patients.

Emotional perception and theory of mind in first episode psychosis: The role of obsessive–compulsive symptomatology

The aim of the present study was to investigate the effects of comorbid obsessive–compulsive symptoms on emotional perception and theory of mind (ToM) in patients with first-episode psychosis. Participants were 65 patients with non-affective first episode psychosis (FEP) and 47 healthy controls. The patient group was divided into two subgroups, those with (FEP+; n=38) and those without obsessive–compulsive symptomatology (FEP−; n=27). Emotion perception and ToM were assessed with the Perception of Social Inference Test. Severity of psychotic and obsessive–compulsive symptoms was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Yale-Brown Obsessive–Compulsive Scale (Y-BOCS), respectively. Deficits in emotion recognition and theory of mind were confirmed in patients with non-affective first-episode psychosis compared to healthy controls. In patients, comorbidity with obsessive–compulsive symptoms was associated with worse performance on certain aspects of social cognition (ToM 2nd order) compared to FEP− patients. Our findings of impaired emotion perception and ToM in patients with first-episode psychosis support the hypothesis that deficits are already present at illness onset. Presence of OCS appears to have further deleterious effects on social cognition, suggesting that these patients may belong to a schizo-obsessive subtype of schizophrenia characterized by more extensive neurobiological impairment.

Psychotic symptoms, cognition and affect as predictors of psychosocial problems and functional change in first-episode psychosis

ObjectiveTo enable further understanding of how cognitive deficits and psychopathology impact psychosocial functioning in first-episode psychosis patients, we investigated how psychopathology and cognitive deficits are associated with psychosocial problems at baseline, and how these predict psychosocial functioning at 12months follow-up. Also, we tested whether the effect of baseline psychopathology on psychosocial functioning decreases between baseline and 12months and the effect of baseline cognition increases. MethodsEight neurocognitive and four social cognitive subdomains and psychopathology (positive and negative symptoms, depression and anxiety) were assessed at baseline in 153 non-affective first-episode psychosis (FEP) patients. Psychosocial functioning (work/study, relationships, self-care, disturbing behavior and general psychosocial functioning) was assessed at baseline and 12months. Spearman correlations were examined and backward regression models were computed to test our hypotheses. ResultsAt baseline, psychosocial functioning was associated strongest with positive and negative symptoms of all assessed clinical domains, followed by neurocognition and social cognition. In contrast, psychosocial functioning at 12months was not predicted by psychotic symptoms, but rather by neurocognition, social cognition and depression. Change in social functioning in the first 12months after baseline was predicted by positive and negative symptoms, but to a similar degree by neurocognition and social cognition. ConclusionsWhereas psychotic symptoms show marked impact on psychosocial functioning at illness onset, cognitive deficits appear to be more accurate longitudinal predictors of psychosocial problems and functional recovery in the early course of psychosis.

CLINICAL AND IMAGING PREDICTION OF SCHIZOPHRENIA IN PEOPLE AT HIGH FAMILIAL RISK

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

COMBINING EXERCISE AND COGNITIVE REMEDIATION

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

DYSGLYCEMIC SIGNALS IN CHILDREN AND ADOLESCENTS TREATED WITH ANTIPSYCHOTICS FOR THE FIRST TIME

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

OUTCOME IN SUBJECTS AT ULTRA HIGH RISK OF PSYCHOSIS: RELATIONSHIP TO DOPAMINERGIC FUNCTION

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

DOPAMINE-1 RECEPTOR STIMULATION IN SCHIZOPHRENIA: A RANDOMIZED, CLINICAL TRIAL

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

DEBATE: ATTENUATED PSYCHOSIS SYNDROME: A NEW DIAGNOSTIC CLASS IS NEEDED

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.

BEHAVIORAL AND IMAGING TRANSLASTIONAL PARADIGMS IN DRUG DEVELOPMENT

The large majority of individuals with a first episode of schizophrenia will experience a remission of symptoms within their first year of treatment. It is not clear how long treatment with antipsychotic medications should be continued in this situation. The possibility that a percentage of patients may not require ongoing treatment and may be unnecessarily exposed to the long-term risks of antipsychotic medications has led to the development of a number of studies to address this question. We carried out a systematic review to determine the risk of experiencing a recurrence of psychotic symptoms in individuals who have discontinued antipsychotic medications after achieving symptomatic remission from a first episode of non-affective psychosis (FEP). Six studies were identified that met our criteria and these reported a weighted mean one-year recurrence rate of 77% following discontinuation of antipsychotic medication. By two years, the risk of recurrence had increased to over 90%. By comparison, we estimated the one-year recurrence rate for patients who continued antipsychotic medication to be 3%. These findings suggest that in the absence of uncertainty about the diagnosis or concerns about the contribution of medication side effects to problems with health or functioning, a trial off of antipsychotic medications is associated with a very high risk of symptom recurrence and should thus not be recommended.