Antidepressant, antipsychotic and psychological interventions in subjects at high clinical risk for psychosis: OASIS 6-year naturalistic study.

BACKGROUND: Recent randomized controlled trials suggest some efficacy for focused interventions in subjects at high risk (HR) for psychosis. However, treating HR subjects within the real-world setting of prodromal services is hindered by several practical problems that can significantly make an impact on the effect of focused interventions. METHOD: All subjects referred to Outreach and Support in South London (OASIS) and diagnosed with a HR state in the period 2001-2012 were included (n = 258). Exposure to focused interventions was correlated with sociodemographic and clinical characteristics at baseline. Their association with longitudinal clinical and functional outcomes was addressed at follow-up. RESULTS: In a mean follow-up time of 6 years (s.d. = 2.5 years) a transition risk of 18% was observed. Of the sample, 33% were treated with cognitive behavioural therapy (CBT) only; 17% of subjects received antipsychotics (APs) in addition to CBT sessions. Another 17% of subjects were prescribed with antidepressants (ADs) in addition to CBT. Of the sample, 20% were exposed to a combination of interventions. Focused interventions had a significant relationship with transition to psychosis. The CBT + AD intervention was associated with a reduced risk of transition to psychosis, as compared with the CBT + AP intervention (hazards ratio = 0.129, 95% confidence interval 0.030-0.565, p = 0.007). CONCLUSIONS: There were differential associations with transition outcome for AD v. AP interventions in addition to CBT in HR subjects. These effects were not secondary to baseline differences in symptom severity.

Are we really mapping psychosis risk? Neuroanatomical signature of affective disorders in subjects at ultra high risk.

BACKGROUND: The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown. METHOD: We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses. RESULTS: The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive-compulsive disorder symptoms. CONCLUSIONS: Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state.

The development of the Early Intervention in Psychosis (EIP) outpatient unit of Eginition University Hospital into an EIP Network.

Over the past 25 years, in the field of psychosis there is an increased interest in early detection of symptoms and treatment provision for people who are either at Ultra High Risk (UHR) of developing psychosis or with First Episode Psychosis (FEP). Extensive research has proved, that by engaging quickly into treatment and addressing the needs of each case individually, clinical outcomes could be improved substantially. The above evidence-based argument has resulted in the establishment of specialized Early Intervention in Psychosis (EIP) services worldwide. Eginition University Hospital (EUH) in Athens has been providing care for Early Psychosis through a specialized outpatient EIP service since 2012, which receives all early psychosis cases. Initially clinical focus was mainly directed towards UHR cases, since EUH had long been providing standard care for FEP. However, over the last 4 years, the EIP Unit has evolved incrementally into a network of directly linked services, involving the EIP outpatient service, an Inpatient Unit for prompt hospitalization and a Day Clinic for partial hospitalization, to address acute treatment, follow-up and recovery/relapse prevention phases. Diagnostic evaluation is made through specialized instruments along with the typical psychiatric interview. The therapeutic approach follows the international guidelines for EIP, namely symptom-based and phase-specific treatment, which includes supportive counselling, coping strategies and psychoeducation both for subjects and family members, as well as pharmacotherapy when needed and preferably in low doses. Regarding our results, in the first 3 years (3/2012-3/2015) the EIP unit received 26 (60%) UHR subjects and 17 (40%) FEP patients. Over the last 4 years (3/2015-3/2019) the referrals rose to 167 with 35 (21%) UHR and 132 (79%) FEP cases. All of the UHR subjects were from the outset followed by the specialized outpatient EIP service for up to 3 years. As to the FEP patients, seventy-seven (60%) were acutely hospitalized for less than a month, and 10 (8%) attended the Day Clinic for 6 - 12 months, before being referred to the outpatient service. Concluding, the development of the EIP network of specialized services has cohesively enabled a broader therapeutic framework, shifting the clinical focus towards FEP, although UHR subjects are still being assessed systematically. However, there is still considerable work to be done, in order to enhance the full potential of all units and promote the interconnection with potential community settings.

Evidence of advanced parental age linked to sporadic schizophrenia.

Νovel emergence of schizophrenia (SCZ) in its sporadic type has been linked, among many candidate epigenetic factors, with advanced paternal age (PA) and advanced maternal age (MA). The most common hypothesis to the paternal age effect is the increased "de novo mutations" during spermatogenesis, while the maternal age hypothesis, though controversial, is at most based on studies that support higher frequency of perinatal complications. Our sample consisted of 462 subjects with DSM-IV-TR SCZ spectrum disorders from the outpatient unit of Eginition Hospital in Athens, Greece, who were further screened for heritability and were divided in a group of sporadic cases (no reported family history for SCZ related disorders up to 2nd degree relatives) and a group of familial SCZ-spectrum disorder cases (positive reported history for SCZ spectrum). These two groups of patients were compared regarding either paternal or maternal age, while the familial type band was used as a control group. The aim of this retrospective file study was to examine whether advanced parental age may contribute in novel appearance of non-affective psychosis in offspring. Using logistic regression analysis, we found that the risk for the sporadic type, as compared to familial type, showed a significant increase for both advanced MA (OR=4.39, p=0.001) and PA (OR=1.92, p=0.012). After adjusting for confounding effects for the other parent's age and gender, the risk effect for the sporadic type of SCZ remained statistically significant for both advanced MA (OR=4.04, p=0.002) and advanced PA, but with a loss of statistical power (OR=1.72, p=0.049). Few studies have been conducted in Greece concerning the role of parental age in SCZ. Our study is consistent with current literature which indicates that both advanced MA and PA may contribute to an increased risk for emergence of sporadic type of SCZ. Furthermore, it is implied that this risk for the sporadic type as compared to the familial type could be higher for advanced MA than advanced PA. Patients with the sporadic type of SCZ, though clinically indistinguishable from the patients with the familial type of the disorder, may share other pathophysiological underlying mechanisms in which parental age, especially advanced MA, may be a candidate mediator. However, future studies could help clarify the role of both PA and MA in the pathophysiology of the disorder.