Clinical psychopathology in youth at familial high risk for psychosis.

AIM: While the course of psychopathology has been explored from an index mental health diagnosis onwards, there are few detailed, prospective studies of the occurrence of clinical psychopathology in youth with familial risk for severe mental illnesses such as psychosis. We sought to describe the appearance of Axis I psychopathology in a unique sample of adolescents with a family history of schizophrenia (FHR). METHODS: One hundred and sixty two first- and second-degree relatives (mean age 15.7 ± 3.6; range 8-25) of probands with schizophrenia or schizoaffective disorder were assessed at baseline and annual intervals for up to 3 years, focusing on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) Axis I psychopathology. RESULTS: Fourteen individuals (8.6%) developed a psychotic disorder. One hundred and five subjects (65%) met criteria for an Axis I disorder over the course of the study, the most common of which was a depressive episode (40 subjects; 25%). Of the 148 individuals who did not develop psychosis, 91 (61%) had one or more Axis I disorders compared with 10/14 converters who had a comorbid Axis I disorder (71%). Ordered by increasing age of onset, diagnoses included cognitive and externalizing disorders, anxiety disorders, affective disorders, substance use disorders and psychotic disorders. CONCLUSIONS: In addition to an elevated risk of psychosis, young FHR relatives manifest a broad range of non-psychotic Axis I psychopathology in childhood and adolescence. This breadth of diagnoses has implications for the structure and function of mental health services for young people.

Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: comparing vulnerability markers.

BACKGROUND: Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree. METHODS: Three groups (n=100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2s & 12s); sustained attention processing was assessed using the Continuous Performance Task-Identical Pairs version. RESULTS: SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls. CONCLUSIONS: These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.

Social cognition deficits among individuals at familial high risk for schizophrenia.

Social cognition in young relatives of schizophrenia probands (N=70) and healthy controls (N=63) was assessed using the Penn Emotion Recognition Test-40 to examine the presence of social cognitive deficits in individuals at risk for the disorder. Measures of neurocognitive function and prodromal psychopathology were collected to assess the cognitive and clinical correlates of social cognitive impairments in at-risk relatives. Results indicated that when compared with healthy controls, individuals at familial high risk for schizophrenia were significantly more likely to overattribute emotions to neutral faces, with such individuals frequently misinterpreting neutral faces as negative. In addition, at-risk individuals had significantly greater reaction times when completing emotion recognition tasks, regardless of valence. Impairments in neurocognition were largely independent of social cognitive performance, and emotion recognition impairments persisted after adjusting for deficits in neurocognitive function. Further, social cognitive impairments in the interpretation of neutral faces were significantly associated with greater positive and general prodromal psychopathology, whereas neurocognitive impairments were only associated with disorganization. These results suggest that impairments in social cognition may be unique endophenotypes for schizophrenia.