Familial liability to schizophrenia and premorbid adjustment

We assessed premorbid functioning during childhood and adolescencein 50 people with schizophrenia from multiply affected families,39 of their unaffected siblings, 69 people with schizophreniawith no family history of psychosis, 67 of their unaffectedsiblings and 83 controls. People with schizophrenia had poorerpremorbid social and academic adjustment and exhibited a declinebetween childhood and adolescence compared with controls. Unaffectedsiblings from multiply affected families also had poor academic functioning in adolescence, with a decline between childhoodand adolescence. This may represent a familial (presumed genetic)effect.

INTRODUCTION

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INTRODUCTION

Cognitive and social deficits pre-date the onset of schizophrenia (Isohanni et al, 2005; Cannon et al, 2006) but it is unclearwhether they reflect genetic liability. We examined the earlysocial and academic functioning of individuals from the MaudsleyFamily Study to determine whether premorbid impairments inthese functional domains are related to familial liabilityfor schizophrenia. We hypothesised that individuals with ahigher presumed genetic liability (i.e. those from multiply affected families) would display more prominent social andacademic impairment than their counterparts from non-affectedfamilies.

METHODS

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METHODS

The recruitment and clinical assessments of the sample are described elsewhere (McDonald et al, 2006). Briefly, multiply affectedfamilies were defined as having two or more first- and/or second-degreerelatives with schizophrenia or another psychotic disorder,and singly affected families were those in which the indexindividual had no known family history of psychosis as far astheir third-degree relatives. None of the control sample hada personal or family history of psychotic illness. All participantswere White/Caucasian, aged 18–50 years and gave informedconsent for their mother to be interviewed. The study had ethicsapproval.

Fifty people with `familial' schizophrenia (37 male, 13 female;mean age 32 years, s.d.=6.1), 39 of their unaffected siblings(14 male, 25 female; mean age 34 years, s.d.=7.8), 69 peoplewith `non-familial' (52 male, 17 female; mean age 31 years,s.d.=6.4), 67 of their unaffected siblings (34 male, 33 female;mean age 35, s.d.=7.6) and 83 controls (42 male, 41 female;mean age 31 years, s.d.=7.1) were recruited. Patients fulfilledDSM–IV (American Psychiatric Association, 1994) criteriafor schizophrenia (n=112), schizo-affective disorder (n=6)or psychotic disorder `not otherwise specified' (n=1). Eleven(2 `non-familial' and 9 `familial') unaffected siblings hadhad an earlier DSM–IV Axis I non-psychotic psychiatricdisorder, predominantly major depressive disorder.

A modified Premorbid Social Adjustment (PSA) scale (Cannon-Spoor et al, 1982)was used to examine childhood and adolescent functioning (Foerster et al, 1991; Hollis, 2003). The PSA scale assessed five areas (socialisation,peer relations, academic achievement, school adaptation andhobbies) over two consecutive time periods: 5–11 years(childhood) and 12–16 years (adolescence). The PSA scalewas then simplified into two categories: social adjustment(socialisation, peer relations and hobbies); and academic adjustment(academic achievement and school adaptation) (Allen et al, 2005).Higher scores indicated poorer functioning. Any developmentaldeterioration was calculated as a `change score' by subtracting childhood adjustment from adolescent adjustment.

The scale was administered to the mothers by face-to-face interview(64%) or using a self-report questionnaire (36%). Reliabilitywas established by asking 21 mothers who had completed face-to-faceinterviews to complete a self-report version of the PSA scaleat a later time (on average 4 years). The scores for both time-pointswere highly consistent (correlation coefficient=0.80).

Multivariate analysis was carried out using STATA version 9.0with clustered robust standard errors to account for the non-independenceof individuals within families and for possible violationsof normality and equal variance assumptions. Multiple linearregression was used to compare premorbid adjustment and changescores (dependent variables) of each patient and sibling group(independent variables) with the control group, controllingfor age and gender. Scores were log-transformed to normalisethe distributions. All tests were two-tailed using a 0.05 levelof significance.

RESULTS

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RESULTS

The groups did not significantly differ in measures of parentalsocial class ( ${chi}$ ²=3.5, d.f.=2, P=0.71) or sibship size (F(2,150)=0.4,P=0.65) but there were significant group differences for age(F(4,151)=2.8, P=0.03) and gender ( ${chi}$ ²=22.2, d.f.=4, P=0.002),which were controlled for in subsequent analyses. Siblingsof people with non-familial psychosis were older than the controlgroup and there was an excess of males in both patient groups.

Premorbid function scores are presented in Table 1. Comparedwith controls, both groups with schizophrenia had significantlyworse social and academic function in childhood and adolescence,both of which deteriorated over time. The deterioration insocial functioning only reached statistical significance forpeople with `familial' schizophrenia. In a post hoc analysisdirectly comparing `familial' and `non-familial' schizophrenia,no significant difference was found in either premorbid socialfunctioning or deterioration over time.

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Table 1 Premorbid Social Adjustment (PSA) scale scores

Neither unaffected sibling group differed significantly fromcontrols in their social functioning during childhood or adolescence (Table 1). However, siblings of people with familial schizophreniademonstrated significantly worse academic functioning thancontrols during adolescence, and had a deterioration in academicfunctioning between childhood and adolescence. Post hoc analysisdemonstrated that siblings of people with familial schizophreniaalso had a significantly greater decline in academic functioningwhen compared directly with `non-familial' siblings (B=–0.31, P=0.02, 95% CI–0.56 to –0.06). Analyses were repeated excluding those 11 unaffected siblings with a history of non-psychotic psychiatric disorders but this made no difference to the results.

DISCUSSION

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DISCUSSION

To our knowledge this is the first study demonstrating thatunaffected siblings of people with familial schizophrenia havepoor academic functioning during adolescence and deteriorationin academic performance between childhood and adolescence comparedwith controls. This finding, coupled with its absence in siblingsof people with non-familial schizophrenia suggests that academic problems may be related to genetic risk for schizophrenia.This is consistent with reports that adult relatives of peoplewith schizophrenia underperform on cognitive tests comparedwith controls (Snitz et al, 2006).

This study has some methodological limitations. Separating familieson the basis of family history of psychosis runs the risk thatsome families may be misclassified. People with non-familialschizophrenia may not represent illness phenocopies but multiplyaffected families are presumed more likely to carry a greatergenetic susceptibility load than those families with only one member affected. This is supported by studies which have foundmore prominent neurobiological deviations among unaffectedrelatives from more densely affected families (McDonald et al, 2006).It is also possible that recall bias was introduced by the retrospectiveassessment of behavioural functioning during childhood and adolescence,i.e. that mothers from multiply affected families were more likely to recall negative events in their children. However,maternal ratings across both patient groups (familial and non-familial)were very similar, arguing against such recall bias operatingin multiply affected families.

Our finding that people who go on to develop schizophrenia haveabnormal premorbid social and academic functioning in childhoodand adolescence is in accordance with previous research (e.g. Isohanni et al, 2000), and other studies (Allen et al, 2005)have suggested that academic and social impairment acceleratesas people who later develop schizophrenia move from childhoodto adolescence.

REFERENCES

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