Negative symptoms of familial schizophrenia breed true in unstable (vs. stable) cerebral-ventricle pedigrees

Abstract A pattern of negative symptoms associated with a high rate of ongoing brain and ventricular instability has been described in a cohort of schizophrenia spectrum probands (patients with schizophrenia, schizoaffective disorder depressed and bipolar, and psychosis NOS) (Garver, D.L., Nair, T.R., Christensen, J.D., Holcomb, J., Ramberg, J., Kingsbury, S., 1999. Differential patterns of premorbid functioning, symptoms and neuroleptic response in stable and unstable ventricular-volume schizophrenia. Neuropsychopharmacology 20, in press). The present study contrasts the prevalence of negative symptoms in first- and second-degree relatives of probands with unstable ventricle volume (UnsVV) and stable ventricle volume (SVV). One hundred and sixteen first- and second-degree relatives of 10 probands were interviewed using the SANS, the ‘Characterization of Course: “Pattern of Symptoms” ’ [from Comprehensive Assessment of Symptoms and History (CASH)], SCID and SCID-II by interviewers blind to the status of the proband. Thirty-five of the 116 family members met DSM-IV criteria for schizophrenia, SA depressed, ‘Cluster A’ of the SCID-II (paranoid, schizotypal, schizoid personality disorder), psychosis NOS, or psychotic affective disorder. These 35 family members were defined as falling within a ‘schizophrenia spectrum’ as described by Farmer, A.E., McGuffin, P., Gottesman, I.I., 1987. Arch. Gen. Psychiatry 44, 634–641, but with the addition of DSM-IV affective psychosis. On that basis, the 35 members were considered ‘affected family members’ (AFMs). The remaining 81 family members were considered unaffected. The ‘predominant symptoms of illness‘ (during the past 2–3 years) for 25 of the 35 AFMs could be characterized according to the ‘Patterns of Symptoms‘ derived from the CASH. Twenty-five of the 35 AFMs were found to maintain a predominant symptom pattern during the course of illness, which could be characterized according to the ‘Pattern of Symptoms‘ as ‘predominantly positive‘ or ‘predominantly negative‘. Three of the probands had UnsVV; seven had SVV. Of the 35 AFMs, 11 were related to the UnsVV probands, and 24 were relatives of the SVV probands. The nine rated AFMs of the UnsVV probands showed a trend toward higher SANS scores (7.3±5.1) (mean±s.d.) than the 20 rated AFMs of SVV probands (4.3±5.1) ( p =0.08) at the time of the interview. Eighty-three per cent (eight of 10) of rated affected pedigree members of the pedigrees delineated by probands with UnsVV probands had a predominantly negative symptom course of illness, and 96% (23 of 24) of rated affected pedigree members of the pedigrees with SVV probands had a predominantly positive symptom course of illness during the preceding 2–3 years ( p =0.002). None of the 12 rated affected pedigree members within pedigrees having UnsVV probands were married at the time of the interview; 45% (14 of 31) of affected pedigree members having SVV probands were married ( p =0.004). A psychiatric disorder, characterized by unstable cerebral ventricles and predominant negative symptoms (including avoidance/failure of marital relationships) appears symptomatically to breed true in pedigrees containing schizophrenia-like illnesses.