Early, non-psychotic deviant behavior in schizophrenia: a possible endophenotypic marker for genetic studies.

Early non-psychotic deviance occurs in some, but not all, pre-schizophrenic patients and has been linked to the later course of the disorder, suggesting its relationship with the schizophrenia syndrome. However, early deviance has rarely been explored as an endophenotypic marker in large samples of schizophrenic patients. We characterized the early childhood behavior and syndrome history of 205 adults with DSM-IV schizophrenia. Sixty percent of our sample had poor socialization, extreme fears/chronic sadness, and/or attention impairment/learning disabilities beginning before age 10. The remaining 40% were without behavioral difficulties until the onset of schizophrenia. Logistic regression analyses suggested that the risk of syndrome onset before age 17 was 2.5 times more likely among patients with poor socialization beginning before age 10. Schizoaffective disorder was 3.75 times greater among patients with extreme fears/chronic sadness in childhood, and schizophrenic patients with early attention impairment/learning disabilities were 2 times more likely to have a 1 degrees, 2 degrees or 3 degrees relative with schizophrenia. We concluded that early deviant behavior indicated a distinct subgroup of patients, and was linked to syndrome characteristics specifically relevant to genetic studies, in particular age at onset and family history of schizophrenia. Since early syndrome onset has been associated with specific genetic anomalies in other complex neuropathologic disorders, it may prove valuable to regard these early deviant behaviors as an indicator of early syndrome onset for future genetic studies of schizophrenia.

Evidence of a schizotypy subtype in OCD.

OCD patients represent a heterogeneous mix of clinical phenotypes, likely reflecting a wide range of genetic vulnerabilities. In other medical illnesses, neurobiologically-based traits with a genetic component that are associated with the target disorder have been successfully used to detect patients with a specific genetic liability to disease. The overlap between symptoms of OCD and Schizophrenia suggested that schizotypal traits could have the potential to distinguish a relatively homogeneous subtype of OCD. We obtained schizotypy scores for 119 affected adult probands who met lifetime criteria for DSM-IV OCD. Five subscales from the Structured Interview of Schizotypy were used to assess ideas of reference, suspiciousness, magical thinking, illusions and psychotic-like thought. Selected for their obvious face validity with the cardinal signs of schizophrenia, Cronbach's alpha suggested that these subscales also provided a reliable measure of positive sign schizotypy (0.83). Fifty percent of our OCD sample had mild to severe positive schizotypy signs. t- and chi2 tests of significance suggested seven variables that distinguished OCD patients with schizotypy, including earlier age of onset, greater number of comorbid diagnoses and increased rates of learning disability, aggressive and somatic obsessions and counting and arranging compulsions. Three of these seven variables, including learning disabilities, counting compulsions and history of specific phobia, significantly increased the odds of schizotypy among patients with lifetime OCD. These findings enhanced the validity of the schizotypy construct in OCD. Whether this schizotypy subtype can distinguish a subgroup of patients with relatively homogeneous genetic characteristics waits further investigation.

Phenotypic characteristics of Obsessive-Compulsive Disorder ascertained in adulthood.

Over the past decade, the increased awareness and knowledge of Obsessive-Compulsive Disorder (OCD) has allowed the in-depth study of its phenotypic characteristics. The largest studies to date have described the symptom and syndrome characteristics of treatment-seeking patients. While usefully homogeneous with regard to their current state, the clinical characteristics of patients seeking treatment may only partially represent the OCD population. We report findings from 100 self-selected volunteers at various stages of their OCD illness who were participating in a genetic study. Many similarities with past reports were found, including high rates of mood disorder, significantly more mood disorder in females as compared with males, and increased social impairment among males despite an equal amount of time in episodes of disorder. On the other hand, mean age of onset in this nontreatment seeking population was younger. Lifetime rates of obsessions and compulsions in this population were substantially higher than previous reports, suggesting that the content of obsessions and compulsions shifted over time, and evolved into a lifetime repertoire. Furthermore, a separate analysis of the age of clinically significant O-C symptom onset without impairment revealed that males and females did not differ, suggesting that previous reports of earlier onset age in males may actually reflect earlier onset of impairment. Future genetic studies may benefit from the analysis of both significant O-C symptom onset, as well as the onset of full-syndromal OCD. These findings may suggest phenotypic characteristics that define homogeneous subgroups of patients with OCD.

Serotonergic function in social phobia: comparison to normal control and obsessive-compulsive disorder subjects.

Eighteen patients with social phobia, 21 normal control subjects, and 42 obsessive-compulsive disorder (OCD) control subjects were challenged with single doses of the partial serotonin agonist oral m-chlorophenylpiperazine (m-CPP) and placebo. Social phobics did not significantly differ from normal or OCD control subjects in prolactin response to m-CPP. There was a significant difference across groups in cortisol response to m-CPP, such that female social phobics had more robust cortisol responses to the m-CPP challenge. Pairwise comparisons only reached trend significance, perhaps due to the relatively small sample sizes. This study offers preliminary evidence for serotonin dysfunction in social phobia, particularly in female social phobics, but needs to be replicated in a larger sample size.