Cornblatt BA, Lencz T, Smith CW, Olsen R, Auther AM, Nakayama E et al. Can antidepressants be used to treat the schizophrenia prodrome? Results of a prospective, naturalistic treatment study of adolescents. J Clin Psychiatry 68: 546-557
ABSTRACT This study reports the results of a prospective, naturalistic treatment study of adolescents considered to be in the prodromal (i.e., prepsychotic) phase of schizophrenia.
Forty-eight adolescents (mean age = 15.8 years) participating in the initial phase of the Recognition and Prevention (RAP) program (1998-2005) were included in the current report. Individuals were selected from the overall sample (N = 152) if they had: (1) displayed attenuated positive symptoms, (2) been treated pharmacologically for at least 8 weeks, and (3) been followed up for at least 6 months (mean follow-up = 30.5 months).
Two types of medication were naturalistically prescribed: antidepressants (N = 20) or second-generation antipsychotics (N = 28), with polypharmacy common. The 2 treatment groups did not differ in baseline symptom profiles, with the exception of disorganized thinking, which was more severe in second-generation antipsychotic-treated adolescents. Twelve of the 48 adolescents (25%) developed a psychotic disorder, with all converters having been prescribed second-generation antipsychotics. There were no conversions among antidepressant-treated adolescents (log-rank chi(2) = 7.36, df = 1, p = .007). Treatment outcome, however, was confounded, since 11 of the 12 converters were nonadherent. Adolescents, in general, were more likely to be nonadherent to second-generation antipsychotics (61%, 17/28) than to antidepressants (20%, 4/20; chi(2) = 7.86, p = .005). Improvement in 3 of 5 positive symptoms over time was significant (p < .001) and similar for both medications. Disorganized thought, however, did not improve regardless of treatment.
Nonrandom assignment limits comparisons between antidepressants and anti-psychotics in this study. However, with follow-up, a number of adolescents meeting criteria for prodromal schizophrenia were successfully treated with antidepressants. At present, a substantial number of false positives among the antidepressant-treated subgroup cannot be ruled out. However, the findings suggest that, in some cases, it might be preferable to begin treatment with antidepressants and progress to antipsychotics once symptoms intensify, since adherence to the latter is difficult to maintain.
- SourceAvailable from: Stefan Borgwardt
[Show abstract] [Hide abstract]
- "Negative symptoms group into two factors, one involving diminished expression of affect and alogia and the second involving avolition, including anhedonia and asociality (Fusar-Poli et al., 2014b). Antidepressants may have a potential benefit for ARMS individuals , as they may target their negative attenuated psychotic symptoms (Cornblatt et al., 2007; Fusar-Poli et al., 2007). These studies indicate that antidepressant treatments in ARMS individuals can impact their longitudinal outcomes. "
ABSTRACT: Individuals with at-risk mental state for psychosis (ARMS) often suffer from depressive and anxiety symptoms, which are clinically similar to the negative symptomatology described for psychosis. Thus, many ARMS individuals are already being treated with antidepressant medication. To investigate clinical and structural differences between psychosis high-risk individuals with or without antidepressants. We compared ARMS individuals currently receiving antidepressants (ARMS-AD; n = 18), ARMS individuals not receiving antidepressants (ARMS-nonAD; n = 31) and healthy subjects (HC; n = 24), in terms of brain structure abnormalities, using voxel-based morphometry. We also performed region of interest analysis for the hippocampus, anterior cingulate cortex, amygdala and precuneus. The ARMS-AD had higher 'depression' and lower 'motor hyperactivity' scores than the ARMS-nonAD. Compared to HC, there was significantly less GMV in the middle frontal gyrus in the whole ARMS cohort and in the superior frontal gyrus in the ARMS-AD subgroup. Compared to ARMS-nonAD, the ARMS-AD group showed more gray matter volume (GMV) in the left superior parietal lobe, but less GMV in the left hippocampus and the right precuneus. We found a significant negative correlation between attenuated negative symptoms and hippocampal volume in the whole ARMS cohort. Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action.Clinical neuroimaging 04/2015; 22. DOI:10.1016/j.nicl.2015.04.016 · 2.53 Impact Factor
[Show abstract] [Hide abstract]
- "The prevalent social dysfunction in CHR patients has been described as non-responsive to pharmacological treatment (Cornblatt et al. 2007a) yet improvement has been observed in some patients, suggesting remediation may be possible (Niendam et al. 2007). Antidepressants may have efficacy not only in treating depressive symptoms in CHR patients but also in preventing the onset of psychosis (Cornblatt et al. 2007b). Case reports suggest efficacy for cognitive behavioral therapy (CBT) in treating negative symptoms in both schizophrenia (Perivoliotis & Cather, 2009) and its putative clinical risk states (Kimhy & Corcoran, 2008). "
ABSTRACT: Social dysfunction is a hallmark symptom of schizophrenia which commonly precedes the onset of psychosis. It is unclear if social symptoms in clinical high-risk patients reflect depressive symptoms or are a manifestation of negative symptoms. We compared social function scores on the Social Adjustment Scale-Self Report between 56 young people (aged 13-27 years) at clinical high risk for psychosis and 22 healthy controls. The cases were also assessed for depressive and 'prodromal' symptoms (subthreshold positive, negative, disorganized and general symptoms). Poor social function was related to both depressive and negative symptoms, as well as to disorganized and general symptoms. The symptoms were highly intercorrelated but linear regression analysis demonstrated that poor social function was primarily explained by negative symptoms within this cohort, particularly in ethnic minority patients. Although this study demonstrated a relationship between social dysfunction and depressive symptoms in clinical high-risk cases, this association was primarily explained by the relationship of each of these to negative symptoms. In individuals at heightened risk for psychosis, affective changes may be related to a progressive decrease in social interaction and loss of reinforcement of social behaviors. These findings have relevance for potential treatment strategies for social dysfunction in schizophrenia and its risk states and predict that antidepressant drugs, cognitive behavioral therapy and/or social skills training may be effective.Psychological Medicine 05/2010; 41(2):251-61. DOI:10.1017/S0033291710000802 · 5.43 Impact Factor
[Show abstract] [Hide abstract]
- "Of course, having said this, early, prodromal intervention strategies must take into consideration that a person diagnosed as having a high risk to develop schizophrenia may cause social stigma and augment stress that can worsen through the side-effects of pharmacological intervention. However, it seems there is evidence of the overweighing positive effect of early intervention of the development of psychotic states (McGorry et al. 2002; McGlashan et al. 2003; Cornblatt et al. 2007; Hafner et al. 2004). While task of early identification seems critical, initial prodrome seems to have been particularly elusive to systematic characterization (Møller and Husby 2000). "
ABSTRACT: Psychotic and prodromal states are characterized by distortions of intersubjectivity, and a number of psychopathologists see in the concrete I-You frame of the clinical encounter the manifestation of such impairment. Rümke has coined the term of ‘praecox-feeling’, designated to describe a feeling of unease emanating in the interviewer that reflects the detachment of the patient and the failure of an ‘affective exchange.’ While the reliability of the praecox-feeling as a diagnostic tool has since been established, the explanation and theoretical framing of the phenomena is still lacking. By drawing on enactivist approaches to social cognition, the paper will attempt to provide such an explanation. This is relevant, since such an explanation could contribute to a more precise understanding of the phenomena in question and possibly add to our knowledge regarding the link between experiential vulnerability to psychosis and disturbed I-Thou intersubjectivity. KeywordsPsychosis-Praecox-feeling-Second-person-Intersubjectivity-EnactivismPhenomenology and the Cognitive Sciences 03/2010; DOI:10.1007/s11097-010-9173-z