Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study

Bartzokis, George; Nuechterlein, Keith H.; Lu, Po; Gitlin, Michael; Rogers, Steven A.; Mintz, Jim

doi:10.1016/s0006-3223(02)01835-8

Cited by 111 publications

(78 citation statements)

References 63 publications

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“…During early to mid-adulthood, WM volumes plateau during the fifth decade of life with the frontal lobe being the last to mature (Mathalon et al 2001;Sowell et al 2003). Schizophrenia patients do not show this normal age-related expansion in WM volume (Bartzokis et al 2003). In fact, schizophrenia patients may actually start out having abnormally enlarged WM brain volumes during adolescence and early adulthood (Bartzokis et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Schizophrenia patients do not show this normal age-related expansion in WM volume (Bartzokis et al 2003). In fact, schizophrenia patients may actually start out having abnormally enlarged WM brain volumes during adolescence and early adulthood (Bartzokis et al 2003). Because patients do not show the normal age-related WM volume expansion during early to mid-adulthood, patient-control differences in WM volumes become increasingly more evident with age such that WM volume reductions are most marked by the fifth decade of life (Bartzokis et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, schizophrenia patients may actually start out having abnormally enlarged WM brain volumes during adolescence and early adulthood (Bartzokis et al 2003). Because patients do not show the normal age-related WM volume expansion during early to mid-adulthood, patient-control differences in WM volumes become increasingly more evident with age such that WM volume reductions are most marked by the fifth decade of life (Bartzokis et al 2003). Thus, our finding of enlarged WM volumes in nonpsychotic relatives and in schizophrenia patients, all of whom were either adolescents or still in their early twenties, may be related to dysmaturation in myelination.…”

Section: Discussionmentioning

confidence: 99%

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MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

2007

Schizophrenia Research

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Schizophrenia is characterized by subtle but well-replicated total and regional (frontal and temporal) brain tissue volume deficits. Studies of individuals at-risk for developing schizophrenia suggest that the onset of brain volume decrement may closely pre-date overt manifestations of schizophrenia, making brain volume abnormalities potential predictors for early identification. In an ongoing longitudinal morphometric MRI study of young, nonpsychotic first-or second-degree relatives of schizophrenia probands, we compared brain volumes in 46 relatives who are still within age range for developing schizophrenia against comparison groups of 46 schizophrenia patients and 46 healthy volunteers without family history of schizophrenia. Relatives had similar brain volume abnormalities as schizophrenia patients albeit less severe. Relatives had significantly larger whole brain, frontal, temporal and parietal gray matter (GM) volumes than patients. Relatives also had significantly smaller frontal GM volumes than healthy volunteers. Both relatives and patients had significantly larger whole brain WM (specifically parietal WM) volumes compared to healthy volunteers. Abnormally greater WM volumes in relatives and patients are suggestive of genetically-mediated dysmaturation of the age-expected myelination during adolescence through mid adulthood. On prodromal symptoms assessed in relatives one year after MRI brain scans, initial GM deficits as well as larger WM volumes correlated significantly with greater severity of subsequent prodromal symptoms. Together with previous genetic high-risk studies of adolescent or young adult relatives, these findings indicate that premorbid MRI brain abnormalities may be of predictive value for the early identification of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

2007

Schizophrenia Research

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“…Although the exact meaning of the volumetric abnormalities is not entirely clear, GM reductions may reflect a variety of neuropathological changes, e.g. exaggerated dendritic or synaptic pruning [94], impaired myelination [90], apoptosis [95], or other neurotoxic effects of first-generation antipsychotic medications [96]. Furthermore, differences in scanning parameters and image analysis may account for inconsistencies in neuroimaging measures.…”

Section: Methodological Issues In Studies Investigating Medication Efmentioning

confidence: 99%

“…Thus, atypical antipsychotics may reduce disturbed myelination and abnormally severe dendritic pruning and/or neurotoxic ablation of synapses [49,90,91] in patients with schizophrenia. Atypical antipsychotics may also induce oligodendrocyte proliferation and compensate for oligodendrocyte reductions [49] and intracortical myelination [90].…”

Section: Mechanisms Of Antipsychotic Action On Brain Structurementioning

confidence: 99%

The Effects of Antipsychotics on the Brain: What Have We Learnt from Structural Imaging of Schizophrenia? – A Systematic Review

Smieskova

Fusar‐Poli²,

Allen³

et al. 2009

CPD

186

131

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Abstract:Despite a large number of neuroimaging studies in schizophrenia reporting subtle brain abnormalities, we do not know to what extent such abnormalities reflect the effects of antipsychotic treatment on brain structure. We therefore systematically reviewed cross-sectional and follow-up structural brain imaging studies of patients with schizophrenia treated with antipsychotics. 30 magnetic resonance imaging (MRI) studies were identified, 24 of them being longitudinal and six cross-sectional structural imaging studies. In patients with schizophrenia treated with antipsychotics, reduced gray matter volume was described, particularly in the frontal and temporal lobes. Structural neuroimaging studies indicate that treatment with typical as well as atypical antipsychotics may affect regional gray matter (GM) volume. In particular, typical antipsychotics led to increased gray matter volume of the basal ganglia, while atypical antipsychotics reversed this effect after switching. Atypical antipsychotics, however, seem to have no effect on basal ganglia structure.

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Long-term Antipsychotic Treatment and Brain Volumes

Andreasen²,

Ziebell³

et al. 2011

Arch Gen Psychiatry

856

297

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Context Progressive brain volume changes in schizophrenia are thought to be due principally to the disease. However, recent animal studies indicate that antipsychotics, the mainstay of treatment for schizophrenia patients, may also contribute to brain tissue volume decrement. Because antipsychotics are prescribed for long periods for schizophrenia patients and have increasingly widespread use in other psychiatric disorders, it is imperative to determine their long-term effects on the human brain. Objective To evaluate relative contributions of 4 potential predictors (illness duration, antipsychotic treatment, illness severity, and substance abuse) of brain volume change. Design Predictors of brain volume changes were assessed prospectively based on multiple informants. Setting Data from the Iowa Longitudinal Study. Patients Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset, yielding a total of 674 high-resolution magnetic resonance scans. On average, each patient had 3 scans (≥2 and as many as 5) over 7.2 years (up to 14 years). Main Outcome Measure Brain volumes. Results During longitudinal follow-up, antipsychotic treatment reflected national prescribing practices in 1991 through 2009. Longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes. Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of the other 3 predictors. More antipsychotic treatment was associated with smaller gray matter volumes. Progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment. Illness severity had relatively modest correlations with tissue volume reduction, and alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted. Conclusions Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use.

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Dysregulated brain development in adult men with schizophrenia: a magnetic resonance imaging study

Cited by 111 publications

References 63 publications

MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

The Effects of Antipsychotics on the Brain: What Have We Learnt from Structural Imaging of Schizophrenia? – A Systematic Review

Long-term Antipsychotic Treatment and Brain Volumes

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