Abstract
Response to antipsychotic drugs, the mainstay treatment for psychosis, is variable and cannot be predicted by quantitative measures. No existing biological predictors of response are available to guide the selection of efficacious antipsychotic treatment for an individual patient. At the same time, our knowledge of the mechanism underlying response remains limited, which contributes to our lack of newer treatments for psychotic disorders. Neuroimaging approaches have been used to examine response-related mechanisms underlying antipsychotic treatment, though a large disparity remains between this work and clinical practice. This chapter examines these studies while providing an overview of functional and structural neuroimaging studies that focus on treatment outcome in individuals both in early phase, and in chronic populations, of schizophrenia spectrum disorders. Similarities in findings from both populations will be discussed as well as future directions.
Access provided by Autonomous University of Puebla. Download chapter PDF
Similar content being viewed by others
Keywords
- Antipsychotic
- Treatment response
- fMRI
- Structural MRI
- Functional connectivity
- Treatment outcomes
- Schizophrenia
- Psychosis
1 Introduction
Schizophrenia spectrum disorders typically emerge during adolescence and early adulthood, severely altering an individual’s natural life course (Millan et al. 2016). Characteristic to these disorders are episodes of psychosis that include hallucinations of various modalities, delusional thought processes, and disorganized behavior. Numerous antipsychotic drugs exist to treat these symptoms and primarily target the dopamine D2 receptor, though response to their administration is variable and cannot be predicted (Kapur and Mamo 2003; Carbon and Correll 2014). Treatment decisions are based on trial and error, with no quantitative guidance, unlike in other areas of medicine where precision medicine strategies are integrated. Poor response to antipsychotic treatment, occurring in up to 40% of patients, accounts for a disproportionate amount of disability and health care expenditure (Kennedy et al. 2014).
Outcome trajectories coalesce over time and are unknown at illness onset. Heterogeneity of outcomes in individuals diagnosed with schizophrenia has been described for many decades. Early longitudinal studies, predating the availability of antipsychotic drugs, showed several illness courses following the emergence of psychotic symptoms (Bleuler 1968). Subsequent to the advent of antipsychotic drugs, Huber et al. demonstrated 12 treatment trajectories, ranging from persistent and refractory to monophasic illnesses in patients with schizophrenia (Huber et al. 1980). More recent evidence supports this vast degree of variation in outcome (Carbon and Correll 2014).
Many studies have sought to understand the neural mechanisms underlying variation of outcomes in schizophrenia. Neuroimaging methods have emerged as key contributors in this effort (See Chaps. 1, 3 and 5 for more details). Numerous studies have applied both structural and functional neuroimaging to examine the complex phenotypic manifestations and illness trajectories observed in disorders such as schizophrenia (See Chaps. 2, 4 and 6 for more details). While ongoing neuroimaging methods have the capacity to follow and predict treatment outcomes in a noninvasive and applicable manner, the gap between existing findings and clinical practice remains significant.
The following chapter focuses on these efforts by reviewing findings from both structural and functional neuroimaging studies. Both early-course and chronic patients with schizophrenia will be considered, given the importance of markers at both onset and in chronic illness. We will also discuss the potential for structural and functional neuroimaging-related measures to be used as prognostic biomarkers of outcomes. Within this text, various definitions of outcomes and response will be considered. Of note, we emphasize and concentrate on measures associated with efficacy and outcomes to treatment, rather than the effect of medications on brain structure and function.
2 Structural Studies of Early-Course Schizophrenia
Structural neuroimaging methods have been used to examine treatment response in individuals with first-episode psychosis or early-course schizophrenia. Patients early in the course of illness offer the advantages of no or limited prior treatment and reduced durations of illness, resulting in potentially less environmental confounds that may serve to decrease study power. Collectively, structural neuroimaging measures, particularly assessments of cortical folding patterns, may reflect developmentally mediated abnormalities that contribute to treatment response.
Initial neuroimaging studies in first-episode and early-course patients with schizophrenia focused on ventricular-brain ratios versus clinical outcomes with magnetic resonance imaging (MRI). Longitudinal studies, using serial MRIs during treatment, reported that in patients with poor outcome to treatment, significant ventricular enlargement was observed over time, whereas the patients with better treatment outcomes and healthy control subjects did not show ventricular enlargements (Lieberman et al. 2001; Ho et al. 2003). Subsequent work focused on ventricular enlargement in relation to antipsychotic type. Lieberman et al. (Lieberman et al. 2005) compared ventricular enlargement between treatment with olanzapine and haloperidol, and found that treatment response, measured by ratings of global psychopathology, correlated with lower increases in ventricular volume in the olanzapine treated group. In a more recently published study, increases in ventricular volume correlated with less reductions of negative symptoms in first-episode psychosis patients during treatment with the second-generation antipsychotic, quetiapine (Ebdrup et al. 2011).
Along with changes in ventricular size, structural neuroimaging studies have shown response-related morphological findings in the prefrontal cortex. Reductions in negative symptoms were found to be related to increased thickness of middle frontal gyrus following treatment with atypical antipsychotics (Goghari et al. 2013). Poorer overall functioning after 1 year of treatment in a small cohort of patients with first-episode schizophrenia was associated with reduced prefrontal grey matter volume (Kasparek et al. 2009). Prasad and colleagues demonstrated that a larger dorsolateral prefrontal cortex volume after 1 year of treatment predicted better functional outcome based on a score that incorporated social contacts, employment, and symptomatology (Prasad et al. 2005).
Multiple findings related to treatment outcome have been reported in medial temporal regions. In a study where first-episode psychosis patients were categorized as responders or non-responders by the Schizophrenia Working Group remission criteria, responders were found to have larger parahippocampal cortex volumes in both left and right hemisphere (Bodnar et al. 2011; 2012a). An analysis of cortical gyrification in first-episode psychosis revealed that non-response to antipsychotic treatment was associated with decreased gyrification in regions of the insula, frontal, and temporal cortices (Palaniyappan et al. 2013). Moreover, responders to antipsychotic treatment displayed more asymmetry between left and right frontal cortices and greater thickness of temporal regions relative to patients with poor response to antipsychotic treatment (Szeszko et al. 2012).
Structural neuroimaging findings associated with treatment response have also been reported outside of fronto-temporal areas. Greater total cortical grey matter was shown to be associated with a percent reduction in psychotic symptoms following antipsychotic treatment (Zipursky et al. 1980). Likewise, a greater decrease in total grey matter volume after 1 year of treatment was associated with a greater need for psychosocial support after long term follow-up 5 years later (Cahn et al. 2006). Findings have been described in non-cortical regions as well. In white matter, a smaller baseline volume of the left anterior limb of the internal capsule was noted in patients with first-episode psychosis who showed a greater clinical deterioration after 1 year of treatment relative to those with more stable measures of psychopathology (Wobrock et al. 2009). In the basal ganglia, increased striatal volume was observed in relation to treatment efficacy after 6 weeks of medications (Li et al. 2012). Sex differences have also been noted in the striatum and thalamus. Larger volumes of these structures at baseline predicted remission after 1 year of treatment in females, but not males (Fung et al. 2014). Recent work has combined structural neuroimaging with graph theoretical measures to examine response to antipsychotic treatment. In a large cohort of patients undergoing treatment for 12 weeks, patterns of structural covariance across the brain were examined that focused on gyrification (Palaniyappan et al. 2016). Treatment non-responders showed increased segregation and impaired integration of structural relationships, possibly resulting in unstable information flow throughout the brain. It should be noted that relationships between structure and treatment response are not universally described, with several non-significant results reported (Molina et al. 2014; van Haren et al. 2003; Robinson et al. 1999).
In addition to studies of grey matter and volumetric analyses, efficacy of antipsychotic treatment has been examined along with white matter integrity. Diffusion tensor imaging (DTI) allows for the measurement of fractional anisotropy (FA), which characterizes water diffusion to provide a proxy measure of the white matter myelination. While most published studies examine changes in DTI measures in relation to antipsychotic exposure (Szeszko et al. 2014; Bartzokis et al. 2011; Samartzis et al. 2014), a few report state-dependent changes in white matter related to the amelioration of psychotic symptoms in early-course patients with schizophrenia. Reduced FA was reported within the uncinate and superior longitudinal fasciculi in first-episode psychosis patients who were characterized by poor treatment outcomes (Luck et al. 2011). Consistent with this report, FA increase in the superior longitudinal fasciculi was associated with more efficacious treatment over the course of 8 weeks of antipsychotic treatment (Zeng et al. 2016). Reis Marques et al. (2014) reported findings from a longitudinal study of 63 first-episode psychosis patients with stringent response criteria (Andreasen et al. 2005). While no change was observed in FA following 12 weeks of antipsychotic treatment, a negative correlation was observed between baseline psychopathology and FA. Other studies in first-episode psychosis patients reported whole-brain increases in fractional anisotropy in patients with greater reductions in ratings of psychopathology (Serpa et al. 2017). More recent work has merged DTI tractography with network-based statistics to examine antipsychotic treatment in a cohort of first-episode patients. Responders to 12 weeks of treatment had more efficient DTI-derived connectomes at baseline, reflecting a higher capacity for information flow throughout the brain (Crossley et al. 2017).
3 Functional Studies of Early-Course Schizophrenia
Task-based functional neuroimaging has been used to examine treatment outcomes in patients with schizophrenia. While some studies describe negative findings relating treatment outcome and neural activation (Snitz et al. 2005; Blasi et al. 2009), others reported treatment-related findings, primarily in decreased engagement of prefrontal and striatal regions with poor response. In treatment-naive first-episode psychosis patients, nonresponse to a 10-week trial of antipsychotic treatment was associated with greater dysfunction of dorsolateral prefrontal activation during a working memory task (van Veelen et al. 2011). Supporting this finding, decreased engagement of executive regions and increased activation of the default mode network has been reported in non-remitters relative to patients who responded to treatment during memory encoding (Bodnar et al. 2012b). Two studies examined longitudinal changes in activation of the striatum during treatment with second-generation antipsychotic drugs. One reported that recruitment of the ventral striatum during reward processing was normalized only in first-episode patients who responded to treatment (Nielsen et al. 2012), while the second study found that activation of the striatum corresponded with drug-related weight gain, suggesting a link between neural engagement and metabolic outcomes to treatment (Nielsen et al. 2016).
Along with activation studies, findings show changes in resting-state functional connectivity during antipsychotic treatment. Resting-state scans are a convenient method for examining the intrinsic functional architecture of the brain. Analytic approaches to resting-state connectivity range from hypothesis-driven inter-regional assessments to more data-driven global connectivity measure that capture small-world network clustering throughout the brain. Recent work, including resting-state findings, has conceptualized schizophrenia as a ‘dysconnectivity’ syndrome, consisting of abnormalities in large-scale functional networks (van den Heuvel and Fornito 2014; Nejad et al. 2012). Supporting this theory, multiple reports characterize functional interactions between subcortical and prefrontal regions across antipsychotic treatment. Treatment-induced increases in functional connectivity of the striatum with important limbic and prefrontal regions, including the hippocampus, the anterior cingulate, and the dorsolateral prefrontal cortex, corresponded with efficacy of treatment in a randomized controlled trial between two second-generation drugs in a cohort of patients with first-episode schizophrenia (Sarpal et al. 2015). In addition, an index of striatal connectivity at treatment initiation predicted ultimate response to treatment in two independent cohorts (Sarpal et al. 2016). Functional interactions of brain regions including the striatum, hippocampus, and the anterior cingulate cortex are additionally implicated in the mechanism of response by other longitudinal, treatment-based studies (Anticevic et al. 2015; Kraguljac et al. 2016a).
Together, the fMRI studies described above suggest that when antipsychotic treatment works, there is an associated increase in either activation or synchronization of neural activity in brain regions important for cognition and emotional processing. Additional studies use more novel connectivity methods and report either negative findings or normalization of fMRI signals with treatment response (Lui et al. 2010; Guo et al. 2017, 2018; Wang et al. 2017). It is worth noting that analytic approaches vary across these fMRI studies, introducing heterogeneity in reported findings. Multisite studies with a uniform analytic approach may yield more conclusive results.
4 Structural Studies of Chronic Schizophrenia
In addition to studies focused on patients early in the course of illness, multiple studies have assessed more chronically ill subjects. These study groups, though perhaps more heterogeneous that early phase patients, represent the vast majority of patients seen in treatment settings, and therefore predictors of response in this group of patients would be of potentially enormous clinical utility.
The first studies to use neuroimaging to examine treatment response examined ventricular-brain ratios with computed tomography imaging (CT scans). Larger ventricles were observed in patients who were poorer responders to treatment (Weinberger et al. 1980; Schroder et al. 1993; Kaplan et al. 1990). Later studies continued to examine ventricular volumes with MRI scans. In a comparison of percent time hospitalized in the previous year and ventricular-brain ratios, smaller frontal lobe volumes and larger ventricles were observed in patients who spent more time hospitalized (Staal et al. 2001). Supporting this finding that gross measures of outcome and structure may be useful markers, Jääskeläinen and colleagues showed that in a large voxel based morphological analysis, individuals with better functional and clinical outcomes following treatment had “denser” frontal and limbic grey matter, relative to those with worse treatment outcomes (Jaaskelainen et al. 2014).
Across analyses, larger volumes of various structures have been associated with response to antipsychotic treatment in chronic patients with schizophrenia. This includes hippocampal volumes in both cross-sectional and longitudinal studies (Savas et al. 2002; Panenka et al. 2007), temporal grey matter volumes compared with reductions of psychotic symptoms (McClure et al. 2006), the thalamic volume after 4 weeks of treatment (Strungas et al. 2003), and cerebellar volume after a 7 year follow-up (Wassink et al. 1999). In addition, a decline in social and occupational functioning was associated with a corresponding decrease in supramarginal gyrus volume (Guo et al. 2015).
Studies focused on white matter in chronic patients with schizophrenia are limited. As with early-course patients, most studies concentrate on the effect of antipsychotic drugs on DTI-based measures, rather than correlates of treatment efficacy. Mitelman et al. (2006) reported widespread increases in FA, driven by treatment response. One additional report found an increase in DTI-based mean diffusivity in patients who demonstrated reduced psychotic symptoms following 1 month of antipsychotic treatment (Garver et al. 2008).
Neuroimaging findings of chronic patients with schizophrenia have also centered on treatment-refractory patients who are often treated with clozapine. Non-responders to clozapine treatment showed reduced grey matter volumes in the middle frontal gyrus, bilaterally, and in the medial temporal cortex (Quarantelli et al. 2014; Arango et al. 2003). In a comparison with cohort of responders, treatment-resistant patients, many treated with clozapine, showed reduced cortical thickness in the dorsolateral prefrontal cortex, perhaps suggesting a neurobiological marker for illness severity (Zugman et al. 2013).
Despite this pattern of larger brain volumes in responders, several structural studies with negative findings have also been reported (Friedman et al. 1992; Lawrie et al. 1995; Roiz-Santianez et al. 2012; Scheepers et al. 2001). Likewise, meta-analyses of treatment-associated changes in both grey matter and ventricular volume did not replicate the results described in individual studies, including ones outlined above (Fusar-Poli et al. 2013). Reasons for this may be due to a lack of overlapping results secondary to variation in treatment approaches and definitions of response, as well as disparate neuroimaging and analytic approaches.
5 Functional Studies of Chronic Schizophrenia
Functional neuroimaging has been used to examine treatment response in chronic patients with schizophrenia spectrum disorders, largely reporting findings in the prefrontal cortex and striatum. Significantly increased activation of the dorsolateral prefrontal cortex, anterior cingulate cortex, and striatum was reported during passive viewing of stimuli with a negative emotional valance in the context of successful antipsychotic treatment over 22 weeks (Fahim et al. 2005). Refractory patients who responded to clozapine showed increased activation of dorsomedial prefrontal regions (Potvin et al. 2015). Furthermore, increased dorsolateral prefrontal activity during working memory paradigm was also noted to predict successful response to cognitive behavioral therapy for psychotic symptoms (Kumari et al. 2009). In addition to prefrontal findings, reward paradigms have been applied in chronic patients. Vanes et al. (2018) reported that responders to treatment failed to functionally engage the striatum during reward processing, compared to both treatment-resistant patients and healthy volunteers. This work differentiates antipsychotic treatment response by a reward-related mechanism, supporting the hypothesis that non-responders to treatment may exhibit a non-dopaminergic pathophysiology.
Functional connectivity analyses have also been applied to capture treatment response in chronic schizophrenia. The connectivity strength between dopaminergic regions, such as the ventral tegmental area and midbrain to the anterior cingulate cortex, positively correlated with good response to a 6-week course of risperidone (Hadley et al. 2014). Moreover, successful treatment with olanzapine was associated with increases in connectivity within the default mode network (Sambataro et al. 2010), and aberrant intra-network connectivity within the dorsal attention network was normalized with successful antipsychotic treatment (Kraguljac et al. 2016b). Like the early-course literature, novel methods for examining large-scale functional connectivity shows both normalization of functional networks with antipsychotic treatment, as well as negative findings (Lottman et al. 2017; Bai et al. 2016).
6 Discussion
In the studies described above, there is evidence that neuroimaging parses the heterogeneity of response to treatment of psychotic symptoms with antipsychotic medications while elucidating potential mechanisms. Relatedly, neuroimaging may assist in clinical treatment by serving as a prognostic assay.
Some important clinical considerations should be noted. Across studies, definitions of response vary. An assortment of outcomes and groupings of patients are represented by the studies described, reflecting the complexity of schizophrenia and the various methods for characterizing outcomes to treatment. Standardization of response criteria has been suggested (Andreasen et al. 2005; Emsley et al. 2007), including a rigorous and uniform definition of nonresponse (Howes et al. 2017). In addition, it should be noted that antipsychotic treatments do not significantly impact the negative and cognitive symptoms of schizophrenia, which may result in the severe functional and social impairments characteristic of the illness (Remington et al. 2016; Kane and Correll 2010). As described above, some studies examined response to clozapine or focused on treatment refractory illness. Clozapine is uniquely efficacious for patients who have failed other antipsychotic drugs and plays an important role in treatment algorithms. For ultra-refractory patients who fail clozapine, electroconvulsive therapy is often delivered, which has long demonstrated efficacy for psychotic symptoms (Petrides et al. 2015). The classification of patients based on responsiveness to these therapies may become standard of care as our knowledge of the neurobiology underlying treatment improves, and if replicable biomarkers are identified (Remington et al. 2015).
Results described in this chapter show that there is an overall convergence of findings from neuroimaging studies in both early-course patients and chronic patients. These results suggest that variation in neural circuitry may encode the potential for response to treatment, preceding the onset of psychosis, and may have its roots in neurodevelopment. Structural neuroimaging findings suggest that non-responders to treatment exhibit greater ventricular volumes, along with decreased grey matter density in regions important for cognitive functioning, including frontal and medial temporal regions, as well as other limbic and subcortical structures. Greater dysfunction within these regions that confer importance for cognition is also observed in functional MRI studies, though the variance of reported results is considerable. Though some evidence suggests that non-responders to antipsychotic treatment display overall decreased white matter integrity, DTI studies are limited in numbers, and distinct conclusions cannot be drawn for early-course and chronic illness. Of note, it is unknown how findings from structural and functional imaging modalities are related to each other and whether neurodevelopmentally encoded structural deficits in patients with poor outcomes precede functional observations.
Existing studies also indicate that the heterogeneity in clinical outcomes to antipsychotic treatment in patients with schizophrenia may be driven by neurobiologically distinct subtypes of illness. The development of novel therapeutic approaches may depend on stratifying our approaches to clinical trials on subgroupings of patients with distinct biological profiles. This approach may maximize the efficacy of therapeutic interventions. Progress in this effort may lead to more efficacious and personalized treatments. Efforts will require consistency across study designs, stringent and uniform outcome criteria, as well as consolidation of neuroimaging datasets via multisite studies. In addition, further integration of clinical trials with neuroimaging will bridge clinical care with neurobiology. Future work may also integrate neuroimaging-derived markers with combinations of demographic, neurocognitive, and pharmacogenomic markers to enhance our prognostic capabilities. While this chapter focuses on antipsychotic drugs, other treatment modalities for psychosis should be examined with neuroimaging, including electroconvulsive therapy, transcranial magnetic stimulation, and evidence-based psychosocial interventions. Future directions for the field include the incorporation of neuroimaging with data-driven, machine learning approaches to transition, from descriptions of differences between groups of patients, to prognostic inferences that can be made for individuals, to usher the field in the direction of precision medicine approaches for schizophrenia treatment.
Summary
-
Overall, there is convergence of findings from studies of treatment response in both early-course and chronic patients with schizophrenia.
-
Early studies focused on ventricular enlargement in first-episode psychosis found greater ventricular size in patients with poorer outcomes to treatment.
-
Morphologic findings in patients with schizophrenia, ranging from first-episode psychosis to chronic, treatment-refractory illness, largely report decreased frontal and temporal gray matter volumes.
-
Functional studies of treatment response via task and resting-state imaging report abnormalities in regions important for cognition within the prefrontal cortex and the striatum.
-
DTI studies suggest that non-response to antipsychotic treatment is associated with overall decreased white matter integrity.
References
Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162(3):441–9. https://doi.org/10.1176/appi.ajp.162.3.441.
Anticevic A, Hu X, Xiao Y, Hu J, Li F, Bi F, Cole MW, Savic A, Yang GJ, Repovs G, Murray JD, Wang XJ, Huang X, Lui S, Krystal JH, Gong Q. Early-course unmedicated schizophrenia patients exhibit elevated prefrontal connectivity associated with longitudinal change. J Neurosci. 2015;35(1):267–86. https://doi.org/10.1523/jneurosci.2310-14.2015.
Arango C, Breier A, McMahon R, Carpenter WT Jr, Buchanan RW. The relationship of clozapine and haloperidol treatment response to prefrontal, hippocampal, and caudate brain volumes. Am J Psychiatry. 2003;160(8):1421–7. https://doi.org/10.1176/appi.ajp.160.8.1421.
Bai Y, Wang W, Xu J, Zhang F, Yu H, Luo C, Wang L, Chen X, Shan B, Xu L, Xu X, Cheng Y. Altered resting-state regional homogeneity after 13 weeks of paliperidone injection treatment in schizophrenia patients. Psychiatry Res. 2016;258:37–43. https://doi.org/10.1016/j.pscychresns.2016.10.008.
Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL, Mintz J, Ventura J, Casaus LR, Luo JS, Subotnik KL, Nuechterlein KH. Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res. 2011;132(1):35–41. https://doi.org/10.1016/j.schres.2011.06.029.
Blasi G, Popolizio T, Taurisano P, Caforio G, Romano R, Di Giorgio A, Sambataro F, Rubino V, Latorre V, Lo Bianco L, Fazio L, Nardini M, Weinberger DR, Bertolino A. Changes in prefrontal and amygdala activity during olanzapine treatment in schizophrenia. Psychiatry Res. 2009;173(1):31–8. https://doi.org/10.1016/j.pscychresns.2008.09.001.
Bleuler M. A 23-year longitudinal study of 208 schizophrenics and impressions in regard to the nature of schizophrenia. J Psychiatr Res. 1968;6(Suppl 1):3–12.
Bodnar M, Harvey PO, Malla AK, Joober R, Lepage M. The parahippocampal gyrus as a neural marker of early remission in first-episode psychosis: a voxel-based morphometry study. Clin Schizophr Relat Psychoses. 2011;4(4):217–28. https://doi.org/10.3371/csrp.4.4.2.
Bodnar M, Malla AK, Joober R, Lord C, Smith E, Pruessner J, Lepage M. Neural markers of early remission in first-episode schizophrenia: a volumetric neuroimaging study of the parahippocampus. Psychiatry Res. 2012a;201(1):40–7. https://doi.org/10.1016/j.pscychresns.2011.07.012.
Bodnar M, Achim AM, Malla AK, Joober R, Benoit A, Lepage M. Functional magnetic resonance imaging correlates of memory encoding in relation to achieving remission in first-episode schizophrenia. Br J Psychiatry. 2012b;200(4):300–7. https://doi.org/10.1192/bjp.bp.111.098046.
Cahn W, van Haren NE, Hulshoff Pol HE, Schnack HG, Caspers E, Laponder DA, Kahn RS. Brain volume changes in the first year of illness and 5-year outcome of schizophrenia. Br J Psychiatry. 2006;189:381–2. https://doi.org/10.1192/bjp.bp.105.015701.
Carbon M, Correll CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. 2014;16(4):505–24.
Crossley NA, Marques TR, Taylor H, Chaddock C, Dell’Acqua F, Reinders AA, Mondelli V, DiForti M, Simmons A, David AS, Kapur S, Pariante CM, Murray RM, Dazzan P. Connectomic correlates of response to treatment in first-episode psychosis. Brain. 2017;140(2):487–96. https://doi.org/10.1093/brain/aww297.
Ebdrup BH, Skimminge A, Rasmussen H, Aggernaes B, Oranje B, Lublin H, Baare W, Glenthoj B. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. Int J Neuropsychopharmacol. 2011;14(1):69–82. https://doi.org/10.1017/s1461145710000817.
Emsley R, Rabinowitz J, Medori R. Remission in early psychosis: rates, predictors, and clinical and functional outcome correlates. Schizophr Res. 2007;89(1–3):129–39. https://doi.org/10.1016/j.schres.2006.09.013.
Fahim C, Stip E, Mancini-Marie A, Gendron A, Mensour B, Beauregard M. Differential hemodynamic brain activity in schizophrenia patients with blunted affect during quetiapine treatment. J Clin Psychopharmacol. 2005;25(4):367–71.
Friedman L, Lys C, Schulz SC. The relationship of structural brain imaging parameters to antipsychotic treatment response: a review. J Psychiatry Neurosci. 1992;17(2):42–54.
Fung G, Cheung C, Chen E, Lam C, Chiu C, Law CW, Leung MK, Deng M, Cheung V, Qi L, Nailin Y, Tai KS, Yip L, Suckling J, Sham P, McAlonan G, Chua SE. MRI predicts remission at 1 year in first-episode schizophrenia in females with larger striato-thalamic volumes. Neuropsychobiology. 2014;69(4):243–8. https://doi.org/10.1159/000358837.
Fusar-Poli P, Smieskova R, Kempton MJ, Ho BC, Andreasen NC, Borgwardt S. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev. 2013;37(8):1680–91. https://doi.org/10.1016/j.neubiorev.2013.06.001.
Garver DL, Holcomb JA, Christensen JD. Compromised myelin integrity during psychosis with repair during remission in drug-responding schizophrenia. Int J Neuropsychopharmacol. 2008;11(1):49–61. https://doi.org/10.1017/s1461145707007730.
Goghari VM, Smith GN, Honer WG, Kopala LC, Thornton AE, Su W, Macewan GW, Lang DJ. Effects of eight weeks of atypical antipsychotic treatment on middle frontal thickness in drug-naive first-episode psychosis patients. Schizophr Res. 2013;149(1–3):149–55. https://doi.org/10.1016/j.schres.2013.06.025.
Guo JY, Huhtaniska S, Miettunen J, Jaaskelainen E, Kiviniemi V, Nikkinen J, Moilanen J, Haapea M, Maki P, Jones PB, Veijola J, Isohanni M, Murray GK. Longitudinal regional brain volume loss in schizophrenia: relationship to antipsychotic medication and change in social function. Schizophr Res. 2015;168(1–2):297–304. https://doi.org/10.1016/j.schres.2015.06.016.
Guo W, Liu F, Chen J, Wu R, Li L, Zhang Z, Chen H, Zhao J. Olanzapine modulates the default-mode network homogeneity in recurrent drug-free schizophrenia at rest. Aust N Z J Psychiatry. 2017;51(10):1000–9. https://doi.org/10.1177/0004867417714952.
Guo W, Liu F, Chen J, Wu R, Li L, Zhang Z, Chen H, Zhao J. Treatment effects of olanzapine on homotopic connectivity in drug-free schizophrenia at rest. World J Biol Psychiatry. 2018;19(Suppl 3):S106–14. https://doi.org/10.1080/15622975.2017.1346280.
Hadley JA, Nenert R, Kraguljac NV, Bolding MS, White DM, Skidmore FM, Visscher KM, Lahti AC. Ventral tegmental area/midbrain functional connectivity and response to antipsychotic medication in schizophrenia. Neuropsychopharmacology. 2014;39(4):1020–30. https://doi.org/10.1038/npp.2013.305.
Ho BC, Andreasen NC, Nopoulos P, Arndt S, Magnotta V, Flaum M. Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch Gen Psychiatry. 2003;60(6):585–94. https://doi.org/10.1001/archpsyc.60.6.585.
Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJ, Birnbaum ML, Bloomfield MA, Bressan RA, Buchanan RW, Carpenter WT, Castle DJ, Citrome L, Daskalakis ZJ, Davidson M, Drake RJ, Dursun S, Ebdrup BH, Elkis H, Falkai P, Fleischacker WW, Gadelha A, Gaughran F, Glenthoj BY, Graff-Guerrero A, Hallak JE, Honer WG, Kennedy J, Kinon BJ, Lawrie SM, Lee J, Leweke FM, MacCabe JH, McNabb CB, Meltzer H, Moller HJ, Nakajima S, Pantelis C, Reis Marques T, Remington G, Rossell SL, Russell BR, Siu CO, Suzuki T, Sommer IE, Taylor D, Thomas N, Ucok A, Umbricht D, Walters JT, Kane J, Correll CU. Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174(3):216–29. https://doi.org/10.1176/appi.ajp.2016.16050503.
Huber G, Gross G, Schuttler R, Linz M. Longitudinal studies of schizophrenic patients. Schizophr Bull. 1980;6(4):592–605.
Jaaskelainen E, Juola P, Kurtti J, Haapea M, Kyllonen M, Miettunen J, Tanskanen P, Murray GK, Huhtaniska S, Barnes A, Veijola J, Isohanni M. Associations between brain morphology and outcome in schizophrenia in a general population sample. Eur Psychiatry. 2014;29(7):456–62. https://doi.org/10.1016/j.eurpsy.2013.10.006.
Kane JM, Correll CU. Past and present progress in the pharmacologic treatment of schizophrenia. J Clin Psychiatry. 2010;71(9):1115–24. https://doi.org/10.4088/JCP.10r06264yel.
Kaplan MJ, Lazoff M, Kelly K, Lukin R, Garver DL. Enlargement of cerebral third ventricle in psychotic patients with delayed response to neuroleptics. Biol Psychiatry. 1990;27(2):205–14.
Kapur S, Mamo D. Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(7):1081–90. https://doi.org/10.1016/j.pnpbp.2003.09.004.
Kasparek T, Prikryl R, Schwarz D, Kucerova H, Marecek R, Mikl M, Vanicek J, Ceskova E. Gray matter morphology and the level of functioning in one-year follow-up of first-episode schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(8):1438–46. https://doi.org/10.1016/j.pnpbp.2009.07.025.
Kennedy JL, Altar CA, Taylor DL, Degtiar I, Hornberger JC. The social and economic burden of treatment-resistant schizophrenia: a systematic literature review. Int Clin Psychopharmacol. 2014;29(2):63–76. https://doi.org/10.1097/YIC.0b013e32836508e6.
Kraguljac NV, White DM, Hadley N, Hadley JA, Ver Hoef L, Davis E, Lahti AC. Aberrant hippocampal connectivity in unmedicated patients with schizophrenia and effects of antipsychotic medication: a longitudinal resting state functional MRI study. Schizophr Bull. 2016a;42(4):1046–55. https://doi.org/10.1093/schbul/sbv228.
Kraguljac NV, White DM, Hadley JA, Visscher K, Knight D, ver Hoef L, Falola B, Lahti AC. Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone. Neuroimage Clin. 2016b;10:146–58. https://doi.org/10.1016/j.nicl.2015.11.015.
Kumari V, Peters ER, Fannon D, Antonova E, Premkumar P, Anilkumar AP, Williams SC, Kuipers E. Dorsolateral prefrontal cortex activity predicts responsiveness to cognitive-behavioral therapy in schizophrenia. Biol Psychiatry. 2009;66(6):594–602. https://doi.org/10.1016/j.biopsych.2009.04.036.
Lawrie SM, Ingle GT, Santosh CG, Rogers AC, Rimmington JE, Naidu KP, Best JJ, O’Carroll R, Goodwin GM, Ebmeier KP, et al. Magnetic resonance imaging and single photon emission tomography in treatment-responsive and treatment-resistant schizophrenia. Br J Psychiatry. 1995;167(2):202–10.
Li M, Chen Z, Deng W, He Z, Wang Q, Jiang L, Ma X, Wang Y, Chua SE, Cheung C, McAlonan GM, Sham PC, Collier DA, Gong Q, Li T. Volume increases in putamen associated with positive symptom reduction in previously drug-naive schizophrenia after 6 weeks antipsychotic treatment. Psychol Med. 2012;42(7):1475–83. https://doi.org/10.1017/s0033291711002157.
Lieberman J, Chakos M, Wu H, Alvir J, Hoffman E, Robinson D, Bilder R. Longitudinal study of brain morphology in first episode schizophrenia. Biol Psychiatry. 2001;49(6):487–99.
Lieberman JA, Tollefson GD, Charles C, Zipursky R, Sharma T, Kahn RS, Keefe RS, Green AI, Gur RE, McEvoy J, Perkins D, Hamer RM, Gu H, Tohen M. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry. 2005;62(4):361–70. https://doi.org/10.1001/archpsyc.62.4.361.
Lottman KK, Kraguljac NV, White DM, Morgan CJ, Calhoun VD, Butt A, Lahti AC. Risperidone effects on brain dynamic connectivity—a prospective resting-state fMRI study in schizophrenia. Front Psychiatry. 2017;8:14. https://doi.org/10.3389/fpsyt.2017.00014.
Luck D, Buchy L, Czechowska Y, Bodnar M, Pike GB, Campbell JS, Achim A, Malla A, Joober R, Lepage M. Fronto-temporal disconnectivity and clinical short-term outcome in first episode psychosis: a DTI-tractography study. J Psychiatr Res. 2011;45(3):369–77. https://doi.org/10.1016/j.jpsychires.2010.07.007.
Lui S, Li T, Deng W, Jiang L, Wu Q, Tang H, Yue Q, Huang X, Chan RC, Collier DA, Meda SA, Pearlson G, Mechelli A, Sweeney JA, Gong Q. Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by “resting state” functional magnetic resonance imaging. Arch Gen Psychiatry. 2010;67(8):783–92. https://doi.org/10.1001/archgenpsychiatry.2010.84.
McClure RK, Phillips I, Jazayerli R, Barnett A, Coppola R, Weinberger DR. Regional change in brain morphometry in schizophrenia associated with antipsychotic treatment. Psychiatry Res. 2006;148(2–3):121–32. https://doi.org/10.1016/j.pscychresns.2006.04.008.
Millan MJ, Andrieux A, Bartzokis G, Cadenhead K, Dazzan P, Fusar-Poli P, Gallinat J, Giedd J, Grayson DR, Heinrichs M, Kahn R, Krebs MO, Leboyer M, Lewis D, Marin O, Marin P, Meyer-Lindenberg A, McGorry P, McGuire P, Owen MJ, Patterson P, Sawa A, Spedding M, Uhlhaas P, Vaccarino F, Wahlestedt C, Weinberger D. Altering the course of schizophrenia: progress and perspectives. Nat Rev Drug Discov. 2016;15(7):485–515. https://doi.org/10.1038/nrd.2016.28.
Mitelman SA, Newmark RE, Torosjan Y, Chu KW, Brickman AM, Haznedar MM, Hazlett EA, Tang CY, Shihabuddin L, Buchsbaum MS. White matter fractional anisotropy and outcome in schizophrenia. Schizophr Res. 2006;87(1–3):138–59. https://doi.org/10.1016/j.schres.2006.06.016.
Molina V, Taboada D, Aragues M, Hernandez JA, Sanz-Fuentenebro J. Greater clinical and cognitive improvement with clozapine and risperidone associated with a thinner cortex at baseline in first-episode schizophrenia. Schizophr Res. 2014;158(1–3):223–9. https://doi.org/10.1016/j.schres.2014.06.042.
Nejad AB, Ebdrup BH, Glenthoj BY, Siebner HR. Brain connectivity studies in schizophrenia: unravelling the effects of antipsychotics. Curr Neuropharmacol. 2012;10(3):219–30. https://doi.org/10.2174/157015912803217305.
Nielsen MO, Rostrup E, Wulff S, Bak N, Broberg BV, Lublin H, Kapur S, Glenthoj B. Improvement of brain reward abnormalities by antipsychotic monotherapy in schizophrenia. Arch Gen Psychiatry. 2012;69(12):1195–204. https://doi.org/10.1001/archgenpsychiatry.2012.847.
Nielsen MO, Rostrup E, Wulff S, Glenthoj B, Ebdrup BH. Striatal reward activity and antipsychotic-associated weight change in patients with schizophrenia undergoing initial treatment. JAMA Psychiat. 2016;73(2):121–8. https://doi.org/10.1001/jamapsychiatry.2015.2582.
Palaniyappan L, Marques TR, Taylor H, Handley R, Mondelli V, Bonaccorso S, Giordano A, McQueen G, DiForti M, Simmons A, David AS, Pariante CM, Murray RM, Dazzan P. Cortical folding defects as markers of poor treatment response in first-episode psychosis. JAMA Psychiat. 2013;70(10):1031–40. https://doi.org/10.1001/jamapsychiatry.2013.203.
Palaniyappan L, Marques TR, Taylor H, Mondelli V, Reinders A, Bonaccorso S, Giordano A, DiForti M, Simmons A, David AS, Pariante CM, Murray RM, Dazzan P. Globally efficient brain organization and treatment response in psychosis: a connectomic study of gyrification. Schizophr Bull. 2016;42(6):1446–56. https://doi.org/10.1093/schbul/sbw069.
Panenka WJ, Khorram B, Barr AM, Smith GN, Lang DJ, Kopala LC, Vandorpe RA, Honer WG. A longitudinal study on the effects of typical versus atypical antipsychotic drugs on hippocampal volume in schizophrenia. Schizophr Res. 2007;94(1–3):288–92. https://doi.org/10.1016/j.schres.2007.05.002.
Petrides G, Malur C, Braga RJ, Bailine SH, Schooler NR, Malhotra AK, Kane JM, Sanghani S, Goldberg TE, John M, Mendelowitz A. Electroconvulsive therapy augmentation in clozapine-resistant schizophrenia: a prospective, randomized study. Am J Psychiatry. 2015;172(1):52–8. https://doi.org/10.1176/appi.ajp.2014.13060787.
Potvin S, Tikasz A, Lungu O, Dumais A, Stip E, Mendrek A. Emotion processing in treatment-resistant schizophrenia patients treated with clozapine: an fMRI study. Schizophr Res. 2015;168(1–2):377–80. https://doi.org/10.1016/j.schres.2015.07.046.
Prasad KM, Sahni SD, Rohm BR, Keshavan MS. Dorsolateral prefrontal cortex morphology and short-term outcome in first-episode schizophrenia. Psychiatry Res. 2005;140(2):147–55. https://doi.org/10.1016/j.pscychresns.2004.05.009.
Quarantelli M, Palladino O, Prinster A, Schiavone V, Carotenuto B, Brunetti A, Marsili A, Casiello M, Muscettola G, Salvatore M, de Bartolomeis A. Patients with poor response to antipsychotics have a more severe pattern of frontal atrophy: a voxel-based morphometry study of treatment resistance in schizophrenia. Biomed Res Int. 2014;2014:325052. https://doi.org/10.1155/2014/325052.
Reis Marques T, Taylor H, Chaddock C, Dell’Acqua F, Handley R, Reinders AA, Mondelli V, Bonaccorso S, Diforti M, Simmons A, David AS, Murray RM, Pariante CM, Kapur S, Dazzan P. White matter integrity as a predictor of response to treatment in first episode psychosis. Brain. 2014;137(Pt 1):172–82. https://doi.org/10.1093/brain/awt310.
Remington G, Agid O, Foussias G, Fervaha G, Takeuchi H, Lee J, Hahn M. What does schizophrenia teach us about antipsychotics? Can J Psychiatry. 2015;60(3 Suppl 2):S14–8.
Remington G, Foussias G, Fervaha G, Agid O, Takeuchi H, Lee J, Hahn M. Treating negative symptoms in schizophrenia: an update. Curr Treat Options Psychiatry. 2016;3:133–50. https://doi.org/10.1007/s40501-016-0075-8.
Robinson DG, Woerner MG, Alvir JM, Geisler S, Koreen A, Sheitman B, Chakos M, Mayerhoff D, Bilder R, Goldman R, Lieberman JA. Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 1999;156(4):544–9. https://doi.org/10.1176/ajp.156.4.544.
Roiz-Santianez R, Tordesillas-Gutierrez D, Ortiz-Garcia de la Foz V, Ayesa-Arriola R, Gutierrez A, Tabares-Seisdedos R, Vazquez-Barquero JL, Crespo-Facorro B. Effect of antipsychotic drugs on cortical thickness. A randomized controlled one-year follow-up study of haloperidol, risperidone and olanzapine. Schizophr Res. 2012;141(1):22–8. https://doi.org/10.1016/j.schres.2012.07.014.
Samartzis L, Dima D, Fusar-Poli P, Kyriakopoulos M. White matter alterations in early stages of schizophrenia: a systematic review of diffusion tensor imaging studies. J Neuroimaging. 2014;24(2):101–10. https://doi.org/10.1111/j.1552-6569.2012.00779.x.
Sambataro F, Blasi G, Fazio L, Caforio G, Taurisano P, Romano R, Di Giorgio A, Gelao B, Lo Bianco L, Papazacharias A, Popolizio T, Nardini M, Bertolino A. Treatment with olanzapine is associated with modulation of the default mode network in patients with schizophrenia. Neuropsychopharmacology. 2010;35(4):904–12. https://doi.org/10.1038/npp.2009.192.
Sarpal DK, Robinson DG, Lencz T, Argyelan M, Ikuta T, Karlsgodt K, Gallego JA, Kane JM, Szeszko PR, Malhotra AK. Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia. JAMA Psychiat. 2015;72(1):5–13. https://doi.org/10.1001/jamapsychiatry.2014.1734.
Sarpal DK, Argyelan M, Robinson DG, Szeszko PR, Karlsgodt KH, John M, Weissman N, Gallego JA, Kane JM, Lencz T, Malhotra AK. Baseline striatal functional connectivity as a predictor of response to antipsychotic drug treatment. Am J Psychiatry. 2016;173(1):69–77. https://doi.org/10.1176/appi.ajp.2015.14121571.
Savas HA, Unal B, Erbagci H, Inaloz S, Herken H, Canan S, Gumusburun E, Zoroglu SS. Hippocampal volume in schizophrenia and its relationship with risperidone treatment: a stereological study. Neuropsychobiology. 2002;46(2):61–6. https://doi.org/10.1159/000065413.
Scheepers FE, de Wied CC, Hulshoff Pol HE, van de Flier W, van der Linden JA, Kahn RS. The effect of clozapine on caudate nucleus volume in schizophrenic patients previously treated with typical antipsychotics. Neuropsychopharmacology. 2001;24(1):47–54. https://doi.org/10.1016/s0893-133x(00)00172-x.
Schroder J, Geider FJ, Sauer H. Can computerised tomography be used to predict early treatment response in schizophrenia? Br J Psychiatry Suppl. 1993;21:13–5.
Serpa MH, Doshi J, Erus G, Chaim-Avancini TM, Cavallet M, van de Bilt MT, Sallet PC, Gattaz WF, Davatzikos C, Busatto GF, Zanetti MV. State-dependent microstructural white matter changes in drug-naive patients with first-episode psychosis. Psychol Med. 2017;47(15):2613–27. https://doi.org/10.1017/s0033291717001015.
Snitz BE, MacDonald A 3rd, Cohen JD, Cho RY, Becker T, Carter CS. Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment. Am J Psychiatry. 2005;162(12):2322–9. https://doi.org/10.1176/appi.ajp.162.12.2322.
Staal WG, Hulshoff Pol HE, Schnack HG, van Haren NE, Seifert N, Kahn RS. Structural brain abnormalities in chronic schizophrenia at the extremes of the outcome spectrum. Am J Psychiatry. 2001;158(7):1140–2. https://doi.org/10.1176/appi.ajp.158.7.1140.
Strungas S, Christensen JD, Holcomb JM, Garver DL. State-related thalamic changes during antipsychotic treatment in schizophrenia: preliminary observations. Psychiatry Res. 2003;124(2):121–4.
Szeszko PR, Narr KL, Phillips OR, McCormack J, Sevy S, Gunduz-Bruce H, Kane JM, Bilder RM, Robinson DG. Magnetic resonance imaging predictors of treatment response in first-episode schizophrenia. Schizophr Bull. 2012;38(3):569–78. https://doi.org/10.1093/schbul/sbq126.
Szeszko PR, Robinson DG, Ikuta T, Peters BD, Gallego JA, Kane J, Malhotra AK. White matter changes associated with antipsychotic treatment in first-episode psychosis. Neuropsychopharmacology. 2014;39(6):1324–31. https://doi.org/10.1038/npp.2013.288.
Vanes LD, Mouchlianitis E, Collier T, Averbeck BB, Shergill SS. Differential neural reward mechanisms in treatment-responsive and treatment-resistant schizophrenia. Psychol Med. 2018;48(14):2418–27.
van den Heuvel MP, Fornito A. Brain networks in schizophrenia. Neuropsychol Rev. 2014;24(1):32–48. https://doi.org/10.1007/s11065-014-9248-7.
van Haren NE, Cahn W, Hulshoff Pol HE, Schnack HG, Caspers E, Lemstra A, Sitskoorn MM, Wiersma D, van den Bosch RJ, Dingemans PM, Schene AH, Kahn RS. Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study. Schizophr Res. 2003;64(1):41–52.
van Veelen NM, Vink M, Ramsey NF, van Buuren M, Hoogendam JM, Kahn RS. Prefrontal lobe dysfunction predicts treatment response in medication-naive first-episode schizophrenia. Schizophr Res. 2011;129(2–3):156–62. https://doi.org/10.1016/j.schres.2011.03.026.
Wang Y, Tang W, Fan X, Zhang J, Geng D, Jiang K, Zhu D, Song Z, Xiao Z, Liu D. Resting-state functional connectivity changes within the default mode network and the salience network after antipsychotic treatment in early-phase schizophrenia. Neuropsychiatr Dis Treat. 2017;13:397–406. https://doi.org/10.2147/ndt.s123598.
Wassink TH, Andreasen NC, Nopoulos P, Flaum M. Cerebellar morphology as a predictor of symptom and psychosocial outcome in schizophrenia. Biol Psychiatry. 1999;45(1):41–8.
Weinberger DR, Bigelow LB, Kleinman JE, Klein ST, Rosenblatt JE, Wyatt RJ. Cerebral ventricular enlargement in chronic schizophrenia. An association with poor response to treatment. Arch Gen Psychiatry. 1980;37(1):11–3.
Wobrock T, Gruber O, Schneider-Axmann T, Wolwer W, Gaebel W, Riesbeck M, Maier W, Klosterkotter J, Schneider F, Buchkremer G, Moller HJ, Schmitt A, Bender S, Schlosser R, Falkai P. Internal capsule size associated with outcome in first-episode schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2009;259(5):278–83. https://doi.org/10.1007/s00406-008-0867-y.
Zeng B, Ardekani BA, Tang Y, Zhang T, Zhao S, Cui H, Fan X, Zhuo K, Li C, Xu Y, Goff DC, Wang J. Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment. Schizophr Res. 2016;172(1–3):1–8. https://doi.org/10.1016/j.schres.2016.01.051.
Zipursky RB, Zhang-Wong J, Lambe EK, Bean G, Beiser M. MRI correlates of treatment response in first episode psychosis. Schizophr Res. 1980;30(1):81–90.
Zugman A, Gadelha A, Assuncao I, Sato J, Ota VK, Rocha DL, Mari JJ, Belangero SI, Bressan RA, Brietzke E, Jackowski AP. Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia. Schizophr Res. 2013;148(1–3):81–6. https://doi.org/10.1016/j.schres.2013.05.002.
Acknowledgements
This work was funded by K23MH110661, and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation awarded to D.K.S.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Sarpal, D.K., Malhotra, A.K. (2020). Structural and Functional Neuroimaging Biomarkers of Antipsychotic Treatment Response in Early-Course and Chronic Schizophrenia. In: Kubicki, M., Shenton, M. (eds) Neuroimaging in Schizophrenia . Springer, Cham. https://doi.org/10.1007/978-3-030-35206-6_18
Download citation
DOI: https://doi.org/10.1007/978-3-030-35206-6_18
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-35205-9
Online ISBN: 978-3-030-35206-6
eBook Packages: MedicineMedicine (R0)