Mark B. Hamner

A potential role for thalamocingulate circuitry in human maternal behavior

BACKGROUND Little is known about the regional brain basis of human maternal behavior. To understand this better, we have been examining brain activity in mothers listening to infant cries. METHODS We measured functional Magnetic Resonance Imaging brain activity in healthy, breastfeeding first-time mothers with young infants while they listened to infant cries, white noise control sounds, and a rest condition. Based on the thalamocingulate theory of maternal behavior and pilot work, we hypothesized that the cingulate, medial thalamus, medial prefrontal cortex, and right orbitofrontal cortex would display more activity with infant cries than with white noise (comparison 1) and would uniquely activate with the cries, meaning that these regions would display activity with cry minus rest but not with white noise minus rest (comparison 2). RESULTS In hypothesized regions, the group displayed more activity in the medial thalamus, medial prefrontal and right orbitofrontal cortices with both comparisons. The anterior and posterior cingulate cortex displayed more activity only with comparison 1. In non-hypothesized brain regions, several other structures thought important in rodent maternal behavior displayed activity with both comparisons including the midbrain, hypothalamus, dorsal and ventral striatum, and vicinity of the lateral septal region. CONCLUSIONS Our results partially support our hypotheses and are generally consistent with neuroanatomical studies of rodent maternal behavior.

Adjunctive risperidone treatment in post-traumatic stress disorder: a preliminary controlled trial of effects on comorbid psychotic symptoms.

Positive and negative symptoms of psychosis may be common in patients with chronic post-traumatic stress disorder (PTSD), but few studies have investigated the use of antipsychotic agents in these patients. This preliminary study examined the potential efficacy of risperidone in treating psychotic symptoms associated with chronic PTSD. In a 5-week, prospective, randomized, double-blind, placebo-controlled trial, adjunctive risperidone treatment was assessed in 40 combat veterans with chronic PTSD and comorbid psychotic features. Most patients were receiving antidepressants and some other psychotics with doses of concurrent medications held constant for at least 1 month prior to and during the study. Thirty-seven patients completed at least 1 week of treatment with risperidone or placebo. The Positive and Negative Syndrome Scale (PANSS) and the Clinician Administered PTSD Scale (CAPS) were used to assess symptoms. The PANSS was the primary outcome measure. At treatment endpoint, risperidone-treated patients showed a significantly greater decrease from baseline, albeit modest, in psychotic symptoms (PANSS total scores) than placebo-treated patients (P<0.05). CAPS ratings declined significantly in both groups but did not differ significantly between groups. However, CAPS re-experiencing subscale scores had greater improvement in the risperidone-treated patients at week 5 (P<0.05, completer analysis) with a trend towards greater improvement versus placebo a endpoint (P<0.1, LOCF). Risperidone was well tolerated with minimal extrapyramidal symptoms. These preliminary results support studying the potential efficacy of risperidone for treating global psychotic symptoms associated with chronic PTSD with a suggestion that core re-experiencing symptoms may also be responsive. Further research using randomized, controlled trial designs in larger patient groups are needed to define more adequately the role of risperidone and other atypical agents in PTSD.

Psychotic features and illness severity in combat veterans with chronic posttraumatic stress disorder

BACKGROUND Psychotic symptoms may be present in up to 40% of patients with combat-related posttraumatic stress disorder (PTSD). In this study, we hypothesized that severity of psychotic symptoms would also reflect severity of PTSD symptoms in patients with well-defined psychotic features. METHODS Forty-five Vietnam combat veterans with PTSD but without a primary psychotic disorder diagnosis underwent a Structured Clinical Interview for DSM-III-R with Psychotic Screen, and the Clinician Administered PTSD Scale (CAPS). Patients identified as having psychotic features (PTSD-P), (n = 22) also received the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). RESULTS There was a significant positive correlation between the CAPS and PANSS global ratings (p < .001) and the HDRS and PANSS (p < .03) in the PTSD-P patients. Many CAPS and PANSS subscales also demonstrated significant intercorrelations; however, the CAPS-B subscale (reexperiencing) and the PANSS positive symptom scale were not correlated, suggesting that psychotic features may not necessarily be influenced or accounted for by more severe reexperiencing symptoms. Fifteen (68%) of the PTSD-P patients had major depression (MDD). Both CAPS and PANSS ratings were significantly higher in the PTSD-P patients with comorbid MDD. CONCLUSIONS As postulated, patients with more severe psychosis ratings are likely to have more severe PTSD disease burden if psychotic features are present. This study further documents the occurrence of psychotic features in PTSD that are not necessarily due to a primary psychotic disorder, suggesting that this may be a distinct subtype; however, a significant interaction likely exists between PTSD, depression, and psychotic features.

Prolonged exposure therapy for combat-related posttraumatic stress disorder: An examination of treatment effectiveness for veterans of the wars in Afghanistan and Iraq

The Veterans Health Administration (VHA) has launched a large-scale initiative to promote prolonged exposure (PE) therapy, an evidence-based treatment for PTSD. While existing randomized controlled trials (RCTs) unambiguously support the efficacy of PE in civilian and some military populations, there is a need to better understand the course of treatment for combat Veterans of the current wars receiving PE in normative mental healthcare settings. The current study investigates 65 Veterans receiving care at an urban VA medical center. All Veterans were diagnosed with PTSD via a structured interview and treated with PE. Measures of PTSD and depression were collected pre- and post-treatment and every two sessions during treatment. Dependent means t-tests were used to estimate pre- and post-treatment d-type effect sizes. Additionally, hierarchical linear models (HLM) were used to investigate treatment effects over time, relationships between patient characteristics and outcomes, and to provide estimates of R(2)-type effect sizes. Results indicate that PE in regular VA mental healthcare contexts can be as effective as when implemented in carefully conducted RCTs.

POTENTIAL ROLE OF THE ANTERIOR CINGULATE CORTEX IN PTSD : REVIEW AND HYPOTHESIS

Many symptoms of PTSD represent conditioned responses to stimuli associated with a traumatic experiences. In this review, we propose that the anterior cingulate—a brain region that appears to be involved in fear‐conditioning—is dysfunctional in PTSD, thus facilitating exaggerated emotional and behavioral responses (hyperarousal) to conditioned stimuli. Preclinical studies suggest that the anterior cingulate may serve a critical gating function in modulating conditioned fear responses. As such, this region would be a key component of a neural circuit involved in the pathophysiology of PTSD. An amygdala‐locus coeruleus‐anterior cingulate circuit may be consistent with evidence for chronic noradrenergic activation documented in PTSD patients. According to this model, efferent noradrenergic projections from the locus coeruleus may dampen anterior cingulate function. This in turn would allow myriad external or internally driven stimuli to produce the exaggerated emotional and behavioral responses characteristic of PTSD. If confirmed in future research, cingulate dysfunction would have important theoretical and treatment implications. Depression and Anxiety 9:1–14, 1999. Published 1999 Wiley‐Liss, Inc.

Quetiapine treatment in patients with posttraumatic stress disorder: An open trial of adjunctive therapy

In this 6-week, open-label trial, combat veterans meeting DSM-IV criteria for posttraumatic stress disorder (PTSD) were treated with the atypical antipsychotic quetiapine. The starting dose was 25 mg at bedtime with subsequent titration based on tolerability and clinical response. Primary outcome was measured using the Clinician Administered PTSD Scale (CAPS). Secondary assessments of efficacy included the Positive and Negative Symptom Scale (PANSS), the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Safety and tolerability evaluations included neurologic ratings, vital signs, and assessment of treatment-emergent side effects. Eighteen of 20 patients enrolled in the study completed 6 weeks of open-label treatment. The dose range of quetiapine was 25 to 300 mg daily, with an average of 100±70 mg/d. There was significant improvement in CAPS scores, from 89.8±15.7 to 67.5±21.0 (t=4.863, df=18, P <0.005), and composite PANSS ratings from baseline to endpoint. General psychopathology (PANSS) and depressive symptoms (HRSD) were also reduced at the 6-week end point. There were no serious adverse events and no clinically significant changes in vital signs or neurologic ratings. This preliminary open trial suggests that quetiapine is well tolerated and may have efficacy in reducing PTSD symptoms in patients who have not had an adequate response other medications. Studies utilizing a randomized, controlled trial design and larger sample sizes are needed to better define the potential role of quetiapine and other atypical antipsychotics in the treatment of PTSD.

Psychotic features in chronic posttraumatic stress disorder and schizophrenia: Comparative severity

Psychotic features are frequent in combat veterans with chronic posttraumatic stress disorder (PTSD), may correlate with severity of PTSD symptoms, and may reflect a distinct subtype of the disorder. These psychotic features include auditory and visual hallucinations and delusional thinking that is usually paranoid in nature. Psychotic features may be under-recognized in chronic PTSD because patients are reluctant to report these symptoms and because they may not have overt changes in affect or bizarre delusions characteristic of other psychoses, e.g., schizophrenia. To further assess these phenomena, we compared clinical ratings on the Positive and Negative Syndrome Scale (PANSS) and other assessments, including the Clinical Global Impression Scale and the Structured Clinical Interview with Psychotic Screen, in veterans meeting DSM-IV criteria for chronic PTSD with well-defined comorbid psychotic features (N = 40) or chronic schizophrenia (N = 40). The patients with schizophrenia had modestly higher composite PANSS scores and positive symptom scores although average scores in both groups were moderate to severe in intensity. Negative symptom and general psychopathology subscale scores were comparable in both groups. Regarding specific positive symptoms, hallucinations were comparable between groups in severity; however, schizophrenia patients had slightly more intense delusions and conceptual disorganization. These data further validate the occurrence of positive as well as negative symptoms of psychosis in chronic PTSD in a range of severity that may approach that of patients with schizophrenia. Although meeting DSM-IV criteria for two different major psychiatric disorders, these two patient populations were remarkably similar with respect to not only positive but also negative symptoms.

Treatment-Resistant Posttraumatic Stress Disorder: Strategies for Intervention

The mainstay of treatment for chronic posttraumatic stress disorder (PTSD) is a combination of psychotherapy and medication treatments. The first-line medications for PTSD are antidepressants, with two selective serotonin reuptake inhibitors (sertraline and paroxetine) currently Food and Drug Administration-indicated for PTSD. However, many patients do not have an adequate response to antidepressants, therefore, combinations with other antidepressants or with other classes of psychotropic medication are often utilized to enhance the therapeutic response. Other agents that have been used include mood stabilizers, anti-adrenergics, anxiolytics, and atypical antipsychotics. The heterogeneity of symptom clusters in PTSD as well as the complex psychiatric comorbidities (eg, with depression or substance abuse) further support the notion that combinations of medications may be needed. To date, there is a paucity of data to support specific strategies for augmenting antidepressants in PTSD. This review will address representative existing studies and discuss several potential pharmacologic strategies for patients suffering from treatment-refractory PTSD.

Psychotic features and combat-associated PTSD.

Psychotic symptoms and psychotic disorder diagnoses have occasionally been reported in association with chronic posttraumatic stress disorder (PTSD). Although psychotic features may be related to core PTSD symptoms, i.e., part of the reexperiencing phenomena, it is possible that they are secondary to certain comorbid disorders which are also prevalent in this patient population, e.g., major depression or substance abuse. In a prospective study, combat associated PTSD patients (n = 25) were administered clinical ratings, including the Structured Clinical Interview for DSM‐III‐R with psychotic screen (SCID‐P), Clinician Administered PTSD Scale (CAPS) and the Impact of Events Scale (IES). Thirty‐six percent (n = 9) endorsed psychotic symptoms with associated comorbidity including: major depressive episode, bipolar disorder, alcohol or polysubstance abuse panic disorder, and phobias. All but one of the patients with psychotic features also met criteria for major depressive episode. None had a primary psychotic disorder diagnosis. There were no significant differences in total CAPS scores between patients with or without psychotic features (82.6 ± 17.6 versus 75.3 ± 22.4, p ns), nor for the different symptom cluster subscales. There were also no differences in the IES scores between groups (34.8 ± 10 versus 32.6 ± 10 p ns). This suggests that these psychotic features may not necessarily reflect severity of PTSD symptoms. PTSD may share a common diathesis with mood disorders including psychotic depression. Further study is needed of these phenomena. Depression and Anxiety 5:34–38, 1997.

Clinical Presentations of Posttraumatic Stress Disorder across Trauma Populations: A Comparison of MMPI-2 Profiles of Combat Veterans and Adult Survivors of Child Sexual Abuse

This investigation examined differences in symptom patterns of two different trauma samples using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). MMPI-2s of 122 male combat veterans seeking outpatient treatment for combat-related PTSD were compared with those of 64 PTSD-diagnosed adults seeking outpatient treatment for the effects of child sexual abuse (CSA). We examined variables related to degree of health concerns, depression, somatization, anger and hostility, masculine-feminine traits, paranoid ideation, anxiety, difficulties thinking and concentrating, elevated mood, and social introversion, as well as test-taking attitude. MANOVAs revealed between-group differences on several variables. However, when analyses controlled for the effect of age, nearly all differences disappeared; the only remaining difference was in a scale measuring anger. Thus, it appears CSA survivors and combat veterans are much more similar than different in their clinical presentation on the MMPI-2. Conceptual issues in the assessment of PTSD are discussed.